Diffusion Weighted Imaging (DWI) or Computerized Tomography Perfusion (CTP) Assessment With Clinical Mismatch in the Triage of Wake Up and Late Presenting Strokes Undergoing Neurointervention (DAWN)
Phase: NA
Conditions: Ischemic Stroke
Sponsor: Stryker Neurovascular

Stryker Neurovascular 
Document Title: DAWN™ Trial Investigational Plan 
Document Number: CDM10000146 
Rev:  AD 
STRYKER CONFIDENTIAL - THIS DOCUMENT CONTAINS CONFIDENTIAL AND PROPRIETARY INFORMATION THAT 
IS THE PROPERTY OF STRYKER CORPORATION. NEITHER THIS DOCUMENT NOR THE INFORMATION HEREIN MAY 
BE REPRODUCED, USED, OR DISCLOSED TO ANY THIRD PARTY WITHOUT THE PRIOR WRITTEN CONSENT OF 
STRYKER CORPORATION                                                                                                                                 
 
 
CDM10000146  Page 1 of 91 
Sponsor: 
Stryker Neurovascular 
47900 Bayside Parkway  
Fremont, California 94538-6515 
Study Responsibility: 
Christine Yang Toruno 
Clinical Project Manager 
Stryker Neurovascular 
47900 Bayside Parkway  
Fremont, California 94538-6515 
Email: christine.toruno@stryker.com   
Tel: (510) 413-2841 
e-Fax: (855) 328-1403 
Coordinating Principal 
Investigators: 
Tudor G. Jovin, MD 
Associate Professor of Neurology and Neurosurgery 
Director UPMC Stroke Institute 
 
UPMC Presbyterian, Fourth Floor, Suite C400  
200 Lothrop Street 
Pittsburgh, PA 15213 
 
Email: jovitg@upmc.edu   
Tel: (412) 647-4999 or (412) 647-3030 
Fax: (412) 647-8445 
 
Raul Nogueira, MD 
Director of Neuroendovascular Service 
Marcus Stroke & Neuroscience Center 
Grady Memorial Hospital 
Associate Professor of Neurology, Neurosurgery and Radiology 
Emory University School of Medicine 
 
Emory Faculty Office Building 
80 Jesse Hill Drive SE Room# 398 
Atlanta, GA 30303 
 
Email: raul.g.nogueira@emory.edu  
Tel: (404) 616-4013 
Fax: (404) 659-0849 
Study Centers: 
A current list of sites will be maintained in the Sponsor’s Study Files. 
Date / Version: 
24 Apr 2014 Rev: AA 
Date(s) of Amendment(s):  14 Sep 2015 Rev: AB; 28 April 2016 Rev: AC; 26 Jan 2017 Rev: AD 
 
This protocol contains confidential information for use by the Investigators and their designated 
representatives participating in this clinical investigation. It should be held confidential and maintained in 
a secure location.  Do not copy or distribute without written permission. 
 

Stryker Neurovascular 
Document Title: DAWN™ Trial Investigational Plan 
Document Number: CDM10000146 
Rev:  AD 
STRYKER CONFIDENTIAL - THIS DOCUMENT CONTAINS CONFIDENTIAL AND PROPRIETARY INFORMATION THAT 
IS THE PROPERTY OF STRYKER CORPORATION. NEITHER THIS DOCUMENT NOR THE INFORMATION HEREIN MAY 
BE REPRODUCED, USED, OR DISCLOSED TO ANY THIRD PARTY WITHOUT THE PRIOR WRITTEN CONSENT OF 
STRYKER CORPORATION                                                                                                                                 
 
 
CDM10000146  Page 2 of 91 
DAWN™ Trial Investigator Agreement 
 
I have read this Investigational Plan and agree to adhere to the requirements of this current 
version of the protocol. 
 
I agree to personally conduct or supervise the research, and ensure all participating investigators 
and research staff are appropriately informed and trained prior to participating in any study 
related activities. 
 
I will ensure that the requirements relating to obtaining informed consent in 21 CFR Part 50, 
ICH E6 and institutional review board/Ethics Committee (IRB/EC) review and approval in 21 
CFR Part 56  are met. I will ensure that the IRB/EC complies with the requirements of ICH E6 
and 21 CFR Part 56 and will be responsible for the initial and continuing review and approval of 
the investigation.  I agree to promptly report to the IRB/EC and to the Sponsor all changes in the 
research activity and all unanticipated problems involving risks to human subjects or others.  I 
will not make any changes in research without IRB/EC approval, except where necessary to 
eliminate apparent immediate hazards to human subjects. 
 
I agree to comply with all other requirements regarding the obligations of clinical investigators 
and all other pertinent requirements in ICH E6 and 21 CFR Part 812, and/or the laws and 
regulatory requirements of the country in which the site is located. 
 
I agree to maintain adequate and accurate records in accordance with 21 CFR 812.140 and to 
make those records available for inspection in accordance with 21 CFR 812.145 and ICH E6. 
 
I agree to comply with all state and federal laws and regulations governing financial disclosure 
and to supply updated disclosure information, as it becomes known to me, during the course of 
the Trial and for one year following completion of the Trial, unless otherwise required by law or 
regulation. 
 
I have not been restricted from participating in clinical research, nor is any action pending that 
could result in such restriction.  If this occurs I shall provide immediate notification to the 
Sponsor.  
 
I have NOT been involved in an investigation or other research that was terminated:   
☐ True    
☐ False  
If False, please provide an explanation (including the circumstances that led to the termination):  
_____________________________________________________________________________ 
 
_____________________________________________________________________________ 
Investigator Name (print) 
Signature 
dd-mmm-yyyy  
 
_____________________________________________________________________________ 
Co-Investigator Name (print)  ☐N/A 
Signature 
dd-mmm-yyyy 

Stryker Neurovascular 
Document Title: DAWN™ Trial Investigational Plan 
Document Number: CDM10000146 
Rev:  AD 
STRYKER CONFIDENTIAL - THIS DOCUMENT CONTAINS CONFIDENTIAL AND PROPRIETARY INFORMATION THAT 
IS THE PROPERTY OF STRYKER CORPORATION. NEITHER THIS DOCUMENT NOR THE INFORMATION HEREIN MAY 
BE REPRODUCED, USED, OR DISCLOSED TO ANY THIRD PARTY WITHOUT THE PRIOR WRITTEN CONSENT OF 
STRYKER CORPORATION                                                                                                                                 
 
 
CDM10000146  Page 3 of 91 
Protocol Synopsis 
DAWN™ Trial 
DWI or CTP Assessment with Clinical Mismatch in the Triage of Wake Up 
and Late Presenting Strokes Undergoing Neurointervention 
Study Objective 
Primary Objective To evaluate the hypothesis that Trevo thrombectomy plus medical management leads to 
superior clinical outcomes at 90 days as compared to medical management alone in 
appropriately selected subjects experiencing an acute ischemic stroke when treatment is 
initiated within 6-24 hours after last seen well. 
Secondary 
Objective(s) 
To provide evidence that endovascular reperfusion with Trevo is associated with a 
significant reduction in median infarct size compared to the control group at 24 (-6/+24) 
hours post randomization. 
Test Device 
Trevo® ProVue™ and Trevo® XP ProVue™ Retrievers 
Study Design  
Study Design 
Prospective, randomized, multi-center, Phase II/III (feasibility/pivotal), adaptive, population 
enrichment, blinded endpoint, controlled trial. 
Planned Number of 
Subjects 
A maximum of 500 subjects is planned to be enrolled; 250 in the Treatment arm and 250 in 
the Control arm. The minimum sample size is 150 subjects. 
Planned Number of 
Sites / Countries 
Worldwide (up to 50 sites). No more than 20 sites will be outside of the U.S. 
Primary Endpoint 
90-day disability assessed by the modified Rankin scale (mRS) 
Secondary 
Endpoints 
1. Proportion of subjects with a good functional outcome at 90 days, defined as mRS 0-2  
2. Proportion of subjects with “early response” at Day 5-7/Discharge (whichever is 
earlier),  defined as a NIHSS drop of ≥10 points from baseline or NIHSS score 0 or 1 
3. Difference in all cause mortality rates between the two groups. 
4. Difference in median final infarct size at 24 (-6/+24) hours from randomization, by 
MRI T2/Flair or CT (if contraindicated for MR)  
5. Difference in revascularization rates at 24 (-6/+24) hours from randomization, by CT-
MR core lab assessment of vessel patency on CTA/MRA. 
6. Treatment Arm Only: Analysis of vessel reperfusion rates (percentages) post device 
and post procedure, by angiography core lab measurement of modified TICI > 2b  
 
 
 

Stryker Neurovascular 
Document Title: DAWN™ Trial Investigational Plan 
Document Number: CDM10000146 
Rev:  AD 
STRYKER CONFIDENTIAL - THIS DOCUMENT CONTAINS CONFIDENTIAL AND PROPRIETARY INFORMATION THAT 
IS THE PROPERTY OF STRYKER CORPORATION. NEITHER THIS DOCUMENT NOR THE INFORMATION HEREIN MAY 
BE REPRODUCED, USED, OR DISCLOSED TO ANY THIRD PARTY WITHOUT THE PRIOR WRITTEN CONSENT OF 
STRYKER CORPORATION                                                                                                                                 
 
 
CDM10000146  Page 4 of 91 
Primary Safety 
Outcome   
Both Arms:  
1. Incidence of stroke-related mortality at 90 days 
Secondary Safety  
Outcomes 
Both Arms:  
1. Incidence of SICH, by ECASS III definition, within 24 (-6/+24) hours post 
randomization (time zero) 
2. Incidence of neurological deterioration from baseline NIHSS score through Day 
5-7/discharge (whichever is earlier) post randomization (time zero). Neurological 
deterioration is defined as ≥ 4 point increase in the NIHSS score from the baseline 
score.  
Treatment Arm:  
3. Incidence of procedure-related and device-related serious adverse events 
(PRSAEs and DRSAEs) through 24 (-6/+24) hours post randomization (time 
zero) as adjudicated by the clinical events committee, and defined as:  
a. 
vascular perforation 
b. intramural arterial dissection 
c. 
embolization to a new territory 
d. access site complication requiring surgical repair or blood transfusion 
e. 
intra-procedural mortality 
f. 
device failure (in vivo breakage) 
g. any other complications adjudicated by the CEC to be related to the 
procedure 
Efficacy Parameter Modified Rankin Scale score at 90 days: 
0 - No symptoms at all 
1 - No significant disability despite symptoms; able to carry out all usual duties and 
     activities 
2 - Slight disability; unable to carry out all previous activities, but able to look after  own  
     affairs without assistance 
3 - Moderate disability; requiring some help, but able to walk without assistance 
4 - Moderately severe disability; unable to walk without assistance and unable to attend to  
     own bodily needs without assistance 
5 - Severe disability; bedridden, incontinent and requiring constant nursing care and  
     attention 
6 - Dead 
Note: For purposes of primary efficacy weighted mRS analysis each mRS category will be 
assigned a numerical value representing its clinical utility, as follows:  
 
 
mRS 
0 
1 
2 
3 
4 
5 
6 
Weight 
10 
9.1 
7.6 
6.5 
3.3 
0 
0 
Randomization 
Subjects will be randomized 1:1 to Trevo thrombectomy plus medical management or 
medical management alone.  
Stratification will occur by:  Clinical Imaging Mismatch (CIM) subgroup (see Imaging 
Inclusion Criteria), Time Last Seen Well (TLSW) ≥ 6 to < 12 hours vs. >12 to ≤ 24 hours, 
and Baseline Occlusion Location (ICA vs. M1).  
 
After randomization, no crossover is permitted. 
 
Enrollment in this study is defined as the moment when the randomization process is 
completed and the subject is assigned to a study arm. 

Stryker Neurovascular 
Document Title: DAWN™ Trial Investigational Plan 
Document Number: CDM10000146 
Rev:  AD 
STRYKER CONFIDENTIAL - THIS DOCUMENT CONTAINS CONFIDENTIAL AND PROPRIETARY INFORMATION THAT 
IS THE PROPERTY OF STRYKER CORPORATION. NEITHER THIS DOCUMENT NOR THE INFORMATION HEREIN MAY 
BE REPRODUCED, USED, OR DISCLOSED TO ANY THIRD PARTY WITHOUT THE PRIOR WRITTEN CONSENT OF 
STRYKER CORPORATION                                                                                                                                 
 
 
CDM10000146  Page 5 of 91 
Study Duration 
 
 Enrollment: approximately 36 months 
 Subject participation: 90 days (± 14) 
 Total Study Duration: approximately 39 months (+/- 9 months) 
Follow-Up 
Schedule 
 
All follow up time points are relative to time of randomization (time zero) with baseline 
data considered as data generated from time of index stroke admission and prior to 
randomization. 
1. 24 (-6/+24) hours:  MRI/MRA or CT/CTA (if MR is contra-indicated) and NIHSS 
assessment. Final infarct volume will be measured by MRI T2/Flair or CT (if MR is 
contraindicated). 
2. Day 5-7 (if subject remains in hospital) or discharge, whichever is earlier: NIHSS and 
blinded mRS (Optional repeat MRI T2/Flair or CT, if MR is contraindicated, may be 
performed to assess infarct volume) 
3. Day 30 (± 14): NIHSS and blinded mRS 
4. Day 90 (± 14): NIHSS and blinded mRS 
General Inclusion 
Criteria 
1. Clinical signs and symptoms consistent with the diagnosis of an acute ischemic stroke, 
and subject belongs to one of the following subgroups: 
a. Subject has failed IV t-PA therapy (defined as a confirmed persistent occlusion 60 
min after administration)  
b. Subject is contraindicated for IV t-PA administration 
2. Age ≥18 
3. Baseline NIHSS ≥10 (assessed within one hour of measuring core infarct volume) 
4. Subject can be randomized between 6 to 24 hours after time last known well 
5. No significant pre-stroke disability (pre-stroke mRS must be 0 or 1) 
6. Anticipated life expectancy of at least 6 months 
7. Subject willing/able to return for protocol required follow up visits 
8. Subject or subject’s Legally Authorized Representative (LAR) has signed the study 
Informed Consent form* 
 
* If approved by local ethics committee and country regulations, the investigator is allowed 
to enroll a patient utilizing emergency informed consent procedures if neither the patient 
nor the representative or person of trust is available to sign the informed consent form. 
However, as soon as possible, the patient is informed and his/her consent is requested for 
the possible continuation of this research. (Not applicable to U.S. Sites.) 
General Inclusion 
Criteria   
(additional 
information) 
1. Subjects receiving heparin or low molecular weight (LMW) heparin e.g. Fragmin® 
(Dalteparin Sodium) or an intravenous direct thrombin inhibitor such as Angiomax® 
(Bivalirudin), or Argatroban within the last 24 hours from screening are eligible for 
participation if their coagulation profile remains acceptable. 
2. Subjects on factor Xa inhibitors (e.g. apixaban) or direct thrombin inhibitors are 
eligible for participation 
Imaging Inclusion 
Criteria 
1. < 1/3 MCA territory involved, as evidenced by CT or MRI 
2. Occlusion of the intracranial ICA and/or MCA-M1, as evidenced by MRA or CTA 
3. Clinical Imaging Mismatch (CIM) defined as one of the following on MR-DWI or 
CTP-rCBF maps: 
a. 0-<21 cc core infarct and NIHSS ≥ 10 (and age ≥ 80 years old) 
b. 0-<31 cc core infarct and NIHSS ≥ 10 (and age  < 80 years old) 
c. 31 cc to <51 cc core infarct and NIHSS ≥ 20 (and age < 80 years old) 

Stryker Neurovascular 
Document Title: DAWN™ Trial Investigational Plan 
Document Number: CDM10000146 
Rev:  AD 
STRYKER CONFIDENTIAL - THIS DOCUMENT CONTAINS CONFIDENTIAL AND PROPRIETARY INFORMATION THAT 
IS THE PROPERTY OF STRYKER CORPORATION. NEITHER THIS DOCUMENT NOR THE INFORMATION HEREIN MAY 
BE REPRODUCED, USED, OR DISCLOSED TO ANY THIRD PARTY WITHOUT THE PRIOR WRITTEN CONSENT OF 
STRYKER CORPORATION                                                                                                                                 
 
 
CDM10000146  Page 6 of 91 
General Exclusion 
Criteria 
1. History of severe head injury within past 90 days with residual neurological deficit, as 
determined by medical history 
2. Rapid improvement in neurological status to an NIHSS <10 or evidence of vessel 
recanalization prior to randomization 
3. Pre-existing neurological or psychiatric disease that would confound the neurological 
or functional evaluations, e.g. dementia with prescribed anti-cholinesterase inhibitor 
(e.g. Aricept)  
4. Seizures at stroke onset if it makes the diagnosis of stroke doubtful and precludes 
obtaining an accurate baseline NIHSS assessment 
5. Baseline blood glucose of <50mg/dL (2.78 mmol) or >400mg/dL (22.20 mmol) 
6. Baseline hemoglobin counts of <7 mmol/L (11.28 g/dL) 
7. Baseline platelet count < 50,000/uL 
8. Abnormal baseline electrolyte parameters as defined by sodium concentration <130 
mmol/L, potassium concentration <3 mEq/L or >6 mEq/L 
9. Renal failure as defined by a serum creatinine >3.0 mg/dL (264 µmol/L)    
NOTE: subjects on renal dialysis may be treated regardless of serum creatinine levels 
10. Known hemorrhagic diathesis, coagulation factor deficiency, or on anticoagulant 
therapy with INR > 3.0 or PTT > 3 times normal.   
NOTE: Patients on factor Xa inhibitor within 24-48 hours must have PTT within 3 
times normal. 
11. Any active or recent hemorrhage within the past 30 days 
12. History of severe allergy (more than rash)  to contrast medium  
13. Severe, sustained hypertension (Systolic Blood Pressure >185 mmHg or Diastolic 
Blood Pressure >110 mmHg) 
NOTE: If the blood pressure can be successfully reduced and maintained at the     
acceptable level using medication the subject can be enrolled 
14. Female who is pregnant or lactating at time of admission 
15. Current participation in another investigational drug or device study  
16. Presumed septic embolus, or suspicion of bacterial endocarditis 
17. Treatment with any cleared thrombectomy devices or other intra-arterial 
(neurovascular) therapies prior to randomization 
Exclusion Criteria 
(additional 
information) 
1. The “correction” of baseline glucose or coagulation laboratory values to meet 
inclusion criteria will not be allowed.  
2. Subjects who have taken Clopidogrel, aspirin, or both within the last 24 hours from 
screening for the trial should not be excluded if their coagulation profile remains 
acceptable.  
3. Subjects with a questionable seizure at onset of stroke should not be excluded if 
CTA/MRA confirms the presence of intracranial ICA and/or M1 occlusion, and 
accurate NIHSS can be obtained. 
Imaging Exclusion 
Criteria 
1. Evidence of intracranial hemorrhage on CT/MRI 
2. CTA or MRA evidence of flow limiting carotid dissection, high-grade stenosis, or 
complete cervical carotid occlusion requiring stenting at the time of the index 
procedure (i.e., mechanical thrombectomy). 
3. Excessive tortuosity of cervical vessels on CTA/MRA that would likely preclude 
device delivery/deployment  
4. Suspected cerebral vasculitis based on medical history and CTA/MRA 
5. Suspected aortic dissection based on medical history and CTA/MRA 
6. Intracranial stent implanted in the same vascular territory that would preclude the safe 
deployment/removal of the Trevo device 

Stryker Neurovascular 
Document Title: DAWN™ Trial Investigational Plan 
Document Number: CDM10000146 
Rev:  AD 
STRYKER CONFIDENTIAL - THIS DOCUMENT CONTAINS CONFIDENTIAL AND PROPRIETARY INFORMATION THAT 
IS THE PROPERTY OF STRYKER CORPORATION. NEITHER THIS DOCUMENT NOR THE INFORMATION HEREIN MAY 
BE REPRODUCED, USED, OR DISCLOSED TO ANY THIRD PARTY WITHOUT THE PRIOR WRITTEN CONSENT OF 
STRYKER CORPORATION                                                                                                                                 
 
 
CDM10000146  Page 7 of 91 
7. Occlusions in multiple vascular territories (e.g., bilateral anterior circulation, or 
anterior circulation/vertebrobasilar system) as confirmed on CTA/MRA, or clinical 
evidence of bilateral strokes or strokes in multiple territories 
8. Significant mass effect with midline shift as confirmed on CT/MRI 
9. Evidence of intracranial tumor (except small meningioma) as confirmed on CT/MRI 
Concomitant 
Medication 
Therapies 
Treatment Arm: 
1. Use of IV or IA lytics, or IA antiplatelets is prohibited in subjects randomized to the 
treatment arm during the procedure and until after follow up imaging is completed. 
2. Systemic anticoagulation with heparin may be used during the procedure, but should 
not exceed a total of 2,000 units of heparin bolus followed by a 500 units/hour drip for 
the duration of the procedure. 
3. Prudent use of anti-vasospasm agents is permitted during the procedure. 
Medical Management Arm: 
4. IV heparin is prohibited until after the 24 (-6/+24) hour neuro-imaging has been 
performed to determine the presence/absence of intracranial hemorrhage.   
5. The administration of medications is at the treating physician’s discretion according to 
local standards of care, but may NOT include any intra-arterial therapies. 
Both Arms: 
6. Newly administered Aspirin (IV or oral) and/or Clopidogrel are the only anti-platelets 
allowed within the first 24 hours post randomization, until after the 24 (-6/+24) hour 
neuro-imaging has been performed to determine the presence/absence of intracranial 
hemorrhage.  
7. Subjects previously treated with antiplatelet agents or combination antiplatelet therapy 
(e.g. for a previously implanted drug eluting stent), may continue this if in the 
investigator’s opinion the benefits of continued therapy outweigh the risks of potential 
neurological deterioration related to hemorrhage.  
8. Subcutaneous Low Molecular Weight (LMW) heparin is allowed for Deep Vein 
Thrombosis (DVT) prophylaxis per the center’s standard of care. 
Multiple 
Interventions  
Once randomized, subjects in either arm may not be treated with any additional planned 
endovascular therapy or endarterectomy until after the 24 (-6/+24) hour post randomization 
assessments have been completed. 
Statistical Methods 
Primary Statistical 
Null Hypothesis 
The null hypothesis is that there is no difference in the proportion of subjects functionally 
independent (mRS 0-2) at 90 days in the Trevo Thrombectomy plus Medical Management 
group compared to Medical Management alone nor in the average of the weighted mRS 
categories at 90 days in the Trevo Thrombectomy plus Medical Management group 
compared to Medical Management alone. 
 
Statistical Test 
Method 
The alternative hypothesis is that the proportion of subjects functionally independent (mRS 
0-2) and the average of the weighted mRS categories at 90 days in the Trevo 
Thrombectomy plus Medical Management group is superior to Medical Management 
alone. The final analysis is a Bayesian analysis of the 90-day mRS scores, and declares 
success if there is sufficiently large posterior probability that the overall treatment effect is 
positive. The threshold for success if no enrichments are made is 0.986, and this threshold 
increases as the enrichment becomes earlier and more aggressive.  The adjusted thresholds 
are to control type I error. Enrichment decisions and early stopping rules are based on 
Bayesian predictive probabilities outlined in the Adaptive Design Plan in Appendix F. 

Stryker Neurovascular 
Document Title: DAWN™ Trial Investigational Plan 
Document Number: CDM10000146 
Rev:  AD 
STRYKER CONFIDENTIAL - THIS DOCUMENT CONTAINS CONFIDENTIAL AND PROPRIETARY INFORMATION THAT 
IS THE PROPERTY OF STRYKER CORPORATION. NEITHER THIS DOCUMENT NOR THE INFORMATION HEREIN MAY 
BE REPRODUCED, USED, OR DISCLOSED TO ANY THIRD PARTY WITHOUT THE PRIOR WRITTEN CONSENT OF 
STRYKER CORPORATION                                                                                                                                 
 
 
CDM10000146  Page 8 of 91 
 
Sample Size 
Parameters 
The sample size for the trial is assessed through simulation, which considered effect sizes 
ranging from zero to a 1.5 increase on the weighted mRS scale. For one-sided Type I error 
probability of 2.5%, the design has 86% power for a 1 unit increase in weighted mRS. 
 
 
 

Stryker Neurovascular 
Document Title: DAWN™ Trial Investigational Plan 
Document Number: CDM10000146 
Rev:  AD 
STRYKER CONFIDENTIAL - THIS DOCUMENT CONTAINS CONFIDENTIAL AND PROPRIETARY INFORMATION THAT 
IS THE PROPERTY OF STRYKER CORPORATION. NEITHER THIS DOCUMENT NOR THE INFORMATION HEREIN MAY 
BE REPRODUCED, USED, OR DISCLOSED TO ANY THIRD PARTY WITHOUT THE PRIOR WRITTEN CONSENT OF 
STRYKER CORPORATION                                                                                                                                 
 
 
CDM10000146  Page 9 of 91 
 
 
 
1 
Introduction and Rationale ........................................................................................................................ 13 
1.1 
Incidence and Burden of Stroke ...................................................................................................... 13 
1.2 
Current Treatment Options ............................................................................................................. 13 
1.3 
Unmet Need in Acute Ischemic Stroke ........................................................................................... 13 
1.4 
Purpose of Study ............................................................................................................................. 15 
2 
Study Device................................................................................................................................................. 15 
2.1 
Study Device Description ............................................................................................................... 15 
2.2 
Study Device Labeling .................................................................................................................... 17 
3 
Study Objective ........................................................................................................................................... 18 
3.1 
Primary Objective ........................................................................................................................... 18 
3.2 
Secondary Objectives ...................................................................................................................... 18 
4 
Study Endpoints and Safety Outcomes ..................................................................................................... 18 
4.1 
Primary Endpoint ............................................................................................................................ 18 
4.2 
Secondary Endpoints....................................................................................................................... 19 
4.3 
Primary Safety Outcome ................................................................................................................. 19 
4.4 
Secondary Safety Outcomes ........................................................................................................... 19 
5 
Study Design ................................................................................................................................................ 20 
5.1 
Overview ......................................................................................................................................... 20 
5.2 
Justification for the Study Design ................................................................................................... 22 
5.2.1 .... Justification for Expansion of Time Window ....................................................... 23 
5.2.2 .... Justification for Inclusion of Wake up and Unclear Onset Strokes ..................... 27 
5.2.3 .... Justification for Inclusion of IV tPA Failures ...................................................... 27 
5.2.4 .... Justification for Non Reliance on Penumbra Imaging......................................... 28 
5.2.5 .... Justification for Use of Clinical Imaging Mismatch Criteria .............................. 29 
5.2.6 .... Justification for Use of Standardized Core Infarct Imaging Software ................ 31 
5.2.7 .... Justification for Use of Weighted mRS as Primary Endpoint .............................. 31 
5.2.8 .... Justification for Use of Adaptive Design ............................................................. 32 
5.3 
Method of Assigning Subjects to Treatments ................................................................................. 33 
5.4 
Blinding and Breaking the Blind ..................................................................................................... 33 
6 
Study Population ......................................................................................................................................... 34 
6.1 
Inclusion Criteria ............................................................................................................................ 34 

Stryker Neurovascular 
Document Title: DAWN™ Trial Investigational Plan 
Document Number: CDM10000146 
Rev:  AD 
STRYKER CONFIDENTIAL - THIS DOCUMENT CONTAINS CONFIDENTIAL AND PROPRIETARY INFORMATION THAT 
IS THE PROPERTY OF STRYKER CORPORATION. NEITHER THIS DOCUMENT NOR THE INFORMATION HEREIN MAY 
BE REPRODUCED, USED, OR DISCLOSED TO ANY THIRD PARTY WITHOUT THE PRIOR WRITTEN CONSENT OF 
STRYKER CORPORATION                                                                                                                                 
 
 
CDM10000146  Page 10 of 91 
6.2 
Exclusion Criteria ........................................................................................................................... 34 
6.3 
Withdrawal and Replacement of Subjects ...................................................................................... 36 
6.4 
Enrollment Controls ........................................................................................................................ 36 
7 
Study Procedures ......................................................................................................................................... 36 
7.1 
Written Informed Consent............................................................................................................... 36 
7.2 
Prior to Randomization ................................................................................................................... 37 
7.3 
Angiography Procedure (Treatment arm only) ............................................................................... 40 
7.3.1 .... Diagnostic Angiography ...................................................................................... 40 
7.3.2 .... Unexpected Diagnostic Angiography Findings ................................................... 41 
7.4 
Trevo Thrombectomy Procedure (Treatment arm only) ................................................................. 43 
7.5 
End of the Trevo Thrombectomy Procedure (Treatment arm only) ................................................ 45 
7.6 
24 (-6 / +24) Hours post Randomization ......................................................................................... 46 
7.7 
Concomitant Medications and Management ................................................................................... 46 
7.7.1 .... Blood pressure management ................................................................................ 47 
7.7.2 .... Glucose management ........................................................................................... 48 
7.8 
Day 5-7 / Discharge ........................................................................................................................ 48 
7.9 
Post Discharge Follow-up ............................................................................................................... 48 
7.9.1 .... Day 30 (± 14) ....................................................................................................... 49 
7.9.2 .... Day 90 (±30) ........................................................................................................ 49 
8 
Statistical Methods ...................................................................................................................................... 50 
8.1 
Sample Size Estimate and Justification ........................................................................................... 50 
8.2 
Control of Systematic Error/Bias .................................................................................................... 50 
8.3 
Eligibility of Subjects, Exclusions, and Missing Data .................................................................... 51 
8.4 
Population Definitions .................................................................................................................... 51 
8.5 
Analysis Populations ....................................................................................................................... 52 
8.6 
Interim Analysis .............................................................................................................................. 52 
8.6.1 .... Interim Monitoring for Early Futility .................................................................. 53 
8.6.2 .... Enrichment ........................................................................................................... 53 
8.6.3 .... Interim Monitoring for Expected Success ............................................................ 53 
8.6.4 .... Longitudinal Model.............................................................................................. 54 
8.7 
Statistical Analysis .......................................................................................................................... 54 
8.7.1 .... Baseline Comparability ....................................................................................... 55 
8.7.2 .... Pooling Across Institutions .................................................................................. 55 

Stryker Neurovascular 
Document Title: DAWN™ Trial Investigational Plan 
Document Number: CDM10000146 
Rev:  AD 
STRYKER CONFIDENTIAL - THIS DOCUMENT CONTAINS CONFIDENTIAL AND PROPRIETARY INFORMATION THAT 
IS THE PROPERTY OF STRYKER CORPORATION. NEITHER THIS DOCUMENT NOR THE INFORMATION HEREIN MAY 
BE REPRODUCED, USED, OR DISCLOSED TO ANY THIRD PARTY WITHOUT THE PRIOR WRITTEN CONSENT OF 
STRYKER CORPORATION                                                                                                                                 
 
 
CDM10000146  Page 11 of 91 
8.7.3 .... Other Pre-planned Analyses ................................................................................ 55 
8.7.4 .... Health Economics Information ............................................................................ 55 
9 
Data Management ....................................................................................................................................... 56 
9.1 
Data Collection and Processing ...................................................................................................... 56 
10 
Monitoring Procedures ............................................................................................................................... 56 
10.1 
Auditing .......................................................................................................................................... 56 
10.2 
Investigational Device Accountability ............................................................................................ 57 
11 
Adverse Events ............................................................................................................................................ 57 
11.1 
Adverse Event Definitions and Classification................................................................................. 57 
11.2 
Adverse Events Reporting Requirements ....................................................................................... 59 
11.3 
Device Failures, Malfunctions, and Product Nonconformities ....................................................... 60 
11.4 
Reporting to Regulatory Authorities / IRBs / ECs / Investigators .................................................. 60 
12 
Risk Benefit Analysis................................................................................................................................... 61 
12.1 
CT/MR Imaging .............................................................................................................................. 62 
12.2 
Investigational procedure (Treatment arm only) ............................................................................. 62 
12.2.1 .. Diagnostic Angiography ...................................................................................... 62 
12.2.2 .. Trevo Thrombectomy ........................................................................................... 63 
12.3 
Risk Minimization........................................................................................................................... 64 
13 
Study Committees and Core Labs ............................................................................................................. 64 
13.1 
Steering Committee......................................................................................................................... 64 
13.2 
Safety Monitoring Committees ....................................................................................................... 65 
13.2.1 .. Clinical Events Committee (CEC) ....................................................................... 65 
13.2.2 .. Data Monitoring Committee (DMC) ................................................................... 66 
13.3 
Imaging Core Labs .......................................................................................................................... 67 
13.3.1 .. Angiographic Core Lab ....................................................................................... 68 
13.3.2 .. CT/MR Core Lab ................................................................................................. 68 
14 
Ethical Considerations ................................................................................................................................ 69 
14.1 
Compliance with Good Clinical Practices (GCP) ........................................................................... 69 
14.2 
Institutional Review Board/ Ethics Committee ............................................................................... 69 
14.3 
Written Informed Consent Form ..................................................................................................... 70 
14.4 
Amending the Protocol ................................................................................................................... 70 
14.5 
Protocol Adherence ......................................................................................................................... 70 
15 
Study Administration .................................................................................................................................. 71 

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Document Title: DAWN™ Trial Investigational Plan 
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STRYKER CONFIDENTIAL - THIS DOCUMENT CONTAINS CONFIDENTIAL AND PROPRIETARY INFORMATION THAT 
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CDM10000146  Page 12 of 91 
15.1 
Pre-Study Documentation Requirements ........................................................................................ 71 
15.2 
Record Retention ............................................................................................................................ 71 
15.3 
Criteria for Terminating Study ........................................................................................................ 71 
15.4 
Criteria for Suspending/Terminating a Study Site .......................................................................... 71 
16 
References .................................................................................................................................................... 73 
17 
Appendices ................................................................................................................................................... 78 
Appendix A. 
Abbreviations .................................................................................................................... 78 
Appendix B. 
Definitions ........................................................................................................................ 83 
Appendix C. 
Angiographic Core Lab Scales ......................................................................................... 87 
Appendix D. 
Informed Consent Form Template [attached] ................................................................... 89 
Appendix E. 
Sample Instructions for Use (IFU) [attached] ................................................................... 90 
Appendix F. 
Adaptive Design Plan [attached] ...................................................................................... 91 
 
List of Figures 
Figure 1. 
Trevo Retrievers ....................................................................................................................................... 17 
Figure 2. 
DAWN™ Trial Flow Chart ...................................................................................................................... 21 
 
List of Tables 
 
Table 1. Key Dimensions of Trevo Family Retrievers ................................................................................................ 16 
Table 2. Zaidi - Anterior LVOs treated  ≤ 8 hrs and > 8 hrs after TLSW.................................................................... 24 
Table 3. Merci Registry - Anterior LVOs treated ≤ 8 hr and > 8 hr after TLSW ........................................................ 25 
Table 4. Pre-DAWN Cohort vs. PROACT II Treatment and Control Arm ................................................................. 26 
Table 5. DAWN™ Trial Time and Events Schedule ................................................................................................... 39 
Table 6. Distribution of mRS outcomes for the control arm in the simulations .......................................................... 50 
Table 7. Intracranial Hemorrhage Types ..................................................................................................................... 69 
 

Stryker Neurovascular 
Document Title: DAWN™ Trial Investigational Plan 
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STRYKER CONFIDENTIAL - THIS DOCUMENT CONTAINS CONFIDENTIAL AND PROPRIETARY INFORMATION THAT 
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CDM10000146  Page 13 of 91 
1 Introduction and Rationale 
1.1 
Incidence and Burden of Stroke 
Stroke represents the fourth leading cause of death in industrialized nations, after heart disease, 
cancer, and chronic lower respiratory disease. Each year approximately 795,000 people 
experience a new or recurrent stroke (ischemic or hemorrhagic) in the U.S. Also, in 2009, 
stroke caused approximately 1 of every 18 deaths in the United States. On average, every 40 
seconds, someone in the United States has a stroke and dies of one approximately every four 
(4) minutes. [1-2]  
Proximal intracranial arterial occlusions are common, cause the most disabling types of 
ischemic strokes, and are predictive of poor neurological outcomes at hospital discharge. [3] 
Stroke survivors constitute the majority of disabled people nationally in the United States. 
Approximately one-quarter of the patients suffering a stroke die within one year after the initial 
event. Stroke brings a dramatic financial and personal burden to society.  Direct medical costs 
related to stroke in the United States is an estimated $28.3 billion per year. Stroke is a leading 
cause of serious long-term disability. [4] 
1.2 
Current Treatment Options 
Intravenous (IV) tPA (alteplase) remains the only approved therapy for acute ischemic stroke 
(AIS). However, IV tPA has many limitations, including a short therapeutic window, with 
administration being restricted in the United States to 3 hours post known symptom onset, and 
in other parts of the world to 4.5 hours post known symptom onset, and a strong time-
dependency. [5-8] The efficacy of IV tPA is limited by the large thrombus burden that occurs 
in the setting of acute ischemic strokes caused by proximal intra-cranial arterial occlusions. [9] 
[10]  
In the 0-8 hours post symptom onset, endovascular revascularization by mechanical 
embolectomy has been shown to be safe and effective in numerous studies, including the 
MERCI and Multi MERCI trials [11-12], the Penumbra Pivotal trial [13], and the SWIFT and 
TREVO 2 trials [14-15]. Clinical outcomes in ischemic stroke have been shown to be strongly 
linked to revascularization. [16-18] Thus, in cases where patients are ineligible for IV tPA or 
where IV tPA fails to result in a clinical improvement, endovascular treatment with mechanical 
thrombectomy devices is a viable treatment option. Mechanical endovascular therapy has been 
linked to higher recanalization rates as compared to IV tPA, and is considered standard of care 
in many institutions within the 0-8 hour time window. [19-21] 
1.3 
Unmet Need in Acute Ischemic Stroke 
Acute ischemic stroke due to large vessel occlusion (LVO) is a potentially devastating event, 
with a poor prognosis in the absence of timely revascularization. The sub-population of interest 
in this study is subjects with intracranial ICA or MCA-M1 vessel occlusions. Evidence from 

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CDM10000146  Page 14 of 91 
prior and ongoing studies suggests that patients with a blockage in these vessels, when 
managed medically, do worse compared to those who are treated with pharmacologic or 
mechanical reperfusion therapies.  
In a single center study conducted in Badalona, Spain of consecutively screened patients within 
6-24 hours of symptom onset or time they were last seen well, the subset of medically managed 
patients with confirmed intracranial ICA or MCA-M1 occlusions, 17.5% of patients 
experienced a good clinical outcome, defined as a modified Rankin Score (mRS) of 0, 1 or 2. 
[22]  
In the multi-center STOPSTROKE study, good outcomes in a clearly defined subset of 
medically managed patients with CTA confirmed intracranial ICA or MCA-M1 occlusion was 
18.4%. Although treated patients in this study presumably had more favorable imaging at 
baseline and therefore their natural history may be more favorable than untreated patients, the 
evidence is suggestive of worse outcomes in untreated patients. [23] 
The ongoing Penumbra FIRST study includes subjects presenting within 0-8 hours from 
symptom onset with documented ICA or M1 occlusions who would normally be candidates 
for endovascular thrombectomy, but for whom the procedure is unavailable. The interim 
outcomes data for the first 63 subjects enrolled demonstrate a good outcome rate of 20.4%. 
[24] 
The seminal PROACT II trial control arm, which included subjects with MCA-M1 and M2 
occlusions, is often referenced as a comparator for results of treatment with pharmacological 
or mechanical revascularization therapies. In PROACT II, the control arm subjects were 
treated with intra-arterial heparin within 0-6 hours of symptom onset. This group of subjects 
experienced good clinical outcomes in 25% of the cases. [25-26] However, in the more 
proximal MCA-M1 occlusion subset of the control arm (n=37) good outcomes were only 22%. 
[27] 
Together, these data support an overall grim prognosis for medically managed intracranial ICA 
or MCA-M1 occlusions, with low rates of good outcomes ranging from 17.5-25%. 
In contrast to patients who are medically managed, those with similar clinical presentation who 
are revascularized experience higher rates of good clinical outcomes. In the SWIFT and 
TREVO 2 trials, Stentrievers™ were used to restore blood flow to the neurovasculature in 
subjects with intracranial large vessel occlusions. Subjects treated within 0-8 hours of symptom 
onset experienced good clinical outcomes in 37% and 40% of cases respectively. [14-15] In a 
retrospective analysis of stroke patients, who were selected by CT Perfusion or MRI for 
endovascular treatment, regardless of time from symptom onset or time last seen well, 
Nogueira et al reported good outcomes of 40% within the subset of patients with confirmed 
intracranial ICA or MCA-M1 occlusions. [28]  

Stryker Neurovascular 
Document Title: DAWN™ Trial Investigational Plan 
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STRYKER CONFIDENTIAL - THIS DOCUMENT CONTAINS CONFIDENTIAL AND PROPRIETARY INFORMATION THAT 
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CDM10000146  Page 15 of 91 
The current guidelines for treatment, including the use of thrombolysis and/or thrombectomy 
are based on time last seen well (TLSW). [29] Yet, the majority of patients presenting with 
AIS symptoms are beyond 8 hours from symptom onset or of unknown onset. [30] It is 
estimated that in between 14-28% of AIS patients, the onset of stroke symptoms is un-
witnessed or occurs during sleep. [31-36] It has also been demonstrated that as many as 71.4% 
of the patients with proximal intra-cranial arterial occlusion may have a significant MRI 
(DWI/PWI) mismatch as far as 9 to 24 hours post stroke onset. [37]  
There is limited data in the literature on the relative risks versus benefits of performing 
mechanical thrombectomy in patients within 6-24 hours from symptom onset or time last seen 
well. The current AHA/ASA guidelines recommend standard medical management only 
(supportive care) for these patients. [29] The AIS stroke population is heterogeneous by nature 
and though some patients may do better than others, in general the more proximal the occlusion 
and the later the patient arrives, the worse the anticipated outcome.  
1.4 
Purpose of Study 
The intent of this study is to support the use of the Trevo Retriever beyond the currently labeled 
8 hour indicated time limit in wake up, unclear onset, and late presenting ischemic stroke 
subjects, who currently have no other option besides medical management of their symptoms.  
Patients with wake-up strokes, strokes with unclear onset time, and witnessed late presenting 
strokes may potentially benefit from intra-arterial reperfusion therapy. [28, 35, 38-44] 
However, an important indicator of whether subjects will benefit or not during this later time 
window is the confirmation of a large vessel occlusion (LVO), and assessment of the core 
infarct volume relative to the volume of salvageable penumbra. [45-47] Therefore, 
standardized imaging selection of subjects is required for inclusion into the study.   
This trial has been designed with subject safety in mind, as a seamless Phase II (feasibility) / 
Phase III (pivotal) adaptive design, in order to address the concerns around potential unknown 
harms to enrolled subjects. This study will help to answer the question of whether carefully 
selecting subjects by using Clinical Imaging Mismatch will allow acute ischemic stroke 
patients who present at or beyond 6 hours from Time Last Seen Well (TLSW) to be considered 
for intra-arterial intervention. If Trevo thrombectomy plus medical management leads to better 
clinical outcomes over medical management alone, more patients in the future could receive 
endovascular treatment (either in addition to or in lieu of IV tPA).   
2 Study Device  
2.1 
Study Device Description 
The study devices include the Trevo ProVue and XP ProVue Retrievers manufactured by 
Concentric Medical, a business unit of Stryker Neurovascular. Compared to the cleared 
devices, the study devices differ only by their modified Indications for Use. Key dimensions 

Stryker Neurovascular 
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STRYKER CONFIDENTIAL - THIS DOCUMENT CONTAINS CONFIDENTIAL AND PROPRIETARY INFORMATION THAT 
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CDM10000146  Page 16 of 91 
of study devices are summarized in Table 1. Various device sizes may be added to the study 
upon receiving regulatory approval including an IDE supplement. Only devices labeled for 
investigational use are to be used. 
Table 1. Key Dimensions of Trevo Family Retrievers 
Trevo 
Retriever 
Size 
Investigational 
Model # 
Overall 
Length 
Clot Capture Area   
(Active Shaped 
Section Length) 
Total Shaped 
Section 
Length 
Shaped 
Section 
Diameter 
Trevo ProVue Retriever 
4x20mm 
90191, 90291 
180cm 
20mm 
37mm 
4mm 
Trevo XP ProVue Retrievers 
3x20mm 
90192, 90292 
190cm 
20mm 
36mm 
3mm 
4x20mm 
90193, 90293 
180cm 
20mm 
32mm 
4mm 
6x25mm 
90194, 90294 
180cm 
25mm 
40mm 
6mm 
4x30mm 
90195, 90295 
180cm 
30mm 
44mm 
4mm 
 
The cleared Indications for Use for the Trevo ProVue and XP ProVue Retrievers is as follows: 
The Trevo Retriever is intended to restore blood flow in the neurovasculature by removing 
thrombus in patients experiencing ischemic stroke within 8 hours of symptom onset. Patients 
who are ineligible for intravenous tissue plasminogen activator (IV t-PA) or who fail IV t-PA 
therapy are candidates for treatment.  
The proposed Indications for Use for the Trevo ProVue and XP ProVue Retrievers utilized in 
the DAWN™ Trial are as follows: 
 The Trevo Retriever is intended to restore blood flow in the neurovasculature by removing 
thrombus in patients experiencing ischemic stroke within 24 hours of symptom onset. The 
Trevo Retriever is also intended to improve neurological outcomes in patients experiencing 
ischemic stroke between 6 – 24 hours of symptom onset.” 
Apart from the modified proposed Indications for Use, the study devices are identical to the 
cleared devices and consist of a flexible, tapered core wire with a shaped Nitinol section at the 
distal end for clot capture. As shown in Figure 1, The Trevo ProVue Retriever has a radiopaque 
platinum coil at the distal end of the shaped section while the Trevo XP ProVue Retrievers 
have platinum markers at their distal ends. All Trevo Retrievers contain platinum wires woven 
throughout the shaped section with radiopaque solder at the proximal end to facilitate 
fluoroscopic visualization. The devices have a proximal shaft marker to indicate proximity of 
the Retriever tip relative to the microcatheter tip and a hydrophilic coating to reduce friction. 
A torque device and an insertion tool are provided with the Trevo Retrievers. Retriever 
dimensions are indicated on the product labels. 

Stryker Neurovascular 
Document Title: DAWN™ Trial Investigational Plan 
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STRYKER CONFIDENTIAL - THIS DOCUMENT CONTAINS CONFIDENTIAL AND PROPRIETARY INFORMATION THAT 
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CDM10000146  Page 17 of 91 
Figure 1. Examples of Trevo Retrievers 
                     
 
During the study procedure, the operator may choose which Trevo Retriever to use, depending 
upon anatomical considerations and personal preference. The Trevo Retriever is delivered to 
the thrombus using a microcatheter. The microcatheter is then retracted to deploy the shaped 
section of the Retriever. The Retriever and microcatheter are pulled back to dislodge the 
thrombus. The Retriever, the thrombus, and the microcatheter are then removed from the body.   
The Trevo Retriever has been designed and tested to perform multiple retrieval attempts in a 
single vessel. Per the IFU no more than six (6) passes within the same vessel should be made 
using any combination of Trevo Retrievers. Each device can be used for up to three retrieval 
attempts. 
After each deployment of the Trevo Retriever it should be thoroughly inspected before 
reloading.  
Refer to the Instructions for Use (IFU) for detailed instructions on how to prepare and use the 
Trevo Retriever.  The devices should not be re-sterilized and reused.  
There are no specific contraindications for the use of the Trevo Retrievers apart from the 
inclusion and exclusion criteria of this protocol.  Refer to the IFU for a listing of warnings and 
precautions.  
2.2 
Study Device Labeling 
The Trevo Retriever study devices are labeled consistent with CFR 812.5 (a), and shall bear 
the following information:  
 the name and place of business of the manufacturer 

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STRYKER CONFIDENTIAL - THIS DOCUMENT CONTAINS CONFIDENTIAL AND PROPRIETARY INFORMATION THAT 
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CDM10000146  Page 18 of 91 
 packer, or distributor (in accordance with 801.1)  
 the quantity of contents, if appropriate 
 the following statement: " CAUTION: Investigational device. Limited by United States 
law to investigational use. Exclusively for Clinical Investigations. Investigational 
Device. To be Used by Qualified Investigators Only.” (Label will be applied to the 
outside of the Trevo Retriever pouch and to the outside of the carton containing the 
Trevo Retriever) 
In addition, the study device labels contain device dimensions, Lot Number, and expiration 
(use before) date.  
The DAWN IDE Investigational Instructions for Use (IFU) shall be packaged with the study 
device, and describes all relevant contraindications, hazards, adverse effects, interfering 
substances or devices, warnings, and precautions. A sample IFU is attached as Appendix E. 
The study device may be provided to sites as single units, or as components within convenience 
packs, which contain a non-investigational microcatheter that is compatible with the Trevo 
Retriever.  
3 Study Objective 
3.1 
Primary Objective 
To evaluate the hypothesis that Trevo thrombectomy plus medical management leads to 
superior clinical outcomes at 90 days as compared to medical management alone in 
appropriately selected subjects experiencing an acute ischemic stroke when treatment is 
initiated within 6-24 hours after last seen well.  
3.2 
Secondary Objectives 
To provide evidence that endovascular reperfusion with Trevo is associated with a significant 
reduction in median infarct size compared to the control group at 24 (-6/+24) hours post 
randomization. 
4 Study Endpoints and Safety Outcomes 
The following clinical endpoints and safety outcomes will be evaluated in all subjects who are 
randomized whether or not the randomized study treatment is successfully administered, also 
called the Intent to Treat (ITT) group of subjects. 
4.1 
Primary Endpoint 
The primary endpoint is the 90-day clinical outcomes assessed by the modified Rankin scale 
(mRS). 

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The primary endpoint analysis will consist of a comparison of the difference in proportion of 
functional independence (mRS 0-2) at 90 days post randomization between the active and 
control arm (dichotomous analysis) as well as the difference between the average weighted 
modified Rankin Scale (mRS) score at 90 days post randomization between the active and 
control groups (weighted mRS analysis). For the latter, each mRS category is assigned a 
numerical value representing its clinical utility, based on the work by Rivero-Arias, et al and 
Hong and Saver, as described in the Adaptive Design Plan in Appendix F. [48-49] 
4.2 
Secondary Endpoints 
Both Arms:  
1. Comparison of the proportion of subjects with a good functional outcome at 90 days, 
defined as mRS 0-2, between the active and control groups. 
2. Comparison of the proportion of subjects with “early response” at Day 5-7/Discharge 
(whichever is earlier), defined as a NIHSS drop of ≥10 from baseline or NIHSS score 
0 or 1, between the active and control groups. 
3. Difference in all cause mortality rates between the two groups. 
4. Comparison of the median final infarct size at 24 (-6/+24) hours from randomization, 
by MRI T2/Flair or CT (if MR is contraindicated), between the active and control 
groups. 
5. Difference in revascularization rates at 24 (-6/+24) hours from randomization, by 
CT-MR core lab assessment of vessel patency on CTA/MRA. 
Treatment Arm only:  
6. Analysis of vessel reperfusion rates (percentages) post device and post procedure, by 
angiography core lab measurement of modified TICI ≥ 2b.  
4.3 
Primary Safety Outcome 
Both Arms:  
1. Incidence of stroke-related mortality at 90 days 
4.4 
Secondary Safety Outcomes 
Both Arms:  
1. Incidence of SICH, by ECASS III definition, within 24 (-6/+24) hours post 
randomization (time zero) 
2. Incidence of neurological deterioration from baseline NIHSS score through Day 5-
7/discharge (whichever is earlier) post randomization (time zero). Neurological 
deterioration is defined as ≥ 4 point increase in the NIHSS score from the baseline 
score.  

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CDM10000146  Page 20 of 91 
Treatment Arm only:  
3. Incidence of procedure-related and device-related serious adverse events (PRSAEs 
and DRSAEs) through 24 (-6/+24) hours post randomization (time zero), as 
adjudicated by the clinical events committee (CEC), and defined as:  
• 
vascular perforation 
• 
intramural arterial dissection 
• 
embolization to new territory 
• 
access site complication requiring surgical repair or blood transfusion 
• 
intra-procedural mortality 
• 
device failure (in vivo breakage) 
• 
any other complications adjudicated by the CEC to be related to the procedure 
5 Study Design 
5.1 
Overview 
The DAWN protocol is a prospective, randomized, multi-center, Phase II/III 
(feasibility/pivotal), adaptive, controlled trial, designed to demonstrate that mechanical 
thrombectomy using the Trevo Retriever with medical management is superior to medical 
management alone in improving clinical outcomes at 90 days in appropriately selected wake 
up and late presenting acute ischemic stroke subjects. Figure 2 shows the flow of subjects 
through the screening, randomization assignment and follow up phases of the study. 
[Remainder of page is intentionally blank.] 
 
 
 

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CDM10000146  Page 21 of 91 
Figure 2. 
DAWN™ Trial Flow Chart 
 
 
 
 

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CDM10000146  Page 22 of 91 
5.2 
Justification for the Study Design 
Previous studies of mechanical embolectomy devices, conducted in order to gain regulatory 
approval, were either single arm studies comparing revascularization rates against the observed 
control rate in PROACT II (18%), or more recently, studies comparing newer generations of 
thrombectomy devices against older ones. Since none of these studies randomized against a 
concurrent control arm, it is not known if the rates of good outcomes, mortality and 
symptomatic ICH are better, the same, or worse with mechanical endovascular intervention 
than without it. [11-15] 
Although a correlation has been demonstrated between good clinical outcomes and 
endovascular reperfusion in numerous independent studies, [16-18] and revascularization rates 
have increased steadily with the advent of Stentrievers™ such as the Trevo and Solitaire 
devices, the corresponding rates of good clinical outcomes have not increased substantially. 
Several non-controlled studies using a variety of endovascular procedures have reported rates 
of successful recanalization ranging from 46% to 90%, and good outcomes at 90 days, ranging 
from 25% to 55%. [13-15, 50-57] 
The neutral results of the IMS III, MR RESCUE and SYNTHESIS Expansion trials bring into 
question the relative benefits of mechanical thrombectomy as adjunctive therapy to IV tPA in 
the earlier time windows. [58-60] These trials have been critiqued for potential flaws in their 
design and execution, including the potential of subject selection bias due to lack of equipoise 
to randomize in the earlier time window; a lack of confirmation of a large vessel occlusion 
(LVO) on initial presentation in some subjects; the use of predominantly older technology 
devices; and the use of combined intra-arterial approaches, making it difficult to know what 
device or therapy resulted in what effect. [61-62]  
There is growing evidence to support selecting patients for reperfusion therapy by using neuro-
imaging to evaluate brain tissue status as opposed to using time from stroke onset.  The results 
of three non-randomized studies which looked at outcomes in patients selected for 
thrombolysis within and beyond 3 hours using MR imaging compared with standard CT-based 
selection criteria suggested that the MRI-based approach might be advantageous. [39-41]  
Following the implementation at Massachusetts General Hospital of the MRI based selection 
for patients with acute large vessel occlusion (LVO) for intra-arterial (IA) therapy, a significant 
one-category improvement in the mRS was demonstrated, presumably by targeting patients 
more likely to benefit and removing patients unlikely to benefit, or even be  harmed, by IA 
therapy. [63] 
Three distinct tissue states in the ischemic brain are defined below, according to their potential 
to return to normal biological functioning: (1) brain that is non-functional and irreversibly 
damaged (infarct core); (2) potentially salvageable hypo-perfused brain that is functionally 
impaired but structurally intact and is destined to undergo infarction in the absence of 
reperfusion (salvageable penumbra); and (3) hypo-perfused brain that is both functionally and 

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CDM10000146  Page 23 of 91 
structurally intact and will not undergo infarction even in the absence of reperfusion (benign 
oligemia). [64-65]  
The DAWN hypothesis is that the greater the ratio of salvageable penumbra to infarct core 
(also referred to in the literature variously as “tissues at risk”, “mismatch”, and “target 
mismatch”), the higher the benefit is likely to be from reperfusion regardless of how much 
time has elapsed since stroke onset. In DAWN, we propose to select subjects for participation 
in the trial based upon a standardized identification and quantification of a “Clinical Imaging 
Mismatch”. See Section 5.2.5.  
5.2.1 
Justification for Expansion of Time Window 
In the dynamic setting of ischemia, there is continuous growth of the infarct core at the 
expense of the penumbral tissue until either the infarct is completed or reperfusion is 
achieved. The pace of expanding cerebral ischemia is highly variable between individuals 
and is likely dependent on multiple factors, including the presence of collateral circulation, 
ischemic pre-conditioning, cerebral perfusion pressure, and cerebral blood volume as well 
as serum glucose, body temperature, and oxygen delivery capacity.  
MRI perfusion and PET studies suggest that the time point at which half of the patients 
with large vessel stroke show evidence of persistent penumbra is between 8 to 12 hours. 
[66] One MRI perfusion study demonstrated that as many as 70-80% of the patients with 
proximal arterial occlusion may have a significant mismatch as far as 9 to 24 hours post 
stroke onset. [37] In a retrospective study of 75 patients with acute ischemic stroke treated 
with endovascular recanalization therapies beyond 8 hours after symptom onset (baseline 
NIHSS 14 ± 4.9 and time to treatment 15.2 ± 8.7 hours), revascularization resulted in 
reduced infarct growth. The infarct growth was significantly greater when the baseline 
volume of infarct tissue was small and revascularization was not achieved. [67] Another 
retrospective study of patients selected by CT or MR perfusion mismatch who were treated 
endovascularly demonstrated similar rates of SICH, good outcomes and mortality whether 
treated at < 6 hours (N=34) or > 6 hours (N=21), concluding that in appropriately selected 
AIS patients endovascular therapy can be performed safely regardless of stroke duration. 
[68] These studies imply that the therapeutic window may be protracted in selected cases 
and support the hypothesis that it is possible to select subjects for endovascular therapy 
beyond 6-8 hours TLSW using advanced multimodal neuro-imaging. 
Zaidi S. et al performed a retrospective analysis involving 160 consecutive patients with 
anterior circulation strokes undergoing endovascular therapy (IA tPA, angioplasty, stent 
and/or Merci Retriever) at a single institution (UPMC) over a five year period. Patients 
were divided into two groups according to TLSW to treatment:  ≤ 8hr (n=123) and >8hr 
(n=37). All patients had <1/3 MCA territory hypodensity on baseline head CT and all 
patients treated >8 hours from TLSW had significant mismatch on MRI or CTP (by 
individual operator assessment). Except for a statistically significant difference in baseline 

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CDM10000146  Page 24 of 91 
NIHSS, the two groups were well matched regarding baseline characteristics and site of 
occlusion. No significant differences were observed in rates of SICH, infarct volume or 
inpatient mortality. See Table 2 below. [44] 
Table 2. Zaidi - Anterior LVOs treated  ≤ 8 hrs and > 8 hrs after TLSW 
 
≤8hr 
(N=123) 
>8hr 
(N=37) 
p-value* 
Baseline NIHSS (mean) 
18 
12 
0.05 
SICH (PH) 
15.3% 
8.3% 
0.40 
Infarct Volume 
101.2 (96.3) 
83.1 (64.6) 
0.27 
Inpatient Mortality 
31%  
20%  
0.29 
                  *Fisher exact test 
 
In PROACT II, the largest randomized trial of anterior LVOs performed to date, time to 
treatment was not found to be a predictor of good clinical outcomes. [69] Conversely, the 
IMS I-II investigators found that, after adjustments were made for age, baseline NIHSS 
score, sex, and baseline glucose, only time from symptom onset to reperfusion and age 
independently predicted good clinical outcomes. [70] The authors concluded that at later 
times, reperfusion may be associated with a poor risk-benefit ratio. However, these findings 
are contradicted by a larger analysis involving the pooled dataset of the MERCI and Multi 
MERCI trials which demonstrated no association between time to treatment and outcomes 
or time to reperfusion and outcomes. [71]  
Using the complete cohort of the prospectively collected “real world” Merci Registry 
subjects (N=1000), Nogueira RG, Jovin T et al. compared the outcomes of subjects with 
anterior circulation LVOs who underwent mechanical thrombectomy ≤ 8 hours to those 
who were treated > 8 hours from TLSW. [72] Earlier subjects were slightly older (67 vs. 
63) and had higher baseline NIHSS scores (18 vs. 15) as compared to later subjects. There 
were no significant differences in terms of site of occlusion, recanalization rates, SICH 
rates, or good outcomes. Mortality was lower in the >8 hour group. The results of this 
comparison are summarized in Table 3. 
[Remainder of page is intentionally blank.] 
 
 
 

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Table 3. Merci Registry - Anterior LVOs treated ≤ 8 hr and > 8 hr after TLSW 
Outcomes 
0-8 hours 
(n= 679) 
>8 hours 
(n= 112) 
Difference  
[95% CI] 
p-value 
Mean TLSW 
4.7±1.5 hr 
13.8±10.6 hr 
n/a 
n/a 
Post-Rx TICI 2-3 
78.9% (534/677) 
81.3% (91/112) 
-2.37% 
[-10.23%, 5.48%] 
n/a 
SICH Definite* 
6.9%  (33/477) 
9.1% (7/77) 
-2.17% 
[ -8.99%, 4.64%] 
n/a 
SICH Uncertain* 
2.1%  (10/477) 
5.2% (4/77) 
-3.10% 
[ -8.22%, 2.02%] 
n/a 
90-Day mRS 0-2 
30.2% (205/679) 
37.8% (42/111) 
-7.65% 
[-17.31%, 2.01%] 
0.12 
90-Day Mortality 
35.8% (243/679) 
18.8% (21/112) 
17.04% 
[ 8.96%, 25.12%] 
0.0003 
* Site reported according to the ECASS III criteria  
 
One hypothetical reason that the subjects treated later in the Merci Registry did better than 
subjects treated earlier is due to more careful patient selection criteria being applied in the 
real world setting prior to intra-arterial interventions being initiated in this later time 
window. The results of this analysis further support that patients treated beyond 8 hours of 
symptom onset may experience similar rates of good clinical outcomes as those patients 
treated < 8 hours from symptom onset, and that they are not necessarily at higher risk of 
SICH, or death because of this treatment. 
Jung et al compared prospectively collected data on endovascular treated stroke patients 
with known symptom onset < 6 hours to those with known symptom onset > 6 hours. 
Though outcomes in the cohort treated beyond 6 hours were worse than those treated within 
6 hours, there were more patients with basilar artery occlusions in the latter group, and 
when multivariate regression analysis was performed correcting for this unequal 
distribution, the difference disappeared and outcomes were comparable. Recanalization 
rates were similar between the two groups, and hemorrhage rates were not increased in the 
patients who were treated later. [73] 
In a retrospective analysis of 237 anterior LVO stroke patients, selected by CT Perfusion 
or MRI for endovascular treatment, Nogueira et al reported that neither time to treatment 
nor the use of adjunctive intra-arterial thrombolytics increased the risk for SICH. The 
overall recanalization rate (TIMI 2-3) was 74% (175/237), good outcomes at 90 days or 
discharge (mRS≤ 2) was 45% (100/223) and mortality was 21.7% (51/235). The overall 
SICH rate, defined as PH-1 or PH-2 per the European Cooperative Acute Stroke Study 
(ECASS) criteria, was 8.9% (21/237). Notably, there was no significant association 
between TLSW and SICH. [74] 

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CDM10000146  Page 26 of 91 
A total of 169 patients from the original cohort discussed in the paragraph above met the 
main entry criteria initially planned for the DAWN trial including (1) baseline NIHSS score 
≥10, (2) ICA or MCA-M1 occlusion (with or without cervical occlusion/severe stenosis), 
and (3) TLSW between 8-24 hours. This subset is also referred to as the “Pre-DAWN” 
dataset. Though not identical to the cohort described by the current study 
inclusion/exclusion criteria, it is similar enough to draw certain conclusions about potential 
outcomes in the proposed treatment arm.  
The Pre-DAWN cohort achieved similar rates of revascularization, SICH, good outcomes, 
and mortality to the PROACT II Treatment Arm (N=121) despite having more severe 
occlusions (ICA terminus and tandem occlusions included, and M2 occlusions excluded) 
and significantly longer TLSW to treatment times. The Pre-DAWN cohort and the 
PROACT II Treatment arm both fared significantly better than the PROACT II Control 
arm. The results of this comparison are summarized on Table 4 below. [25, 38] 
Clinical equipoise regarding potential benefit of neuro-thrombectomy in these subjects is 
well-established, as pivotal registration trials of neuro-thrombectomy devices did not 
include greater than 8 hour subjects and no randomized trial of any recanalization 
intervention has yet demonstrated benefit at this late time window. [75]  
Table 4. Pre-DAWN Cohort vs. PROACT II Treatment and Control Arm 
Variable 
Pre-DAWN 
PROACT II 
Treatment 
PROACT II 
Control 
Number of subjects 
169 
121 
59 
Age (years) Mean ± SD 
64 ± 16 
64 ± 14 
64 ± 14 
Median Baseline NIHSS (Min-Max) 
17 (10 - 29) 
17 (5 - 27) 
17 (4 - 28) 
Female 
54% 
42% 
39% 
TLSW to Treatment (Hr) 
Median (IQR) 
 
12 (9.5-14.4) 
4.7 (4.0-5.3)* 
5.1 (4.2-5.5) 
Site of Occlusion (%) 
MCA-M2 
MCA-M1 
ICA-T 
Tandem ICA/MCA 
Tandem ICA/ICA-T 
 
0% 
54% 
22% 
17% 
7% 
35% 
61% 
0% 
0% 
0% 
37% 
63% 
0% 
0% 
0% 
Revascularization (TIMI 2-3) 
74% 
66% 
18% 
Symptomatic ICH 
10% 
10% 
2% 
90-day mRS ≤2 
40% (57/142) 
40% 
25% 
90-day Mortality 
25% (42/167) 
25% 
27% 
 
*Time to randomization 
 
The preceding analyses support the hypothesis that endovascular recanalization therapies 
may be safely employed between 6-24 hours from witnessed or un-witnessed stroke onset 
or TLSW in appropriately selected subjects. 

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CDM10000146  Page 27 of 91 
5.2.2 
Justification for Inclusion of Wake up and Unclear Onset 
Strokes  
It is estimated that 10-25% of ischemic stroke patients awaken with their deficits. [31, 33-
36] In a study involving 100 subjects it was demonstrated that wake up stroke (WUS) 
subjects have similar DWI and PWI volumes to subjects with known stroke onset times. 
DWI-PWI mismatch was present in over 70% of the WUS subjects and MRA-detected 
vascular occlusion was documented in over 50% of the cases. [31] In another study, no 
significant difference was found in hyper-acute CT findings between 17 WUS subjects and 
46 stroke subjects with known onset times when evaluated within 3 hours after stroke 
detection. [33]  
Silva G. et al analyzed a prospectively acquired cohort of 676 consecutive subjects with 
AIS who underwent CTA within 24 hours of symptom onset, including 420 subjects with 
known onset time, 125 with unclear onset time, and 131 with WUS. The frequencies of 
LVO and CBF/CBV mismatch was not significantly different among the three groups, at 
37%, 40.7%, and 37.1% respectively, suggesting that use of advanced neuro-imaging to 
determine the presence of LVO and mismatch may be particularly useful in this population. 
[32]  
In contrast to the above findings, WUS subjects in the AbESTT-II trial experienced higher 
rates of symptomatic ICH (13.6% vs. 4%) and significantly lower rates of favorable 
outcomes (9.3% vs. 29.2%) as compared to non WUS subjects. However, in this trial the 
subjects were selected for inclusion based on a non-contrast head CT only, and the 
treatment arm subjects received IV abciximab. Of note, the rate of favorable outcomes 
among placebo-treated WUS subjects was lower than the placebo-treated non-WUS 
subjects, a finding that further highlights the need for more aggressive management of 
WUS patients. [34] 
It is acknowledged that in the broadest cohort of AIS patients, as time from stroke onset 
increases so too does the risk to benefit ratio and not every patient will benefit, while some 
may be harmed by late reperfusion. [21, 38, 70] Many centers do not treat wake up or 
unclear onset strokes. Therefore, equipoise exists to randomize these subjects between 
endovascular treatment plus medical management or medical management alone.  
The combination of advances in neuro-imaging acquisition and post-processing techniques 
and algorithms, and newer generation thrombectomy devices may enable these patients to 
be appropriately triaged for further therapy, thereby improving overall good clinical 
outcomes in this patient population. 
5.2.3 
Justification for Inclusion of IV tPA Failures 
IV tPA has a short plasma half-life and its ability to revascularize large clot burdens is 
negligible. The recanalization rates of IV tPA for proximal arterial occlusions ranges from 

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CDM10000146  Page 28 of 91 
only 10% for internal carotid artery (ICA) occlusions to 30% for proximal middle cerebral 
artery (MCA) occlusions. [76]  
In earlier time windows it has been shown that combining IV tPA with neuro-
thrombectomy does not substantially increase the risk of symptomatic intra-cerebral 
hemorrhage or other complications over that of neuro-thrombectomy alone. [77] 
In subjects who are eligible, IV tPA should be administered as per the labeled indication 
and local practice guidelines, as this is considered best medical practice, and it should not 
be withheld from those who are eligible. However, if symptoms persist beyond 60 minutes 
after completion of IV tPA administration, and the presence of an intracranial ICA or 
MCA-M1 occlusion is confirmed by CTA/MRA, then the subject may be considered for 
eligibility in this trial.  
If a subject presents to the participating site after having received IV tPA at an outside 
hospital, the participating site must repeat all relevant assessments, including the baseline 
NIHSS and CTA/MRA to confirm the presence of an occlusion in the intracranial ICA or 
MCA-M1, in order to qualify the subject as a potential candidate for participation in the 
trial. If the subject continues to meet all inclusion and none of the exclusion criteria they 
may be randomized and enrolled. 
5.2.4 
Justification for Non Reliance on Penumbra Imaging 
Several studies have been reported in the literature demonstrating the general safety and 
effectiveness of using the ratio of “core infarct” to “salvageable penumbra” concept to 
select patients for reperfusion therapies. The methods of measuring and/or defining “core 
infarct” and “salvageable penumbra” however vary from study to study. [31, 37, 42, 78-
83]  
In DEFUSE 2, which included subjects within 12 hours from symptom onset, those with a 
“target mismatch” (favorable ratio of salvageable penumbra to infracted core tissue) who 
were reperfused, had an increased rate of good outcomes at 90 days compared to those who 
were not reperfused (57% vs. 31%). SICH rates were 7% vs. 19% respectively, suggesting 
that a randomized controlled trial of endovascular treatment for subjects with a target 
mismatch profile is warranted, [84] and does not expose subjects to an excessive risk of 
SICH. 
The MR RESCUE trial used DWI-PWI mismatch to identify favorable penumbral patterns 
versus non-favorable penumbral patterns in subjects enrolled into the trial. Surprisingly, 
the trial failed to show a differential benefit of endovascular intervention among favorable 
penumbral pattern subjects. [59] However, the results are not definitive, given the small 
sample size, large core lesions at baseline, and modest rates of substantial recanalization.  
The results also raise the question of the validity of relying upon perfusion measurements 
to identify salvageable penumbra, as the perfusion study parameters used to categorize 

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favorable versus non favorable penumbral patterns in this trial failed to predict how much 
infarct growth would occur in the absence of reperfusion. 
The STAIR VIII consensus statement recommends that in addition to vessel imaging to 
confirm large artery occlusion, full-scale penumbral imaging should be employed to select 
patients for possible inclusion into randomized therapy trials in the 8-24 hour timeframe, 
given the high proportion of subjects with already-completed infarcts. [75]  However, there 
is no consensus in the literature on what the correct imaging modalities, maps or thresholds 
are for determining the extent of salvageable penumbra versus benign oligemia, versus 
already infarcted tissue. [85-86] Perfusion imaging is not yet a consistently reliable means 
of identifying salvageable penumbra. [87] 
5.2.5 
Justification for Use of Clinical Imaging Mismatch Criteria 
Some data show that infarct core volume is a better predictor of outcomes than perfusion 
based imaging selection. [38, 88-89]  DEFUSE 2 pre-procedure infarct volume along with 
age were the only independent predictors of outcome and core infarct volumes of less than 
or equal to 15 cc is the best discriminator of good versus bad outcome. Perfusion MR in 
addition to DWI did not add anything to this model. [90] In another retrospective analysis 
of 201 endovascularly treated patients, age and final infarct volume were found to be 
independent predictors of outcome. [91] 
However, because patients with small core infarcts tend to do well even without 
treatment it is possible that infarct core by itself may not demonstrate a significant 
difference in outcomes between treated and a matched cohort of control subjects. The 
larger the mismatch between infarct core measurement and salvageable penumbra the 
greater the treatment effect is likely to be with reperfusion therapy, and the more substantial 
the infarct growth is likely to be without reperfusion therapy. No mismatch signals that the 
subject is not going to grow their infarct and thus will not benefit from reperfusion. [78, 
82] 
A Clinical Mismatch is the difference between the expected neurological deficits and the 
actual neurological deficits observed on examination of a patient, by National Institutes of 
Health Stroke Scale (NIHSS) in comparison to their occlusion location and size of core 
infarct. In the presence of small core infarct and confirmed LVO, baseline NIHSS appears 
to be a reliable indicator of "at risk" tissue. [87] 
Patients with a low baseline NIHSS are likely to do well even in the presence of large 
vessel occlusion and no reperfusion therapy. In PROACT II there was a minimal treatment 
effect for M1 occlusions in the NIHSS 4-10 and a negative treatment effect for M2 
occlusions in this same group (the control group did better). Larger treatment effects were 
noted both for M1 occlusions and M2 occlusions in the NIHSS 11-20 strata. [92] 

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CDM10000146  Page 30 of 91 
Higher baseline NIHSS scores are generally well correlated with more proximal LVOs. In 
one study, NIHSS scores ≥10 demonstrated a positive predictive value for arterial 
occlusions in 97% of carotid and 96% of vertebrobasilar strokes. [93] In the EMS pilot 
study there was a significant correlation between the baseline NIHSS and the likelihood of 
presence of clot on initial angiography. All patients with a baseline NIHSS ≥15 and 44% 
of patients with NIHSS of 10 to 14 had appropriate clots. [94]  
For subjects with a core infarct volumes between 0 and 30 cc, a baseline NIHSS cutoff of 
≥10 was chosen to define the clinical imaging mismatch because it is thought to be a 
reasonable predictor of likely progression of stroke and/or poor outcome in the absence of 
reperfusion. [95]  
For subjects with larger core infarct volumes, above 30 cc but less than 50 cc, a baseline 
NIHSS cutoff of ≥20 was chosen to define the clinical imaging mismatch, based upon this 
same subgroup of subjects in IMS III. Though not statistically significant at the p=0.05 
level, the group treated with endovascular therapy had a higher rate of good clinical 
outcomes compared to the IV tPA group (23.8% versus 16.8% respectively). [58] 
Stricter inclusion criteria are defined for subjects greater than 80 years of age. In one study 
of IV tPA treated patients, the overall rate of symptomatic ICH (SICH) in the octogenarians 
was 6.9%, compared with 5.3% in younger patients. The use of MRI to select octogenarians 
for thrombolytic therapy seemed to decrease the risk of SICH, but did not influence the 
overall outcome after 3 months. [96] In another published study comparing outcomes in 
IV tPA treated and non-treated subjects ≥ 80 and < 80 years old, although age was 
associated with poorer outcomes the association between thrombolysis treatment and 
improved outcomes was maintained in the very elderly subjects, and their conclusion is 
that age alone should not be considered a barrier to treatment.[97] However, in order to 
mitigate the potential risks associated with endovascular treatment in the elderly as well as 
to maximize the chance of a good outcome, the core infarct volume in subjects who are ≥ 
80 years will be restricted to ≤ 20 cc. 
In the absence of a “gold standard” to define salvageable penumbra, DAWN subject 
selection is based on a Clinical Imaging Mismatch using standardized collection and post 
processing of MRI-DWI or CTP-rCBF maps to calculate core infarct volumes, across all 
study sites.  
A Clinical Imaging Mismatch is the observed difference between the size of the core infarct 
and the magnitude of the neurological deficit, in the presence of confirmed LVO by 
CTA/MRA, and appears to be a reliable and efficient surrogate for assessing salvageable 
penumbra. [87] Using this method we aim to select subjects at risk of further infarct growth 
without rapid reperfusion.  

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CDM10000146  Page 31 of 91 
Based upon the above justifications, there are three distinct Clinical Imaging Mismatch 
subgroups defined in DAWN: 
a. 0-<21 cc core infarct and NIHSS ≥ 10 (and ≥ 80 years old) 
b. 0-<31 cc core infarct and NIHSS ≥ 10 (and < 80 years old) 
c. 31 cc to <51 cc core infarct and NIHSS ≥ 20 (and < 80 years old) 
5.2.6 
Justification for Use of Standardized Core Infarct Imaging Software 
In order to select subjects who are most likely to benefit from mechanical thrombectomy 
and less likely to be harmed by it, the inclusion criteria are limited to subjects with core 
infarct volumes between 0-50 cc. In DAWN, core infarct volume measurements will be 
standardized using a validated, FDA-cleared software platform for measuring core infarct 
(RAPID software, iSchemaView, Palo Alto, CA, or alternatively Olea Sphere, Olea, 
Cambridge, MA)  
Diffusion/perfusion imaging software for core infarct assessment is 510(k) cleared in the 
United States, and has been/is being used in several global stroke trials to date, including 
DEFUSE, DEFUSE 2, EXTEND, EXTEND IA, CRISP, and SWIFT PRIME. The software 
takes DICOM images acquired on a variety of CT or MR scanners and uses an automated 
algorithm to post-process the resulting ADC maps (MRI-DWI) or r-CBF maps (CTP) in 
order to consistently measure core infarct volumes. All raw data/maps will be visible to the 
treating physician such that if an artifact or error is suspected the scans can be assessed 
visually to confirm that the patient is appropriate for enrollment.  
The CT/MR Core Lab will verify, and record, the core infarct volumes generated by the 
software as well as "cleaned" volumes following removal of any artifact. The core lab will 
also provide timely feedback to the study sites regarding quality control issues. 
Since it is recognized that any image of the brain is a “snapshot in time”, DAWN requires 
that the corresponding clinical “mismatch” be evaluated using the baseline NIHSS obtained 
within 1 hour of the processed images used to qualify the subject for the study.  
Though MRI-DWI is the preferred method to measure the core infarct volume, due to 
logistic barriers such as unavailability of MRI equipment or technicians, and subject 
contra-indications for MR, sites are permitted to use either MRI-DWI or CTP-rCBF to 
measure the core infarct volume.  
5.2.7 
Justification for Use of Weighted mRS as Primary Endpoint 
Analysis 
 
The primary endpoint is 90-day clinical outcomes assessed by the modified Rankin Scale 
(mRS), analyzed using both the average weighted mRS categories (weighted mRS 

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CDM10000146  Page 32 of 91 
analysis) and proportions of subjects with good functional independence (mRS 0-2) 
(dichotomous analysis). 
It is possible that widespread use of dichotomized outcome scales can potentially lead to 
the discarding of important information about treatment effects. Analysis over ranks, taking 
into account all assessed gradations of outcome along the disability spectrum, provides a 
more comprehensive assessment of intervention effects and has been recommended by 
both the US and European consensus expert groups on trial design. [98-99] 
An important advancement is the development of utility values for each level of the 
modified Rankin Scale of global disability. [75] Weighting the seven Rankin levels by 
utilities further improves the precision of the scale as a measure of disability, converting 
the scale from a somewhat arbitrary fixed interval instrument to a measure with rank 
distances that directly reflect patient and society valuation of outcome health states. 
Formal derivations of utility values for each Rankin grade has recently been completed 
by two groups, using patient informants from a population-based study and using health 
professional informants following the World Health Organization Global Burden of 
Disease methodology. [48,49] Both methods yielded similar values, which were averaged 
to derive the utility-weighted Rankin Scale used in this trial. Use of a utility-weighted 
Rankin Scale permits a trial to capture all the effects a treatment can have on a subject to 
the degree each is important to the subject and society [104].  
5.2.8 
Justification for Use of Adaptive Design 
The combined feasibility / pivotal design increases trial efficiency, allowing the study to 
be stopped early if there is no evidence of a meaningful treatment effect, or allowing it to 
continue if a meaningful treatment effect is perceived after the first interim analysis. The 
adaptive design allows for early and frequent interim analyses so that rather than waiting 
until the maximum number of subjects have been enrolled, decisions about stopping early 
for either predicted success or failure, are made based on pre-specified rules and patients 
are spared from unnecessary randomization. 
The adaptive design also allows for refinement of the target population to smaller infarct 
sizes based on the data that accumulates during the course of the trial, thereby sparing the 
randomization of future subjects who are unlikely to benefit from the treatment. Refer to 
Appendix F, which contains the Adaptive Design Plan, prepared by Berry Consultants. 
Currently there is clinical equipoise to randomize subjects between these two arms because 
there is no evidence of improved clinical outcome in patients who are treated either way 
within 6-24 hours from time last seen well. Adaptive trial design techniques may be helpful 
in identifying subgroups of subjects with enhanced treatment benefit and delineating the 
thresholds at which benefits fade. Several biomarkers have been identified that are 
hypothesized to identify patients with substantially increased benefit from neuro-
thrombectomy, including infarct core size, presence of salvageable penumbra, etc. A 

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STRYKER CONFIDENTIAL - THIS DOCUMENT CONTAINS CONFIDENTIAL AND PROPRIETARY INFORMATION THAT 
IS THE PROPERTY OF STRYKER CORPORATION. NEITHER THIS DOCUMENT NOR THE INFORMATION HEREIN MAY 
BE REPRODUCED, USED, OR DISCLOSED TO ANY THIRD PARTY WITHOUT THE PRIOR WRITTEN CONSENT OF 
STRYKER CORPORATION                                                                                                                                 
 
 
CDM10000146  Page 33 of 91 
Bayesian adaptive trial design permits information gained about subgroups collected 
within the trial to modify enrollment criteria as the study progresses. [100] The core volume 
threshold at which benefit no longer accrues, if one exists, is likely to be most efficiently 
identified by using adaptive modification of trial entry criteria. [75]  
5.3 
Method of Assigning Subjects to Treatments 
Randomization will be accomplished at each site using either a block of randomization 
envelopes, or by using a commercially available Interactive Voice Response System (IVRS) 
or Interactive Web Response System (IWRS). Subjects will be randomized 1:1 to Trevo 
thrombectomy plus medical management or medical management alone. In order to ensure 
both groups are balanced, subjects will be stratified by Clinical Imaging Mismatch (CIM) 
subgroups (see Imaging Inclusion Criteria in Section 6.1.1), TLSW between 6 and < 12 hours 
and >12 to 24 hours, and baseline occlusion location (ICA vs. M1). Enrollment in this study is 
defined as the moment when the randomization process is completed and the subject is 
assigned to a study arm. After randomization, no crossover is permitted. 
5.4 
Blinding and Breaking the Blind 
This protocol is designed as an open label treatment assignment. The presence or absence of 
hemorrhage will be determined by the CT/MR core lab which is blinded to each subject’s 
group assignment.  Core infarct volume at baseline will be measured by automated 
calculations, using standardized software at each participating site. Review of all images and 
calculations will be conducted by the CT/MR core lab on an ongoing basis as images are 
collected (within 72 hours will be the goal), and feedback will be provided to the sites to ensure 
that the Core Infarct volumes are not impacted by artifacts or equipment upgrade issues at the 
site. The Angiographic Core Lab assessing angiograms for revascularization/reperfusion will 
not be blinded, as this evaluation will only be made for subjects in the Trevo Thrombectomy 
plus medical management arm. 
Each site must designate one or more individual(s) to perform the blinded mRS assessments at 
Day 5-7 or discharge (whichever is earlier), Day 30 (±14) and Day 90 (±14). This individual 
will be identified on the Delegation of Authority Log, and must not perform data entry or other 
tasks that would reveal the study arm assignment of subjects. Moreover, the blinded 
evaluator(s) will be instructed to follow a scripted interview to minimize the chance of subjects 
disclosing their treatment group to the evaluator, and will also be required to self-certify that 
they remained blinded throughout the interview with the subject. If the blind is broken for any 
reason, this will be documented on the data collection forms. 
 
[Remainder of page is intentionally blank.] 
 

Stryker Neurovascular 
Document Title: DAWN™ Trial Investigational Plan 
Document Number: CDM10000146 
Rev:  AD 
STRYKER CONFIDENTIAL - THIS DOCUMENT CONTAINS CONFIDENTIAL AND PROPRIETARY INFORMATION THAT 
IS THE PROPERTY OF STRYKER CORPORATION. NEITHER THIS DOCUMENT NOR THE INFORMATION HEREIN MAY 
BE REPRODUCED, USED, OR DISCLOSED TO ANY THIRD PARTY WITHOUT THE PRIOR WRITTEN CONSENT OF 
STRYKER CORPORATION                                                                                                                                 
 
 
CDM10000146  Page 34 of 91 
6 Study Population 
6.1 
Inclusion Criteria 
General Inclusion 
Criteria 
1. Clinical signs and symptoms consistent with the diagnosis of an acute ischemic stroke, 
and subject belongs to one of the following subgroups: 
a. Subject has failed IV t-PA therapy (defined as a confirmed persistent 
occlusion 60 min after administration)  
b. Subject is contraindicated for IV t-PA administration 
2. Age ≥18 
3. Baseline NIHSS ≥10 (assessed within one hour of  measuring core infarct volume) 
4. Subject can be randomized between with 6 to 24 hours after time last known well 
5. No significant pre-stroke disability (pre-stroke mRS must be 0 or 1) 
6. Anticipated life expectancy of at least 6 months 
7. Subject willing/able to return for protocol required follow up visits 
8. Subject or subject’s Legally Authorized Representative (LAR) has signed the study 
Informed Consent form* 
 
* If approved by local ethics committee and country regulations, the investigator is allowed 
to enroll a patient utilizing emergency informed consent procedures if neither the patient 
nor the representative or person of trust is available to sign the informed consent form. 
However, as soon as possible, the patient is informed and his/her consent is requested for 
the possible continuation of this research. (Not applicable to U.S. Sites.) 
General Inclusion 
Criteria   
(additional 
information) 
1. Subjects receiving heparin or low molecular weight (LMW) heparin e.g. Fragmin® 
(Dalteparin Sodium) or an intravenous direct thrombin inhibitor such as Angiomax® 
(Bivalirudin), or Argatroban within the last 24 hours from screening are eligible for 
participation if their coagulation profile remains acceptable. 
2. Subjects on factor Xa inhibitors (e.g. apixaban) or direct thrombin inhibitors are 
eligible for participation 
Imaging Inclusion 
Criteria 
1. < 1/3 MCA territory involved, as evidenced by CT or MRI 
2. Occlusion of the intracranial ICA and/or MCA-M1 as evidenced by MRA or CTA 
3. Clinical Imaging Mismatch (CIM) defined as one of the following on MR-DWI or 
CTP-rCBF maps: 
a. 0-<21 cc core infarct and NIHSS ≥ 10 (and age ≥ 80 years old) 
b. 0-<31 cc core infarct and NIHSS ≥ 10 (and age < 80 years old) 
c. 31 cc to <51 cc core infarct and NIHSS ≥ 20 (and age < 80 years old) 
6.2 
Exclusion Criteria 
General Exclusion 
Criteria 
1. History of severe head injury within past 90 days with residual neurological deficit, as 
determined by medical history 
2. Rapid improvement in neurological status to an NIHSS <10 or evidence of vessel 
recanalization prior to randomization 
3. Pre-existing neurological or psychiatric disease that would confound the neurological 
or functional evaluations, e.g. dementia with prescribed anti-cholinesterase inhibitor 
(e.g. Aricept)  
4. Seizures at stroke onset if it makes the diagnosis of stroke doubtful and precludes 
obtaining an accurate baseline NIHSS assessment 
5. Baseline blood glucose of <50mg/dL (2.78 mmol) or >400mg/dL (22.20 mmol) 

Stryker Neurovascular 
Document Title: DAWN™ Trial Investigational Plan 
Document Number: CDM10000146 
Rev:  AD 
STRYKER CONFIDENTIAL - THIS DOCUMENT CONTAINS CONFIDENTIAL AND PROPRIETARY INFORMATION THAT 
IS THE PROPERTY OF STRYKER CORPORATION. NEITHER THIS DOCUMENT NOR THE INFORMATION HEREIN MAY 
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CDM10000146  Page 35 of 91 
6. Baseline hemoglobin counts of <7 mmol/L (11.28 g/dL) 
7. Baseline platelet count < 50,000/uL 
8. Abnormal baseline electrolyte parameters as defined by sodium concentration <130 
mmol/L, potassium concentration <3 mEq/L or >6 mEq/L 
9. Renal failure as defined by a serum creatinine >3.0 mg/dL (264 µmol/L)    
NOTE: subjects on renal dialysis may be treated regardless of serum creatinine levels 
10. Known hemorrhagic diathesis, coagulation factor deficiency, or on anticoagulant 
therapy with INR > 3.0 or PTT > 3 times normal.   
NOTE: Patients on factor Xa inhibitor within 24-48 hours must have PTT within 3 
times normal. 
11. Any active or recent hemorrhage within the past 30 days 
12. History of severe allergy (more than rash)  to contrast medium  
13. Severe, sustained hypertension (Systolic Blood Pressure >185 mmHg or Diastolic 
Blood Pressure >110 mmHg) 
NOTE: If the blood pressure can be successfully reduced and maintained at the     
acceptable level using medication the subject can be enrolled 
14. Female who is pregnant or lactating at time of admission 
15. Current participation in another investigational drug or device study  
16. Presumed septic embolus, or suspicion of bacterial endocarditis 
17. Treatment with any cleared thrombectomy devices or other intra-arterial 
(neurovascular) therapies prior to randomization 
Exclusion Criteria 
(additional 
information) 
1. The “correction” of baseline glucose or coagulation laboratory values to meet 
inclusion criteria will not be allowed.  
2. Subjects who have taken Clopidogrel, aspirin, or both within the last 24 hours from 
screening for the trial should not be excluded if their coagulation profile remains 
acceptable.  
3. Subjects with a questionable seizure at onset of stroke should not be excluded if 
CTA/MRA confirms the presence of intracranial ICA and/or M1 occlusion, and 
accurate NIHSS can be obtained. 
Imaging Exclusion 
Criteria 
1. Evidence of intracranial hemorrhage on CT/MRI 
2. CTA or MRA evidence of flow limiting carotid dissection, high-grade stenosis, or 
complete cervical carotid occlusion requiring stenting at the time of the index 
procedure (i.e., mechanical thrombectomy). 
3. Excessive tortuosity of cervical vessels on CTA/MRA that would likely preclude 
device delivery/deployment  
4. Suspected cerebral vasculitis based on medical history and CTA/MRA 
5. Suspected aortic dissection based on medical history and CTA/MRA 
6. Intracranial stent implanted in the same vascular territory that would preclude the safe 
deployment/removal of the Trevo device 
7. Occlusions in multiple vascular territories (e.g., bilateral anterior circulation, or 
anterior circulation/vertebrobasilar system) as confirmed on CTA/MRA, or clinical 
evidence of bilateral strokes or strokes in multiple territories  
8. Significant mass effect with midline shift as confirmed on CT/MRI 
9. Evidence of intracranial tumor (except small meningioma) as confirmed on CT/MRI 

Stryker Neurovascular 
Document Title: DAWN™ Trial Investigational Plan 
Document Number: CDM10000146 
Rev:  AD 
STRYKER CONFIDENTIAL - THIS DOCUMENT CONTAINS CONFIDENTIAL AND PROPRIETARY INFORMATION THAT 
IS THE PROPERTY OF STRYKER CORPORATION. NEITHER THIS DOCUMENT NOR THE INFORMATION HEREIN MAY 
BE REPRODUCED, USED, OR DISCLOSED TO ANY THIRD PARTY WITHOUT THE PRIOR WRITTEN CONSENT OF 
STRYKER CORPORATION                                                                                                                                 
 
 
CDM10000146  Page 36 of 91 
6.3 
Withdrawal and Replacement of Subjects 
While study withdrawal is discouraged, subjects may withdraw from the study at any time, 
with or without reason and without prejudice to further treatment. Withdrawn subjects will not 
undergo any additional follow-up, nor will they be replaced.  
6.4 
Enrollment Controls 
Enrollment will be monitored to ensure that no more than the maximum planned number of 
subjects is enrolled. An electronic data capture system will be used, and the system will be set 
to automatically notify the CRA or Project Manager of all subject enrollments being entered 
within the system. As enrollment nears the maximum allowed one of two methods will be 
employed to notify sites of status of enrollment: 
1. If an automated randomization system is utilized, sites will be notified via automatic pre-
programmed notifications within the IVRS/IWRS system, when they attempt to randomize a 
patient, specifically when enrollment is no longer available. 
2. If randomization envelopes are utilized, the Project Manager or designee will monitor the 
enrollment status daily (when enrollment is within 10 subjects of the maximum allowed 
enrollment) and send out an e-mail requesting sites to call a specific telephone number or e-
mail a designated person to ask permission before randomizing and enrolling a subject. 
7 Study Procedures 
The schedule of events is the same for all subjects in the trial except those subjects randomized to 
the Trevo plus Medical Management arm will undergo an intra-arterial Trevo thrombectomy 
procedure.  All subjects who are enrolled into the trial will be followed for 90 days (± 14) unless 
they withdraw early from the trial, expire before the 90 day follow up window is reached, or are 
lost to follow up. The Time and Events schedule is outlined in Table 5. 
7.1 
Written Informed Consent 
Written Informed Consent must be obtained for all subjects who are screened and meet the 
general inclusion/exclusion criteria prior to randomization/enrollment.  
Note - If approved by local ethics committee and country regulations, the investigator is 
allowed to enroll a patient utilizing emergency informed consent procedures if neither the 
patient nor the representative or person of trust is available to sign the informed consent form. 
However, as soon as possible, the patient is informed and his/her consent is requested for the 
possible continuation of this research. (Not applicable to U.S. Sites.) 
The subject or the subject’s Legally Authorized Representative (LAR) will be asked to sign 
the Informed Consent form before any study-specific tests or procedures are performed. The 
Informed Consent Form (ICF) must be approved by the study Institutional Review Board 

Stryker Neurovascular 
Document Title: DAWN™ Trial Investigational Plan 
Document Number: CDM10000146 
Rev:  AD 
STRYKER CONFIDENTIAL - THIS DOCUMENT CONTAINS CONFIDENTIAL AND PROPRIETARY INFORMATION THAT 
IS THE PROPERTY OF STRYKER CORPORATION. NEITHER THIS DOCUMENT NOR THE INFORMATION HEREIN MAY 
BE REPRODUCED, USED, OR DISCLOSED TO ANY THIRD PARTY WITHOUT THE PRIOR WRITTEN CONSENT OF 
STRYKER CORPORATION                                                                                                                                 
 
 
CDM10000146  Page 37 of 91 
(IRB)/ Ethics Committee (EC). For U.S. Sites, electronic informed consent procedures may be 
utilized if approved by the IRB and consistent with FDA guidance on use of electronic 
informed consent in clinical investigations.1 Study personnel should explain that even if a 
subject agrees to participate in the study and signs an Informed Consent Form, non invasive 
baseline imaging or cerebral angiography may demonstrate that the subject is not a suitable 
candidate for the assigned study treatment.  
A Screening and Enrollment Log will be maintained by the site to document basic information 
such as date screened and reason for screen failures for subjects who fail to meet the study 
eligibility criteria. Screen failed subjects and their reason(s) for screen failure will be 
documented and may be entered into the electronic database, but they will not be followed 
beyond the screening visit, and no further data will be collected/recorded. 
7.2 
Prior to Randomization 
The following pre-procedure data must be collected before randomization and enrollment for 
all subjects (and before the index procedure for those subjects randomized to the Trevo 
Thrombectomy plus medical management arm):  
• 
Confirmation that all inclusion and none of the exclusion criteria have been met  
• 
Demographics and medical history 
• 
Neurological examination 
• 
Platelets/Hemoglobin 
• 
PT/PTT/INR 
• 
Blood glucose  
• 
Sodium concentration 
• 
Potassium concentration 
• 
Serum creatinine  
• 
Pregnancy test (required for females of child bearing potential; not required for 
females who are surgically sterile or post-menopausal) 
• 
MRI/MRA or CT/CTA/CTP (if MR is contra-indicated or unavailable) to assess for 
hemorrhage, confirm the presence of an anterior large vessel occlusion in the ICA 
or MCA-M1 arteries, and to measure the core infarct volume 
 
To facilitate consistency and clarity, a time standard is established for this study, with time 
zero “t = 0” defined as the time of randomization, which occurs after initial MRI/MRA or 
CT/CTA/CTP to assess for hemorrhage, confirm the presence of an anterior large vessel 
occlusion in the ICA or MCA-M1 arteries, and to measure the  core infarct volume.  Baseline 
is defined as the period of time from initial stroke admission up to time of randomization. 
                                                          
1 Food and Drug Administration. Use of Electronic Informed Consent in Clinical Investigations – Questions and 
Answers. Guidance for Industry.  Draft Guidance issued March, 2015. 

Stryker Neurovascular 
Document Title: DAWN™ Trial Investigational Plan 
Document Number: CDM10000146 
Rev:  AD 
STRYKER CONFIDENTIAL - THIS DOCUMENT CONTAINS CONFIDENTIAL AND PROPRIETARY INFORMATION THAT 
IS THE PROPERTY OF STRYKER CORPORATION. NEITHER THIS DOCUMENT NOR THE INFORMATION HEREIN MAY 
BE REPRODUCED, USED, OR DISCLOSED TO ANY THIRD PARTY WITHOUT THE PRIOR WRITTEN CONSENT OF 
STRYKER CORPORATION                                                                                                                                 
 
 
CDM10000146  Page 38 of 91 
All subsequent time points (e.g. 24-hours, Day 5-7, Day 30 and Day 90) will be in reference 
to time of randomization (time zero).  Refer to Table 5, DAWN Study Time and Events 
Schedule, for all required tests and time windows (with allowed ranges). The following time 
references will be used in this study during the screening phase:  
• 
Time Last Seen Well - This is the time the subject was last seen (or known to be) well 
in “wake-up” stroke cases or the time that subject’s symptoms were first noticed in 
witnessed stroke cases. 
• 
Time of symptom onset – This is the time that subject’s symptoms were first noticed 
for subjects with witnessed events.  
• 
Time of treatment initiation – In the treatment arm treatment is considered to have 
begun at the time of access site puncture; in the control arm it is the time of 
randomization. 
All subjects enrolled/randomized into the trial will be categorized as one of the following: 
• 
Wake-up Stroke: Subject known to have symptoms first detected on awakening from 
sleep. 
• 
Witnessed Stroke: Subject last known well time and symptoms first observed time 
known to be the same. 
• 
Un-witnessed Stroke: Subject last know well time and symptoms first observed time 
known to be different, but not known to have symptoms first detected on awakening 
from sleep. 
For the purposes of trial enrollment the subject must have a thrombus identified within the 
intracranial ICA, and/or MCA-M1 arteries by pre-procedure MRA or CTA. The MCA-M1 
segment is defined as the first branch of the intracranial ICA which courses horizontally from 
its branching point off the ICA through the sylvian fissure up to the first bifurcation distal to 
the lenticulostriate arteries, in the Sylvian fissure. 
[Remainder of page is intentionally blank.] 
 

Stryker Neurovascular 
Document Title: DAWN™ Trial Investigational Plan 
Document Number: CDM10000146 
Rev:  AD 
STRYKER CONFIDENTIAL - THIS DOCUMENT CONTAINS CONFIDENTIAL AND PROPRIETARY INFORMATION THAT IS THE PROPERTY OF STRYKER 
CORPORATION. NEITHER THIS DOCUMENT NOR THE INFORMATION HEREIN MAY BE REPRODUCED, USED, OR DISCLOSED TO ANY THIRD PARTY WITHOUT 
THE PRIOR WRITTEN CONSENT OF STRYKER CORPORATION                                                                                                                                                                             
 
 
CDM10000146 Page 39 of 91 
Table 5. DAWN™ Trial Time and Events Schedule 
*NIHSS within 1 hour of corresponding core infarct measurement.  
** NIHSS should be obtained within approximately 2 hours of the 24 (-6/+24) hour neuro-imaging to determine presence/absence of hemorrhage.  
† mRS must be conducted by an individual blinded to the treatment arm.  
†† Randomization should occur within 1 hour of obtaining neuro imaging used to determine core infarct measurement. 
*** CT/MR and Angiographic images should be de-identified before being submitted to Stryker NV or core lab. 
Event 
Screening/ 
Baseline 
Procedure 
(Treatment Arm 
Only) 
24 Hr (-6/+24) 
(post 
randomization) 
Day 5-7 / Discharge 
(whichever is 
earlier) 
 
Discharge 
Day 30 
± 14 
Day 90 
± 14 
Inclusion/Exclusion Criteria 
 
 
 
 
 
 
 
Demographics/Medical History/Baseline 
Medications 
 
 
 
 
 
 
 
Baseline Characteristics 
 
 
 
 
 
 
 
Baseline Labs 
 
 
  
 
 
 
 
Informed Consent 
 
 
 
 
 
 
 
Randomization (= time zero) 
†† 
 
 
 
 
 
 
Angiography Procedure Details (Treatment 
Arm only) *** 
 
 
 
 
 
 
 
mRS †  
 
(pre stroke) 
 
 
† 
 
† 
† 
NIHSS  
* 
 
** 
 
 
 
 
Neuro imaging (to assess for hemorrhage, 
occlusion location/vessel patency & infarct 
volume)*** 
  
MRI/MRA or 
CT/CTA/CTP 
 
 
 MRI/MRA or 
CT/CTA 
  
MRI or CT 
(optional) 
 
 
 
AEs/SAEs (from time of randomization) 
 
 
 
 
 
 
 
Concomitant Medications 
 
 
 
 
 
 
 
In Hospital Med Management 
 
Intubation Details 
 
 
UB04 / Health Economics 
 

Stryker Neurovascular 
Document Title: DAWN™ Trial Investigational Plan 
Document Number: CDM10000146 
Rev:  AD 
STRYKER CONFIDENTIAL - THIS DOCUMENT CONTAINS CONFIDENTIAL AND PROPRIETARY INFORMATION THAT 
IS THE PROPERTY OF STRYKER CORPORATION. NEITHER THIS DOCUMENT NOR THE INFORMATION HEREIN MAY 
BE REPRODUCED, USED, OR DISCLOSED TO ANY THIRD PARTY WITHOUT THE PRIOR WRITTEN CONSENT OF 
STRYKER CORPORATION                                                                                                                                                                             
 
 
  CDM10000146  Page 40 of 91 
7.3 
Angiography Procedure (Treatment arm only) 
7.3.1 
Diagnostic Angiography 
For the subjects randomized to the Trevo Thrombectomy plus medical management arm, 
treatment initiation is defined as the date and time of arterial access. Arterial Access using 
appropriate anesthesia, should be obtained per standard practice at the treating institution, 
and should be obtained within 60 minutes of randomization.  Treatment initiation, 
defined as time of access site puncture, must occur after six hours, but before 24 hours 
since the subject was last seen well.  
A diagnostic angiogram must be performed in order to determine the appropriateness of 
the occlusion for treatment with the Trevo Retriever. The occlusion location(s) will be 
recorded by the site on the appropriate CRF. Angiographic evaluations will be done before 
Trevo device use, after Trevo device use, and post procedure to determine vessel patency 
as well as the presence of embolization to new territory (ENT) or distal emboli (DE), and 
contrast extravasation (a sign of hemorrhage). Angiography must be performed in the 
involved territory. If angiographic images are missing from the sequence of acquisitions, 
the core lab will request the site to resend the entire angiography dataset. 
Embolization to new territory (ENT) is defined as any new infarct on CT or DWI at 24 (-
6/+24) hours compared to baseline CT or MRI in the ipsilateral ACA for MCA occlusions. 
Any new neurological deficit not referable to the affected hemisphere occurring post 
intervention with or without MRI lesion equivalent will also be adjudicated as embolization 
to new territory. ACA infarcts ipsilateral to a carotid terminus occlusion will not be 
considered as a procedure-related adverse event unless no infarct is seen on baseline DWI. 
Any new vessel occlusions in previously unaffected territories including ACA ipsilateral 
to a carotid terminus occlusion if absent on the baseline DWI will be considered procedure 
related. 
If the suspected distribution of ischemia is in the anterior circulation, a contrast injection 
into the common carotid artery to examine the carotid bifurcation and intracranial arteries 
should be performed. If an occlusion is identified, with failure to visualize the terminal 
internal carotid artery, the opposite carotid artery and/or vertebral artery should be injected 
to identify collaterals across the Circle of Willis pial collateral blood supply and patency 
of the ACA and MCA unless catheterization of the contralateral carotid artery would pose 
unacceptable procedural  risk or significant delays.  
Prior to the start of the procedure, the modified TICI scores within the vascular territory 
being treated should be assessed. Angiographic films of the occlusion being treated must 
allow clear visualization of the target artery. The same orientation should be used before 
and after the Trevo Thrombectomy in order to allow a valid analysis of the reperfusion 
status of the vessel(s). The late venous phase should be included in all angiogram 

Stryker Neurovascular 
Document Title: DAWN™ Trial Investigational Plan 
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Rev:  AD 
STRYKER CONFIDENTIAL - THIS DOCUMENT CONTAINS CONFIDENTIAL AND PROPRIETARY INFORMATION THAT 
IS THE PROPERTY OF STRYKER CORPORATION. NEITHER THIS DOCUMENT NOR THE INFORMATION HEREIN MAY 
BE REPRODUCED, USED, OR DISCLOSED TO ANY THIRD PARTY WITHOUT THE PRIOR WRITTEN CONSENT OF 
STRYKER CORPORATION                                                                                                                                                                             
 
 
  CDM10000146  Page 41 of 91 
acquisitions.  Sites should submit all angiographic data to the Core Lab, rather than pre-
selecting a subset of images. If angiographic images are missing from the sequence of 
acquisitions, the core lab will request the site to resend the angiography dataset. 
In the event of a procedural complication or adverse event, detailed angiographic images 
should be obtained and submitted.  All adverse events that occur during the procedure must 
be documented and recorded on the applicable CRFs. 
7.3.2 
Unexpected Diagnostic Angiography Findings 
One of the main inclusion criteria for the study is the presence of an Intracranial ICA and/or 
MCA M1 segment occlusion on the pre-randomization CTA/MRA. Subjects with isolated 
proximal cervical ICA occlusions, isolated M2 occlusions, and subjects with occlusions in 
multiple vascular territories (e.g., bilateral anterior circulation, or anterior/posterior 
circulation) on the pre-randomization CTA/MRA are excluded from the study. Given the 
high accuracy of CTA/MRA in detecting proximal intracranial occlusions we expect near 
perfect correlation with the findings on conventional angiography. However, the following 
unexpected situations may arise: 
A. If there is no thrombus in any treatable vessel on the initial diagnostic 
angiography (e.g. Intracranial ICA with or without MCA involvement, or MCA 
M1) no Trevo device will be used and the procedure will be terminated.  
After review of the multimodal CT/MRI and Angiograms by the Core Labs, the 
data from these cases will be analyzed according to one of the following rules:  
1. If the occlusion (enrollment criteria) was misdiagnosed by the enrolling 
center on the initial CTA/MRA evaluation (as per CT/MR Core Lab 
determination), this will be considered a major protocol violation and these 
subjects will be analyzed in the “intent-to-treat” analysis, but not the “per 
protocol” analysis, utilizing their “actual” mRS score as the primary 
outcome measure.  
2. If a treatable occlusion was present on the initial CTA/MRA evaluation (as 
per CT/MR Core Lab determination) but is not visualized on the baseline 
diagnostic Angiogram by the Angiographic Core Lab, these subjects will be 
categorized as having achieved spontaneous recanalization and will be 
analyzed in both the “intent-to-treat analysis” and the “per protocol” 
analysis, utilizing their “actual” mRS score as the primary outcome 
measure.  
 
Additional sensitivity analyses will be performed excluding subjects who 
do not receive the assigned therapy. 
 

Stryker Neurovascular 
Document Title: DAWN™ Trial Investigational Plan 
Document Number: CDM10000146 
Rev:  AD 
STRYKER CONFIDENTIAL - THIS DOCUMENT CONTAINS CONFIDENTIAL AND PROPRIETARY INFORMATION THAT 
IS THE PROPERTY OF STRYKER CORPORATION. NEITHER THIS DOCUMENT NOR THE INFORMATION HEREIN MAY 
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STRYKER CORPORATION                                                                                                                                                                             
 
 
  CDM10000146  Page 42 of 91 
B. If thrombus is identified in one or more proximal non treatable arteries per 
protocol and in none of the per-protocol treatable arteries on the initial 
diagnostic angiography (e.g. Proximal cervical ICA, anterior cerebral artery 
(ACA), posterior cerebral artery (PCA), vertebral artery (VA) or basilar artery 
(BA)) these occlusions may be treated as per local standards and guidelines.      
After review of the multimodal CT/MRI and Angiograms by the Core Labs, the 
data from these cases will be analyzed according to one of the following rules:  
 
1. Except for a core lab adjudicated M2 occlusion that is considered M1 
occlusion by the local investigator, if the occlusion location (enrollment 
criteria) was misdiagnosed by the enrolling center on the initial CTA/MRA 
evaluation (as per CT/MR Core Lab determination), this will be considered 
a major protocol violation and these subjects will be analyzed in the “intent-
to-treat” analysis, but not the “per protocol” analysis, utilizing their “actual” 
mRS score as the primary outcome measure. 
2. Except for a core lab adjudicated M2 occlusion that is considered M1 
occlusion by the local investigator, if there is a new occlusion present in a 
non treatable vessel per protocol that was not present on the initial 
CTA/MRA evaluation (as per CT/MR Core Lab determination), this will be 
considered a Procedure-related serious adverse event (e.g. Embolization to 
a new territory) and these subjects will be analyzed in both the “intent-to-
treat” analysis and the “per protocol” analysis, utilizing their “actual” mRS 
score as the primary outcome measure. 
 
Sensitivity analyses will be performed excluding subjects who do not have 
a protocol specified lesion and are treated off protocol with any device. 
 
C. If thrombus is identified in one or more distal non treatable arteries, per protocol 
(e.g. the ipsilateral M2 or M3 MCA segment), and none of the per protocol 
treatable arteries on the initial diagnostic angiography, and the occlusion in the 
opinion of the physician caring for the subject could potentially lead to major 
disability it may be treated as per the local management guidelines.  
 
After review of the multimodal CT/MRI and Angiograms by the Core Labs, 
the data from these cases will be analyzed according to one of the following 
rules:  
 
1. If the occlusion location (enrollment criteria) was misdiagnosed by the 
enrolling center on the initial CTA/MRA evaluation (as per CT/MR Core 
Lab determination), this will be considered a major protocol violation and 
these subjects will be analyzed in the “intent-to-treat” analysis, but not the 

Stryker Neurovascular 
Document Title: DAWN™ Trial Investigational Plan 
Document Number: CDM10000146 
Rev:  AD 
STRYKER CONFIDENTIAL - THIS DOCUMENT CONTAINS CONFIDENTIAL AND PROPRIETARY INFORMATION THAT 
IS THE PROPERTY OF STRYKER CORPORATION. NEITHER THIS DOCUMENT NOR THE INFORMATION HEREIN MAY 
BE REPRODUCED, USED, OR DISCLOSED TO ANY THIRD PARTY WITHOUT THE PRIOR WRITTEN CONSENT OF 
STRYKER CORPORATION                                                                                                                                                                             
 
 
  CDM10000146  Page 43 of 91 
“per protocol” analysis, utilizing their “actual” mRS score as the primary 
outcome measure. 
2. If a treatable occlusion was present on the initial CTA/MRA evaluation (as 
per CT/MR Core Lab determination), but is not visualized on the baseline 
diagnostic Angiogram by the Angiographic Core Lab, these subjects will be 
categorized as having achieved spontaneous recanalization with distal clot 
migration and will be analyzed in both the “intent-to-treat analysis” and the 
“per protocol” analysis, utilizing their “actual” mRS score as the primary 
outcome measure. 
Sensitivity analyses will be performed excluding subjects who do not have 
a protocol specified lesion and are treated off protocol with any device. 
Of note, for randomized subjects who meet clinical, imaging and laboratory criteria 
for entry into the study and who are randomized to the treatment arm, but who are 
not treated with endovascular therapy due to spontaneous recanalization or other 
factors (inability to access the lesion, etc.) the subject is considered enrolled and 
the site must still follow the subject through 90 days and collect all relevant data. 
7.4 
Trevo Thrombectomy Procedure (Treatment arm only) 
In subjects randomized to the Trevo thrombectomy plus medical management arm, the 
procedure should be performed using only the Trevo Retriever. If for any reason, the Trevo 
Retriever cannot be used, the subject will still be analyzed in the Trevo Thrombectomy plus 
medical management arm in an intent-to-treat (ITT) analysis. 
NOTE: The procedure must be started (defined as the time of arterial access) no earlier than 
6 hours, but before 24 hours, from the time of symptom onset or the Time Last Seen Well 
(TLSW). This is when treatment is considered to be initiated in this group. 
The interventional procedure should be completed within two (2) hours of arterial access.  
Heparin anticoagulation may be used but should not exceed a total of 2,000 units of Heparin 
bolus followed by 500 units/hour Heparin drip for the duration of the procedure. 
Prudent use of anti-vasospasm agents is permitted.  
Use of the Trevo device should be terminated if there is any angiographic evidence leading to 
the suspicion of an intracranial hemorrhage, such as extravasation of contrast during the 
procedure. 
Physicians should follow the most current Instructions for Use (IFU) at all times with regards 
to the device compatibility, preparation and the recommended retrieval procedure. Key 
preparation and procedure steps are described below: 

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  CDM10000146  Page 44 of 91 
1. Using conventional catheterization techniques, place Microcatheter into target vessel using 
a standard neurovascular guidewire. Anatomy permitting, position Microcatheter tip distal 
to thrombus.  
2. Important: If insertion tool is not properly flushed, it may be difficult to advance the 
Retriever through the insertion tool. 
3. Advance 
Retriever 
until 
distal 
tip 
aligns 
with 
tip 
of 
Microcatheter. 
Note: Retriever tip will be within 15 cm of exiting Microcatheter tip when (a) distal end of 
Retriever shaft marker reaches Microcatheter hub, or (b) proximal end of Retriever shaft 
marker reaches proximal end of rotating hemostasis valve. 
4. Retract Microcatheter while applying gentle forward force to Retriever to deploy shaped 
section of Retriever within clot. Position Microcatheter tip marker just proximal to shaped 
section 
of 
Retriever. 
Warning: To reduce risk of fracture, maintain Microcatheter tip marker just proximal to 
shaped section of Retriever during manipulation and withdrawal. 
5. After deploying Retriever, allow sufficient time for clot to integrate into the Retriever 
(approximately 5 minutes). 
6. If using a Balloon Guide Catheter, inflate balloon to occlude vessel as specified in Balloon 
Guide Catheter labeling. 
7. Position and lock torque device onto Retriever at Microcatheter hub. 
8. Slowly withdraw Retriever and Microcatheter as a unit to Balloon Guide Catheter or Guide 
Catheter tip while applying aspiration to Guide Catheter using 60 mL syringe.  
9. Apply vigorous aspiration to Balloon Guide Catheter or Guide Catheter using 60 mL 
syringe and withdraw Retriever and Microcatheter inside Guide Catheter. Continue 
aspirating until Retriever and Microcatheter are nearly withdrawn from Guide Catheter. 
Note: If withdrawal into Balloon Guide Catheter or Guide Catheter is difficult, deflate 
Balloon Guide Catheter balloon and simultaneously withdraw Guide Catheter, 
Microcatheter and Retriever as a unit through sheath. Remove sheath if necessary. 
10. Deflate Balloon Guide Catheter balloon. 
11. Disconnect Guide Catheter rotating hemostasis valve and fully remove Retriever, 
Microcatheter and rotating hemostasis valve as a unit from Guide Catheter.  
12. Clean the device with saline. Inspect Retriever for damage. Do not reuse Retriever if core 
wire, shaped section or platinum coil appears different than when first removed from 
package. If not damaged, the Retriever may be used for up to three (3) retrieval attempts. 
A retrieval attempt is one (1) advancement and complete withdrawal cycle. 
 
Warning: Do not perform more than six (6) retrieval attempts in the same vessel using 
Retriever devices. This total number applies for any combination of retrieval devices.  
Immediately after each retrieval attempt with the Trevo Retriever, perform biplane 
angiography in order to assess the vessel patency in the neurovascular tree that is being treated. 
Angiography should include ipsilateral AP and lateral imaging of the involved arterial system, 
including potential collateral vessels. 

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a. If reperfusion has been successful with the Trevo Retriever (defined as at least TICI 
2b(reperfusion of > 2/3 MCA territory)  in the territory treated) the Trevo 
thrombectomy procedure should be stopped and no further interventions performed. 
b. If reperfusion has not been successful with the Trevo Retriever (defined as modified 
TICI 0-2a in the territory treated) continue with additional retrieval attempts (up to the 
maximum allowed per the IFU). Adjunctive treatment (rescue therapy) may be initiated 
after the 6 passes if deemed appropriate by the treating physician, but it is discouraged 
as it constitutes a major protocol violation and its clinical benefit is unclear. 
Adjunctive therapy (e.g. use of another stent retriever or stent) is strongly discouraged and 
represents a major protocol violation. Participants who receive rescue adjunctive therapy will 
be imputed as mRS=6.  If adjunctive treatment (rescue therapy) is used AFTER the Trevo 
Retriever, biplane angiography should be performed immediately afterwards in order to 
reassess vessel patency and determine the effect of the adjunctive rescue treatment. 
Angiography should include ipsilateral AP and lateral imaging in the involved arterial system, 
including potential collateral vessels. This information will be used to quantify the overall 
procedural reperfusion rates after the use of the Trevo Retriever versus at the end of the 
procedure. 
NOTE: The last angiogram prior to the use of rescue therapy will be considered when rating 
post-Trevo Retriever reperfusion. However, use of any intra arterial lytic or intra-arterial 
antiplatelet agent, or other mechanical devices, during or after the Trevo Retriever will 
automatically categorize the subject as a Trevo revascularization “failure” regardless of their 
revascularization status prior to the rescue therapy. Therefore interventionalists will be 
discouraged from using intra arterial lytics or antiplatelets, or other mechanical devices during 
the procedure, unless it is deemed that not performing rescue therapy will put the subject at 
more significant risk than by performing rescue therapy. Use of rescue therapy will be 
considered a protocol violation. 
7.5 
End of the Trevo Thrombectomy Procedure (Treatment arm only) 
The Trevo thrombectomy procedure should be terminated if any of the following occur:  
1. Neurological deterioration or alteration in function is detected leading to the suspicion of 
an intracranial hemorrhage 
2. The time from groin puncture reaches 2 hour   
3. TICI grade 2b or 3flow (reperfusion of > 2/3 MCA territory) is established 
4. The occlusion is refractory to six retrieval attempts in a single vessel  
 
Neurological deterioration or alteration in function leading to the suspicion of an intracranial 
hemorrhage will necessitate an emergent head CT or MRI scan.  At the discretion of the 
investigator, this evaluation may also include angiography or other diagnostic tests to 

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  CDM10000146  Page 46 of 91 
determine the etiology of the clinical alteration.  Management of an intracranial hemorrhage 
will be performed according to each institution’s usual practice. 
7.6 
24 (-6 / +24) Hours post Randomization 
The following data will be collected at 24 (-6/+24) hours post randomization: 
• 
In hospital medical management details 
• 
NIHSS  
• 
MRI/MRA or CT/CTA in order to assess for hemorrhage, vessel patency and infarct core 
volume. The same imaging modality should be used at 24 (-6/+24) hours to measure 
vessel patency as was used at baseline to identify occlusion location. MRI T2 Flair or CT 
may be used to assess core infarct volume. 
• 
Adverse events and any treatment administered  
For all subjects who expire prior to the 24 (-6/+24) hour assessment, available information 
regarding the primary cause of death and date/time of death will be recorded, as well as whether 
the subject was made “do not resuscitate” (DNR) or “comfort care only” prior to expiration.  
Deaths MUST be reported to Stryker NV within 24 hours of becoming aware, preferably by 
CRF completion. In the event that the EDC system is unavailable a written report by e-mail or 
fax is acceptable. 
7.7 
Concomitant Medications and Management 
Treatment Arm: 
 
 Use of IV or IA lytics, or IA antiplatelets is prohibited in subjects randomized to the 
treatment arm during the procedure and until after follow up imaging is completed. 
 Systemic anticoagulation with heparin may be used during the procedure, but should 
not exceed a total of 2,000 units of heparin bolus followed by a 500 units/hour drip for 
the duration of the procedure. 
 Prudent use of anti-vasospasm agents is permitted during the procedure. 
Medical Management Arm: 
 IV heparin is prohibited until after the 24 (-6/+24) hour neuro-imaging has been 
performed to determine the presence/absence of intracranial hemorrhage.   
 The administration of medications is at the treating physician’s discretion according to 
local standards of care, but may NOT include any intra-arterial therapies. 
[Remainder of page is intentionally blank.] 

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  CDM10000146  Page 47 of 91 
Both Arms: 
 Newly administered aspirin (IV or oral) and/or Clopidogrel  are the only anti-platelets 
allowed within the first 24 hours post randomization, until after the 24 (-6/+24) hour 
neuro-imaging has been performed to determine the presence/absence of intracranial 
hemorrhage.  
 Subjects previously treated with antiplatelet agents or combination antiplatelet therapy 
(e.g. for a previously implanted drug eluting stent), may continue this regimen if in the 
investigator’s opinion the benefits of continued therapy outweigh the risks of potential 
neurological deterioration related to hemorrhage.  
 Subcutaneous Low Molecular Weight (LMW) heparin is allowed for Deep Vein 
Thrombosis (DVT) prophylaxis per the center’s standard of care.  
 All subjects enrolled into this study should be medically managed according to the 
2013 AHA guidelines, and specifically as follows with regards to blood pressure and 
glucose management.[29]  
7.7.1 
Blood pressure management 
The management of arterial hypertension remains controversial. Data to guide 
recommendations for treatment are inconclusive or conflicting. Many patients have 
spontaneous declines in blood pressure during the first 24 hours after onset of stroke. Until 
more definitive data are available, it is generally agreed that a cautious approach to the 
treatment of arterial hypertension should be recommended. Subjects who have other 
medical indications for aggressive treatment of blood pressure should be treated.  
In subjects who received IV tPA blood pressure should be managed according to post IV 
tPA management protocols (systolic blood pressure is <185 mm Hg and their diastolic 
blood pressure is <105 mm Hg) within the first 24 hours. 
In subjects who are reperfused after mechanical embolectomy (defined as achieving TICI 
2b or TICI 3) systolic blood pressure should be maintained at 140 mm Hg in the first 24 
hours to minimize the risk of reperfusion related ICH. In subjects who do not achieve 
recanalization after thrombectomy similar B/P management orders should be applied as for 
the control subjects within each center.  
Some centers use induced hypertension in patients with occlusive disease and in these 
centers, management of subjects should occur per local guidelines and protocols. In 
exceptional cases, a physician may prescribe vasopressors to improve cerebral blood flow. 
If drug induced hypertension is used, close neurological and cardiac monitoring is 
recommended. 

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  CDM10000146  Page 48 of 91 
Because arterial blood pressure is a dynamic parameter, it is important to monitor it 
frequently, especially during the first day of stroke, to identify trends and extreme 
fluctuations that would require intervention. If/when lowering the blood pressure is 
indicated, it should be done in a well-controlled manner. 
7.7.2 
Glucose management 
Evidence indicates that persistent in-hospital hyperglycemia during the first 24 hours after 
stroke is associated with worse outcomes than normoglycemia, and thus, it is reasonable to 
treat hyperglycemia to achieve blood glucose levels in a range of 140 to 180 mg/dL and to 
closely monitor to prevent hypoglycemia in subjects with acute ischemic stroke. 
7.8 
Day 5-7 / Discharge 
The subject may be discharged from the hospital when clinically stable, at the Investigator’s 
discretion. The following data will be collected between Day 5-7 (if subject remains in the 
hospital) or prior to discharge, whichever is earlier: 
• 
In hospital medical management details 
• 
NIHSS 
• 
mRS (blinded assessor) 
• 
Repeat imaging - MRI T2 Flair is not required but may be performed to re-assess 
final core infarct volume, at the treating physician’s discretion, per local practice. CT 
may be performed if MRI is contra-indicated. If performed, this imaging will be 
collected and reviewed by the Core Lab. 
• 
Adverse events and any treatment administered 
• 
Subject disposition 
 
For all subjects who remain in hospital after the Day 5-7 assessments, adverse events and any 
treatment administered will also be recorded through Discharge. For all subjects who expire 
prior to the Day 5-7/Discharge assessment, available information regarding the primary cause 
of death and date/time of death will be recorded, as well as whether the subject was made “do 
not resuscitate” (DNR) or “comfort care only” prior to expiration.  
Deaths MUST be reported to Stryker NV within 24 hours of becoming aware, preferably by 
CRF completion. In the event that the EDC system is unavailable a written report by e-mail or 
fax is acceptable. 
7.9 
Post Discharge Follow-up 
The designated staff at the clinical site will review the study requirements with the subject to 
maximize compliance with the follow-up schedule. The staff will instruct subjects to return for 

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  CDM10000146  Page 49 of 91 
follow-up assessments according to the study Time and Events Schedule in Table 5. Study 
staff should establish a date for the follow-up visits with the subject and if possible, schedule 
the visits at the time of hospital discharge. 
The study will be considered complete (with regard to the primary endpoint) after all subjects 
have completed Day 90 (± 14) follow-up assessments. Requirements of each follow-up 
evaluation are detailed below. 
7.9.1 
Day 30 (± 14) 
At Day 30 (± 14) the following study assessments should be performed via an in person 
visit:  
• 
NIHSS  
• 
mRS (by blinded assessor) - If subject is unable to return to the clinic for the 
Day 30 ± 14 visit, a telephone mRS assessment is preferable to no assessment 
• 
Adverse events and any treatment administered  
 
For all subjects who expire prior to the Day 30 assessment, available information regarding 
the primary cause of death and date/time of death will be recorded, as well as whether the 
subject was made “do not resuscitate” (DNR) or “comfort care only” prior to expiration.  
Deaths MUST be reported to Stryker NV within 24 hours of becoming aware, preferably 
by CRF completion. In the event that the EDC system is unavailable a written report by e-
mail or fax is acceptable. 
7.9.2 
Day 90 (± 14) 
At Day 90 (± 14) the following study assessments should be performed via an in person 
visit:  
• 
NIHSS  
• 
mRS (by blinded assessor) - If subject is unable to return to the clinic for the 
Day 90 ± 14 visit, a telephone mRS assessment is preferable to no assessment 
• 
Adverse events and any treatment administered  
 
For all subjects who expire prior to the Day 90 assessment, available information regarding 
the primary cause of death and date/time of death will be recorded, as well as whether the 
subject was made “do not resuscitate” (DNR) or “comfort care only” prior to expiration.  
Deaths MUST be reported to Stryker NV within 24 hours of becoming aware, preferably 
by CRF completion. In the event that the EDC system is unavailable a written report by e-
mail or fax is acceptable. 

Stryker Neurovascular 
Document Title: DAWN™ Trial Investigational Plan 
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  CDM10000146  Page 50 of 91 
8 Statistical Methods 
8.1 
Sample Size Estimate and Justification 
The adaptive sample size was judged through simulations based on the following assumptions: 
The maximum trial size is 500 subjects, randomized equally between the two arms. Because 
of the adaptive nature of the design, the actual sample size may be less, with the minimum 
being 150 subjects. 
We investigated treatment effects that increased the expected weight by 0, 0.5, 0.75, 1.0, 1.25, 
and 1.5 units above control for all infarct sizes. The effect size of 0.5 units of weight is small, 
and consequently a trial of this size is unlikely to detect it, the trial offers roughly 30% power 
in scenarios with this effect size.  The effect sizes of 1.25 and 1.5, on the other hand, are very 
large and the trial offers better than 95% power to detect such improvements. The design 
provides 86% power to detect an effect size of 1 unit. The Type I error probability is controlled 
to be no more than 2.5%.   
Expected sample sizes are smallest when the treatment effect is very small (when early 
stopping for futility is likely) and when the treatment effect is very large (when early stopping 
for expected success is likely). The trial enrolls more subjects when the data are inconclusive 
about whether the device has a substantial positive effect. 
The distribution of mRS outcomes for the control arm in the simulations was based on 
combined data from the following study sub-populations: IMS III IV tPA arm (N=222)[58]; 
MR RESCUE penumbral pattern with IV tPA arm (N=34) [59]; PROACT II heparin arm 
(N=59) [25]; MELT no treatment arm (N=57) [26]; DEFUSE 2 Target Mismatch without 
reperfusion arm (N=32) [90]; Merci Registry non-revascularized, non-intubated, treated ≥ 6 
hours (N=30) [Sponsor-derived from raw dataset]; Natural History of MCA and ICA 
occlusions (N=40) [22]; and SENTIS no treatment arm (N=106) [101]. The distribution of the 
mRS outcomes for the control arm used in the simulations is shown in Table 6.  
Table 6. Distribution of mRS outcomes for the control arm in the simulations 
mRS 
0 
1 
2 
3 
4 
5 
6 
Proportion 
0.07 
0.13 
0.12 
0.17 
0.20 
0.11 
0.19 
8.2 
Control of Systematic Error/Bias 
In order to control systematic error/bias, the randomization will be take place using either the 
use of an independent IVRS or web based system or through pre-printed, block randomization 
envelopes prepared by a qualified and independent biostatistician. 

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  CDM10000146  Page 51 of 91 
In order to protect the status of the blind and minimize potential bias, an independent 
statistician who is not involved with the conduct of the study will perform the interim analyses 
for the primary endpoint. 
The design mitigates potential bias due to the enrichment by preventing early stopping for 
expected success immediately following an enrichment decision. We require an additional 100 
subjects to be enrolled in the enriched population before making a decision to stop enrollment. 
8.3 
Eligibility of Subjects, Exclusions, and Missing Data 
Based on previous experiences in clinical trials of acute stroke, minimal loss to follow-up 
(LTFU) is expected for the 90-day assessment of the primary outcome measure.  In the MERCI 
study, 7.2% (11/151) of subjects were LTFU, in Multi MERCI 2.4% (4/164) were LTFU, and 
in the TREVO 2 study, 3.4% (6/178) were LTFU.  All efforts should be made to ensure near 
complete follow-up, with particular focus on the assessment of primary outcome (mRS at 90 
days) and mortality.   
Nevertheless, some missing data may still occur.  All randomized subjects will be included in 
the primary endpoint analysis (ITT). In case of missing 90-day mRS values, the 30-day mRS 
values will be incorporated into the imputation model. Refer to the adaptive design plan for 
details in Appendix F. 
8.4 
Population Definitions 
Screened:  Includes any subject who is considered for participation for the trial, whether or 
not they sign an informed consent. 
Screen-failed: Includes any subject who is considered for participation for the trial, who 
either fail to meet one or more of the inclusion criteria or who meet one or more of the 
exclusion criteria; subjects can be screen failed based on general inclusion/exclusion criteria, 
or imaging inclusion/exclusion criteria (these subjects may or may not have signed an 
informed consent). 
Enrolled: Includes any subject who has been randomized based upon the results of the post-
processing of the baseline MRI-DWI or CTP-rCBF baseline images, and Clinical Imaging 
Mismatch profile (informed consent must be obtained prior to randomization). 
Completed: Includes any subject who is enrolled/randomized and completes the study follow 
up at Day 90 (± 14), or is known to have expired before 90 days post randomization. 
Discontinued: Includes any subject who is enrolled/randomized but who fails to complete the 
study follow up at Day 90 (± 14), and who has not expired before 90 days post 
randomization. 
Wake-up Strokes: Subjects known to have symptoms first detected on awakening from sleep. 

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  CDM10000146  Page 52 of 91 
Witnessed Strokes: Subjects with last known well time and symptoms first observed time 
known to be the same. 
Un-witnessed Strokes: Subjects with last known well time and symptoms first observed time 
known to be different, but not known to have symptoms first detected on awakening from 
sleep. 
8.5 
Analysis Populations 
Intent-to-Treat (ITT): Includes all enrolled/randomized subjects. This includes all subjects 
randomized to receive the Trevo device (even if they never receive it or receive treatment 
with another device), and all subjects randomized to the control arm (regardless of actual 
treatment received).  Final analysis is only on the enriched population (refer to adaptive 
design plan in Appendix F). This population is the primary population for all efficacy 
parameters.  
Modified ITT (mITT): The same as the ITT population except subjects are analyzed based 
upon actual treatment received. Subjects who receive only medical therapy are included in 
the control arm, and subjects who receive any device-based therapy are included in the Trevo 
arm. 
Per-Protocol (PP): A subset of the intent-to-treat population, including subjects who did not 
violate the inclusion/exclusion criteria or experience significant protocol deviations. 
8.6 
Interim Analysis 
Primary endpoint interim analyses will begin after 150 subjects have been enrolled, and 
subsequent interim analyses will take place after every 50 subjects. 
The analysis performed at each interim analysis will include: 
• 
Modeling of the treatment effect for each infarct size in the population, 
• 
Longitudinal modeling to impute final outcomes for subjects for which we have 30-
day mRS scores but not 90-day mRS scores, and 
• 
Estimation of the distribution of infarct sizes. 
The mathematical details and assumptions for these analyses are described in Appendix F. 
The possible decisions that may be made at the interims are to: 
• 
Stop the trial early for futility, 
• 
Enrich the population if it appears that the device benefits one subset of the 
population considerably more than another, or 
• 
Stop enrollment for expected success. 

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  CDM10000146  Page 53 of 91 
 
Each decision is based on the predictive probability that the trial would be a success if subjects 
were enrolled to the end of the trial. The rules for each decision are defined below. Additional 
details pertaining to statistical models are given in the adaptive design plan in Appendix F. 
8.6.1 
Interim Monitoring for Early Futility 
Interim safety analyses will be performed concurrently with the primary endpoint analyses. 
The trial stops for futility if there is less than 10% predictive probability that the trial would 
be successful if enrolled to the maximum sample size under any enrichment possibility.  
8.6.2 
 Enrichment 
Enrichment decisions can occur starting at 150 subjects enrolled and the last opportunity 
to enrich is at 400 subjects. The candidate enriched populations that the trial considers are 
based on infarct sizes. The five possible subpopulations are defined by infarct size as 
measured using MR-DWI or CTP-rCBF maps: 
1. The full population of infarct sizes 0 to 50 cc 
2. Infarct sizes of 0 to 45 cc 
3. Infarct sizes of 0 to 40 cc 
4. Infarct sizes of 0 to 35 cc 
5. Infarct sizes of 0 to 30 cc 
 
If the population is enriched, subjects with larger infarct sizes are no longer enrolled, and 
the final efficacy analysis omits subjects with larger infarct sizes from consideration. 
Enrichment decisions are irreversible, but the trial can enrich the population further after it 
has already been enriched. 
The design will enrich if one of the following conditions is met: 
If the highest currently open group of five (5) infarct sizes has less than 40% posterior 
probability of an average positive treatment effect, then this group of infarct sizes will no 
longer be enrolled in the trial. This rule is applied before the second enrichment rule, and 
may only be applied once per interim analysis. 
If the predictive probability of a positive trial increases by at least 10% by enriching to a 
smaller subpopulation, then the trial will enrich to the smallest subpopulation that satisfies 
this criterion. 
8.6.3 
Interim Monitoring for Expected Success 
The trial may only stop enrollment for expected success if at least 100 subjects have been 
enrolled since the last enrichment. The decision is based on the predictive probability of 

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STRYKER CORPORATION                                                                                                                                                                             
 
 
  CDM10000146  Page 54 of 91 
trial success for both the weighted mRS analysis and dichotomous mRS analysis, and if no 
further subjects are enrolled. The threshold for this predictive probability is 95% for the 
200 and 250 subject interim analyses, 90% for the 300 and 350 subject interim analyses, 
85% for the 400 subject interim analysis, and 80% for the 450 and 500 subject analyses. If 
the predictive probability exceeds the threshold at an interim analysis, then enrollment 
stops for expected success.  
 
 
All subjects will be followed through their 90 day assessment and the final analysis for trial 
success will be based on the full data through 90 days. 
8.6.4 
 Longitudinal Model 
At the time of each interim analysis, some subjects may not have completed the 90-day 
follow-up period for mRS. Because subjects will also be evaluated for mRS at 30 days 
these scores will be used to assist in making decisions at the interims. We estimate the 
probability distribution of 90-day mRS conditional on 30-day mRS and use this estimated 
distribution to inform a longitudinal model for imputing final mRS outcomes for subjects 
with known 30-day mRS but unknown 90-day mRS. 
8.7 
Statistical Analysis 
The final weighted and dichotomous analyses will be performed only on the enriched 
population, and assumes a constant treatment effect over all infarct sizes that are in the 
population at the end of the trial. 
The trial is considered successful if there is sufficiently high posterior probability that the 
treatment effect is positive. The threshold for success is adjusted to account for the degree to 
which the population has been enriched, and depends on the following factors: 
• 
The number of enrolled subjects in the enriched population at the time of the 
enrichment decision (N1) 
• 
The number of enrolled subjects outside the enriched population (N2) 
• 
The number of subjects enrolled after the enrichment decision (N3). 
 
 
 
 
Specifically, the threshold is calculated as: 

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  CDM10000146  Page 55 of 91 
Φ(√1 +
𝑁2
𝑁1+𝑁3 Φ−1(𝑝𝑐𝑟𝑖𝑡)), 
where Φ is the standard normal cumulative distribution and pcrit = 0.986 is a critical probability 
evaluated via simulation to control Type I error probability. If no enrichments are made during 
the trial, then the success threshold is equal to pcrit, and the threshold increases as enrichment 
becomes earlier and more aggressive. 
The primary analysis of mRS scores for the interim and final analyses will be performed by 
Berry Consultants, LLC using custom code developed in Java and R software. 
The Secondary efficacy and safety analyses will be performed by Stryker NV Biostatistics 
personnel using SAS, version 9.2 or higher. Pooling of data across institutions and stratification 
will be described in the Statistical Analysis Plan. 
8.7.1 
Baseline Comparability 
Baseline comparability between the two arms will be done using descriptive statistics and 
will be described in detail within the Statistical Analysis Plan. 
8.7.2 
Pooling Across Institutions 
Results for the primary efficacy endpoint will be presented by site and treatment group. 
Poolability across institutions will be assessed using an ANCOVA on the weighted mRS 
with terms for treatment group, site, and the interaction of treatment group and site. A p-
value less than 0.10 for the interaction term will be taken as evidence that there are 
significant differences in treatment effect between sites. If the effect is found to vary by 
site, then the effect will be analyzed using a hierarchical model with random site effect. 
8.7.3 
Other Pre-planned Analyses 
Both Arms: 
1. Incidence of symptomatic ICH (per the SITS MOST definition) 
Treatment Arm only: 
2. Frequency of functional independence (mRS 0-2) by reperfusion status post-
device and post-procedure 
8.7.4 
Health Economics Information 
Sites will be asked to collect hospital billing and resource utilization information for all 
randomized subjects. The UB-04 form will be collected within the United States while in 
other countries a CRF containing similar information will be completed.  This information 
may be used for future analyses to compare overall health care costs and resource 
utilization between mechanical intervention and standard medical care.   

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9 Data Management 
9.1 
Data Collection and Processing 
Subject data will be collected in a secure electronic data capture (EDC) system via the Internet. 
All pertinent data will be entered by the study site personnel into the electronic Case Report 
Forms (CRFs).  A unique subject ID number will be assigned to each subject.  Every reasonable 
effort should be made to complete data entry within one week of data collection. Any data 
discrepancies may be queried during ongoing review of data by Stryker NV or may be 
identified and queried during routine monitoring visits.  Data monitoring will be performed to 
verify data accuracy and ensure queries are resolved. The Principal Investigator or Sub-
investigator must ensure the accuracy and completeness of the recorded data and then provide 
his/her electronic signature on the appropriate CRFs. Changes to data previously submitted to 
the sponsor will require a new electronic signature by the investigator to acknowledge/approve 
the changes.  
Results from Core Labs and CEC reviews will also be entered into the EDC system and will 
be electronically signed by the reviewer responsible for entering this data. Ongoing data review 
will be performed to identify possible data discrepancies. Manual and/or automatic queries will 
be created in the EDC system and will be issued to Core Labs or Clinical Events Committee 
for appropriate resolution.   
10 Monitoring Procedures 
Monitoring visits to the clinical sites will be made periodically during the study, to ensure that all 
aspects of the current, approved protocol/amendment(s) are followed. Original source documents 
will be reviewed for verification of data in the electronic database. The Investigator/institution 
must allow direct access to original source documents by Stryker NV personnel, its designees, and 
appropriate regulatory authorities. In the event that the original medical records cannot be obtained 
for a subject that is seen by a non-study physician at a non-study institution, photocopies of the 
original source documents must be made available for review.  
It is important that the Investigator and/or relevant study site personnel are available during the 
monitoring visits and that sufficient time is devoted to the process. In order to perform her or his 
role well, the monitor must be given access to primary subject medical records, which support the 
data that has been entered into the study CRFs. Access to Protected Health Information (PHI) by 
the study monitor will be disclosed to the subject within the Informed Consent Form. See ICF 
template provided in Appendix D. 
10.1 
Auditing 
The study may be subject to a quality assurance audit by Stryker NV or a designee, as well as 
inspection by appropriate regulatory authorities. It is important that the Investigator and 

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  CDM10000146  Page 57 of 91 
relevant study personnel are available during any audits and that sufficient time is devoted to 
the process.  
10.2 
Investigational Device Accountability 
Investigational device accountability records must be maintained at the study site. The quantity 
of devices received by the study site, those returned to Stryker NV, and those devices used at 
the study site will be recorded in the device accountability log. The Investigator must explain 
in writing the reasons for any discrepancies noted in device accountability log. Investigational 
devices will be shipped to sites after all essential documents are collected, the Site Initiation 
Visit and training of all required study personnel is completed, and the site is approved to 
enroll. In some circumstances, at the discretion of the Project Manager, the investigational 
devices may be shipped to coincide with the Site Initiation Visit, if a site is anticipated to 
complete all requirements to be eligible to begin enrollment during the visit. 
11 Adverse Events 
11.1 
Adverse Event Definitions and Classification 
Term 
Definition 
Reference 
Adverse 
Event (AE) 
Any untoward medical occurrence in a subject. This definition 
does not imply that there is a relationship between the adverse 
event and the device under investigation. 
ISO 14155-1 
Adverse 
Device Effect 
(ADE)  
Any untoward and unintended response to a medical device.  
Note 1: This definition includes any event resulting from 
insufficiencies or inadequacies in the instructions for use or the 
deployment of the device.  
Note 2: This definition includes any event that is a result of a user 
error.  
ISO 14155-1 

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  CDM10000146  Page 58 of 91 
Term 
Definition 
Reference 
Serious 
adverse event 
(SAE) 
An adverse event that:  
 
led to death 
 
resulted in a life-threatening illness or injury 
 
resulted in a permanent impairment of a body structure or 
a body function 
 
required inpatient hospitalization or prolongation of 
existing hospitalization  
 
resulted in medical or surgical intervention to prevent 
permanent impairment to body structure or a body 
function 
 
led to fetal distress, fetal death or a congenital abnormality 
or birth defect 
ISO 14155-1 
Serious 
Adverse 
Device Effect 
(SADE) 
An adverse device effect that has resulted in any of the 
consequences characteristic of a serious adverse event or that 
might have led to any of these consequences if suitable action had 
not been taken or if circumstances had been less fortunate.  
ISO 14155-1 
Unanticipated 
Adverse 
Device Effect 
(UADE)  
Any serious adverse effect on health or safety or any life-
threatening problem or death caused by, or associated with a 
device, if that effect, problem, or death was not previously 
identified in nature, severity, or degree of incidence in the 
investigational plan or application (including a supplementary plan 
or application), or any other unanticipated serious problem 
associated with a device that relates to the rights, safety, or welfare 
of subjects.  
21 CFR Part 
812 
 
Underlying (pre-existing) symptoms or diseases are not reported as Adverse Events (AEs) 
unless there is an increase in severity or frequency during the course of the investigation. Death 
should not be recorded as an adverse event, but should only be reflected as an outcome to 
another specific AE. Any AE experienced by the study subject after enrollment (equal to the 
time of randomization) must be recorded in the CRF. 
All AEs and SAEs will be monitored and collected from the time of enrollment (equal to the 
time of randomization) through 90 day follow-up visit.  All SAEs and UADEs must be reported 
to Stryker NV within 24 hours of becoming aware of their occurrence in order to comply with 
Stryker NV’s regulatory reporting requirements.  
In subjects who are randomized to the Treatment Arm, the Investigator must assess the 
relationship of the adverse event to the study device using the following criteria categories and 
definitions: 

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Unrelated - The adverse event is determined to be due to a concurrent illness or effect of 
another device/drug and is not related to the investigational product. 
Possible - The adverse event is determined to be potentially related to the 
investigational product, and an alternative etiology is equally or less likely compared to 
the potential relationship to the investigational product. 
Probable - There is a strong relationship to the investigational product, or recurs on re-
challenge, and another etiology is unlikely. 
Highly Probable - There is no other reasonable medical explanation for the event. 
 
In subjects who are randomized to the Treatment Arm, the Investigator must assess the 
relationship of the adverse event to the index procedure using the following categories and 
definitions: 
Unrelated - The adverse event is determined to be due to a concurrent illness or effect of 
a device/drug and is not related to the index procedure. 
Possible - The adverse event is determined to be potentially related to the index 
procedure, and an alternative etiology is equally or less likely compared to the potential 
relationship to the index procedure. 
Probable - There is a strong relationship to the index procedure, or recurs on re-
challenge, and another etiology is unlikely. 
Highly Probable - There is no other reasonable medical explanation for the event. 
 
11.2 
Adverse Events Reporting Requirements 
All AEs will be recorded in the appropriate CRFs.  
All SAEs and UADEs shall be reported within 24 hours of becoming aware to Stryker 
Neurovascular via data entry into the CRFs. All procedure or device-related deaths shall be 
reported to the IRB/EC no later than 24-48 hours of becoming aware or per the IRB/EC 
reporting requirements. If access to CRFs is not available then the information can be faxed to 
the Stryker Neurovascular Safety Department personnel listed in current Study Contacts List 
provided in the Study binder. 
The site Principal Investigator is responsible for informing the IRB/EC of UADE, SAE, and/or 
Adverse Events as required by local procedure. A copy of this report should be provided to 
Stryker NV. 

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11.3 
Device Failures, Malfunctions, and Product Nonconformities 
All Trevo device failures, malfunctions, and product nonconformities will be documented on 
the appropriate CRF and the involved device(s) should be returned to Stryker NV for analysis, 
if possible. Instructions for returning the investigational device(s) will be provided to the study 
sites in their Study binder. Device failures and malfunctions should also be documented in the 
subject’s medical record. 
All Trevo device failures, malfunctions, and product nonconformities shall be reported within 
24 hours of becoming aware to Stryker Neurovascular via data entry into the CRFs. If access 
to the EDC system is not available then the information can be faxed to the Stryker 
Neurovascular Safety Department personnel listed in the current Study Contacts List provided 
in the Study binder. 
NOTE: Trevo device failures, malfunctions, and product nonconformities should be reported 
as soon as possible after becoming aware of them, on the appropriate CRF, and should not to 
be reported as adverse events (in and of themselves). However, if there is an adverse event that 
results from a device failure or malfunction, that specific event would be recorded on the 
appropriate CRF. 
All Stryker Neurovascular nonstudy device malfunctions and nonconformities related to 
ancillary devices used in the procedure should be reported to the local Stryker customer service 
center. 
11.4 
Reporting to Regulatory Authorities / IRBs / ECs / Investigators 
Stryker NV is responsible for the coding and reporting of all verbatim adverse events to all 
participating investigators and regulatory authorities, as applicable. Stryker NV will utilize the 
MedDRA (Medical Dictionary for Regulatory Affairs) to code all AEs reported in the trial. 
UADEs will be reported to FDA by Stryker NV as per 21 CFR 803. 
The Site Principal Investigator is responsible for informing the IRB/ Ethics Committee (EC) 
of UADE, SAE, and/or as required by local procedures. A copy of this report should be sent 
to the Stryker NV Clinical Research Associate. Refer to Section 13.2.1 for information 
pertaining to the Clinical Events Committee (CEC).  
Stryker NV will identify sites at which adverse events (AEs) and protocol deviations occur in 
annual reports and correspondence with the FDA. 
For Canadian sites, Health Canada Mandatory Problem Reporting requirements as stated in the 
Medical Device Regulations must be followed: 
The manufacturer and importer of a medical device are required to report any event that is: 

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  CDM10000146  Page 61 of 91 
 Related to a failure of the device or a deterioration in its effectiveness, or any 
inadequacy in its labeling or in its direction for use 
 Has led to death or a serious deterioration in the state of health of a patient, user or 
other person, or could do so were it to recur 
A preliminary report is required within 10 days of the manufacturer or importer becoming 
aware of the incident if the incident has led to the death or a serious deterioration in the 
state of health of a patient, user or other person or within 30 days if it has not led to a death 
or serious deterioration but could do so were it to recur.   
For German sites, the process for reporting SAEs as documented in “Procedure Regarding 
SAE Reporting: In line with Directive 93/42/EEC as amended – Annex X – Section 2.3.5” and 
according to § 3 (6) of the Ordinance on Medical Devices Vigilance will be followed.  
Generally: 
 SAEs occurring in Germany must be reported to BfArM immediately if a causal 
relationship between the SAE and the investigational medical device cannot be 
excluded.  
 An overall assessment of all SAEs must be reported to BfArM quarterly.  
Additionally, Stryker NV must report all SAEs occurring in Germany to the competent 
authorities of other contractual states of the Agreement on the European Economic Area 
immediately if the clinical trial is also performed in those countries. 
12 Risk Benefit Analysis 
It is possible that subjects enrolled into this trial will receive no direct benefit from participation. 
There may be additional risks to subjects randomized to the Trevo thrombectomy plus medical 
management arm in addition to those that are currently known or anticipated for patients treated 
within 6 hours from symptom onset or time last seen well. See Section 12.3.  
All subjects screened for the trial will undergo MR or CT multi-modal diagnostic imaging to assess 
for hemorrhage, to verify occlusion location, and to measure the core infarct volume. Risks 
associated with the baseline imaging conducted as part of the trial are as follows in Sections 12.1 
and 12.2. 
Benefits of Trevo thombectomy plus medical management may include higher revascularization 
rates which in turn are predictive of better clinical outcomes. [17] Potential benefits justify the 
anticipated risks, given the safeguards in place to monitor patient safety throughout the trial. 

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12.1 
CT/MR Imaging  
CT/MR scans of the brain obtained at baseline, 24 (-6/+24) hours post procedure, and 
sometimes at discharge are considered standard medical care. The risk associated with 
performing a CT/MR scan is the ionizing radiation exposure. The radiation dose that is 
received is the same dose that would be received from the clinical care to assess and treat the 
underlying medical condition. There is no additional risk of increased ionizing radiation 
exposure as a result of participation in this study. 
A small amount of radiation is used to obtain a CT Angiogram (CTA).  The radiation dose 
from this study is below the levels that are thought to result in a significant risk of harmful 
effect.  There is some chance of an allergic reaction to the x-ray contrast (dye) used during the 
CTA. 
During an MRI or MR Angiogram (MRA) no harmful radiation is involved.  The MR contrast 
dye could cause one of the following in rare cases: mild to moderate headaches; coldness in 
the arm where dye is being injected; infection; nausea; dizziness; changes in heart rate and/or 
blood pressure; sneezing; dry mouth; or rash. 
Due to differences in standards of care between sites, it is possible that some subjects may 
receive additional follow-up imaging or neurologic examinations other than those required by 
the protocol. The risks of these neurologic examinations are negligible, and the subject would 
likely benefit from enhanced care due to these additional tests.  
12.2 
Investigational procedure (Treatment arm only)   
12.2.1 
Diagnostic Angiography 
Risks associated with angiography have been well documented and are understood by the 
medical community. The arteriogram itself can cause problems with brain function and it 
can potentially make the subject’s condition worse. Angiography requires the placement 
of an intra-arterial catheter for the injection of contrast media to image vessels in the brain, 
and the most common complication is access-site hematoma (4.2%). [102]  Other risks 
related to the diagnostic angiographic procedure are relatively low but may include: 
• 
Infection  
• 
Bleeding 
• 
Hematoma 
• 
Vessel thrombosis 
• 
Dissection 
• 
Distal embolization 
• 
Pseudoaneurysm and arteriovenous fistula formation 
• 
Vessel injury 
• 
Allergy to the contrast material 
• 
Neurological injury 

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  CDM10000146  Page 63 of 91 
• 
Death 
The risk of bleeding may be increased when diagnostic angiography is performed in 
individuals who are receiving anticoagulation and/or antiplatelet therapy.  Neurological 
injury associated with these vascular complications may occur.  Renal toxicity and 
idiosyncratic responses to the injected contrast medium including anaphylactic reactions 
have also been reported.  
12.2.2 
Trevo Thrombectomy 
For any individual subject, participation and randomization to the treatment arm is no 
guarantee that they will receive a direct benefit.  Completion of the study may benefit the 
subject’s community at large through enhanced knowledge about the risks and benefits of 
these two treatment modalities: Trevo Retriever plus medical management versus medical 
management alone.  
The potential risks associated with the use of the Trevo Retriever include:  
• 
An air bubble introduced into the blood vessels (air embolism) 
• 
Bleeding or bruising in the access site, or where the puncture is made (hematoma) 
• 
Infection at the access site, or sepsis  
• 
Embolization of a fragment, or the entire thrombus, to a previously uninvolved 
territory (emboli) 
• 
Vessel spasm  
• 
Pain/headache 
• 
New clot formation (thrombosis) 
• 
A blood vessel tear or puncture (dissection or perforation) 
• 
Distal thrombus –  embolization of pieces of the original thrombus “downstream” in 
the same vascular territory as the original thrombus (distal embolization) 
• 
Blood vessel becomes acutely occluded (re-thrombosis/acute occlusion) 
• 
Ischemia (reduced blood flow) in the brain  
• 
Intra-cerebral hemorrhage (bleeding into the brain) 
• 
False aneurysm formation 
• 
Neurological deficits, including a new stroke 
• 
Death  
Refer to the sample Instructions for Use (IFU) in Appendix E for table of previously 
observed rates of procedural risks. 
Only trained and experienced physicians will use this device within the trial. The 
investigational device will be used as per the steps listed within the current Instructions for 
Use. 
However, since the time window in which the device will be used within this study is 
expanded to between 6 - 24 hours after stroke symptom onset or time last seen well, 

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  CDM10000146  Page 64 of 91 
participation in the study adds a currently unknown level of risk to the subjects who are 
randomized to the Treatment arm. Some publications have reported increased rates of 
cerebral edema, intracranial hemorrhage, and mortality in patients treated with 
revascularization therapy beyond 6 hours. However other publications have not confirmed 
this finding, and the potential benefits of Trevo thrombectomy include revascularization, 
and revascularization has been shown to be correlated with improved clinical outcomes 
and reduced mortality, [17] therefore potential benefits outweigh the anticipated risks. 
12.3 
Risk Minimization  
Each site must obtain IRB or EC approval prior to screening and enrolling subjects. Every 
subject or Authorized Legal Representative (LAR) will be required to provide signed Informed 
Consent prior to participation which will explain their treatment choices and the risks and 
benefits of being in the study.  Finally, several independent committees and core labs will assist 
in oversight of the study which ensures that any risks to subjects will be minimized.   
MRI-DWI or CTP-rCBF neurological imaging maps will be used to measure the core infarct 
volume and only those subjects who have small to moderate core infarct volumes will be 
considered for randomization into the trial.  
Additionally, risk will be mitigated in the Trevo thrombectomy plus medical management arm 
by implementation of an adaptive trial design which allows for early and frequent assessment 
of efficacy and safety parameters in the two study arms, to ensure that the number of subjects 
exposed to a potentially non-beneficial treatment is minimized. 
Safety monitoring of the data, consisting of individual event and aggregate data review, will 
be ongoing and conducted at a rate commensurate with subject enrollment in the trial.  
The DMC will provide subject safety oversight and make recommendations to Stryker NV 
regarding continuing enrollment, modifying, or stopping the study early based upon a review 
of the comparative rates of SICH, neurological worsening, stroke-related mortality and all 
other site-reported SAEs. They will take into account in their decision making and 
recommendations the rates of procedure-related and device-related events in the treatment arm.  
13 Study Committees and Core Labs 
13.1 
Steering Committee 
A Steering Committee has been convened. Responsibilities include oversight of the overall 
conduct of the study with regard to protocol review and development, study progress, ensuring 
adequate subject safety oversight, and overall data quality and integrity. The Steering 
Committee will oversee dissemination of study results through appropriate scientific sessions 
and publications. The Steering Committee may select additional investigators, based on 
enrollment and adherence to the protocol, to participate on a Publication Committee.  The 

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  CDM10000146  Page 65 of 91 
Publication Committee will participate in the review and approval of all requests for data 
analysis, abstract and manuscript preparation and submission. 
13.2 
Safety Monitoring Committees 
To promote early detection of safety issues routine medical monitoring will be conducted on 
an ongoing basis. In addition, the CEC and DMC charters will provide for evaluation of safety 
events at routine intervals. Process flow, supporting documents, and software programming 
will allow for 21 CFR Part 11 compliant electronic database access, to CEC members for real 
time case review and event adjudication.  
The CEC and DMC may be un-blinded due to the fact one study group receives an intervention 
while the second study group does not. The dataset will contain obvious AEs/SAEs specific to 
the interventional procedure that will, simply by their presence, un-blind those individuals 
reviewing the data. The DMC procedures are described in more detail in the DMC Charter.      
This process requires the dynamic collection of unmonitored data as soon as an event is 
reported. This is expedited by designated Stryker NV Safety personnel, who are responsible 
for reviewing safety data within the trial on an ongoing basis, and coordinating the collection 
of information for inclusion within the CEC event dossier from the sites and Core Labs.  
During regularly scheduled monitoring visits, the clinical research monitors will support the 
dynamic reporting process through their review of source document information. 
13.2.1 
Clinical Events Committee (CEC)  
The CEC will include specialists in stroke neurology and/or neuro-intervention as well as other 
experts with the necessary therapeutic and subject matter expertise who are not participating 
in the trial and have no affiliation with Stryker NV. CEC responsibilities, qualifications, 
membership, and committee procedures are outlined in the CEC charter. The CEC will be 
responsible to review and adjudicate the following protocol-defined safety outcome measures 
and relevant adverse events reported by study investigators. Relevant information and source 
documents will be provided to assist with their review and adjudication of events. 
• 
Vessel perforation 
• 
Intramural Arterial dissection  
• 
Symptomatic ICH  
• 
Embolization to a new territory  
• 
Neurological worsening (associated with a 4 or more point increase in NIHSS) or 
possible or confirmed evolution/progression of the index stroke 
• 
All deaths 

Stryker Neurovascular 
Document Title: DAWN™ Trial Investigational Plan 
Document Number: CDM10000146 
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STRYKER CONFIDENTIAL - THIS DOCUMENT CONTAINS CONFIDENTIAL AND PROPRIETARY INFORMATION THAT 
IS THE PROPERTY OF STRYKER CORPORATION. NEITHER THIS DOCUMENT NOR THE INFORMATION HEREIN MAY 
BE REPRODUCED, USED, OR DISCLOSED TO ANY THIRD PARTY WITHOUT THE PRIOR WRITTEN CONSENT OF 
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  CDM10000146  Page 66 of 91 
In cases where their expertise is required the CEC will be asked for an opinion on the following 
events. However, the Stryker NV safety department will be responsible for their initial review 
and coding and they will not automatically be sent to the CEC for adjudication: 
• 
In vivo device failure (in vivo breakage) 
• 
Access site complication requiring surgical repair or blood transfusion  
• 
Other confirmed or suspected Procedure and/or Device-related SAEs with an 
outcome other than death occurring at any time during subject participation  
13.2.2 
Data Monitoring Committee (DMC)  
The DMC will include specialists in stroke neurology and/or neuro-intervention as well as 
biostatistics, who are not participating in the trial and have no affiliation with Stryker NV. The 
DMC is responsible for monitoring subject safety through pre-defined, periodic review of the 
clinical study safety data. DMC responsibilities, qualifications, membership, meeting 
frequencies, and procedures are outlined in the DMC charter. 
The DMC’s role is to monitor and advocate for subject safety throughout the lifecycle of the 
trial and they will review all SAEs and mortality between both arms, as well as standard tables 
(as outlined within the DMC charter) at regularly scheduled meetings, and at ad hoc meetings 
if requested by the Safety Monitor.  To ensure the safety of the study and its participants, 
enrollment for the trial will be held within 24-48 hours of sponsor awareness of 5 consecutively 
enrolled patient mortalities occurring in either arm.  The DMC will be convened within that 
time interval to review the mortality data and provide its recommendation of study termination, 
modification, or continuance without modification.  Special attention will be given for review 
of peri-procedural mortality in the treatment arm. If the DMC does not convene within that 
time interval, then patient enrollment will be automatically suspended. In addition, 
measurements of safety and effectiveness are integrated within the weighted mRS primary 
endpoint analysis. The stopping rule for this trial is equivalent to the threshold set for early 
stopping for futility at the scheduled interim analyses of the primary endpoint, as described 
within the Adaptive  Design Plan (ADP) in Appendix F. The DMC assessment of benefit 
versus harm will take into account both the 90 day dichotomous mRS as well as the average 
utility weighted mRS at 90 days between the two arms, and the thresholds for early stopping 
for futility, or success, as described within the ADP.  
The DMC will weigh the risk/benefit of continuing the study and will report to the Sponsor, 
who remains blinded to the raw endpoint analysis data, to continue the study as is, modify the 
study enrollment population (based on the pre-specified allowed enrichment possibilities), or 
stop the study because a threshold for futile, or success, has been met. In addition, the DMC 
may make a recommendation to the Sponsor to stop the study at any time because of non pre-
specified ethical or safety concerns, e.g. one group is experiencing a specific harm at a rate 
that is deemed ethically unacceptable.  

Stryker Neurovascular 
Document Title: DAWN™ Trial Investigational Plan 
Document Number: CDM10000146 
Rev:  AD 
STRYKER CONFIDENTIAL - THIS DOCUMENT CONTAINS CONFIDENTIAL AND PROPRIETARY INFORMATION THAT 
IS THE PROPERTY OF STRYKER CORPORATION. NEITHER THIS DOCUMENT NOR THE INFORMATION HEREIN MAY 
BE REPRODUCED, USED, OR DISCLOSED TO ANY THIRD PARTY WITHOUT THE PRIOR WRITTEN CONSENT OF 
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  CDM10000146  Page 67 of 91 
During the course of the trial, the DMC will review accumulating safety data to monitor the 
incidence of Adverse Events and other trends that would warrant modification or termination 
of the trial. The DMC will meet at pre-specified intervals to assess the data against the pre-
specified safety and efficacy stopping rule as described within the ADP in Appendix F, and 
review the safety outcomes in both arms to ensure that the risks do not exceed the benefits.  In 
addition to the pre-specified meetings, the DMC will meet for any other safety concerns that 
might arise during the active enrollment phase of the trial. In addition, a designated member 
of the DMC will be sent SAE data at regular time intervals, independent from the pre-planned 
DMC meeting schedule.   
Data will be supplied to, and reviewed by, the DMC as tables and/or listings. After review of 
the aggregate data, the DMC may request additional information.  The DMC can also consider 
external data when appropriate, (e.g. published articles).  Any DMC recommendations for 
study modification or termination because of concerns over subject safety or issues relating to 
data monitoring or quality control will be submitted in writing to Stryker NV for consideration 
and final decision. However, if the DMC at any time determines that a potential serious risk 
exists to subjects in this trial, the DMC chairman will immediately notify Stryker NV.  
An added essential responsibility/function of the DMC is the monitoring and implementing the 
adaptive design aspects of the trial.   The DMC will include a specialist in adaptive design and 
biostatistics and will be completely independent of the sponsor (Stryker NV).  The DMC 
charter will specify all operating procedures. The DMC will be charged with analyzing the 
accruing data and implementing the prospectively defined design, as specified within the 
Adaptive Design Plan.  The DMC will report the results of the analysis to Stryker NV.  
13.3 
Imaging Core Labs  
The independent angiographic core lab will review angiographic images from the procedure 
to determine revascularization and clot location.  
The independent CT/MR core lab will review CT/MR images obtained at baseline and at 24 (-
6/+24) hours post randomization to determine vessel patency, hemorrhage, and extent of 
infarcts.   
Centralized imaging core labs will be used in this study to provide consistent, independent 
evaluation of images for confirmation of inclusion criteria. Sites will be provided with 
instructions for how images should be collected and submitted to Stryker NV within 2 weeks 
of acquisition of the final required imaging time point at 24 (-6/+24) hours after the procedure.  
If this timeline cannot be met for any reason, the site should communicate this delay to Stryker 
NV so that the pending images can be tracked until received. 
Ideally MR imaging will be used whenever possible to screen subjects for inclusion into the 
trial. However, if MR imaging is contraindicated or is unavailable then CT based imaging may 
be utilized.   

Stryker Neurovascular 
Document Title: DAWN™ Trial Investigational Plan 
Document Number: CDM10000146 
Rev:  AD 
STRYKER CONFIDENTIAL - THIS DOCUMENT CONTAINS CONFIDENTIAL AND PROPRIETARY INFORMATION THAT 
IS THE PROPERTY OF STRYKER CORPORATION. NEITHER THIS DOCUMENT NOR THE INFORMATION HEREIN MAY 
BE REPRODUCED, USED, OR DISCLOSED TO ANY THIRD PARTY WITHOUT THE PRIOR WRITTEN CONSENT OF 
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  CDM10000146  Page 68 of 91 
Ideally the same imaging modality used at baseline will be used at 24 (-6/+24) hours post 
randomization. However, for subjects with compromised renal function who had a CT/CTA at 
baseline, but in whom the treating physician wishes to avoid an additional load of contrast, an 
MRI/time-of-flight MRA of the intracranial arteries may be obtained instead. 
An imaging core lab charter will ensure that consistent policies and procedures are applied 
throughout the imaging core lab review and determination process. Stryker NV is responsible 
for tracking images received, requesting required imaging from the sites, performing basic 
verification of the images received, archiving all images, transmitting and tracking images sent 
to the core labs, and forwarding the applicable results to the CEC.  
13.3.1 
Angiographic Core Lab 
For each enrolled subject, angiograms must be appropriately de-identified, and sent to the 
imaging core lab for evaluation. It is important that the images be saved in native DICOM 
format, and that all imaging sequences are sent (without pre-selecting specific frames). It 
is also important that the imaging sequences are captured chronologically and are clearly 
labeled with date and time stamps so that they can be correlated to pre-procedure, post-
retriever, and post-procedure time points. Specific imaging transmittal instructions will be 
provided to the sites by Stryker NV and/or the imaging core lab.  
The Angiographic Core Lab will provide an independent assessment of all angiographic 
inclusion criteria, as well as the secondary efficacy endpoint of modified TICI reperfusion 
scores post device and post procedure. Additional angiographic scales of interest will also 
be assessed, including but not limited to AOL, TIMI, and Collateral Flow grade. Refer to 
Appendix C for a description of the scales to be assessed by the Angiographic Core Lab, 
and the scoring systems that will be used. 
13.3.2 
CT/MR Core Lab 
Baseline and 24 (-6/+24) hour multi-modal CT or MRI imaging will be collected and 
submitted to the  CT/MR Core lab to assess for vessel patency, hemorrhage, and core 
infarct volume. Vessel patency will be assessed in the Intra cranial ICA; MCA M1 
(proximal to striates & distal to striates); MCA M2 (inferior/superior branches); ACA A1; 
Basilar (proximal, mid, distal segments); and P1 at baseline and at 24 (-6/+24 hours) using 
CTA/MRA according to the following scale: 
0 - occluded  
1 - partial patency 
2 - patent 
N/A - not available or able to assess (based on available imaging) 
 
Hemorrhages will be assessed by CT or MRI and will be categorized according to the 
ECASS III definitions [103] and/or as RIH, IVH, Subdural, Epidural, or SAH. See Table 
7. 

Stryker Neurovascular 
Document Title: DAWN™ Trial Investigational Plan 
Document Number: CDM10000146 
Rev:  AD 
STRYKER CONFIDENTIAL - THIS DOCUMENT CONTAINS CONFIDENTIAL AND PROPRIETARY INFORMATION THAT 
IS THE PROPERTY OF STRYKER CORPORATION. NEITHER THIS DOCUMENT NOR THE INFORMATION HEREIN MAY 
BE REPRODUCED, USED, OR DISCLOSED TO ANY THIRD PARTY WITHOUT THE PRIOR WRITTEN CONSENT OF 
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  CDM10000146  Page 69 of 91 
Core infact volume will be measured by MR-DWI or CTP-rCBF maps at baseline, and by 
MRI T2 Flair or CT at later time points.   
Table 7. Intracranial Hemorrhage Types 
HI-1 
Small petechiae within ischemic field without mass effect 
HI-2 
Confluent petechiae within ischemic field without mass effect 
PH-1 
Hematoma within ischemic field with some mild space-occupying effect but 
involving ≤ 30% of the infarcted area 
PH-2 
Hematoma within ischemic field with space-occupying effect involving > 
30% of the infarcted area 
RIH 
Any intraparenchymal hemorrhage remote from the ischemic field 
IVH 
Intraventricular hemorrhage 
Subdural 
Blood between the dura mater and the arachnoid mater 
Epidural 
Blood between the dura mater and the skull 
SAH 
Subarachnoid hemorrhage 
14 Ethical Considerations 
14.1 
Compliance with Good Clinical Practices (GCP) 
The Investigator will ensure that this study is conducted in accordance with the ethical 
principles that have their origins in the Declaration of Helsinki and that are consistent with 
GCP and applicable regulatory (local) requirements; whichever affords the greater protection 
to the subject. 
14.2 
Institutional Review Board/ Ethics Committee 
A copy of the protocol, proposed Informed Consent form, other written subject information, 
and any proposed advertising material must be submitted to the IRB/EC for written approval. 
A copy of the written IRB/EC approval of the protocol and Informed Consent form must be 
received by Stryker NV before recruitment of subjects into the study and shipment of 
investigational product. 
The Investigator must submit and, where necessary, obtain approval from the IRB/EC for all 
subsequent protocol amendments and changes to the Informed Consent form. The Investigator 
must notify the IRB/EC of deviations from the SAEs/UADEs occurring at the site and other 
SAE/UADE reports received from Stryker NV in accordance with local IRB/EC procedures 
and regulations. 
The Investigator is responsible for obtaining annual IRB/EC approval and renewal throughout 
the duration of the study. Copies of the Investigator’s reports and the IRB/IEC continuance of 
approval must be sent to Stryker NV.  

Stryker Neurovascular 
Document Title: DAWN™ Trial Investigational Plan 
Document Number: CDM10000146 
Rev:  AD 
STRYKER CONFIDENTIAL - THIS DOCUMENT CONTAINS CONFIDENTIAL AND PROPRIETARY INFORMATION THAT 
IS THE PROPERTY OF STRYKER CORPORATION. NEITHER THIS DOCUMENT NOR THE INFORMATION HEREIN MAY 
BE REPRODUCED, USED, OR DISCLOSED TO ANY THIRD PARTY WITHOUT THE PRIOR WRITTEN CONSENT OF 
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  CDM10000146  Page 70 of 91 
14.3 
Written Informed Consent Form 
Stryker NV will provide a sample Informed Consent Form (ICF) to the Investigator to prepare 
for use at his/her site, attached as Appendix D. The ICF documents should be translated into 
the language(s) understandable to potential subject population(s). 
Stryker NV and the reviewing IRB/IEC must approve the ICF before use at that site. The ICF 
must be in agreement with current Good Clinical Practices (GCP) guidelines, the Declaration 
of Helsinki, and the International Conference on Harmonization (ICH).  
Before participating in the clinical trial, each subject or his/her legally authorized 
representative (LAR) must give written Informed Consent after the context of the study has 
been fully explained in a language that is easily understood by the subject or LAR. The subject 
or LAR must also be given the opportunity to ask questions and have those questions answered 
to his/her satisfaction. 
Written Informed Consent must be recorded appropriately by means of the subject’s, or LAR’s 
dated signature. The consent process must be documented in the subject’s medical chart. At 
U.S. sites, electronic informed consent may be utilized in accordance with FDA’s Guidance 
on the Use of Electronic Informed Consent in Clinical Investigations if approved by the site’s 
IRB. 
Note - If approved by local ethics committee and country regulations, the investigator is 
allowed to enroll a patient if, the subject or the representative or person of trust is not available 
to sign. However, as soon as possible, the patient is informed and his/her consent is requested 
for the possible continuation of this research. (Not applicable to US. Sites.) 
14.4 
Amending the Protocol 
This protocol must be followed exactly.  It can be altered only by written amendments made 
by Stryker NV. Following appropriate approval by Stryker NV, the amended protocol will be 
submitted to the required regulatory agencies before being distributed to all participating sites. 
Each site must obtain IRB/EC approval before implementing the revised protocol. 
14.5 
Protocol Adherence 
Prior to beginning the study, the Investigator must sign the Investigator Agreement and 
Signature page documenting his/her agreement to conduct the study in accordance with the 
protocol. An Investigator must not make any changes or deviate from this protocol, except to 
protect the life and physical well-being of a subject in an emergency. Each deviation from the 
protocol must be documented with the date and reason for the deviation and reported to Stryker 
NV as soon as possible, and to the IRB/EC per local guidelines and government regulations. 
Major and minor protocol deviations are defined within Appendix B.  

Stryker Neurovascular 
Document Title: DAWN™ Trial Investigational Plan 
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STRYKER CONFIDENTIAL - THIS DOCUMENT CONTAINS CONFIDENTIAL AND PROPRIETARY INFORMATION THAT 
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  CDM10000146  Page 71 of 91 
15 Study Administration 
15.1 
Pre-Study Documentation Requirements 
Prior to enrolling any subjects into the trial the site must complete all pre-study essential 
documents, and these must be confirmed to be on file with Stryker NV:  
 Site PI’s CV and current medical license  
 An operator qualification form (statement of experience) for at least one operator 
 W-9 (or equivalent in other countries) to facilitate payment 
 A fully executed clinical trial agreement 
 IRB/EC approval of the study and the Informed Consent Form 
 Documentation of all required study training  
 Documentation of a completed Site Initiation Visit  
 
No site may begin enrolling subjects until they receive written approval/authorization from 
Stryker NV.  
15.2 
Record Retention 
The Investigator will maintain all essential trial documents and source documentation, in 
original format, that support the data collected on the study subjects in compliance with the 
ICH/GCP guidelines. Documents must be retained for at least 2 years after the last approval of 
marketing application or until at least 2 years have elapsed since the formal discontinuation of 
the clinical investigation of the product. These documents will be retained for a longer period 
of time by agreement with Stryker NV or in compliance with other regulatory requirements. 
The Investigator will take measures to ensure that these essential documents are not 
accidentally damaged or destroyed. If for any reason the Investigator withdraws responsibility 
for maintaining these essential documents, custody must be transferred to an individual who 
will assume responsibility. Stryker NV must receive written notification of this custodial 
change.  
15.3 
Criteria for Terminating Study 
Stryker NV reserves the right to terminate the study but intends only to exercise this right for 
valid scientific or administrative reasons and reasons related to protection of subjects. 
Investigators and associated IRB/EC will be notified in writing in the event of termination. 
15.4 
Criteria for Suspending/Terminating a Study Site 
Stryker NV reserves the right to stop the enrollment of subjects at a study site at any time after 
the study initiation visit if no subjects have been enrolled or if the site has multiple or major 
protocol violations without justification or fails to follow remedial actions. Notification of 
termination of a Study Site will be made by Stryker NV to the appropriate regulatory agencies, 
as required. 

Stryker Neurovascular 
Document Title: DAWN™ Trial Investigational Plan 
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Stryker Neurovascular 
Document Title: DAWN™ Trial Investigational Plan 
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STRYKER CONFIDENTIAL - THIS DOCUMENT CONTAINS CONFIDENTIAL AND PROPRIETARY INFORMATION THAT 
IS THE PROPERTY OF STRYKER CORPORATION. NEITHER THIS DOCUMENT NOR THE INFORMATION HEREIN MAY 
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  CDM10000146  Page 73 of 91 
16 References 
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Stryker Neurovascular 
Document Title: DAWN™ Trial Investigational Plan 
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  CDM10000146  Page 74 of 91 
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Nogueira, R.G., et al. Preliminary Data for the DAWN Trial (DWI and CTP Assessment in the Triage of 
Wake-Up and Late Presenting Strokes Undergoing Neurointervention): Results of Imaging-Based 
Endovascular Therapy for Proximal Anterior CirculationOcclusions beyond 8 Hours from Last Seen Well 
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34. 
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Stroke, 2008. 39(12): p. 3277-82. 
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Thomalla, G., et al., Outcome and symptomatic bleeding complications of intravenous thrombolysis within 
6 hours in MRI-selected stroke patients: comparison of a German multicenter study with the pooled data of 
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40. 
Kohrmann, M., et al., MRI versus CT-based thrombolysis treatment within and beyond the 3 h time window 
after stroke onset: a cohort study. Lancet Neurol, 2006. 5(8): p. 661-7. 
41. 
Schellinger, P.D., et al., MRI-based and CT-based thrombolytic therapy in acute stroke within and beyond 
established time windows: an analysis of 1210 patients. Stroke, 2007. 38(10): p. 2640-5. 

Stryker Neurovascular 
Document Title: DAWN™ Trial Investigational Plan 
Document Number: CDM10000146 
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STRYKER CONFIDENTIAL - THIS DOCUMENT CONTAINS CONFIDENTIAL AND PROPRIETARY INFORMATION THAT 
IS THE PROPERTY OF STRYKER CORPORATION. NEITHER THIS DOCUMENT NOR THE INFORMATION HEREIN MAY 
BE REPRODUCED, USED, OR DISCLOSED TO ANY THIRD PARTY WITHOUT THE PRIOR WRITTEN CONSENT OF 
STRYKER CORPORATION                                                                                                                                                                             
 
 
  CDM10000146  Page 75 of 91 
42. 
Janjua, N., et al., Late endovascular revascularization in acute ischemic stroke based on clinical-diffusion 
mismatch. AJNR Am J Neuroradiol, 2009. 30(5): p. 1024-7. 
43. 
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Outcomes, a Pre-Post Study in International Stroke Conference Oral Abstracts; A161. 2012. 

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STRYKER CONFIDENTIAL - THIS DOCUMENT CONTAINS CONFIDENTIAL AND PROPRIETARY INFORMATION THAT 
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  CDM10000146  Page 76 of 91 
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66. 
Saver, J.L., Time is brain--quantified. Stroke, 2006. 37(1): p. 263-6. 
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Leiva-Salinas, C., et al., Tissue at risk in acute stroke patients treated beyond 8 h after symptom onset. 
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Abou-Chebl, A., Endovascular treatment of acute ischemic stroke may be safely performed with no time 
window limit in appropriately selected patients. Stroke, 2010. 41(9): p. 1996-2000. 
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Wechsler, L.R., et al., Factors influencing outcome and treatment effect in PROACT II. Stroke, 2003. 
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dependent. Neurology, 2009. 73(13): p. 1066-72. 
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Removal in Cerebral Ischemia (MERCI) and Multi MERCI Trials. Stroke, 2009. 40(12): p. 3777-83. 
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Hours from Time Last Seen Well: A Subset Analysis of the Merci Registry. in Eighth Society of 
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Nogueira, Neither Time to Treatment Nor the Use of Adjunctive Intra-arterial Thrombolytics Increase the 
Risk for Symptomatic Intracranial Hemorrhage After Endovascular Treatment of CT Perfusion or MRI-
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2010: Austin, Tx. 
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STAIR. Stroke Treatment Academic Industry Roundtable. March 9-10, 2013. Washington D.C. 
"Accelerating the Evolution of Stroke Therapy". In Press. 2013. 
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tissue plasminogen activator. The rt-PA Acute Stroke Study Group. AJNR Am J Neuroradiol, 1993. 14(1): 
p. 3-13. 
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Shi, Z.-S., et al., Endovascular Thrombectomy for Acute Ischemic Stroke in Failed Intravenous Tissue 
Plasminogen Activator Versus Non–Intravenous Tissue Plasminogen Activator Patients Revascularization 
and Outcomes Stratified by the Site of Arterial Occlusions. Stroke, 2010. 41(6): p. 1185-1192. 
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infarction. Neurology, 2004. 62(12): p. 2187-92. 
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Stryker Neurovascular 
Document Title: DAWN™ Trial Investigational Plan 
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STRYKER CONFIDENTIAL - THIS DOCUMENT CONTAINS CONFIDENTIAL AND PROPRIETARY INFORMATION THAT 
IS THE PROPERTY OF STRYKER CORPORATION. NEITHER THIS DOCUMENT NOR THE INFORMATION HEREIN MAY 
BE REPRODUCED, USED, OR DISCLOSED TO ANY THIRD PARTY WITHOUT THE PRIOR WRITTEN CONSENT OF 
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  CDM10000146  Page 77 of 91 
translational medicine research collaboration multicentre acute stroke imaging study. Stroke, 2012. 43(2): 
p. 563-6. 
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the Science before Changing Clinical Practice. Radiology, 2013. 266(1): p. 16-21. 
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Jovin, T.G., et al., The cortical ischemic core and not the consistently present penumbra is a determinant of 
clinical outcome in acute middle cerebral artery occlusion. Stroke, 2003. 34(10): p. 2426-33. 
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Nogueira, R.G., et al., Infarct Volume Thresholds for Prediction of Independent Functional Outcomes after 
Acute Ischemic Stroke. Stroke 2012. 43: p. A4030. 
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Lansberg, M.G., et al., MRI profile and response to endovascular reperfusion after stroke (DEFUSE 2): a 
prospective cohort study. The Lancet Neurology, 2012. 
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Zaidi, S.F., et al., Final infarct volume is a stronger predictor of outcome than recanalization in patients 
with proximal middle cerebral artery occlusion treated with endovascular therapy. Stroke, 2012. 43(12): p. 
3238-3244. 
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Furlan, Personal Communication to Tudor Jovin re: ProAct II - Outcomes by Occlusion Location and 
NIHSS, T. Jovin, Editor. 2013. 
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p. 2121-5. 
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acute ischemic stroke: Emergency Management of Stroke (EMS) Bridging Trial. Stroke, 1999. 30(12): p. 
2598-605. 
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stratification in future trials. Stroke, 1999. 30(6): p. 1208-1212. 
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comparison in patients from the Virtual International Stroke Trials Archive (VISTA). Stroke, 2010. 41(12): 
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Bath, P.M., et al., Statistical analysis of the primary outcome in acute stroke trials. Stroke, 2012. 43(4): p. 
1171-1178. 
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approval of acute stroke therapies: stroke therapy academic industry roundtable. Stroke, 2005. 36(8): p. 
1808-1813. 
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Analysis of Acute Stroke Trials Using a Utility-Weighted Modified Rankin Scale. Stroke. 2015. 46:2238-
2243 
 
 
 

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Document Title: DAWN™ Trial Investigational Plan 
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STRYKER CONFIDENTIAL - THIS DOCUMENT CONTAINS CONFIDENTIAL AND PROPRIETARY INFORMATION THAT 
IS THE PROPERTY OF STRYKER CORPORATION. NEITHER THIS DOCUMENT NOR THE INFORMATION HEREIN MAY 
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  CDM10000146  Page 78 of 91 
17 Appendices 
Appendix A. 
Abbreviations  
Abbreviation 
Full Term 
ACA 
Anterior Cerebral Artery 
ADC 
Apparent Diffusion Co-efficient 
ADP 
Adaptive Design Plan 
AE 
Adverse Event 
AHA 
American Heart Association 
AIS 
Acute Ischemic Stroke 
AOL 
Arterial Occlusive Lesion 
ASA 
American Stroke Association 
AT 
As Treated 
CA 
Competent Authority 
CEC 
Clinical Events Committee 
CIM 
Clinical Imaging Mismatch 
CRF 
Case Report Form 
CT 
Computerized Tomography 
CTA 
Computerized Tomography Angiography 
CTP 
Computerized Tomography Perfusion 

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STRYKER CONFIDENTIAL - THIS DOCUMENT CONTAINS CONFIDENTIAL AND PROPRIETARY INFORMATION THAT 
IS THE PROPERTY OF STRYKER CORPORATION. NEITHER THIS DOCUMENT NOR THE INFORMATION HEREIN MAY 
BE REPRODUCED, USED, OR DISCLOSED TO ANY THIRD PARTY WITHOUT THE PRIOR WRITTEN CONSENT OF 
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  CDM10000146  Page 79 of 91 
Abbreviation 
Full Term 
DBP 
Diastolic Blood Pressure 
DE 
Distal Embolization 
DMC 
Data Monitoring Committee 
DNR 
Do Not Resuscitate 
DRSAE 
Device-related SAE 
DWI 
Diffusion Weighted Imaging 
EC 
Ethics Committee 
EE 
Efficacy Evaluable 
ENT 
Embolization to New Territory 
ESO 
European Stroke Organization 
GCP 
Good Clinical Practice 
HCT 
Hematocrit 
HI-I 
Petechial hemorrhage type I 
HI-II 
Petechial hemorrhage type II 
Hr/Hrs 
Hour/Hours 
IA 
Intra-Arterial 
ICA 
Internal Carotid Artery 

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STRYKER CONFIDENTIAL - THIS DOCUMENT CONTAINS CONFIDENTIAL AND PROPRIETARY INFORMATION THAT 
IS THE PROPERTY OF STRYKER CORPORATION. NEITHER THIS DOCUMENT NOR THE INFORMATION HEREIN MAY 
BE REPRODUCED, USED, OR DISCLOSED TO ANY THIRD PARTY WITHOUT THE PRIOR WRITTEN CONSENT OF 
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  CDM10000146  Page 80 of 91 
Abbreviation 
Full Term 
ICA-T 
Internal Carotid Artery Terminus 
ICF 
Informed Consent Form 
ICH 
Intracranial Hemorrhage 
IFU 
Instructions For Use 
INR 
International Normalized Ratio 
IRB 
Institutional Review Board 
ITT 
Intent-To-Treat 
IV 
Intravenous 
IVH 
Intraventricular Hemorrhage 
IVRS/IWRS 
Interactive Voice Response System / Interactive Web Response System 
LAR 
Legally Authorized Representative 
LTFU 
Lost To Follow Up 
LVO 
Large Vessel Occlusion 
M-1 
The initial horizontal segment of the MCA, prior to the first bifurcation or 
trifurcation 
M-2 
The portions of the MCA distal to the first bifurcation or trifurcation, but 
prior to the second bifurcation 
MCA 
Middle Cerebral Artery 

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STRYKER CONFIDENTIAL - THIS DOCUMENT CONTAINS CONFIDENTIAL AND PROPRIETARY INFORMATION THAT 
IS THE PROPERTY OF STRYKER CORPORATION. NEITHER THIS DOCUMENT NOR THE INFORMATION HEREIN MAY 
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  CDM10000146  Page 81 of 91 
Abbreviation 
Full Term 
MR/MRI 
Magnetic Resonance / Magnetic Resonance Imaging 
MRA 
Magnetic Resonance Angiography 
mRS 
Modified Rankin Scale 
mTICI 
Modified Thrombolysis in Cerebral Infarction 
NIHSS 
National Institute of Health Stroke Scale 
PH-I 
Parenchymal hemorrhage type 1 
PH-II 
Parenchymal hemorrhage type 2 
PP 
Per Protocol 
PRSAE 
Procedure-related SAE 
PT 
Prothrombin Time 
PTT 
Partial Thromboplastin Time  
PWI 
Perfusion Weighted Imaging 
rCBF 
Relative Cerebral Blood Flow 
RIH 
Remote Intracerebral Hemorrhage  
SAE 
Serious Adverse Event 
SADE 
Serious Adverse Device Effect  
SAH 
Subarachnoid Hemorrhage 

Stryker Neurovascular 
Document Title: DAWN™ Trial Investigational Plan 
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STRYKER CONFIDENTIAL - THIS DOCUMENT CONTAINS CONFIDENTIAL AND PROPRIETARY INFORMATION THAT 
IS THE PROPERTY OF STRYKER CORPORATION. NEITHER THIS DOCUMENT NOR THE INFORMATION HEREIN MAY 
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  CDM10000146  Page 82 of 91 
Abbreviation 
Full Term 
SBP 
Systolic Blood Pressure 
SICH 
Symptomatic Intracranial Hemorrhage 
TICI 
Thrombolysis in Cerebral Infarction 
TIMI 
Thrombolysis in Myocardial Infarction 
TLSW 
Time Last Seen Well 
tPA 
Tissue Plasminogen Activator (alteplase) 
UADE 
Unanticipated Adverse Device Effect 
UK 
Urokinase 
USADE 
Unanticipated Serious Adverse Device Effect 
WUS 
Wake Up Stroke 

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  CDM10000146  Page 83 of 91 
Appendix B. 
Definitions 
Access Site Complication: Complication related to the vascular access site for the index 
procedure including but not limited to bleeding, hematoma, pseudoaneurysm, tears, pain or 
occlusion. Some of these complications may require additional treatment such as blood 
transfusion or surgical repair. 
Adverse Event (AE): Any unintended disease or injury or untoward clinical sign in a research 
subject.  NOTE - This definition does not imply that there is a relationship between the adverse 
event and the device under investigation. 
Device Malfunction/Nonconformity: The failure of a device to meet its performance 
specifications or otherwise perform as intended. Performance specifications include all claims 
made in the labeling for the device. The intended performance of a device refers to the intended 
use for which the device is labeled or marketed.  
Device-Related Serious Adverse Event (DRSAE): Trevo device related vascular perforation 
or intramural arterial dissection, symptomatic ICH, embolization to a new territory, intra-
procedural death, or device failure (in vivo breakage). 
Distal Embolization (DE): Any downstream occlusion distal to the target artery lesion (TAL), 
into the target ischemic territory, is considered DE unless complete angiogram or pre procedure 
non-invasive imaging demonstrated patency of these distal branches. 
Early Response: A NIHSS drop of ≥10 from baseline or an excellent score of NIHSS 0 or 1 
at Day 5-7 / Discharge (whichever is earlier). 
Embolization to New Territory (ENT): Embolization into a previously uninvolved area of 
the brain, e.g. ACA embolization during MCA-M1 thrombectomy procedure. In ICA terminus 
occlusion, any MCA or ACA occlusion post procedure is considered distal embolization (DE) 
and not ENT. However, if pre procedure patency of these previously uninvolved territories is 
documented by complete angiogram or pre-intervention non-invasive imaging, then it would 
be considered ENT.  
Epidural hemorrhage: Blood between the dura mater and the arachnoid mater. 
Good Clinical Outcome: A measure of neurologic functional outcome with a score of 0–2 on 
the modified Rankin Scale (mRS), usually assessed 90 days after treatment. 
Intracranial hemorrhage: A hemorrhage, or bleeding, within the skull 
Intramural arterial dissection:  A tear or damage to the inner arterial wall that occurs during 
the index procedure.  The intramural arterial dissection may be identified angiographically as 
minor radiolucent area to luminal filling defect on imaging.   

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STRYKER CONFIDENTIAL - THIS DOCUMENT CONTAINS CONFIDENTIAL AND PROPRIETARY INFORMATION THAT 
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  CDM10000146  Page 84 of 91 
Intraprocedure Mortality:  Death occurring during the index thrombectomy procedure 
Intra-ventricular Hemorrhage (IVH): Bleeding into the brain's ventricular system.  
In vivo (breakage) device failure:  Breakage of the Trevo device in the vasculature during 
the index procedure. 
Medical Management: In broad terms, medical management as the label for the Control arm 
means no intra-arterial intervention with drugs or devices.  Furthermore, after randomization, 
a subject cannot be placed on intravenous thrombolytic therapy.  The specific implementation 
of best medical management should be consistently applied and in accord with the relevant 
AHA or ESO guidelines, as applicable in the country of treatment.   
Modified Rankin Scale: Scale for measuring the degree of disability or dependence in the 
daily activities of people who have suffered a stroke or other causes of neurological disability. 
Neurological worsening:  A 4 or more point increase in NIHSS from baseline.  Neurological 
worsening could be new or evolution/progression of the index stroke. 
NIHSS Score: An assessment to objectively quantify the impairment caused by a stroke. It is 
composed of 11 items, each of which scores a specific ability between a 0 and 4. For each item, 
a score of 0 typically indicates normal function in that specific ability, while a higher score is 
indicative of some level of impairment. The individual scores from each item are summed in 
order to calculate a total NIHSS score. The maximum possible score is 42, with the minimum 
score being a 0. 
Parenchymal hemorrhage type 1 (PH-1):  A hematoma in < 30% of the infarcted area with 
some slight space-occupying effect.  
Parenchymal hemorrhage type 2 (PH-2):  Dense hematoma > 30% total of the infarcted area 
with substantial space-occupying effect or any hemorrhage area outside the infarcted area. 
Petechial hemorrhage type I (HI-1): Small petechiae along the margins of the infarct. 
Petechial hemorrhage type II (HI-2): More confluent petechiae within the infarcted area but 
without space-occupying effect 
Pre-stroke disability: Obtained at baseline, but representative of the subject’s status before 
the index stroke, assessed by mRS on medical history obtained from subject’s medical chart, 
or family members. 
Procedure-Related Serious Adverse Event (PRSAE): Procedure-related  events that 
include, but are not limited to vascular perforation or intramural arterial dissection, 

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STRYKER CONFIDENTIAL - THIS DOCUMENT CONTAINS CONFIDENTIAL AND PROPRIETARY INFORMATION THAT 
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  CDM10000146  Page 85 of 91 
symptomatic ICH, embolization to a new territory, or access site complication requiring 
surgical repair or blood transfusion, intra-procedural death, or device failure (in vivo breakage). 
Protocol Deviation:  Any alteration/modification to the current IRB/EC-approved protocol. 
The protocol includes the detailed protocol, protocol summary, consent form, recruitment 
materials, questionnaires, and any other information relating to the research study.   Note: Any 
permanent change to the protocol constitutes an amendment that must be submitted to the 
Institutional Review Board/Ethics Committee for approval prior to initiation. Deviations may 
be further classified as:  
• 
Major deviation: a deviation that may impact subject safety, affect the integrity of study 
data and/or affect subject’s willingness to participate in the study, such as but not 
limited to: enrollment without obtaining appropriate informed consent; violation of 
inclusion/exclusion criteria; randomization irregularities including treatment arm 
crossover; confounding procedure by using non allowed therapies; non reporting of 
SAEs/UADEs and study product non conformities; and protocol required assessments 
repeatedly not completed at the required time windows 
• 
Minor deviation: a deviation that does not impact subject safety, compromise the 
integrity of study data and/or affect subject’s willingness to participate in the study, 
such as but not limited to: follow up assessments not conducted or conducted outside 
of the required time windows.  
Protocol Exception: Any single protocol deviation that is approved by Stryker NV prior to its 
initiation, and documented in writing.  Note: Any permanent change to the protocol constitutes 
an amendment that must be submitted to the IRB/EC for approval prior to initiation.   
Remote Intracerebral Hemorrhage (RIH): Any intraparenchymal hemorrhage remote from 
the ischemic field. 
Serious Adverse Device Effect (SADE):  Any serious adverse effect on health or safety or 
any life-threatening problem or death caused by, or associated with, a device, if that effect, 
problem, or death was not previously identified in nature, severity, or degree of incidence in 
the investigational plan or application (including a supplementary plan or application), or any 
other unanticipated serious problem associated with a device that relates to the rights, safety 
or welfare of subjects.   
Serious Adverse Event (SAE): An adverse event in a research subject that led to a death, or 
led to a serious deterioration in the health of the subject that resulted in a life-threatening illness 
or injury, or resulted in a permanent impairment of a body structure or a body function, or 
required in-patient hospitalization or prolongation of existing hospitalization, or resulted in 
medical or surgical intervention to prevent permanent impairment to body structure or a body 
function. SAEs are a subset of AEs.  

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IS THE PROPERTY OF STRYKER CORPORATION. NEITHER THIS DOCUMENT NOR THE INFORMATION HEREIN MAY 
BE REPRODUCED, USED, OR DISCLOSED TO ANY THIRD PARTY WITHOUT THE PRIOR WRITTEN CONSENT OF 
STRYKER CORPORATION                                                                                                                                                                             
 
 
  CDM10000146  Page 86 of 91 
• 
NOTE 1 – This definition does not imply that there is a relationship between the serious 
adverse event and the device under investigation.  
• 
NOTE 2 – A planned hospitalization/procedure for a pre-existing condition or a 
condition required by the protocol, without serious deterioration in health is not 
considered serious but should be recorded as an AE.  Deterioration in health as a result 
of the planned hospitalization/procedure should be recorded as a new AE. 
Stroke:  An acute neurological event with focal symptoms and signs lasting ≥ 24 hours.  Stroke 
can be sub-classified as Hemorrhagic or Ischemic. 
 Hemorrhagic Stroke:  A symptomatic intracerebral, subarachnoid, or primary 
intraventricular hemorrhage.  To be considered a hemorrhagic stroke, the patient must 
experience new symptoms (e.g., new severe headache) that last for at least 24 hours 
(symptoms do not need to be associated with a new neurological deficit). 
 Ischemic Stroke:  A neurological deficit that is thought to have an ischemic cause and 
is detectable on examination at least 24 hours after onset of symptoms.       
Stroke-related Death: Death related to the index stroke; to systemic complications associated 
with the index stroke, or a new stroke. 
Subarachnoid Hemorrhage (SAH): Bleeding into the subarachnoid space - the area between 
the arachnoid membrane and the pia mater surrounding the brain.  
Subdural hemorrhage: Blood between the dura mater and the skull. 
Symptomatic ICH (SICH): The primary protocol definition is adapted from ECASS III as 
any apparently extravascular blood in the brain or within the cranium that is associated with 
clinical deterioration as defined by an increase of four points or more in the NIHSS, or that led 
to death and was judged to be the predominant cause of a neurologic deterioration.  The SITS-
MOST definition of SICH is: Any PH-2 with a four point or more increase in NIHSS. 
Unanticipated Serious Adverse Device Effects (USADEs): A subset of SADEs that are 
unanticipated, or not previously identified in the labeling of the investigational device, 
including the Investigator Brochure, Clinical Investigational Plan and Informed Consent Form 
Vessel Perforation:  A hole or puncture (perforation) in the vessel wall that occurs 
unintentionally during the index procedure.  The perforations may be seen angiographically 
during the index procedure by frank or free extravasation of the contrast into the surrounding 
tissue or blush or localized contrast extending outside the vessel lumen. 
Weighted mRS: A numerical value representing the clinical utility of each mRS category. 

Stryker Neurovascular 
Document Title: DAWN™ Trial Investigational Plan 
Document Number: CDM10000146 
Rev:  AD 
STRYKER CONFIDENTIAL - THIS DOCUMENT CONTAINS CONFIDENTIAL AND PROPRIETARY INFORMATION THAT 
IS THE PROPERTY OF STRYKER CORPORATION. NEITHER THIS DOCUMENT NOR THE INFORMATION HEREIN MAY 
BE REPRODUCED, USED, OR DISCLOSED TO ANY THIRD PARTY WITHOUT THE PRIOR WRITTEN CONSENT OF 
STRYKER CORPORATION                                                                                                                                                                             
 
 
  CDM10000146  Page 87 of 91 
Appendix C. Angiographic Core Lab Scales 
 
TIMI Grade Scale 
0 - No perfusion 
1 - Penetration with minimal perfusion 
2a - Partial perfusion of the artery & its main branches < 50% 
2b - Partial perfusion of the artery & its main branches >50% 
3 - Complete perfusion 
 
Collateral Flow Grade 
0 - No collaterals visible to the ischemic site 
 
1 - Slow collaterals to the periphery of the ischemic site with persistence of some of the defect 
 
2 - Rapid collaterals to the periphery of ischemic site with persistence of some of the defect 
and to only a portion of the ischemic territory 
 
3 - Collaterals with slow but complete angiographic blood flow of the ischemic bed by the late 
venous phase 
 
4 - Complete and rapid collateral blood flow to the vascular bed in the entire ischemic territory 
by retrograde perfusion 
 
 
AOL Grade 
0 - No recanalization of the primary occlusive lesion 
 
I - Incomplete or partial recanalization of the primary occlusive lesion with no distal flow  
II - Incomplete or partial recanalization of the primary occlusive lesion with any distal flow 
III - Complete recanalization of the primary occlusion with any distal flow 
 
TICI Scale 
0 - No Perfusion - No antegrade flow beyond the point of occlusion 
1 - Penetration with Minimal Perfusion - The contrast material passes beyond the area of 
obstruction but fails to opacify the entire cerebral bed distal to the obstruction for the duration 
of the angiographic run 
2 - Partial Perfusion - The contrast material passes beyond the obstruction and opacifies the 
arterial bed distal to the obstruction; However, the rate of entry of the contrast into the vessel 
distal to the obstruction and/or its rate of clearance from the distal bed are perceptibly slower 
than its entry into and/or clearance from comparable areas not perfused by the previously 
occluded vessel, e.g. the opposite cerebral artery of the arterial bed proximal to the obstruction 
   2a - Only partial filling (<2/3) of the entire vascular territory is visualized  
 
   2b - Complete filling (≥ 2/3) of all the expected vascular territory is visualized, but the  
     filling is slower than normal 
 
3 - Complete Perfusion - Antegrade flow into the bed distal to the obstruction occurs as 
promptly as into the obstruction and clearance of contrast material from the involved bed is as 
rapid as from an uninvolved other bed of the same vessel or the opposite cerebral artery  
 
 

Stryker Neurovascular 
Document Title: DAWN™ Trial Investigational Plan 
Document Number: CDM10000146 
Rev:  AD 
STRYKER CONFIDENTIAL - THIS DOCUMENT CONTAINS CONFIDENTIAL AND PROPRIETARY INFORMATION THAT 
IS THE PROPERTY OF STRYKER CORPORATION. NEITHER THIS DOCUMENT NOR THE INFORMATION HEREIN MAY 
BE REPRODUCED, USED, OR DISCLOSED TO ANY THIRD PARTY WITHOUT THE PRIOR WRITTEN CONSENT OF 
STRYKER CORPORATION                                                                                                                                                                             
 
 
  CDM10000146  Page 88 of 91 
Modified TICI Scale (mTICI Scale) 
0 - No Perfusion - No antegrade flow beyond the point of occlusion 
1 - Penetration with Minimal Perfusion - The contrast material passes beyond the area of 
obstruction but fails to opacify the entire cerebral bed distal to the obstruction for the duration of 
the angiographic run 
2 - Partial Perfusion - The contrast material passes beyond the obstruction and opacifies the 
arterial bed distal to the obstruction; However, the rate of entry of contrast into the vessel distal 
to the obstruction and/or its rate of clearance from the distal bed are perceptibly slower than its 
entry into and/or clearance from comparable areas not perfused by the previously occluded 
vessel, e.g., the opposite cerebral artery or the arterial bed proximal to the obstruction 
2a - Only partial filling (< 50%) of the entire vascular territory is visualized 
2b - Filling of  > 50% all of the expected vascular territory is visualized, but the filling is  
 slower than normal 
3 - Complete Perfusion - Antegrade flow into the bed distal to the obstruction occurs as promptly 
as into the obstruction and clearance of contrast material from the involved bed is as rapid as 
from an uninvolved other bed of the same vessel or the opposite cerebral artery. 
 
 

Stryker Neurovascular 
Document Title: DAWN™ Trial Investigational Plan 
Document Number: CDM10000146 
Rev:  AD 
STRYKER CONFIDENTIAL - THIS DOCUMENT CONTAINS CONFIDENTIAL AND PROPRIETARY INFORMATION THAT 
IS THE PROPERTY OF STRYKER CORPORATION. NEITHER THIS DOCUMENT NOR THE INFORMATION HEREIN MAY 
BE REPRODUCED, USED, OR DISCLOSED TO ANY THIRD PARTY WITHOUT THE PRIOR WRITTEN CONSENT OF 
STRYKER CORPORATION                                                                                                                                                                             
 
 
  CDM10000146  Page 89 of 91 
Appendix D. Informed Consent Form Template [attached] 
 
 

Stryker Neurovascular 
Document Title: DAWN™ Trial Investigational Plan 
Document Number: CDM10000146 
Rev:  AD 
STRYKER CONFIDENTIAL - THIS DOCUMENT CONTAINS CONFIDENTIAL AND PROPRIETARY INFORMATION THAT 
IS THE PROPERTY OF STRYKER CORPORATION. NEITHER THIS DOCUMENT NOR THE INFORMATION HEREIN MAY 
BE REPRODUCED, USED, OR DISCLOSED TO ANY THIRD PARTY WITHOUT THE PRIOR WRITTEN CONSENT OF 
STRYKER CORPORATION                                                                                                                                                                             
 
 
  CDM10000146  Page 90 of 91 
Appendix E. Sample Instructions for Use (IFU) [attached] 
 
 

Stryker Neurovascular 
Document Title: DAWN™ Trial Investigational Plan 
Document Number: CDM10000146 
Rev:  AD 
STRYKER CONFIDENTIAL - THIS DOCUMENT CONTAINS CONFIDENTIAL AND PROPRIETARY INFORMATION THAT 
IS THE PROPERTY OF STRYKER CORPORATION. NEITHER THIS DOCUMENT NOR THE INFORMATION HEREIN MAY 
BE REPRODUCED, USED, OR DISCLOSED TO ANY THIRD PARTY WITHOUT THE PRIOR WRITTEN CONSENT OF 
STRYKER CORPORATION                                                                                                                                                                             
 
 
  CDM10000146  Page 91 of 91 
Appendix F. Adaptive Design Plan [attached]