A Multicentre Prospective Natural History Study Using Multimodality Imaging in Patients With ACS- PROSPECT II (Natural History Study), Combined With a Randomized, Controlled, Intervention Study - PROSPECT ABSORB (Randomized Trial)
Phase: NA
Conditions: Acute Coronary Syndrome (ACS)
Sponsor: Uppsala University

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PROSPECT II/PROSPECT ABSORB Investigational Plan 
FINAL AM04; 28 APR 2020 
 
 
INVESTIGATIONAL PLAN 
PROSPECT II and PROSPECT ABSORB 
An integrated natural history study and randomized 
trial 
 
 
Providing Regional Observations to Study Predictors of Events in the Coronary 
Tree  
 
A multicenter prospective natural history study using multimodality imaging in 
patients with acute coronary syndromes - PROSPECT II (Natural History Study), 
combined with a randomized, controlled, intervention study - PROSPECT ABSORB 
(Randomized Trial) 
 
 
Project Identification: 
PROSPECT II and PROSPECT ABSORB 
Study Plan version: 
Version 4; 28 APR 2020 
Study Medical Devices: 
I: TVC Imaging system by InfraReDx, Burlington, MA, USA 
II: Absorb™ Bioresorbable Vascular Scaffold by Abbott 
Vascular, Santa Clara, CA, USA 
 
Study Chairs: 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
David Erlinge, MD, PhD 
Professor of Cardiology 
Department of Cardiology, Lund University 
Skane University Hospital 
SE-22185 Lund, Sweden 
Tel. +46 733 746165 
Email: david.erlinge@gmail.com 
 
Gregg W. Stone, MD 
Professor of Medicine 
Director of Academic Affairs for the Mount Sinai Heart Health 
System 
Professor of Medicine (Cardiology) 
Professor of Population Health Sciences and Policy 
The Zena and Michael A. Wiener Cardiovascular Institute 
Icahn School of Medicine at Mount Sinai, New York, NYCo-
Director of Medical Research and Education 
Cardiovascular Research Foundation 
New York, NY, USA 
Tel. +1-646-434-4134 
Email: gregg.stone@mountsinai.org 

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PROSPECT II/PROSPECT ABSORB Investigational Plan 
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Coordinating Principal 
Investigator of PROSPECT II: 
 
Coordinating Principal 
Investigator of PROSPECT 
ABSORB: 
 
David Erlinge, MD, PhD 
 
 
 
 
Gregg W. Stone, MD 
Sponsor and Coordinating 
Academic Research Organization 
Representative 
Uppsala Clinical Research Center (UCR) 
Lars Wallentin, MD, PhD 
Professor of Cardiology  
Uppsala Science Park, Hubben 
Dag Hammarskjölds väg 38 
751 85 Uppsala universitet  
Tel: +46 70 631 3566 
 
Coordinating Academic 
Research Organization 
Representative: 
Cardiovascular Research Foundation (CRF) 
Ori Ben-Yehuda, MD 
Executive Director, Clinical Trials Center 
Cardiovascular Research Foundation 
1700 Broadway 
New York, NY 10019, USA 
Tel 646-582-6582 
 
Quality Register Representative 
Stefan James, MD, PhD 
Associate Professor of Cardiology  
Uppsala Clinical Research Center 
Uppsala Science Park, Hubben 
Dag Hammarskjölds väg 38 
751 85 UPPSALA  
Tel: +46 70 594 4404 
 
Clinical Endpoint Classification 
Representative 
Claes Held, MD, PhD 
Associate Professor of Cardiology  
Uppsala Clinical Research Center 
Uppsala Science Park, Hubben 
Dag Hammarskjölds väg 38 
751 85 UPPSALA  
Tel: +46 70 616 4775 
 
 

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PROSPECT II/PROSPECT ABSORB Investigational Plan 
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PROTOCOL SIGNATURE PAGE 
I, the undersigned, have read and understand the Investigational Plan and agree that it 
contains all necessary information for conducting the study.  
I agree to conduct the study according to this Investigational Plan, and according to the 
ethical principles that have their origin in the Declaration of Helsinki and that are 
consistent with Good Clinical Practice, EN ISO 14155:2011(E) and the applicable 
national laws and regulations. 
  
Sponsor and Coordinating 
Academic Research 
Organization 
Representative 
 
Lars Wallentin, MD, PhD 
Signature and date:  
 
_______________________________________ 
 
Coordinating Academic 
Research Organization 
Representative 
 
Ori Ben-Yehuda, MD 
Signature and date:  
 
_________________________________________ 
 
Chair and Coordinating 
Principal Investigator 
PROSPECT II 
 
 
David Erlinge, MD, PhD 
Signature and date:  
 
_______________________________________ 
 
Chair and Coordinating 
Principal Investigator  
PROSPECT ABSORB 
 
 
Gregg W. Stone, MD 
Signature and date:  
 
_______________________________________ 
 
 
 

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PROSPECT II/PROSPECT ABSORB Investigational Plan 
FINAL AM04; 28 APR 2020 
 
 
 
 
LOCAL PRINCIPAL INVESTIGATOR SIGNATURE PAGE 
Title of the study: A multicenter natural history study using multimodality imaging in 
patients with unstable atherosclerotic lesions - PROSPECT II (Natural History 
Study), combined with a randomized, controlled, intervention study PROSPECT 
ABSORB (Randomized Trial) 
 
 
Local Principal Investigator: _________________________________________ 
 
Site: 
 
_______________________________ 
 
_______________________________ 
 
 
 
I, the undersigned, have read and understand the Investigational Plan specified above 
and agree on the contents. The Investigational Plan, the Clinical Study Agreement and 
additional information given serve as a basis for co-operation in this study. 
I agree to conduct the study according to this Investigational Plan and according to the 
ethical principles that have their origin in the Declaration of Helsinki and that are 
consistent with Good Clinical Practice, EN ISO 1455:2011(E) and applicable national 
laws and regulations. 
Signature and Date: 
 
____________________________________________________ 
 
____________________________________________________ 
Name (Print) 

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PROSPECT II/PROSPECT ABSORB Investigational Plan 
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SYNOPSIS 
Study identification: PROSPECT II (Natural History Study) and PROSPECT ABSORB 
(Randomized Trial) 
Title of study:  
A multicenter natural history study using multimodality imaging in patients with acute coronary 
syndromes - PROSPECT II (Natural History Study), combined with a randomized, controlled, 
intervention study PROSPECT ABSORB (Randomized Trial) 
Name of Investigational Products: 
TVC Imaging system (CE marked), InfraReDx Inc, Burlington, MA, USA 
Absorb Bioresorbable Vascular Scaffold (CE marked), Abbott Vascular, Santa Clara, CA, USA 
Study Chairmen  
David Erlinge, MD, PhD, Department of Cardiology, Lund University, Lund, Sweden 
Gregg W. Stone, MD, Columbia University, New York, NY, USA 
Coordinating Principal Investigators: 
PROSPECT II: David Erlinge, MD, PhD, Department of Cardiology, Lund University, Lund, Sweden 
PROSPECT ABSORB: Gregg W. Stone, MD, Columbia University, New York, NY, USA 
Coordinating Academic Research Organizations: 
Cardiovascular Research Foundation (CRF), New York, NY, USA 
Uppsala Clinical Research Center (UCR), Uppsala University Hospital, Uppsala, Sweden 
Sponsor: 
Uppsala Clinical Research Center (UCR), Uppsala University Hospital, Uppsala, Sweden 
Funding support: 
InfraReDx Inc, Burlington, MA, USA 
Abbott Vascular, Santa Clara, CA, USA 
The Medicines Company, Basel, Switzerland 
Study centers: 
Approximately 16 sites in Sweden, Denmark, and Norway. 
Planned study period: 
2014-2019 with registry follow-up for an additional 15 years (to 2034) 
Objectives:  
PROSPECT II (Natural History Study): To test the ability of two coronary artery imaging modalities 
(intravascular ultrasound [IVUS] and near infrared spectroscopy [NIRS]) to identify angiographically 
non-obstructive high-risk (vulnerable) plaques that are subsequently responsible for unanticipated 
coronary events.  
PROSPECT ABSORB (Randomized Trial): To determine whether the Absorb Bioresorbable Vascular 
Scaffold (BVS) can safely enlarge luminal dimensions as measured approximately 2 years after 
implantation in high-risk but angiographically non-obstructive lesions with site-determined IVUS 
plaque burden ≥65%. 
Methodology:  
PROSPECT II: Multicenter, prospective, natural history study of troponin positive patients with acute 
coronary syndromes (ACS) examined with angiography and intended for PCI for the initial culprit 
lesion(s). Prior to PCI all target lesions (those lesions for which PCI is planned) will be examined (if 
possible) by IVUS/NIRS. After successful PCI of all flow-limiting lesions determined angiographically 
and/or by FFR/iFR intended to be treated (termed “culprit lesions,” whether responsible for the original 
ACS or otherwise flow-limiting and requiring PCI for complete revascularization), intravascular 
ultrasound (IVUS), and intracoronary near infrared spectroscopy (NIRS) will be performed over a 6-10 
cm length in all three coronary arteries with a combined IVUS/NIRS catheter. Clinical and register 
follow-up will identify all new coronary events, the origin of which will be determined by follow-up 
angiography when clinically indicated. These lesions will be identified and compared to the baseline 
examination at a central angiographic and IVUS/NIRS core laboratory, and adjudicated to have arisen 
from either originally treated culprit lesions or untreated “non-culprit lesions.” This will allow 
determination of the baseline patient-related and lesion-related variables in culprit and non-culprit 
lesions that increase the risk for future unanticipated cardiovascular events. 

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PROSPECT ABSORB (Randomized Trial): Patients with angiographically non-obstructive lesions 
that are not intended to undergo PCI based on the current standard of care, and that are site-assessed 
by IVUS to have plaque burden of ≥65% (which has previously been shown in the first PROSPECT 
study to identify lesions at high risk of causing future coronary events despite their non-obstructive 
angiographic appearance) will be randomized (1:1) to treatment with ABSORB BVS + guideline 
directed medical therapy (GDMT) versus GDMT alone. All such randomized patients will undergo 
repeat angiography and IVUS/NIRS after 25 months of follow-up. 
Estimated number of subjects: 
Approximately 900 patients will be enrolled in the PROSPECT II natural history follow-up study. 
From these 900 patients the aim is to randomize ~300 patients with a (1:1) treatment allocation to BVS 
+ GDMT or GDMT alone in PROSPECT ABSORB. The enrolled patients who do not fulfill the 
criteria for PROSPECT ABSORB will be followed in PROSPECT II (~600 patients). 
 
Patient enrollment and procedure overview:  
PROSPECT II: Patients with a troponin positive ACS within the prior 4 weeks (STEMI >12 hours or 
NSTEMI) in whom coronary angiography is planned will be screened and asked to participate in the 
study. After informed consent has been obtained and prior to PCI, all target lesions (those lesions for 
which PCI is planned) will be examined (if possible) by IVUS/NIRS. If the patient is successfully 
treated with PCI of all intended culprit lesions without major procedural complication(s), all three 
coronary arteries will be examined with IVUS/NIRS. The IVUS results will be visible (unblinded) to 
the operator, but the NIRS data will be blinded. The patient will be considered formally enrolled in 
PROSPECT II only after PCI of all intended target culprit lesions has been successfully completed 
with no major complication(s), and after the study imaging catheter is passed out of the guide catheter 
into a coronary artery (n = approximately 900 patients). If a staged procedure is required to achieve 
revascularization of all intended lesions, the patient will not be enrolled until after the staged 
procedure has been performed without major procedural complication(s). Once enrolled, IVUS and 
NIRS will be performed over a 6-10 cm length in all three coronary arteries with a combined 
IVUS/NIRS catheter to assess both the treated culprit lesion(s) and long segments of the untreated 
coronary tree. Patient enrollment and 3-vessel IVUS and NIRS imaging may be performed either in 
the same procedure during which the culprit PCI lesion(s) are treated, or during a subsequent 
angiographic procedure as long as this occurs within 4 weeks of the initial ACS presentation, and after 
successful and uncomplicated treatment of all target lesions. If the imaging catheter passed into a 
coronary artery for imaging a non-culprit segment of the coronary tree and no non-culprit segment 
imaging data is obtained (e.g. the catheter fails and a second catheter is not used), the patient will be 
disenrolled (discontinued) from the study, and only be followed up for safety purposes for 30 days.  
 
PROSPECT ABSORB: Patients in whom one or more lesions are identified with (a) an 
angiographically visually estimated diameter stenosis of <70%; (b) a visually estimated reference 
vessel diameter (RVD) of 2.5 – 4.0 mm; (c) a visually estimated lesion length ≤50 mm; d) a site 
determined IVUS PB ≥65%; and (e) is located at least 10 mm from a previous stent and at least 10 mm 
of intervening segment between the previous stent and the non-culprit lesion does not have PB >50% 
will be enrolled in the PROSPECT ABSORB trial and randomized 1:1 to treatment with ABSORB 
BVS + GDMT versus GDMT alone (n = approximately 300 patients, 150 patients in each group). For 
patients with multiple qualifying lesions, a single lesion will be selected for randomization prior to 
assignment to BVS + GDMT versus GDMT alone.  
 
Inclusion and Exclusion Criteria: 
PROSPECT II (Natural History Study) All patients 
Clinical inclusion criteria (all must be present):  
1. Troponin positive ACS (STEMI >12 hours or NSTEMI) occurring within the prior 4 weeks of 
enrollment, with symptoms consistent with acute ischemia lasting >10 minutes, intended for 
angiography and PCI if appropriate.  
Clinical exclusion criteria (none must be present):  
1. Known estimated creatinine clearance <30 mL/min. 

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2. Cardiogenic shock, decompensated hypotension, or heart failure requiring intubation, 
inotropes, intravenous diuretics, or a hemodynamic support device. 
3. Patient has a known hypersensitivity, allergy, or contraindication to any of the following: 
Aspirin, both heparin and bivalirudin, all 3 of clopidogrel, prasugrel, and ticagrelor, or to 
contrast that cannot be adequately pre-medicated. 
4. Refractory ventricular arrhythmias (eg, ventricular tachycardia or fibrillation) requiring either 
intravenous pharmacologic treatment or defibrillation during the index PCI procedure.  
5. Persistent acute conduction system disease requiring temporary pacemaker insertion during the 
index PCI procedure. 
6. Prior CABG at any time or planned CABG. 
7. Patient has any medical illness (eg, cancer or severe congestive heart failure) or recent history 
of substance abuse that may cause non-compliance with the protocol (including follow-up 
angiography if enrolled in PROSPECT ABSORB), confound the data interpretation or is 
associated with a life expectancy less than 3 years. 
8. Patient is currently enrolled in another investigational use device or drug study that has not 
reached its primary endpoint. If the patient is enrolled in another study that is not 
investigational, required visits for that trial must not interfere with the conduct of this study. 
9. Prior participation in this study. 
Angiographic inclusion criteria (all must be present):  
1. Patient must have 1-vessel, 2-vessel, or 3-vessel disease in native coronary arteries requiring 
PCI.  
Note: Culprit lesions (those responsible for the ACS or which otherwise require PCI) may 
be either de novo, restenotic, or due to stent thrombosis.  
2. Successful PCI without major complications must be performed in all intended culprit lesions, 
including the lesion(s) responsible for the ACS, and any other angiographically evident flow-
limiting lesions that by standard of care require treatment. This may be accomplished either 
during a single procedure or after a staged procedure, but in the case of staging the patient may 
not be enrolled until after all stages are successfully completed without major complications, 
and this must occur within 4 weeks of initial ACS presentation.  
Note: At operator discretion FFR, iFR, or other cath lab techniques to assess physiologic 
lesion significance may be used to guide the decision whether to intervene on borderline 
lesions, but IVUS and NIRS should not be used for this purpose. 
Angiographic exclusion criteria (none must be present):  
1. PCI is required of the left main coronary artery or a left main stenosis is present with a visually 
estimated angiographic DS of >30%. 
2. Angiographic evidence of severe calcification and/or marked tortuosity of the target (culprit) 
or a non-culprit vessel is present that would preclude the feasibility of safe imaging of at least 
the proximal 6 cm of all vessels. 
3. The presence of a chronic total occlusion of a major epicardial coronary vessel that is not 
successfully recanalized during the PCI procedure, and thus would preclude intravascular 
imaging.  
Note: A side branch of a major vessel (eg, a diagonal branch) may be occluded as long as the 
major epicardial vessel (eg, the left anterior descending artery) is patent and can be imaged. 
 
PROSPECT ABSORB (Randomized Trial):  
Angiographic inclusion criteria (all must be present):  

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After PCI of all intended target culprit lesions, and following successful and uncomplicated imaging 
of at least one, but preferably all 3 coronary vessels (culprit and non-culprit) in the PROSPECT II 
natural history phase of the study, the patient is eligible for randomization in the PROSPECT 
ABSORB Trial if one or more eligible lesions are identified which meet all of the following 
angiographic criteria: 
1. The lesion is a de novo lesion (may be located in either the target or non-target vessel) 
2. The lesion has an angiographic diameter stenosis <70%, and is not intended for 
revascularization based on angiographic criteria and FFR/iFR.  
Note: FFR/iFR should be performed on all noncritical lesions of >40% visually estimated 
angiographic stenosis that are candidates for the PROSPECT ABSORB substudy. 
3. The lesion has a site-determined IVUS plaque burden in at least one frame ≥65%.  
Note: Such a lesion may or may not be angiographically evident, i.e., the visually 
estimated angiographic diameter stenosis may range from 0% to <70%. 
4. The reference vessel diameter of an eligible lesion is ≥2.5 mm to ≤4.0 mm (visually estimated) 
capable of being treated with a 2.5 mm, 3.0 mm, or 3.5 mm diameter BVS. 
5. The lesion length of an eligible lesion is ≤50 mm (visually estimated), capable of being treated 
by no more than two BVS (maximum length of each BVS 28 mm), allowing for 2 mm BVS 
overlap and 2 mm of “normal” reference segment treatment at each edge. 
6. The lesion must be at least 10 mm from a previously implanted stent/scaffold and an 
intervening 10 mm segment between the previous stent and the non-culprit lesion must not 
have plaque burden (PB) >50% 
7. A bifurcation lesion may be enrolled only if the side branch is (a) ≤2.5 mm in reference vessel 
diameter, AND (b) has either no lesion requiring treatment, or atherosclerotic disease limited 
to within 5 mm of its origin from the parent vessel such that the operator believes that the side 
branch can be successfully treated with balloon angioplasty only (without a stent). If a stent 
subsequently becomes necessary, only a metallic drug-eluting stent (DES; Xience [Abbott 
Vascular, Santa Clara, CA] strongly recommended) may be used to treat the side branch with 
a T-stent technique. 
8. Randomization must occur immediately after the 3-vessel imaging run in the PROSPECT II 
protocol. If the patient randomizes to BVS, BVS placement must be performed immediately 
after randomization. 
Note: If 2 or more lesions meeting eligibility criteria are present, only one may be 
randomized. Priority should be given to an eligible lesion not in a culprit vessel. In 
general, the lesion most proximal in the coronary tree and supplying the greatest 
amount of myocardium should be randomized. The CASS segment of this lesion will be 
identified prior to randomization allocation. 
 
Angiographic exclusion criteria (none must be present):  
1. The randomized lesion cannot be within 10 mm of a lesion previously treated by PCI. 
2. The randomized lesion may not be in the left main coronary artery.  
3. The randomized lesion may not be an ostial LAD or ostial LCX lesion (defined as within 3 mm 
of the left main coronary artery). 
4. The randomized lesion may not be an ostial RCA lesion (defined as within 3 mm of the aorto-
ostium). 
5. Angiographic evidence of severe calcification and/or marked tortuosity of the target vessel 
and/or lesion intended for randomization is present that would make it unlikely that the BVS 
could be advanced to or across the lesion or be adequately expanded. 
 
 

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Study follow-up:  
PROSPECT II (Natural History Study) 
 
Clinical follow-up: 
Patients will be followed in the Scandinavian quality registers (eg, SWEDEHEART). Patients will 
undergo follow-up through register data collection and by calls by study coordinators at 1 month (30 
days), 6 months (180 days), 12 months, and 24 months, assessing MACE and safety parameters. MACE 
will be followed in all patients throughout the whole study period until last patient has been followed for 
24 months. Patients will then undergo follow-up through register data collection at yearly intervals 
starting at 3 years and through 15 years. Additional phone follow-up to patients may also be performed.  
 
PROSPECT ABSORB (Randomized Trial) 
Clinical follow-up: 
Patients will be followed in the Scandinavian quality registers (eg, SWEDEHEART). Patients will 
undergo follow-up through register data collection and by calls by study coordinators at 1 month (30 
days), 6 months (180 days), 12 months, and 24 months. MACE will be followed in all patients throughout 
the whole study period until last patient has been followed for 24 months. Patients will then undergo 
follow-up through register data collection at yearly intervals starting at 3 years and through 15 years, 
with additional phone follow-up subject to Executive Committee approval. 
Angiographic follow-up: 
All patients randomized in PROSPECT-ABSORB will undergo routine angiographic and 3-vessel 
IVUS/NIRS follow-up at 25 months; ie, 1 month after the 24 month telephone follow-up. The 25 month 
angiogram may be performed within a window of between 24.5 months and 28 months after enrollment. 
 
Note: 25-month angiographic follow-up will not be required in PROSPECT-ABSORB 
randomized patients who either a) have had scaffold thrombosis or in-scaffold restenosis 
(DS>50% as determined by the angiographic core laboratory) at any time point prior to 
25 months, OR b) have had a repeat angiogram ≥12 months after enrollment and in 
whom IVUS/NIRS of the randomized target lesion was performed.  
 
Primary and Major Secondary Endpoints (Outcome Variables): 
PROSPECT II (Natural History Study) 
Primary endpoint: Patient-level rate of non-culprit lesion-related major adverse cardiac events (NC-
MACE) at the time when the last patient enrolled reaches at least 24-month follow-up defined as an event 
arising from an originally untreated NCL consisting of the composite of 1) cardiac death, 2) myocardial 
infarction, 3) unstable angina, or 4) progressive angina or anginal equivalent symptoms either 4a) 
requiring revascularization by CABG or PCI, and/or 4b) with ACL-confirmed rapid lesion progression. 
Major secondary endpoint: Lesion level rate of NC-MACE at the time when the last patient enrolled 
reaches at least 24-month follow-up.  
Primary safety endpoint: major complications of IVUS/NIRS imaging, defined as imaging-related 
death, or vessel dissection/perforation/spasm or other complication requiring percutaneous or surgical 
treatment (including pericardiocentesis), as adjudicated by an angiographic core lab. 
PROSPECT ABSORB (Randomized Trial) 
Primary efficacy endpoint: The minimum luminal area (MLA) at the randomized non-culprit lesion site 
in patients treated with the ABSORB BVS + GDMT compared to GDMT only measured at 25 months. 

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Primary safety endpoint: Target lesion failure (cardiac death, target-vessel myocardial infarction, or 
ischemia-driven target lesion revascularization) up to 24 months (prior to routine imaging follow-up). 
 
Statistical methods: 
PROSPECT II (Natural History Study) 
Baseline demographic, clinical, angiographic, grayscale IVUS, NIRS, and outcome variables will be 
summarized for lesions with and without high-risk (vulnerable) plaque defined by both NIRS and IVUS 
as well as for the overall population. 
 
Pre-specified criteria for vulnerable plaque: 
1) For NIRS the pre-specified cutoff is defined as the highest quartile (25%) of the maximum lipid core 
burden index over a 4-mm length (maxLCBI4mm). As a secondary sensitivity analysis, a cutoff of ≥400 
will be used. 
 
2) For IVUS, plaque burden of ≥70% and/or MLA ≤4.0 mm2 will be used as pre-specified cutoff values 
to identify high-risk (vulnerable) plaque, both features having been identified in the first PROSPECT 
natural history study as independent predictors of future MACE. 
 
These analyses will include all untreated non-culprit lesions from the register (n=~600 patients), the 
GDMT only arm from PROSPECT ABSORB (n=~150 patients), and the untreated non-culprit lesions 
from the BVS arm of PROSPECT ABSORB (n=~150 patients). Subject-level analyses will also be 
presented for patients with versus without lesions containing high-risk features (including core lab 
assessed PB ≥70%, and/or MLA ≤4.0 mm2, and/or maxLCBI4mm greater than or equal to the upper 
quartile cutoff). Exploratory analyses at the lesion and subject level may be conducted to identify other 
high-risk features of vulnerable plaque and patients. 
 
PROSPECT ABSORB (Randomized Trial) 
Baseline demographic, clinical, angiographic, grayscale IVUS, NIRS, and outcome variables (including 
follow-up imaging data) for the randomized cohort (~300 patients) will be summarized for ABSORB 
BVS + GDMT versus GDMT alone as well as the overall population. 
 
Analyses will be conducted for the Safety Analysis Set (SA) and the Full Analysis Set (FAS) for patients 
in PROSPECT II, and for the Safety Analysis Set (SAA), Full Analysis Set (FASA) and the Per Protocol 
Set (PPA) for patients in the PROSPECT ABSORB randomized substudy. 
 
Note: The Intravascular Imaging (IVI) core lab analysis in the Registry (PROSPECT II) 
will define high-risk plaque based on PB ≥70%. At the site level, the cutoff for inclusion 
in PROSPECT ABSORB will be 65% to account for an observed tendency for sites to 
under-estimate plaque burden during acute treatment of ACS patients. 
 
 

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PROSPECT II/PROSPECT ABSORB Investigational Plan 
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TABLE OF CONTENTS 
PAGE 
PROTOCOL SIGNATURE PAGE 
3 
PROTOCOL SIGNATURE PAGE (CONT.) 
4 
LOCAL PRINCIPAL INVESTIGATOR SIGNATURE PAGE 
5 
1 
BACKGROUND INFORMATION AND RATIONALE 
16 
2 
STUDY DESIGN 
18 
3 
STUDY TIME TABLE 
18 
4 
STUDY OBJECTIVES 
19 
4.1 
PRIMARY OBJECTIVES 
19 
4.2  
SECONDARY OBJECTIVES 
19 
5 
ENDPOINTS (OUTCOME VARIABLES) 
20 
5.1 
PRIMARY ENDPOINTS 
20 
5.2 
SECONDARY ENDPOINTS 
20 
5.3 
SAFETY ENDPOINTS 
21 
5.4 
TIMEPOINTS 
22 
6 
SELECTION AND WITHDRAWAL OF SUBJECTS 
22 
6.1 
SUBJECT INCLUSION AND EXCLUSION CRITERIA 
22 
6.1.1 
PROSPECT II (all patients - Natural History Study) 
22 
6.1.2 
PROSPECT ABSORB (randomized trial) 
24 
6.2 
WITHDRAWAL OF SUBJECTS 
25 
7 
DESCRIPTION OF DEVICES 
26 
7.1 
TVC IMAGING SYSTEM 
26 
7.2 
ABSORB BIORESORBABLE VASCULAR SCAFFOLD 
26 
8 
RISK ASSESSMENT 
26 
8.1 
TVC IMAGING SYSTEM 
26 
8.2 
ABSORB BIORESORBABLE VASCULAR SCAFFOLD 
26 
9 
STUDY PROCEDURES (SEE ALSO APPENDIX II: TABLE OF 
STUDY PROCEDURES) 
27 
9.1 
BASELINE ANGIOGRAPHY 
30 

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9.2 
PROCEDURE FOR ENROLLMENT 
30 
9.3 
PERCUTANEOUS CORONARY INTERVENTION (PCI) 
30 
9.4 
IMAGING FOLLOWING PERCUTANEOUS INTERVENTION 
31 
9.5 
CONCOMITANT MEDICATIONS 
32 
9.6 
CLINICAL AND LABORATORY PROCEDURES 
32 
9.6.1 
Laboratory Assessments 
32 
9.6.2 
Biomarker/Genetics Evaluation and Biobank 
32 
9.6.3 
Post-procedure and Discharge 
33 
9.6.4 
One month (30-day) Follow-up 
33 
9.6.5 
6 months (180 days) Follow-up 
33 
9.6.6 
12-months (1-year) Follow-up 
33 
9.6.7 
24-months (2-years) Follow-up 
33 
9.6.8 
Sweep Follow-Up 
34 
9.6.9 
25 months Imaging Follow up - PROSPECT ABSORB (Randomized 
trial) 
34 
9.6.10 
Annual Clinical Follow-up at 3 years through 15 years 
34 
9.6.11 
Event-driven imaging in PROSPECT II (Natural History Study) 
35 
10 
ADVERSE EVENTS 
35 
10.1 
ADVERSE DEVICE EFFECT (ADE) 
35 
10.2 
SERIOUS ADVERSE EVENT (SAE) 
35 
10.3 
SERIOUS ADVERSE DEVICE EFFECT (SADE) 
35 
10.4 
UNANTICIPATED SERIOUS ADVERSE DEVICE EFFECT (USADE) 
36 
10.5 
RECORDING AND REPORTING OF NON-SERIOUS AND SERIOUS 
ADVERSE EVENTS AND ADVERSE DEVICE EFFECTS. 
36 
10.6 
SAFETY MONITORING 
37 
11 
ADJUDICATION OF EVENTS 
37 
12 
DATA HANDLING AND RECORD KEEPING 
38 
12.1 
QUALITY REGISTRY DATA 
38 
12.2 
MEDICAL RECORD/SOURCE DOCUMENTATION 
38 
12.3 
RECORD RETENTION 
38 
13 
SELECTION OF CLINICAL SITES AND INVESTIGATORS 
39 
13.1 
SITE TRAINING 
39 
13.2 
INVESTIGATOR RESPONSIBILITIES 
40 
14 
IRB/EC APPROVAL OF THE INVESTIGATIONAL PLAN AND 
INFORMED CONSENT 
40 
14.1 
PATIENT INFORMED CONSENT 
40 
14.2  
INVESTIGATIONAL PLAN AMENDMENTS 
40 

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14.3 
INVESTIGATIONAL PLAN DEVIATIONS 
41 
15 
DATA MANAGEMENT 
41 
15.1 
DATA VALIDATION AND CODING 
41 
15.2 
QUALITY CONTROL AND CLEAN FILE 
41 
16 
STATISTICAL ANALYSIS 
42 
16.1  
DESIGN OF THE STUDY 
42 
16.1.1  
HYPOTHESES TESTED 
42 
16.2  
GENERAL METHODS 
42 
16.3  
ANALYSIS POPULATIONS 
43 
16.3.1  
PROSPECT II (NATURAL HISTORY STUDY) 
43 
16.3.2  
PROSPECT ABSORB (RANDOMIZED TRIAL) 
44 
16.4  
RANDOMIZATION 
44 
16.5 
DETERMINATION OF SAMPLE SIZE 
44 
16.5.1 
POWER ANALYSIS AND SAMPLE SIZE ESTIMATE FOR PROSPECT II 
(NATURAL HISTORY STUDY) 
44 
16.5.2 
PATIENT-LEVEL ANALYSIS 
45 
16.5.3  
LESION-LEVEL ANALYSIS 
46 
16.5.4 
POWER ANALYSIS AND SAMPLE SIZE ESTIMATE FOR PROSPECT-
ABSORB (RANDOMIZED TRIAL) 
48 
16.6  
STATISTICAL ANALYSIS FOR PROSPECT II (NATURAL HISTORY STUDY)
 
48 
16.6.1  
 PRIMARY ENDPOINT ANALYSIS 
48 
16.6.2  
 MAJOR SECONDARY ENDPOINT ANALYSIS 
49 
16.6.3 
SENSITIVITY ANALYSIS 
49 
16.6.4 
ADDITIONAL SECONDARY ANALYSES 
49 
16.6.5 
SAFETY ANALYSIS 
50 
16.6.7 
ANALYSIS WINDOW 
50 
16.6.8 
HANDLING OF DROPOUTS AND MISSING DATA 
50 
16.7 
STATISTICAL ANALYSIS FOR PROSPECT ABSORB (RANDOMIZED 
TRIAL) 
50 
16.7.1  
 PRIMARY EFFICACY ENDPOINT ANALYSIS 
51 
16.7.2  
SENSITIVITY ANALYSIS 
51 
16.7.3  
 SECONDARY EFFICACY ENDPOINTS ANALYSIS 
51 
16.7.4  
SAFETY ENDPOINT ANALYSIS 
51 

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16.7.5 
ANALYSIS WINDOW 
52 
16.7.6 
HANDLING OF DROPOUTS AND MISSING DATA 
52 
16.8 
SUBGROUP ANALYSIS 
53 
16.9  
DEVIATIONS FROM PROTOCOL ANALYSIS PLAN 
53 
16.10  
INTERIM ANALYSIS AND STOPPING RULES 
53 
17 
MONITORING PLAN 
54 
18 
CRITERIA FOR TERMINATION OF THE STUDY 
54 
19 
QUALITY ASSURANCE 
54 
20 
CONFIDENTIALITY 
55 
21 
COMPLIANCE TO STANDARDS AND REGULATIONS 
55 
22 
INSURANCE 
55 
23 
PUBLICATION POLICY 
55 
24 
COMMITTEES 
56 
24.1 
DATA SAFETY MONITORING BOARD (DSMB) 
56 
24.2 
CLINICAL ENDPOINT CLASSIFICATION (CEC) 
56 
24.3 
OPERATIONS COMMITTEE (OC) 
56 
24.4 
STEERING COMMITTEE (SC) 
56 
24.5 
EXECUTIVE COMMITTEE (EC) 
57 
25 
STUDY ADMINISTRATIVE STRUCTURE 
57 
26 
REFERENCES 
58 
27  
LIST OF APPENDICES 
59 
APPENDIX I  ACRONYMS AND ABBREVIATIONS 
60 
APPENDIX II STUDY FLOW CHART/SCHEDULE OF PROCEDURE 
62 
APPENDIX III 
ANGIOGRAPHY GUIDELINES 
65 
APPENDIX IV  IVUS/NIRS GUIDELINES 
66 
APPENDIX V:  ENDPOINT DEFINITIONS (COPIED FROM CEC   CHARTER) 
68 
 
 
 
 

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1 
BACKGROUND INFORMATION AND RATIONALE 
Ischemic heart disease is the leading cause of death in the world, causing 12.2% of all 
worldwide deaths, a total of 7.2 million deaths each year (1). In high income countries, 
16.3% of all deaths are caused by ischemic heart disease. More than 3 million people 
worldwide have ST-segment elevation myocardial infarctions (STEMIs) and 4 million 
have non–ST-segment elevation myocardial infarctions (NSTEMIs) each year. In total, 
7 million acute coronary syndromes (ACS) occur each year (2). 
 
Cholesterol accumulation in the vessel underlies the development of atherosclerosis, 
the underlying substrate for coronary artery disease. Cholesterol is also one of the most 
important factors in development of ACS, demonstrated both in large genetic studies 
and in intervention studies in which cholesterol-lowering therapies reduced the 
incidence of ACS. In autopsy studies, the most common cause of ACS is rupture and 
subsequent thrombosis of a thin-cap fibroatheroma (TCFA) in the coronary tree. TCFA 
is a metabolically active lesion consisting of an inflamed fibrous cap overlying a 
necrotic core consisting of cholesterol, cholesterol esters, and necrotic cellular debris 
(3). 
 
The challenge is to be able to identify high-risk (vulnerable)* plaques in living subjects 
before they cause an ACS and to develop a pre-emptive strategy to stabilize the plaque, 
protect against ACS, and save lives (4). Identification and stabilization of high-risk 
plaque may reduce the high incidence of morbidity and mortality caused by coronary 
artery disease. 
 
The PROSPECT study was a multimodality imaging natural history in 697 patients with 
ACS undergoing successful PCI. After successful PCI of target culprit lesions, 
intravascular ultrasound (IVUS) with radiofrequency IVUS (virtual histology – VH-
IVUS) was performed in the proximal 6-8 cm of all 3 coronary arteries, after which 
patients were followed for a median of 3.4 years (5). Plaque burden (PB) ≥70% in 
untreated non-culprit, non-stenotic lesions was the most important plaque characteristic 
associated with future coronary events arising from that lesion, with an approximately 
5× adjusted risk by multivariable analysis during the 3.4-year median follow-up study 
period. The non-culprit lesion (NCL)-related event rate in lesions with a PB ≥70% was 
~10% over 3 years, despite high compliance with guideline directed medical therapy 
(GDMT). The importance of PB >70% as a predictor of coronary events has been 
confirmed in the smaller VIVA (8× increased risk) and PREDICTION trials (6,7). In 
PROSPECT, TCFA lesion morphology, as defined by VH-IVUS, was the second most 
important factor predicting NCL-related MACE, with an approximately 3.5-fold 
adjusted risk. Of note, approximately 23% of lesions in PROSPECT were defined as 
TCFAs by VH-IVUS, similar to the rate seen in pathologic studies.  
 
Although VH-IVUS was capable of identifying high-risk NCLs in PROSPECT, 
interpretation of these images is difficult (requiring a core laboratory), and it is difficult 
with VH-IVUS to distinguish calcium from necrotic core, possibly explaining why the 
adjusted hazard ratio of a VH-TCFA was “only” 3.5. Intravascular imaging with near-
infrared spectroscopy (NIRS) is a CE-marked technology developed for the explicit 
                                                 
*The terms vulnerable and high-risk are used interchangeably throughout this protocol 

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purpose of detecting lipids, which are present in most vulnerable plaques. NIRS has 
been validated in vitro to be highly specific for lipid rich plaque (LRP) detection (8). 
NIRS has detected LRP in ~85% of lesions responsible for ACS cases (9). More 
recently, an IVUS/NIRS study evaluating culprit lesions in 20 patients with STEMI 
found that almost all STEMI culprit lesions are characterized by a large LRP 
concentrated at the culprit site (9). A NIRS signature of STEMI culprit lesions, defined 
by a maximum lipid core burden index (LCBI) over a 4-mm length of >400, was found 
to be both a sensitive and specific marker for identification of the STEMI culprit 
segments. The maxLCBI >400 signature of a segment causing STEMI has been 
confirmed in a validation study of 85 STEMI patients (10). These NIRS studies are 
consistent with post-mortem observations implicating rupture of LRP as the cause of 
acute myocardial infarction and highlight the role of LRP in culprit lesions across the 
spectrum of ACS; however, this signature of a vulnerable plaque causing ACS needs 
to be confirmed in a prospective natural history study. 
 
The Absorb bioresorbable vascular scaffold (BVS; Abbott Vascular, Santa Clara, CA) 
is a CE-marked, fully bioresorbable, everolimus-eluting, stent-like device 
manufactured of polylactic acid (PLA). Preliminary experience with this device in >500 
patients with lesions more severe than these NCLs in PROSPECT has demonstrated a 
low rate of 1-year MACE events (<3%), with a low rate of restenosis. Within 12 months 
of implantation of the Absorb BVS, vasoreactivity has started to return to the vessel. 
Within 24 months of implantation of the Absorb BVS, only small remnants of the 
device are visible by sensitive techniques such as optical coherence tomography (OCT). 
By 3 years, the BVS has completely resorbed, leaving behind a vessel with its native 
architecture intact. Use of the Absorb BVS to passivate vulnerable plaques is 
particularly attractive given the potential for this device to be devoid from long-term 
adverse effects 
such as 
very 
late scaffold 
thrombosis, 
restenosis, 
and 
neoatherosclerosis. In addition, Absorb BVS implantation may result in a new fibrous 
cap forming over prior TCFAs (11), and possibly lead to a reduction in plaque burden 
over time. Treatment of vulnerable plaques with Absorb (especially those with large 
plaque burden) is thus a promising therapy to prevent death, MI, and ACS in patients 
at high risk for future events, such as those already presenting with ACS or with 
diabetes mellitus. 
 
In conclusion, the pathophysiology of plaque rupture and identification of plaques at 
risk for rupture (vulnerable plaque) is complex and incompletely understood. 
Pathologic studies have shown that patients presenting with ACS (typically due to 
thrombosis of a LRP) are likely to have one or more quiescent but high-risk LRPs 
elsewhere in the coronary tree. In patients with ACS, these plaques tend to progress, 
over a 12-month period, with an increasing amount of necrotic core and decreasing 
minimum lumen area (12). 
 
The present study has two components, an overall prospective observational study 
using multimodality imaging (PROSPECT II) that will examine the natural history of 
patients with unstable atherosclerotic coronary artery disease with the specific goal to 
establish the utility of low-risk intracoronary imaging modalities, IVUS and NIRS, to 
identify plaques prone to future rupture and clinical events. The randomized 
PROSPECT ABSORB substudy will examine whether treatment of vulnerable plaques 

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with the Absorb BVS plus GDMT safely increases the MLA at 24 months compared 
with GDMT alone. 
 
The cutoff for inclusion in PROSPECT ABSORB will be a site-determined PB ≥65% 
(rather than the 70% cutoff identified in the original PROSPECT analysis (Stone et al., 
NEJM, 2011(5)) to account for an observed tendency for sites to underestimate plaque 
burden during acute treatment of ACS patients. Nonetheless, in PROSPECT, a core 
laboratory determined PB ≥65% was also associated with a high (7.0%) rate of MACE 
during 3-year follow-up, a rate which may be reduced with a bioresorbable scaffold. 
 
2 
STUDY DESIGN 
The current protocol is a 2-component integrated clinical study consisting of the main 
PROSPECT II study (Natural History Study) and the PROSPECT ABSORB substudy 
(randomized trial).  
PROSPECT II is a multicenter, prospective, natural history study of ACS patients 
undergoing standard of care angiography and PCI for treatment of the initial culprit 
lesion(s). Participants will be examined with IVUS and NIRS in all three coronary 
arteries. Clinical follow-up for up to 15 years with a minimum of 24 months for any 
one patient will identify new coronary events. Angiography as per standard of care is 
expected to be performed in >85% of patients with events during follow-up. The 
coronary segment(s) responsible for these events will be identified by angiography and 
compared to the baseline examination by the core lab. The primary endpoint will be 
assessed at the 24-month follow-up time period. 
The substudy PROSPECT ABSORB is a multicenter, prospective, randomized, open-
label study. Patients enrolled in PROSPECT II in whom one or more angiographically 
non-obstructive lesions are identified by IVUS with a high risk of causing future 
coronary events (site-determined plaque burden ≥65%) will be randomized (1:1) to 
treatment with Absorb BVS + GDMT or GDMT alone. Patients in PROSPECT 
ABSORB will undergo repeat angiography and IVUS/NIRS imaging after 25 months 
and clinical follow-up for up to 15 years. The primary endpoint will be assessed at the 
25-month follow-up time period. 
The PROSPECT II study is expected to screen 1500 patients in order to enroll 
approximately 900 patients. From these 900 patients the aim is to randomize ~300 
patients for the PROSPECT ABSORB. The included patients that do not fulfill the 
criteria for PROSPECT ABSORB will be followed in PROSPECT II (~600 patients). 
The patients will be enrolled from approximately 16 sites in Sweden, Denmark, and 
Norway. 
 
3 
STUDY TIME TABLE  
Subject enrollment is planned to start in Q2 2014 aiming for last patient enrolled in Q4 
2017. The primary 24-month follow-up will continue until Q4 2019 or beyond, 

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depending on the timing of the last patient enrolled. Patients will then be followed for 
up to an additional 15 years, through approximately Q4 2034. 
 
4 
STUDY OBJECTIVES 
4.1 
PRIMARY OBJECTIVES 
PROSPECT II (Natural History Study) 
To test the ability of two coronary artery imaging modalities, IVUS and NIRS, to 
identify angiographically non-obstructive vulnerable plaques that are subsequently 
responsible for future unanticipated coronary events. 
PROSPECT ABSORB (Randomized Trial) Substudy 
To determine whether the Absorb Bioresorbable Vascular Scaffold (BVS) can safely 
enlarge luminal dimensions as measured 25 months after implantation in high-risk, 
angiographically non-obstructive lesions with site-determined IVUS plaque burden 
≥65% (roughly equivalent to core lab assessed lesions with PB 70%). 
 
4.2  
SECONDARY OBJECTIVES 
PROSPECT II (Natural History Study) 
1. To determine in patients with successfully treated ACS the proportion of MACE 
during follow-up that are attributable to recurrent disease at the originally 
treated culprit lesion site(s) versus those arising from previously untreated non-
culprit lesion (NCL) sites. 
2. To examine the association of maxLCBI4mm (upper quartile of all measured 
values) in untreated NCLs as a signature for high-risk plaques causing future 
ACS. 
3. To examine the association of lipid core burden index (LCBI) and future NCL-
related, vessel-related, and patient-related MACE. 
4. To examine the association of maxLCBI4mm and LCBI for culprit lesion peri-
PCI MACE.  
5. To examine the association of maxLCBI4mm and LCBI at the index culprit site 
with future restenosis and stent thrombosis. 
6. To assess the safety and procedural success of 3-vessel IVUS/NIRS imaging 
during PCI. 
7. To identify serologic biomarkers that correlate with findings on angiographic, 
IVUS, and NIRS imaging and subsequent coronary events. 
8. To identify genetic markers that correlate with findings on angiographic, 
IVUS, and NIRS imaging and subsequent coronary events. 
 
The last two objectives will be analyzed within two separate substudies, and their 
respective analyses will be detailed in separate SAPs, as appropriate. 
 
 
 
 

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PROSPECT ABSORB (Randomized Trial) 
 
1.  To determine whether implantation of the Absorb BVS in angiographically 
non-obstructive lesions with high plaque burden plus GDMT compared to 
GDMT alone:  
 
a. Is safe, with a low rate of periprocedural complications. 
b. Results in significant enlargement of luminal dimensions at 
approximately 2-year follow-up. 
c. Results in significant plaque regression at approximately 2-year 
follow-up.  
d. Results in the conversion of a high-risk plaque phenotype (large lipid 
core plaque) to a low-risk phenotype (small or absent lipid core 
plaque) at approximately 2-year follow-up. 
e. Results in a low 2-year absolute rate of NCL MACE, with fewer 
NCL MACE than in those patients treated with GDMT only. 
Although this trial is under-powered for clinical events, the results 
will serve to inform a large pivotal randomized trial. 
 
5 
ENDPOINTS (OUTCOME VARIABLES) 
5.1 
PRIMARY ENDPOINTS 
PROSPECT II (Natural History Study) 
Patient-level rate of NCL-related MACE (NC-MACE) evaluated at the longest 
follow-up available, assessed at the time when the last patient enrolled reaches at least 
24 months. NC-MACE is defined as an event arising from an originally untreated NCL 
consisting of the composite of 1) cardiac death, 2) MI,  3) unstable angina, or 4) 
progressive angina or anginal equivalent symptoms either 4a) requiring 
revascularization by CABG or PCI, and/or 4b) with ACL-confirmed rapid lesion 
progression. 
PROSPECT ABSORB (Randomized Trial) 
The MLA at the randomized NCL site in patients treated with Absorb BVS + 
GDMT compared to GDMT only as measured at 25 months. 
5.2 
SECONDARY ENDPOINTS 
PROSPECT II (Natural History Study) 
Major secondary endpoint: Lesion level rate of NC-MACE in all patients 
throughout the whole study period until last patient has been followed for 24 months. 
Secondary imaging endpoints: Angiographic diameter stenosis and other 
qualitative and quantitative angiographic measures (eg, stent thrombosis, plaque 
rupture), as well as (for patients in whom it is available) plaque burden/regression and 
remodeling, external elastic membrane (EEM), maxLCBI4mm, LCBI, and other IVUS 

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and NIRS endpoints, during follow-up in culprit lesions and NCLs (and their change 
from baseline to follow-up).  
Other secondary clinical endpoints: Total MACE, culprit lesion-related MACE, 
NC-MACE, indeterminate MACE and their components at the patient level, vessel 
level ,and lesion level, measured at 48 hours post-procedure, in-hospital, at 1 month 
(30 days), 6 months, 12 months, 24 months, and yearly through 15 years.  
PROSPECT ABSORB (Randomized Trial) 
Secondary imaging endpoints: Angiographic diameter stenosis, plaque 
burden/regression and remodeling, EEM, maxLCBI4mm, LCBI, NIRS plaque 
composition and cap thickness, and other angiographic, IVUS, and NIRS measures at 
25 months in culprit lesions, NCLs, and the randomized lesions (and their change from 
baseline to 25-month follow-up).  
Secondary clinical endpoints: Total MACE, culprit lesion-related MACE, NC-
MACE, randomized lesion-related MACE, indeterminate MACE and their 
components at the patient level, vessel level, and lesion level measured at 48 hours 
post-procedure, in-hospital, at 1 month (30 days), 6 months (180 days), 12 months, 24 
months, and yearly through 15 years.  
5.3 
SAFETY ENDPOINTS  
PROSPECT II (Natural History Study) 
Primary Safety Endpoint: Major complications of IVUS/NIRS imaging defined as 
imaging-related death or vessel dissection/perforation/spasm or other complication 
requiring percutaneous or surgical treatment (including pericardiocentesis), as 
adjudicated by an angiographic core lab. 
Other Safety endpoints: 
 In-hospital (index culprit-lesion PCI-related) MACE 
 
PROSPECT ABSORB (Randomized Trial) 
The primary safety endpoint is target lesion failure (TLF) (cardiac death, target vessel 
myocardial infarction, or ischemia-driven target lesion revascularization) up to 24 months 
(prior to routine imaging follow-up).  
 
Other Safety endpoints: TLF measured at 1 month, 6 months, 12 months, 24 
months, and possibly yearly through 15 years 
 Periprocedural (Absorb BVS PCI procedure) MACE 
 
Scaffold thrombosis (definite or probable per ARC definition) as per CEC and 
Core Lab adjudication measured at 1 month, 6 months, 12 months, 24 months, 
and possibly yearly through 15 years 
o Temporal classification: 
 All 
 Acute (0 to 24 hours after stent implantation) 
 Subacute (>24 hours to 30 days after stent implantation) 
 Late (>30 days to 1 year after stent implantation) 

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 Very late (>1 year after stent implantation) 
 Measurements of Interest 
As detailed in the statistics section as well as the statistical analysis plan, multiple 
measurements will be made and used in the analyses and assessed for their prognostic 
value. These include but are not limited to:  
1. Max LCBI-4mm (upper quartile and ≥400) and LCBI in 10 mm and 30 
mm segments and coronary arteries not treated with PCI at inclusion. 
2. Total LCBI in all coronary arteries  
3. Max LCBI-4mm (upper quartile and ≥400) and LCBI in segments 
treated with PCI at inclusion. 
4. Plaque burden ≥70%, as well as ≥65%, in coronary segments not 
treated with PCI at inclusion. 
5. MLA <4 mm2 in coronary segments not treated with PCI at inclusion. 
6. EEM in coronary segments not treated with PCI at inclusion. 
7. Remodeling in coronary segments not treated with PCI at inclusion. 
8. IVUS and NIRS measures of fibrous cap thickness 
9. Disease angle defined as an angle with plaque thickness>0.5mm and 
disease arc≥330 degree 
10. Angiographic diameter stenosis, minimum luminal diameter, reference 
vessel diameter, and lesion length. 
11. Angiographic measures of plaque rupture, including ulceration and 
thrombosis. 
5.4 
TIMEPOINTS  
Event rates will be determined at the following periods: In-hospital, 1 month (30 
days), 6 months (180 days), 12 months, 24 months, and then yearly (1 year = 365 
days). The study follow-up will be terminated according to the decision of the 
Steering Committee after all patients have achieved a minimum follow-up of 2 years 
and a maximum of 15 years.  
 
6 
SELECTION AND WITHDRAWAL OF SUBJECTS 
6.1 
SUBJECT INCLUSION AND EXCLUSION 
CRITERIA 
6.1.1 
PROSPECT II (ALL PATIENTS - NATURAL HISTORY STUDY) 
Clinical inclusion criteria (all must be present): 
1. Troponin positive ACS (STEMI >12 hours or NSTEMI) occurring within the 
prior 4 weeks of enrollment, with symptoms consistent with acute ischemia 
lasting >10 minutes, intended for angiography and PCI, if appropriate.  
Clinical exclusion criteria (none must be present): 
1. Known estimated creatinine clearance <30 mL/min. 

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2. Cardiogenic shock, decompensated hypotension or heart failure requiring 
intubation, inotropes, intravenous diuretics, or a hemodynamic support device. 
3. Patient has a known hypersensitivity, allergy, or contraindication to any of the 
following: Aspirin, both heparin and bivalirudin, all 3 of clopidogrel, prasugrel 
and ticagrelor, or to contrast that cannot be adequately pre-medicated. 
4. Refractory ventricular arrhythmias (eg, ventricular tachycardia or fibrillation) 
requiring either intravenous pharmacologic treatment or defibrillation during 
the index PCI procedure. 
5. Persistent acute conduction system disease requiring temporary pacemaker 
insertion during the index PCI procedure. 
6. Prior CABG at any time or planned CABG. 
7. Any medical illness (eg, cancer or severe congestive heart failure) or recent 
history of substance abuse that may cause non-compliance with the protocol 
(including follow-up angiography if enrolled in PROSPECT ABSORB), 
confound the data interpretation, or is associated with a life expectancy less than 
3 years. 
8. Patient is currently enrolled in another investigational use device or drug study 
that has not reached its primary endpoint. If the patient is enrolled in another 
study that is not investigational, required visits for that trial must not interfere 
with the conduct of this study. 
9. Prior participation in this study. 
Angiographic inclusion criteria (all must be present): 
1. Patient must have 1-vessel, 2-vessel, or 3-vessel disease in native coronary 
arteries requiring PCI.  
Note: Culprit lesions (those responsible for the ACS or which otherwise 
require PCI) may be either de novo, restenotic, or due to stent thrombosis.  
2. Successful PCI without major complications must be performed in all treated 
culprit lesions, including the lesion(s) responsible for the ACS, and any other 
angiographically evident flow-limiting lesions that by standard of care require 
treatment. This may be accomplished either during a single procedure or after a 
staged procedure, but in the case of staging the patient may not be enrolled until 
after all stages are successfully completed without major complications and this 
must occur within 4 weeks of initial ACS presentation.  
Note: At operator discretion FFR, iFR, or other cath lab techniques to assess 
physiologic lesion significance may be used to guide the decision whether 
to intervene on borderline lesions, but IVUS and NIRS should not be used 
for this purpose. 
Angiographic exclusion criteria (none must be present):  
1. PCI is required of the left main coronary artery or a left main stenosis is present 
with a visually estimated angiographic DS of >30%. 

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2. Angiographic evidence of severe calcification and/or marked tortuosity of the 
target (culprit) or a non-culprit vessel is present that would preclude the 
feasibility of safe imaging of at least the proximal 6 cm of all vessels. 
3. The presence of a chronic total occlusion of a major epicardial coronary vessel 
that is not successfully recanalized during the PCI procedure, and thus would 
preclude intravascular imaging. 
Note: A side branch of a major vessel (eg, a diagonal branch) may be 
occluded as long as the major epicardial vessel (eg, the left anterior 
descending artery) is patent and can be imaged.  
 
6.1.2 
PROSPECT ABSORB (RANDOMIZED TRIAL) 
Angiographic inclusion criteria (all must be present):  
After PCI of all intended target culprit lesions and following successful and 
uncomplicated imaging of at least one, but preferably all 3 coronary vessels (culprit 
and non-culprit) in the PROSPECT II natural history phase of the study, the patient 
is eligible for randomization in the PROSPECT ABSORB study if one or more 
eligible lesions are identified that meet all of the following angiographic criteria: 
1. The lesion is a de novo lesion (may be located in either the target or non-target 
vessel) 
2. The lesion has an angiographic diameter stenosis <70% and is not intended for 
revascularization based on angiographic criteria and FFR/iFR.  
Note: FFR/iFR should be performed on all non-critical lesions of >40% 
visually estimated angiographic stenosis that are candidates for the 
PROSPECT ABSORB substudy.  
3. The lesion has a site-determined IVUS plaque burden in at least one frame 
≥65%. 
Note: Such a lesion may or may not be angiographically evident, ie, the 
visually estimated angiographic diameter stenosis may range from 0% to 
<70%. 
4. The reference vessel diameter of an eligible lesion is ≥2.5 mm to ≤4.0 mm 
(visually estimated) capable of being treated with a 2.5 mm, 3.0 mm, or 3.5 mm 
diameter BVS. 
5. The lesion length of an eligible lesion is ≤50 mm (visually estimated), capable 
of being treated by no more than two BVS (maximum length of each BVS 28 
mm), allowing for 2 mm BVS overlap and 2 mm of “normal” reference segment 
treatment at each edge. 
6. The lesion must be at least 10 mm from a previously implanted stent/scaffold 
and an intervening 10 mm segment must not have plaque burden (PB) >50% 
 

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7. A bifurcation lesion may be enrolled only if the side branch (a) has a reference 
vessel diameter ≤2.5 mm, and (b) has either no lesion requiring treatment or 
atherosclerotic disease limited to within 5 mm of its origin from the parent 
vessel such that the operator believes that the side branch can be successfully 
treated with balloon angioplasty only (ie, without a stent). If a stent 
subsequently becomes necessary, only a metallic drug-eluting stent (DES; 
Xience [Abbott Vascular, Santa Clara, CA] strongly recommended) may be 
used to treat the side branch with a T-stent technique. 
8. Randomization must occur immediately after the 3-vessel imaging run in the 
PROSPECT II protocol. If the patient randomizes to BVS, BVS placement must 
be performed immediately after randomization. 
Note: If 2 or more lesions meeting eligibility criteria are present, only one 
may be randomized. Priority should be given to an eligible lesion not in a 
culprit vessel. In general, the lesion most proximal in the coronary tree 
and supplying the greatest amount of myocardium should be randomized. 
The CASS segment of this lesion will be identified prior to randomization 
allocation. 
 
Angiographic exclusion criteria (none can be present):  
1. The eligible lesion cannot be within 10 mm of lesion previously treated by 
PCI. 
2. The randomized lesion may not be in the left main coronary artery.  
3. The randomized lesion may not be an ostial LAD or ostial LCX lesion (defined 
as within 3 mm of the left main coronary artery). 
4. The randomized lesion may not be an ostial RCA lesion (defined as within 3 
mm of the aorto-ostium).  
5. Angiographic evidence of severe calcification and/or marked tortuosity of the 
target vessel and/or lesion intended for randomization is present that would 
make it unlikely that the BVS could be advanced to or across the lesion or be 
adequately expanded. 
6.2 
WITHDRAWAL OF SUBJECTS 
A patient can be withdrawn from the natural history study and/or the randomized trial 
at any time if it is the wish of the patient or if it is medically necessary, as judged by 
the Investigator. If a patient does not return for a scheduled visit, every effort should be 
made to contact the patient. In any circumstance, every effort should be made to 
document patient outcome, if possible. Patients will consent to continued merging of 
data from the study database (collected up to withdrawal date) with data from the 
Scandinavian quality registers even if they have withdrawn from the study. If a patient 
decides to withdraw from the study, and if the patient agrees, he/she will be contacted 
in order to obtain information about the reason(s) for discontinuation and any 
experienced endpoint events or serious adverse device effects (see section 10). The date 
and reason for the withdrawal will be recorded in the case report form (eCRF).  

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Public databases will be used to ascertain the vital status of subjects withdrawn from 
the study.  
 
7 
DESCRIPTION OF DEVICES 
7.1 
TVC IMAGING SYSTEM  
The InfraReDx TVC Imaging System is a CE-marked diagnostic intravascular imaging 
catheter intended for NIRS and IVUS examination of coronary arteries in patients 
undergoing invasive coronary angiography. The system is intended for imaging the 
lumen and vessel wall structures in addition to the detection of lipid core containing 
plaques of interest (LCP) within one automated co-registered pullback. See the 
Instructions For Use/User’s Guide Model No. TVC-MC8, IFU0144rC in the 
Investigator’s File. 
7.2 
ABSORB 
BIORESORBABLE 
VASCULAR 
SCAFFOLD 
The Absorb BVS is a CE-marked temporary scaffold indicated for improving coronary 
luminal diameter that will eventually resorb and facilitate normalization of vessel 
function in patients with ischemic heart disease due to de novo native coronary artery 
lesions. The Absorb BVS System includes a pre-mounted polymer poly (L-lactide) 
(PLLA) scaffold coated with a blend of the antiproliferative drug everolimus and 
polymer poly (D,L-lactide) (PDLLA) in a 1:1 ratio. See latest released/effective 
Instructions For Use (IFU, BVSS, Absorb, International) in the Investigator’s File. 
 
8 
RISK ASSESSMENT 
8.1 
TVC IMAGING SYSTEM 
Additional imaging with IVUS may benefit patients enrolled in the study. The 
knowledge of vessel diameter will help operators choose the correct stent size, which 
in turn can reduce restenosis and stent thrombosis. There is increased risk associated 
with IVUS imaging; 3-vessel imaging performed in the previous PROSPECT study 
resulted in a 0.3% rate of dissection that caused non-fatal procedure-related myocardial 
infarction. The IVUS/NIRS TVC Imaging System is designed to be similar in mode of 
use to an IVUS catheter. The safety record of the IVUS/NIRS catheter in the over 3,000 
patients in whom it has been used has been similar to that expected with an IVUS 
catheter. See also the IFU. 
 
Overall the risk/benefit ratio is reasonable for the PROSPECT II study. 
 
 
8.2 
ABSORB BIORESORBABLE VASCULAR SCAFFOLD 
In the original PROSPECT study, the per patient 24-month NC-MACE rate attributed 
to patients with ≥1lesion with a core laboratory-assessed PB ≥70% was 17.7% vs 6.0% 

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in patients with no lesions with PB ≥70%, and for PB ≥65% was 13.2% vs 5.4% in 
patients with no lesions with PB ≥65%. It is hypothesized that this risk may be reduced 
by treatment with Absorb BVS, thereby providing patients with a potential benefit. The 
Absorb BVS has demonstrated a favorable safety profile with only 0.6% scaffold  
thrombosis during the first year of placement as shown in pooled analysis of the 
ABSORB Cohort B and EXTEND trials (13). Overall the risk/benefit ratio is reasonable 
for the PROSPECT ABSORB substudy. 
9 
STUDY PROCEDURES (SEE ALSO APPENDIX II: TABLE OF 
STUDY PROCEDURES) 
PROSPECT II: Patients with a troponin positive ACS within the prior 4 weeks (STEMI 
or NSTEMI) in whom coronary angiography is planned will be screened and asked to 
participate in the study. It is estimated that approximately 1500 patients will need to be 
screened to enroll 900 patients. After informed consent has been obtained and prior to 
PCI, all target lesions (those lesions for which PCI is planned) will be examined (if 
possible) by IVUS/NIRS. If the patient is successfully treated with PCI of all intended 
culprit lesions without major procedural complication(s), all three coronary arteries will 
be examined with IVUS/NIRS. The IVUS results will be visible (unblinded) to the 
operator, but the NIRS data will be blinded. The patient will be considered formally 
enrolled in PROSPECT II only after PCI of all intended target culprit lesions has 
been successfully completed and after the study imaging catheter is passed out of 
the guide catheter into a coronary artery (n = approximately 900 patients). If a 
staged procedure is required to achieve revascularization of all intended lesions, the 
patient will not be enrolled until after the staged procedure has been performed without 
major procedural complication(s). Once enrolled, IVUS and NIRS will be performed 
over a 6-10 cm length in all three coronary arteries with a combined IVUS/NIRS 
catheter to assess both the treated culprit lesion(s) and long segments of the untreated 
coronary tree. Patient enrollment and 3-vessel IVUS and NIRS imaging may be 
performed either in the same procedure during which the culprit PCI lesion(s) are 
treated, or during a subsequent angiographic procedure as long as this occurs within 2 
weeks of the initial ACS presentation, and after successful and uncomplicated treatment 
of all target lesions. 
 
All patients in whom a successful IVUS/NIRS of at least one major coronary artery 
was performed will constitute the analysis population. The angiography and the 
IVUS/NIRS for all included patients will be sent to the core lab according to 
Appendix III and the study Manual of Operations. If the imaging catheter passed into 
a coronary artery for imaging a non-culprit segment of the coronary tree and no non-
culprit segment imaging data is obtained (e.g. the catheter fails and a second catheter 
is not used),, the patient will be disenrolled (discontinued) from the study, and only be 
followed up for safety purposes for 30 days.  
 
All patients will be followed in the Scandinavian quality registers (eg, 
SWEDEHEART). Patients will undergo follow-up through register data collection and 
by calls by study coordinators at 1 month (30 days), 6 months (180 days), 12 months, 
and 24 months, assessing MACE and safety parameters. Patients will then undergo 
follow-up through register data collection starting at 3 years and continuing through 15 

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years. Additional phone follow-up may be performed as needed to obtain more 
complete follow-up information. 
 
For at least the first 24 months after enrollment, and possibly for up to 15 years, every 
time patients are examined with coronary angiography during the follow-up period 
(documented in the register), the study monitor will be informed and will contact the 
local hospital to make sure copies of charts, lab values, examinations, and a copy of the 
angiogram and all diagnostic procedures performed (eg, IVUS, NIRS, OCT, FFR, iFR) 
are forwarded to Uppsala Clinical Research Center (UCR) and the angiographic core 
lab (ACL) (Cardiovascular Research Foundation [CRF]). The events will be 
adjudicated by the independent clinical endpoint classification group (CEC) at UCR. In 
parallel, the ACL will be responsible for reviewing and analyzing all repeat 
angiograms.  
 
PROSPECT ABSORB: Patients in whom one or more lesions in a non-target 
(untreated) vessel are identified with (a) an angiographically visually estimated 
diameter stenosis <70%; (b) a visually estimated reference vessel diameter (RVD) of 
2.5-4.0 mm; (c) a visually estimated lesion length ≤50 mm; and (d) a site-determined 
IVUS plaque burden ≥65% (site reading) will be enrolled in the PROSPECT ABSORB 
trial and randomized 1:1 to treatment with Absorb BVS + GDMT vs GDMT alone (n 
= approximately 300 patients; 150 patients in each group). For patients with multiple 
qualifying lesions, a single lesion will be selected for randomization prior to assignment 
to BVS + GDMT versus GDMT alone. 
 
Patients who do not fulfill the criteria to be included in PROSPECT ABSORB 
(Randomized Trial) or who refuse consent for PROSPECT ABSORB will continue as 
part of the main study PROSPECT II (Natural History Study). 
 
For the patients included in PROSPECT ABSORB (Randomized Trial), coronary 
angiography with 3-vessel IVUS/NIRS will be performed at 25-month follow-up to 
evaluate the randomized lesion for vascular changes and the non-randomized coronary 
segments for atherosclerosis progression. The 25 month angiogram can be performed 
within a window of between 24.5 months and 28 months after enrollment. A study 
flowchart and schedule of procedures are presented in Appendix II.  
Note: 25-month angiographic follow-up will not be required in PROSPECT-ABSORB 
randomized patients who either a) have had scaffold thrombosis or in-scaffold restenosis 
(DS>50% as determined by the angiographic core laboratory) at any time point prior to 25 
months, OR b) have had a repeat angiogram ≥12 months after enrollment and in whom 
IVUS/NIRS of the randomized target lesion was performed.  
 
Randomization at Site 
For patients enrolled in PROSPECT II (Natural History Study) there is no 
randomization. For the substudy PROSPECT ABSORB (Randomized Trial) 
randomization is performed 1:1 to treatment with Absorb BVS + GDMT vs GDMT 
alone stratified for site. When a patient is determined to be eligible for inclusion in the 
study the patient will be randomized to one of the two treatment arms using sealed, 
opaque, consecutively numbered envelopes. For patients with multiple qualifying 
lesions, a single lesion will be selected prior to randomization allocation. The 

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randomization procedure is described in the study Manual of Operation. If the patient 
is assigned to BVS, the procedure must be performed immediately after randomization 
assignment.  
Based on findings from PROSPECT I we assume that approximately a third of subjects 
in PROSPECT II (Natural History Study) will be eligible for randomization in 
PROSPECT-ABSORB. In order to maintain the power of both parts of the study, if 
during the conduct of the study the ratio of subjects enrolled in the main PROSPECT 
II study and the PROSPECT ABSORB substudy is different than the 3:1 anticipated, 
the Operations Committee will assess whether sufficient power is maintained in the 
ABSORB substudy and will consider prolonging enrollment (vs. completing the trial 
with fewer than 300 subjects randomized to PROSPECT ABSORB) and will be 
responsible for monitoring the enrollment and communicating with the sites (see 
Section 16.5.4 in Statistical Section for possible power scenarios).  
Stenting with ABSORB BVS 
 
Prepare the vessel: 
 Avoid very small vessels (QCA RVD <2.25 mm, roughly equivalent to visual 
estimated 2.5 mm).  
 1:1 balloon-to-artery ratio predilatation (sized with OCT/IVUS etc.) 
 The usage of a non-compliant (NC) balloon is recommended 
 Enable full expansion of pre-dilatation balloon to facilitate full scaffold 
expansion 
 Achieve a residual stenosis between 20% and 40% after predilatation 
  
Size the vessel appropriately: 
 The reference vessel diameter of an eligible lesion is ≥2.5 mm to ≤4.0 mm 
(visually estimated) capable of being treated with a 2.5 mm, 3.0 mm, or 3.5 mm 
diameter BVS. 
 Use standard dose of intracoronary nitroglycerine prior to determining RVD 
 Size the scaffold according to the exact vessel size based on information from 
vessel preparation and imaging – avoid undersizing! 
 Deploy the scaffold slowly, 2 atm increments over 5 seconds, until the scaffold 
is completely expanded 
 Maintain target deployment pressure for 30 sec. or as long as patient can tolerate 
 
Post-dilate the scaffold: 
 Obligatory post-dilatation with a NC balloon at high pressure (>16 atm) 
 
The nominal NC balloon diameter should be equal to or 0.25 mm or 0.5 mm 
larger than the nominal scaffold diameter; in no case should the nominal NC 
balloon diameter be >0.5 mm larger than the nominal scaffold diameter 
 Ensure <10% final residual stenosis and a complete apposition of the scaffold 
 

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9.1 
BASELINE ANGIOGRAPHY 
Following intracoronary injection of nitroglycerin (at least 100 µg, 200 µg preferred), 
baseline angiography of all 3 major epicardial coronary arteries will be performed per 
the ACL guidelines (see Appendix III).  
9.2 
PROCEDURE FOR ENROLLMENT 
Assessment of angiographic eligibility must be done by visual assessment prior to 
enrollment. Angiograms will be submitted to the ACL for analysis. 
 
Patients are eligible for enrollment if PCI of at least one lesion has been performed and 
3-vessel IVUS/NIRS is judged by the investigator to be feasible and capable of being 
performed safely. There may be situations where the procedure is stopped prior to the 
imaging device being delivered beyond the guide catheter into a coronary artery (eg, 
patient becomes clinically unstable, power outage). In these situations, the patient will 
not be considered enrolled in the study. Once the IVUS/NIRS catheter is advanced out 
of the guiding catheter, the patient is considered enrolled in the study. 
 
If the imaging catheter passed into a coronary artery for imaging a non-culprit 
segment of the coronary tree and no non-culprit segment imaging data is obtained 
(e.g. the catheter fails and a second catheter is not used) the patient will be disenrolled 
(discontinued) from the study and only be followed up for safety purposes for 30 
days.  
9.3 
PERCUTANEOUS CORONARY INTERVENTION 
(PCI) 
The decision as to which lesions should undergo PCI should be made on the basis of 
angiography and other clinical factors, as per standard of care. FFR and iFR should be 
used to assess borderline lesions (angiographic stenosis ≥40%). IVUS/NIRS may not 
be utilized to determine the suitability of angiographically non-obstructive lesions for 
revascularization. 
 
Once the target lesion(s) have been identified, IVUS/NIRS of all target lesions will be 
performed prior to PCI. The IVUS images are unblinded, and may be used to guide the 
interventional procedure as per standard of care. The NIRS images will be blinded. 
 
The interventional procedure will be performed per the institutional standard of care. 
Eligible patients may then be enrolled into PROSPECT II if PCI of all attempted target 
culprit lesions was successful and uncomplicated. 
 
Definition of successful PCI: Successful PCI is defined as a residual diameter stenosis 
of <50% in all lesions attempted and TIMI 3 flow in the target vessel.  
 
Definition of uncomplicated PCI: PCI will be considered uncomplicated if all of the 
following occur: (a) the patient has had no intra-procedural chest pain lasting >10 
minutes; (b) the patient has had no intra-procedural ST-segment changes lasting >10 
minutes; (c) there is no angiographic evidence of sustained vessel closure, slow or no 

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reflow, side branch loss, distal embolization, perforation, or residual dissection (>type 
B); (d) the patient has not required cardiopulmonary resuscitation; (e) the patient has 
not had ventricular arrhythmias requiring cardioversion or intravenous medication or 
conduction system disease requiring temporary pacemaker insertion; (f) the patient has 
not had hypotension, heart failure, or respiratory failure requiring any of the following: 
Intubation, intra-aortic balloon insertion, or other hemodynamic support device use or 
requirement for intravenous pressors; (g) the patient has not had other situations that in 
the judgment of the investigator may result in a MACE within 30 days, including the 
likely diagnosis of periprocedural MI (SCAI criteria, see CEC Charter,). Successful 
PCI of all attempted target culprit lesion(s) must be completed before patient 
enrollment, and no major complications can have occurred for the patient to be enrolled 
in the study. If staged procedures are required for revascularization, the patient may 
only be enrolled after the last stage is successfully completed and as long as there were 
no procedural complications in either stage and the final stage is completed within 4 
weeks of patient presentation with the ACS.  
9.4 
IMAGING FOLLOWING PERCUTANEOUS 
INTERVENTION 
Once the patient is formally enrolled in PROSPECT II, 3-vessel IVUS/NIRS imaging 
must be performed in the culprit vessel(s) and all non-culprit vessel(s), including the 
LAD, the LCX, and the RCA. IVUS/NIRS is initially performed in the culprit vessel(s) 
after successful, uncomplicated intervention. Following successful PCI of the culprit 
vessel(s), and after injection of intracoronary nitroglycerin (at least 100 µg, 200 µg 
preferred), the proximal 6-10 cm of the culprit vessel (in addition to the left main 
coronary segment of the left coronary artery) will be imaged and recorded with the 
IVUS/NIRS system using automated pullback. If possible, a distal fiduciary branch 
should be identified as the starting point to serve as an anatomic locator. If IVUS of the 
culprit lesion(s) indicates that stent deployment is not optimal, additional post-dilatation 
may be performed at operator discretion after which a final IVUS/NIRS imaging run 
should be performed to document the final result. 
 
Following final imaging and intervention in the culprit vessel(s), the proximal 6-10 cm 
of the non-culprit vessel(s) should be imaged with IVUS/NIRS. If the culprit lesion was 
in the LAD, the LCX and RCA should be imaged as the non-culprit vessel(s). If the 
culprit lesion was in a LCX, the LAD and RCA should be imaged as the non-culprit 
vessels. (In these cases imaging should progress from left to right.) If the culprit lesion 
was in the RCA, the LAD and LCX should be imaged as the non-culprit vessels 
(typically the LAD and left main coronary artery first). These additional imaging 
procedures should never unduly jeopardize patient safety. Note that if one of the major 
vessels (LAD, LCX, or RCA) has a very large side branch supplying the left ventricle 
(eg, a diagonal or obtuse marginal which by visual estimation is ≥3.0 mm in diameter), 
it is desirable to perform IVUS/NIRS imaging of a long segment of this large branch as 
well. 
 
All image data (angiography and IVUS/NIRS) must be submitted to the core laboratory 
as detailed in Appendix III and in the study Manual of Operations. 
 

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For patients returning to the enrolling institution during the 24-month follow-up period 
with a cardiac event that requires cardiac catheterization, 3-vessel angiography is 
mandatory, and 3-vessel IVUS/NIRS imaging is strongly recommended. These images 
must be submitted to the core laboratory for analysis. These additional procedures 
should never unduly jeopardize patient safety. 
9.5 
CONCOMITANT MEDICATIONS 
All prescribed medications will be at the discretion of the investigator taking into 
consideration patient safety and institutional standards of care and guidelines. Data 
regarding prescribed cardiac and diabetes medications will be recorded at the time of 
admission, during the catheterization and hospitalization, at discharge, and at the time 
of regularly scheduled follow-up periods. Use of the following classes of cardiac 
medications will be collected: Aspirin, glycoprotein IIb/IIIa inhibitors, pre- and intra-
procedural anti-thrombin agents, clopidogrel, ticlopidine, prasugrel, ticagrelor, 
angiotensin-converting enzyme inhibitors/angiotensin receptor blockers, beta blockers, 
vitamin K antagonists, statins, and other lipid-lowering agents. GDMT (including dual 
antiplatelet therapy and lipid-lowering therapy) should be applied based on the 
appropriate ACC/AHA and ESC guidelines (eg, ACC/AHA Secondary Prevention for 
Patients With Coronary and Other Atherosclerotic Vascular Disease [2011 update] and 
ESC Management of Dyslipidemia Guidelines). In addition, guidelines for the 
management of patients with STEMI and ACS should be followed, including the choice 
of antiplatelet therapies (presently ticagrelor and prasugrel preferred to clopidogrel as 
P2Y12 inhibitor).  
 
Investigational Device Accountability 
The use of catheters for the InfraReDx TVC imaging system and the Abbott BVS will 
be documented in an accountability log and kept in the Investigator’s File at each study 
site. 
9.6 
  CLINICAL AND LABORATORY PROCEDURES 
9.6.1 
LABORATORY ASSESSMENTS 
Laboratory analysis should be performed according to local clinical practice. Local 
measurement results of hemoglobin, creatinine, HbA1c, cholesterol, LDL, HDL, 
triglyceride levels, p-glucose, white blood cell count, platelet count, hs-Troponin 
(before and after PCI) and hs-CRP will be reported in the eCRF according to 
instructions. 
9.6.2 
BIOMARKER/GENETICS EVALUATION AND BIOBANK 
Blood samples for analyses of possible biomarkers for cardiovascular disease will be 
obtained from all patients.  
An arterial blood sample (maximum 100 mL) will be collected at baseline. The blood 
sample should be taken from the arterial sheath after the diagnostic angiogram to ensure 
all inclusion and exclusion criteria are met, but before PCI is performed. 
 

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The samples must be centrifuged and frozen in aliquots at -20C for a maximum period 
of one month and then transferred to a -70C freezer and shipped to the Core Biomarker 
Lab (UCR Laboratory) in Uppsala, Sweden at regular intervals. If the site does not have 
a -70C freezer, samples must be shipped within the first month to the UCR Laboratory. 
Sampling material and a detailed sampling handling instructions will be provided by 
the UCR Laboratory at the study initiation visit.  
A biobank will be created for explorative analysis of biomarkers possibly linked to 
cardiovascular disease in the circulating blood and genetic analysis will be performed 
also in relation to cardiovascular disease. Proteomic, lipidomic, transcriptomic, and 
metabolomic analysis will be performed. 
9.6.3 
POST-PROCEDURE AND DISCHARGE 
The care of the patient in the post-procedure period and the timing of discharge will be 
at the discretion of the investigator. Medications at discharge will also be at the 
discretion of the investigator according to guidelines and local routines. GDMT is 
strongly recommended. 
9.6.4 
ONE MONTH (30-DAY) FOLLOW-UP  
Telephone follow-up at 30 days (± 7 days) including: 
• Data regarding any endpoint events or serious adverse device effects (see section 10), 
including repeat hospitalization and coronary angiography  
• Use of cardiac medications (see section 9.6.) 
9.6.5 
6 MONTHS (180 DAYS) FOLLOW-UP  
Telephone follow-up at 6 months (180 days) (±14 days) including: 
• Data regarding any endpoint events or serious adverse device effects (see section 10), 
including repeat hospitalization and coronary angiography  
• Use of cardiac medications (see section 9.6.) 
9.6.6 
12-MONTHS (1-YEAR) FOLLOW-UP  
Telephone follow-up at 12 months (±30 days) including: 
• Data regarding any endpoint events or serious adverse device effects (see section 10), 
including repeat hospitalization and coronary angiography  
• Use of cardiac medications (see section 9.6.) 
9.6.7 
24-MONTHS (2-YEARS) FOLLOW-UP 
Telephone or hospital visit at 24 months (±14 days) including: 
• Data regarding any endpoint events or serious adverse device effects (see Section 10), 
including repeat hospitalization and coronary angiography  
• Use of cardiac medications (see Section 9.6).  
 
 
 
 

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9.6.8 
SWEEP FOLLOW-UP  
At the time the last patient enrolled reaches 24 month follow-up, an additional registry 
(or medical record review) sweep will be performed in all patients.  
• Data regarding any MACE events including coronary angiography will be collected  
 
 
9.6.9 
25 MONTHS IMAGING FOLLOW UP - PROSPECT ABSORB 
(RANDOMIZED TRIAL) 
Three-vessel angiography and 3-vessel IVUS/NIRS should be performed at 25 months 
(window from 24.5 months to 28 months)  in all patients after the 24-month (±2 weeks) 
clinical follow-up has been performed and documented.  
Note:  25-month angiographic follow-up will not be required in PROSPECT-
ABSORB randomized patients who either a) have had scaffold thrombosis or 
in-scaffold restenosis (DS>50% as determined by the angiographic core 
laboratory) at any time point prior to 25 months, OR b) have had a repeat 
angiogram ≥12 months after enrollment and in whom IVUS/NIRS of the 
randomized target lesion was performed.  
Additional follow-up visits 
Any patient who develops cardiac symptoms or a MACE during the follow-up period 
should be evaluated by the investigator by telephone contact or clinic visit as deemed 
appropriate. Requisite data are listed: 
• Data regarding any endpoint events or serious adverse device effects (see Section 10), 
including repeat hospitalization and coronary angiography 
• Use of medications 
 
For any occurrence during follow-up of an adverse cardiac event, detailed records of 
that event, including but not limited to hospitalization records (admission record, 
discharge summary, catheterization and operative reports, and other supporting data as 
required) must be collected and sent to the CEC for adjudication. Any repeat coronary 
angiographic and IVUS/NIRS imaging procedures must be collected and sent to the 
core laboratory, whether performed at the enrolling hospital or a non-enrolling hospital. 
Further details can be found in the Study Manual of Operations. 
 
Additional phone follow-up may be performed as needed to obtain more complete 
follow-up information. 
 
9.6.10 
ANNUAL CLINICAL FOLLOW-UP AT 3 YEARS THROUGH 15 
YEARS 
Clinical follow-up by telephone may be extended at yearly intervals from 3 years (±1 
month) up to 15 years (±1 month). Based on the findings of the study at 24 months, the 
Executive Committee will determine whether follow-up will be extended and for how 
long, and sites will be notified. Such visits will assess: 

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• Data regarding any endpoint events including repeat hospitalization and coronary 
angiography 
• Use of cardiac medications (see Section 9.6.) 
9.6.11 
EVENT-DRIVEN 
IMAGING 
IN PROSPECT II (NATURAL 
HISTORY STUDY) 
For patients returning to the enrolling institution with a subsequent cardiac event that 
requires catheterization, it is strongly recommended that 3-vessel IVUS/NIRS follow-
up be conducted at the time of the catheterization. A 3-vessel angiogram should also be 
performed. These images will be sent to their respective core laboratories for analysis. 
As patients may have multiple events during follow-up period, all efforts should be 
made to image the first event. 
 
10 
ADVERSE EVENTS 
An adverse event is defined as any untoward medical occurrence in a subject. This 
definition does not imply that there is a relationship between the adverse event and the 
procedure or device. 
10.1 
ADVERSE DEVICE EFFECT (ADE) 
An adverse device effect is defined as any untoward and unintended response to a 
medical device/imaging tool/scaffold. This definition includes any event resulting from 
insufficiencies or inadequacies in the instructions for use. It also includes any event that 
is a result of a user error. Observed and potential adverse device effects for the 
InfraReDx TVC Imaging System and the Absorb BVS can be found in the respective 
IFU/User’s Guide in the Investigator’s File. 
10.2 
SERIOUS ADVERSE EVENT (SAE) 
An SAE is defined as an adverse event that: 
 Led to death. 
 Led to a serious deterioration in the health of the subject that: 
 Resulted in a life-threatening illness or injury 
 Resulted in a permanent impairment of a body structure or a body function 
 Required in patient 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 
10.3 
SERIOUS ADVERSE DEVICE EFFECT (SADE) 
An SADE is defined as 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 intervention had not been 
made or if circumstances had been less opportune. A list of serious adverse events, 
which may result from the use of the device/imaging tool or occur as a result of the 

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imaging procedure, is described in the TVC Imaging system and the Absorb BVS 
Instructions For Use (IFU). 
10.4 
UNANTICIPATED SERIOUS ADVERSE DEVICE 
EFFECT (USADE) 
A USADE is defined as any serious adverse effect on health or safety, or any life-
threatening problem or death caused by, or associated with, the device if that effect, 
problem, or death was not identified in nature, severity, or degree of incidence in the 
current risk analysis report, or any other unanticipated serious problem associated with 
the device that relates to the rights, safety, or welfare of the subjects. (Significant device 
failure may constitute an adverse event if an undesirable experience occurs.) This 
definition includes any event resulting from insufficiencies or inadequacies in the 
instructions for use or the deployment of the device or any event that is a result of a 
user error.  
10.5 
RECORDING AND REPORTING OF NON-SERIOUS 
AND SERIOUS ADVERSE EVENTS AND ADVERSE 
DEVICE EFFECTS. 
Any adverse event, whether device related or not, occurring at the baseline visit and at 
the 25-month visit (PROSPECT ABSORB) will be collected.  
 
Any event the investigator deems to be serious MUST be reported to the Sponsor within 
one business day from the knowledge and determination of the event. The SAEs will 
be monitored until they are adequately resolved or explained. 
 
Between visits, up to 24 months of follow-up (or 25 months in the case of subjects in 
the PROSPECT ABSORB substudy), only endpoint events, as defined below and in 
Section 11, and SADEs will be collected. 
 
Death, myocardial infarction, hospitalization for unstable or progressive angina, 
symptom-driven revascularization, and scaffold thrombosis are defined as potential 
endpoints and will be reported to the CEC group for central adjudication (see Section 
11). The events will be collected for all patients throughout the study after the patient 
is enrolled. These adjudicated events will not be reported to health authorities as SAEs 
as they are considered part of the natural history of the condition under investigation 
and will be monitored regularly by an independent DSMB throughout the study.  
 
SADEs, endpoint related or not, will be collected throughout the study up to 25 months 
follow-up (PROSPECT ABSORB). The Investigator shall report all SADEs to the 
Sponsor within one business day from the knowledge and determination of the event 
and to the reviewing IEC/IRB as soon as possible (per the overseeing policy of the 
IEC/IRB) after the Investigator first learns of the effect. The Sponsor will report 
USADEs to the manufacturer within 24 hours from the knowledge and determination 
of the event and will report SADEs and USADEs to the National Competent Authority 
according to local regulations. 
 

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All events listed above should be documented in the patient eCRF including time of 
onset, a complete description of the event, severity, duration, actions taken, and event 
outcome. 
10.6 
SAFETY MONITORING 
All events associated with the baseline imaging and/or scaffold deployment procedure 
will be reported to the Data and Safety Monitoring Board (DSMB) and reviewed on a 
regular basis. The DSMB may request additional information as needed. Based on 
safety data, the DSMB may recommend to the Executive Committee to stop or 
otherwise modify the study. After weighing the recommendation of the DSMB, the 
Executive Committee will make the final decision whether the study should be stopped, 
modified, or continued without change. The DSMB procedures will be described in the 
DSMB Charter. 
 
11 
ADJUDICATION OF EVENTS 
All suspected major adverse cardiac events (NC-MACE) will be adjudicated by the 
independent CEC group at UCR. The CEC Charter defines the specific criteria and 
definitions for each study endpoint (both primary and secondary) as detailed below, 
and will be approved by the Executive Committee. The details of the adjudication 
process are described in the CEC Charter. 
 
In parallel, the ACL at Cardiovascular Research Foundation, will be responsible for 
reviewing and analyzing all repeat angiograms to determine lesion progression and if 
an event was related to the culprit lesion or NCL or the randomized BVS lesion and if 
revascularization was performed. Regular meetings will be held by the CEC group 
with the ACL and, if needed, the intravascular core lab to accurately adjudicate lesion 
assignment. The ACL will use a work process defined in a separate work process 
plan. 
 
The result of the angiographic review will determine if the event (adjudicated by the 
CEC group) will finally be classified and analyzed as a culprit lesion or an NCL. 
 
The following endpoints will be adjudicated by the CEC group:  
 
 Death 
 Myocardial infarction 
 Unstable angina 
 Progressive angina or anginal equivalent symptoms 
 Symptom-driven revascularization 
 Stent/Scaffold thrombosis 
 
On the basis of the findings from the ACL, each event will be attributed to either the 
culprit lesion/vessel, non-culprit lesion/vessel, randomized lesion (PROSPECT 
ABSORB substudy – considered an untreated NCL if randomized to control or a treated 
[non–ACS-related] culprit lesion if randomized to BVS), or indeterminate. 

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In addition, all IVUS/NIRS related AEs are to be reviewed by CEC and ACL in order 
to capture any unidentified study endpoints, as listed above.  
 
12 
DATA HANDLING AND RECORD KEEPING 
12.1 
QUALITY REGISTRY DATA 
Data from the Scandinavian quality registers for included patients in the study will be 
used for clinical follow-up at all pre-specified periods. In addition, telephone follow-
up will be performed at all intervals up to 24 months and optionally after 24 months 
through 15 years. Study-specific data up to 24-month follow-up (or 25 months in the 
case of subjects in the PROSPECT ABSORB substudy) will be accurately recorded by 
authorized personnel on electronic CRFs (eCRF). eCRFs will be completed in a timely 
manner. 
12.2 
MEDICAL RECORD/SOURCE DOCUMENTATION 
All digital or paper hospital records regarding the treatment of the patient included in 
the study, whether obtained at the enrollment hospital or another treating hospital, are 
considered source data. In order to comply with these regulatory requirements, at a 
minimum, the following is a list of information that should be maintained: 
 Clinical study identification 
 Subject identification 
 Date when patient information was given and when signed informed consent 
was obtained 
 Diagnosis 
 Fulfillment of inclusion criteria 
 Specification of visit dates, concomitant medication, and any AEs 
 Specification of the subject’s cessation in the study (eg, completion or 
premature withdrawal) 
 Specification of the subject’s outcome in the study 
 
In addition, the raw (digital) data from all angiograms and intravascular imaging 
studies, whether obtained at the enrollment hospital or another treating hospital, are 
considered source data and must be collected and sent to the core laboratory. 
12.3 
RECORD RETENTION 
To enable audits and evaluations by the Sponsor and inspections by regulatory 
authorities, the Investigator shall keep records (essential documents) of the study for 15 
years following study completion unless otherwise instructed by regulatory agencies. 
This includes any original source data related to the study, the subject identification list 
(with subject numbers, full names and addresses), the original signed informed consent 
forms, copies of all case report forms, and detailed records of investigational/device 
products disposition. The investigator will obtain permission from the Sponsor in 
writing before destroying or transferring control of any study records.  
 

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13 
SELECTION OF CLINICAL SITES AND INVESTIGATORS 
The Sponsor is responsible for selecting qualified investigators, obtaining a signed 
investigators’ agreement, and providing the investigators with the information needed 
to conduct the investigation properly, ensuring proper monitoring of the investigation, 
ensuring the protection of human patients enrolled in the study, and identifying and 
distributing significant new information relevant to the investigation to the 
investigators. The Sponsor will evaluate circumstances where an investigator deviates 
from the Investigational Plan, and will retain the right to remove either the investigator 
or the investigational site from the study. 
 
The Sponsor and study management will select investigators qualified by training and 
experience to participate in this observational study. The sites will be selected based 
upon review of a recent site assessment, proficiency with the use of IVUS, and the 
qualifications of the primary investigator at the site. Investigators may be selected to 
participate in the study only after submitting recent curriculum vitae. 
 
The Investigators should provide a curriculum vitae or equivalent documentation of 
suitability to be responsible for the study, and should sign a financial disclosure on 
conflict of interests. All Investigators and other responsible personnel should be listed 
together with their function in the study on the signature and delegation list to be filed 
in the Investigators File. 
The study sites may also be subject to quality assurance audits by the sponsor or its 
designee as well as inspection by a regulatory authority. The Investigator and other 
responsible personnel must be available during the monitoring visits, audits, and 
inspections and should devote sufficient time to these processes.  
13.1 
SITE TRAINING  
All investigators are required to attend Sponsor training sessions including training 
sessions by InfraReDx and Abbott Vascular as appropriate, which may be conducted at 
an investigator’s meeting, a site initiation visit, or other appropriate training sessions. 
Training will include, but not be limited to, the Investigational Plan with manuals and 
instructions, imaging device usage, scaffold usage, quality registry completion, eCRF 
completion, and study personnel responsibilities. All Investigators/study personnel that 
are trained must sign a training log. No Investigator/study personnel will perform any 
study-related procedures prior to signing a signature and delegation log and training log 
as appropriate. 
 
A minimum of five (5) BVS implantations on non-study patients need to have been 
performed by each interventionalist who will be implanting the BVS prior to 
participation in the PROSPECT II study. A site will only be activated after there has 
been at least one such trained interventionalist at the site. 
 
At the initiation of the study, the study monitor or designee will visit each site where 
the study is conducted. The study monitor will ensure that clinical study site personnel 
are informed about and understand the study requirements. 

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13.2 
INVESTIGATOR RESPONSIBILITIES 
The Investigator shall ensure that all work and services described herein, or incidental 
to those described herein, shall be conducted in accordance with the highest standards 
of medical and clinical research practice. The Investigator will provide copies of the 
Investigational Plan to all co-investigators or other staff responsible for study conduct. 
The Investigator and representative will provide the Sponsor with notification of 
relocation to another institution. The Investigator shall ensure also that the data entry 
will be done in a timely manner. 
 
14 
IRB/EC APPROVAL OF THE INVESTIGATIONAL PLAN AND 
INFORMED CONSENT 
The Investigator prior to participation in this study will obtain institutional review board 
or independent ethics committee (IRB/IEC) approval for the Investigational Plan and 
informed consent form. The approval letter must be signed by the IRB/IEC chairman 
or authorized representative prior to the start of this study and must be provided to the 
Sponsor. No changes will be made to the Investigational Plan or informed consent form 
without Sponsor and IRB/EC approval.  
 
14.1 
PATIENT INFORMED CONSENT 
A copy of the template consent form from each site must be forwarded to the Sponsor 
for review and approval prior to implementation. All patients must provide written 
informed consent in accordance with the local IRB/IEC. Patients must be consented 
using an IRB/IEC-approved informed consent form. The approved consent form must 
clearly reflect the Investigational Plan version number. The Investigator or 
representative must be available to answer all of the patient’s study-related questions 
during the consent process. 
 
It should be clearly stated that the data will not identify any subject taking part in the 
study, in accordance with the European Union Data Protection Directive (95/46/EU) 
and any local law on personal data, compare Personuppgiftslagen, (PuL), SFS 
1998:204, in Sweden. 
A copy of the patient information and the signed Informed Consent form should be 
given to the patient. The Investigator (or the designated representative) who gave the 
verbal and written information to the subject shall sign the informed consent form. The 
Investigator should file the signed informed consent forms in the Investigator’s File for 
possible future audits and inspections.  
 
14.2  
INVESTIGATIONAL PLAN AMENDMENTS 
Approved Investigational Plan amendments will be provided to the Investigators by the 
Regulatory Sponsor prior to implementing the amendment. The Investigator will be 
responsible for notifying the IRB/IEC of the Investigational Plan amendment 
(administrative changes) or obtaining IRB/IEC approval of the Investigational Plan 

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amendment (changes in patient care or safety), according to the instructions provided 
by the Sponsor.  
 
14.3 
INVESTIGATIONAL PLAN DEVIATIONS 
It is the responsibility of the Investigator to ensure that there are no deviations from the 
Investigational Plan without notification and approval of the Sponsor and full 
compliance with all established procedures of the IRB/IEC. The investigator will not 
deviate from the Investigational Plan for any reason without prior written approval from 
the Sponsor, except in cases of medical emergencies, when the deviation is necessary 
to eliminate an apparent immediate hazard to the patient. In that event, the investigator 
will notify the Sponsor and the IRB/IEC. 
 
15 
DATA MANAGEMENT  
An eCRF will be used in this study covering all study specific data up to the 24-month 
follow-up (or 25 months in the case of subjects in the PROSPECT ABSORB substudy). 
For all follow-up coronary events the patients chart, angiograms and intravascular 
imaging studies will be source data. Data management will be conducted by the 
Sponsor, according to the study-specific Data Management Plan (DMP). The 
investigator is responsible for ensuring the accuracy, completeness, and legibility of the 
data reported in the eCRF. The monitor will check in accordance with the monitoring 
plan the accuracy, completeness, and legibility of the data reported in the eCRFs before 
the database is locked. The transfer of laboratory data (biomarker, NIRS, IVUS, and 
ACL data) will be done according to the study specific DMP and in accordance with 
the Sponsor standard operating procedures (SOPs). 
 
15.1 
DATA VALIDATION AND CODING 
The eCRF/study database will be subject to both logical computerized checks and 
manual validation checks against listings in accordance with the study-specific Data 
Validation Plan (DVP). All inconsistencies detected during these procedures will be 
resolved through Data Clarification Forms (DCF’s) as specified in the DVP. 
Adverse Events will be coded by the Sponsor according to appropriate version of the 
Medical Dictionary for Regulatory Activities (MedDRA). The correctness of the codes 
used will verified by medical expertise. 
 
15.2 
QUALITY CONTROL AND CLEAN FILE 
When all data entered into the database, including all coding, are deemed final, a clean 
file procedure will be initiated, including a quality control process preceding the actual 
Clean File meeting. Post clean file procedure, the database will be locked and the data 
will be prepared for the final analysis for the primary endpoint and other efficacy and 
safety parameters. The clean file process will be defined in more detail in the DMP. 
Export of final data to involved parties in accordance with respective agreement will be 
performed as specified within the DMP. Data management and the data handling 
process will be conducted in accordance with Good Clinical Practice (GCP), Good 
Clinical Management Practice (GCMP), and EN ISO 14155:2011. 

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16 
STATISTICAL ANALYSIS  
16.1  
DESIGN OF THE STUDY 
PROSPECT II (Natural History Study) is a multicenter, prospective, observational, 
900-patient study of troponin-positive ACS patients designed to test the hypothesis that 
angiographically non-obstructive lesions with large plaque burden and small minimum 
luminal area as identified by grayscale IVUS and large lipid content as identified by 
intracoronary NIRS are associated with an increased risk for future acute coronary 
events. 
 
This study also includes a substudy, PROSPECT ABSORB (Randomized Trial) 
randomizing 300 patients with one or more lesions with plaque burden ≥65% as 
assessed at the site by IVUS in a 1:1 fashion to Absorb BVS + GDMT or GDMT alone 
designed to determine whether the Absorb BVS in such large plaque burden lesions 
safely increases luminal dimensions at 25-month follow-up. 
 
 
16.1.1  
HYPOTHESES TESTED 
The primary analysis will test the ability of the two coronary artery imaging modalities 
(IVUS and NIRS) to identify angiographically non-obstructive vulnerable plaques that 
are subsequently responsible for future unanticipated coronary events, in particular to 
distinguish lesions pre-specified as high-risk: lesion with/without PB ≥70% by IVUS 
Core Lab assessment and lesions with/without maxLCBI4mm greater than or equal to the 
upper quartile (25%) of all measured values. 
 
A Cox proportional hazards regression model will be run, assuming that the hazard 
function λ(t) for time to NC-MACE given a single binary predictor X1 has the following 
regression form:  
 
log[λ(t|X1)/λ0(t)] = β0 + β1X1 
 
where λ0(t) is the baseline hazard, and X1 is the imaging measure as an indicator 
variable (patients with and without the high-risk imaging characteristic).  
 
The null and alternative hypotheses in Cox regression model are: 
H0: β1 = 0 
Ha: β1 = B ≠ 0, 
where β1 (the log hazard ratio of the two groups) is the regression slope coefficient for 
X1. 
16.2  
GENERAL METHODS 
All statistical analyses will be performed using SAS version 9.4 or higher (SAS 
Institute, Cary, NC) or other widely accepted statistical or graphical software. Subject 

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data listings and tabular and graphical presentations of results will be provided. Unless 
otherwise indicated, all statistical tests will be performed at the 2-sided α = 0.05 
significance level. 
 
Baseline demographic, clinical, angiographic, grayscale IVUS, NIRS, and outcome 
variables will be analyzed.  
 
The primary endpoint analysis will be adjusted for covariates, chosen a priori and partly 
based on the results of the original PROSPECT study: age, sex, diabetes mellitus (none, 
medically-treated without insulin, insulin-treated); hypertension, prior PCI, clinical 
presentation (STEMI versus NSTEMI), high-dose statin (atorvastatin ≥40 mg or 
rosuvastatin ≥20 mg) and/or any PCSK9 inhibitor (evolocumab or alirocumab) use as 
a time-dependent variable (updated at baseline, discharge, and each subsequent follow-
up visit), and total imaged NIRS-IVUS length (mm). An unadjusted analysis will also 
be conducted, as well as a covariate analyses that will also include LCBI as a continuous 
variable. Adjusted analyses may also be performed using continuous data for all non-
binary variables.  
 
For continuous variables, descriptive statistics such as the N, mean, median, standard 
deviation, and range will be presented. For discrete variables, counts and percentages 
will be presented. Where formal statistical hypothesis testing is to be performed, the 
details will be presented in the Statistical Analysis Plan (SAP). A survival analysis will 
be used to analyze time-to-event variables such as time to NC-MACE. Survival curves 
will be constructed using Kaplan-Meier estimation. 
 
The analysis of 2-year imaging (angiographic, IVUS, NIRS) endpoints will be 
performed separately for PROSPECT ABSORB randomized patients and non-
PROSPECT ABSORB patients, as all of the PROSPECT ABSORB randomized 
patients are scheduled to have imaging assessments done at 25 months, while for the 
rest of the PROSPECT II patients, repeat imaging will be performed only in patients 
with an unexpected visit. 
16.3  
ANALYSIS POPULATIONS 
16.3.1  
PROSPECT II (NATURAL HISTORY STUDY) 
1. Full Analysis Set (FAS): All patients in whom NIRS imaging of at least one major 
coronary artery was successful. This is the primary analysis dataset for the PROSPECT 
II natural history study. 
2. Safety Analysis set (SA): All patients in whom an IVUS/NIRS catheter exited the 
guide catheter and entered a coronary artery after successful and uncomplicated target 
lesion PCI. All patient-level outcome variables/safety analyses will be performed in this 
analysis set.  

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16.3.2  
PROSPECT ABSORB (RANDOMIZED TRIAL) 
1. Intention to Treat Set - PROSPECT ABSORB (ITT): All patients who were 
randomized into the PROSPECT ABSORB substudy. The ITT set is the primary 
analysis dataset for the PROSPECT ABSORB randomized trial. 
2. Per Protocol – PROSPECT ABSORB (PPA): All patients randomized into the 
PROSPECT ABSORB substudy who meet all inclusion criteria and none of the 
exclusion criteria, and are treated according to the randomized assignment, with no 
major protocol violations. 
3. Safety Analysis set – PROSPECT ABSORB (SAA): All patients randomized into 
PROSPECT ABSORB, excluding those randomized to Absorb BVS arm in whom the 
Absorb BVS did not exit the guide catheter, whether implanted or not.  
16.4  
RANDOMIZATION 
Randomization into the PROSPECT ABSORB (Randomized Trial) will be conducted 
via block randomization with random block size, stratified by site, in a 1:1 fashion (BVS 
+ GDMT to GDMT alone). The randomization list is generated by computer in a 
permuted block fashion and transferred to a sequence of sealed, opaque, consecutively 
numbered envelopes before the start of the study. When a patient has consented and is 
found eligible for the study, randomization is performed by opening the next envelope 
in sequence. For patients with multiple qualifying lesions, a single lesion will be 
selected and declared prior to randomization allocation. 
16.5 
DETERMINATION OF SAMPLE SIZE 
16.5.1 
POWER ANALYSIS AND SAMPLE SIZE ESTIMATE 
FOR PROSPECT II (NATURAL HISTORY STUDY)  
PASS 2008 Software (NCSS LLC, Kaysville, UT), for a Cox Regression model, was 
used to calculate the sample size for the primary endpoint. 
 
The sample size estimation is based on the results for plaque burden reported in the 
original PROSPECT study and considers all patients with untreated lesions and all 
untreated lesions. That is, NCLs (those not treated in the index PCI), as well as IVUS-
defined lesions that are not treated as part of the randomized substudy are taken into 
consideration both at patient-level and lesion-level  
 
The power of PROSPECT II (Natural History Study) is calculated based on testing the 
ability of the two coronary artery imaging modalities (intravascular ultrasound [IVUS] 
and near infrared spectroscopy [NIRS]) to identify patients with angiographically non-
obstructive vulnerable plaques which are subsequently responsible for future 
unanticipated coronary events. In particular, lesions with core laboratory-assessed PB 
≥70% or MLA ≤4.0 mm2 by IVUS and lesions with maxLCBI4mm greater than or equal 
to the upper quartile (25%) of all measured values are pre-specified as high-risk 
plaques.  
 
Additional assumptions used in the power calculations are as follows: 

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 Two-tailed test α = 0.05 
 R-squared of high-risk lesions with other variables in the model is 0.1 for 
adjusted analyses (conservatively estimated from PROSPECT) 
 Proportional hazards 
 
16.5.2 
PATIENT-LEVEL ANALYSIS  
In the original PROSPECT study, by grayscale IVUS, 220 patients were identified 
among 660 patients with at least 1 lesion with PB ≥70%. Among these 220 patients, 
288 observed lesions had PB ≥70%, which equates to 1.3 high-risk lesions per patient. 
For the purpose of the sample size calculation, all 600 patients in PROSPECT II who 
are entered directly into the natural history study are assumed to have no lesions with 
PB ≥70%. In the randomized substudy approximately 300 patients will have a mean of 
1.3 lesions per patients with PB ≥70%. 150 of these patients are randomized to GDMT 
alone. 150 of these patients will have 1 PB ≥70% lesion treated by BVS and thus will 
have mean 0.3 untreated lesions per patient with PB ≥70%, equivalent to 45 patients 
with 1 untreated PB ≥70%.  
 
Therefore, it is estimated that approximately 195 of 900 patients (22%) would be 
considered high-risk according to the criteria of having one or more untreated lesions 
with plaque burden ≥70%. 
 
In the original PROSPECT study, the per patient 24-month NC-MACE rate attributed 
to patients with ≥1 lesion with PB ≥70% was 17.7% vs 6.0% in patients with no lesions 
with PB ≥70%. Thus, the assumed overall per patient 2-year NC-MACE rate given the 
calculations above is 8.5%. 
 
The primary analysis will be adjusted for covariates, chosen a priori and partly based 
on the results of the original PROSPECT study. The list of covariates includes: age, 
sex, diabetes mellitus (none, medically-treated without insulin, insulin-treated); 
hypertension, prior PCI, clinical presentation (STEMI versus NSTEMI), high-dose 
statin (atorvastatin ≥40 mg or rosuvastatin ≥20 mg) and/or any PCSK9 inhibitor 
(evolocumab or alirocumab) use as a time-dependent variable (updated at baseline, 
discharge, and each subsequent follow-up visit), and total imaged NIRS-IVUS length 
(mm). An unadjusted analysis will also be conducted. The power analysis will be 
presented under both conditions. 
 
In an adjusted analysis for PB ≥70%, assuming an overall event rate of 8.5%, an 
adjusted hazard ratio of 2.5 and 900 patients (of which 22% are high-risk), there would 
be 88.3% power to detect the relationship between high-risk patients and NC-MACE. 
The adjusted hazard ratio of 2.5 is based on the results for PB ≥70% in the original 
PROSPECT study. It is expected that a similar or higher rate of high-risk patients will 
be detected based on maxLCBI4mm greater than or equal to the upper quartile of 
observed values. Based on the VH-TCFA data from PROSPECT (in which 23% of 
lesions were classified as TCFAs according to VH-IVUS, and 51% of patients had ≥1 
TCFA), it is assumed that approximately 50% of patients will be categorized as high-
risk, defined as those with at least one lesion with maxLCBI4mm greater than or equal 

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to the upper quartile of observed values. Therefore, assuming a prevalence of 50% high-
risk patients, the overall effect on a patient level will be similar for plaque burden and 
maxLCBI4mm (that is, that the hazard ratio is similar for these two modalities) and an 
overall event rate remaining constant at 8.5%, there will be 96.7% power to detect an 
adjusted hazard ratio of 2.5. Note that in the original PROSPECT study, the adjusted 
patient-level HR for VH-TCFA was 1.7. For the patient-level analysis in PROSPECT 
II (Natural History Study), it is assumed that the HR for maxLCBI4mm will be similar 
to the HR for PB, thus the adjusted hazard ratio of 2.5 is based on the results for PB 
≥70% in the original PROSPECT study. 
 
In an unadjusted analysis for plaque burden, assuming an overall event rate of 8.5%, an 
unadjusted HR of 3.0 and 900 patients (of which 22% are high risk), there would be 
97.8% power to detect the relationship between high-risk patients (those with at least 
one lesion with PB ≥70%) and NC-MACE. The unadjusted HR of 3.0 is based on the 
results for PB in the original PROSPECT study. 
 
Assuming the prevalence of high-risk patients will be 50% based on maxLCBI4mm > 
the upper quartile of observed values and an overall event rate remaining constant at 
8.5%, the register will have >99% power to detect an unadjusted HR of 3.0 on a patient-
level analysis. In the patient-level analysis, it is again assumed that the HR for 
maxLCBI4mm will be similar to the HR for PB, and thus the unadjusted HR of 3.0 is 
based on the results for PB in the original PROSPECT study. 
16.5.3  
LESION-LEVEL ANALYSIS 
In the original PROSPECT study, by VH and grayscale IVUS, 2880 NCL were 
identified in 609 patients or 4.7 lesions per patient. Thus, it is estimated that in the 600 
patients in the register having no NCL with PB <70% there will be 2820 NCL detected. 
Based on grayscale IVUS in the original PROSPECT study, 288 lesions with PB ≥70% 
were identified in 220 patients, or approximately 1.3 lesions per patient. Thus, in the 
300 patients randomized into PROSPECT ABSORB (Randomized Trial), it is 
estimated that 1020 untreated NCL with PB <70% and 240 untreated NCL with PB 
≥70% will be detected. This includes 195 untreated NCL with PB ≥70% and 510 
untreated NCL with PB <70% in the 150 patients from the control arm of the 
PROSPECT ABSORB (Randomized Trial), and 45 untreated NCL with PB ≥70% and 
510 untreated NCL with PB <70% in the 150 patients from the BVS arm of PROSPECT 
ABSORB (Randomized Trial). Assuming 2% of the images will be unable to be read 
leaves a total of 3763 untreated NCL with PB <70% and 235 untreated NCL with PB 
≥70%. 
 
Thus, 5.9% of all untreated NCL would be considered high-risk according to the criteria 
of plaque burden ≥70% (as compared to 9% of lesions in the PROSPECT study). The 
reduction occurs because approximately 150 lesions with PB ≥70% as assessed by the 
site and treated with BVS are excluded from the analysis, thus reducing the overall 
prevalence. 
 
In the original PROSPECT study, the per-lesion 2-year event rate attributed to lesions 
with PB ≥70% was 8.7% vs 0.8% in lesions with PB <70%. Thus, the assumed overall 
per-lesion event rate given the number of lesions calculated above is 1.3%. 

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Additional assumptions used in the power calculations are as follows: 
 Two-tailed test α = 0.05 
 R-squared of high-risk lesions with other variables in the model is 0.1 for 
adjusted analyses (conservatively estimated from PROSPECT) 
 Proportional hazards 
 
The primary analysis will be adjusted for covariates, chosen a priori and partly based 
on the results of the original PROSPECT study. The preliminary list of covariates 
includes: age, sex, diabetes mellitus (none, medically-treated without insulin, insulin-
treated); hypertension, prior PCI, clinical presentation (STEMI versus NSTEMI), high-
dose statin (atorvastatin ≥40 mg or rosuvastatin ≥20 mg) and/or any PCSK9 inhibitor 
(evolocumab or alirocumab) use as a time-dependent variable (updated at baseline, 
discharge, and each subsequent follow-up visit), and total imaged NIRS-IVUS length 
(mm). An unadjusted analysis will also be conducted. The power analysis will be 
presented under both conditions. 
 
Given the above assumptions and using a Cox regression of time to NC-MACE on the 
binary independent variable (positive versus negative observation), the power for 
various scenarios are shown below. 
 
In an adjusted analysis for PB, assuming an overall event rate of 1.3%, an adjusted HR 
of 5.0 and 3998 lesions (of which 5.9% are high-risk lesions), there would be 73.4% 
power to detect the relationship between high-risk NCL and NC-MACE. The adjusted 
HR of 5.0 is based on the results for PB  ≥70% in the original PROSPECT study. 
 
With NIRS, it is expected that a similar or higher rate of high-risk lesions will be 
detected based on maxLCBI4mm greater than or equal to the upper quartile of observed 
values compared with PB. Based on the VH-TCFA data from PROSPECT, it is 
assumed that the prevalence of high-risk lesions based on maxLCBI4mm greater than or 
equal to the upper quartile of observed values will be approximately 19%. Given the 
overall event rate remaining constant at 1.3%, there will be 91.9% power to detect an 
adjusted HR of 3.5. The adjusted HR of 3.5 is conservatively based on the results for 
VH-TCFA in the original PROSPECT study, although it is expected that analysis for 
maxLCBI4mm will result in a stronger association. 
 
In an unadjusted analysis for PB, assuming an overall event rate of 1.3%, an unadjusted 
HR of 8.0 and 3998 lesions (of which 5.9% are high-risk lesions), there would be 94.2% 
power to detect the relationship between high-risk NCL and NC-MACE. The 
unadjusted HR of 8.0 is based on the results for PB in the original PROSPECT study. 
 
Assuming again that the prevalence of high-risk lesions based on maxLCBI4mm greater 
than or equal to the upper quartile of observed values will be approximately 19% and 
an overall event rate remaining constant at 1.3%, there will be 97.5% power to detect 
an unadjusted HR of 4.0. The unadjusted HR of 4.0 is conservatively based on the 
results for VH-TCFA in the original PROSPECT study, although it is expected that 
analysis for maxLCBI4mm will result in a stronger association. 

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16.5.4 
POWER ANALYSIS AND SAMPLE SIZE ESTIMATE 
FOR PROSPECT-ABSORB (RANDOMIZED TRIAL)  
Patients are entered into the randomized trial with lesions with site-determined PB 
≥65%, which should be equivalent to core laboratory assessed PB ≥70%. Assuming a 
mean MLA at baseline of 4.41 ± 1.60 mm2 in each group at baseline (data from 
PROSPECT in NCL with PB ≥70%), and assuming the MLA at 25 months will 
decrease in the control group to 4.01 ± 1.60 mm2 versus an increase to 5.16 mm2 in the 
Absorb BVS arm (an absolute 1.15 mm2 difference between the groups), and assuming 
the same standard deviation in each group, then evaluating  140 patients (each with 1 
randomized lesion with PB ≥70%) 1:1 to Absorb BVS + GDMT versus GDMT alone 
yields 99% power to demonstrate this difference with a 2-sided α = 0.05. Assuming 
~75% angiographic and IVUS follow-up, a minimum of 187 subjects would need to  be 
randomized. With 196 subjects randomized and 75% angiographic follow up, Prospect-
Absorb would also have 80% power to detect a smaller absolute difference of 0.75 mm2.  
The trial would also have 80% power to detect an absolute difference of 1.15 mm2 with 
64 evaluable subjects (86 subjects randomized assuming 75% angiographic and IVUS 
follow-up).  
 
For patients with multiple lesions with PB ≥70%, only 1 lesion will be randomized, 
generally the lesion in the most proximal non-target vessel supplying the largest amount 
of myocardium. This lesion will be declared to the IVRS system prior to randomization. 
16.6  
STATISTICAL ANALYSIS FOR PROSPECT II 
(NATURAL HISTORY STUDY) 
Baseline demographic, clinical, angiographic, grayscale IVUS, NIRS, and outcome 
variables will be summarized for lesions with and without vulnerable plaque defined 
by both NIRS and IVUS as well as the overall population. For NIRS, the cutoff is 
defined as maxLCBI4mm greater than or equal to the upper quartile of observed values. 
Additional cutoffs of (1) maxLCBI4mm ≥400 (2) ≥lower quartile vs <lower quartile, and 
(2) ≥400 vs ≥100 and <400 vs <100 (definition of lipid-rich plaque (LRP) category) 
will also be examined. For IVUS, PB ≥70% and MLA ≤4.0 mm2 will be used as pre-
specified cutoff values (both features having been identified in PROSPECT as 
independent predictors of future AEs). These analyses will include all untreated lesions 
from the PROSPECT II natural history study (n=600 patients), the GDMT-only arm 
from the PROSPECT ABSORB randomized trial (n=150 patients), and the untreated 
NCL from the BVS arm of the PROSPECT ABSORB randomized trial (n=150 
patients). Subject-level analyses will also be presented for patients with versus without 
lesions containing high-risk features (including PB ≥70%, and/or maxLCBI4mm greater 
than or equal to the upper quartile of observed values (and ≥400), and/or MLA ≤4.0 
mm2, and/or other characteristics as identified by univariate and multivariate analysis.  
16.6.1  
 PRIMARY ENDPOINT ANALYSIS  
The primary endpoint in PROSPECT II is rate of NC-MACE in all patients throughout 
the whole study period assessed when the last patient has been followed for 24 months 
on a patient level. Cox proportional hazards model will be used to test the relationship 
between vulnerable plaque patients and NC-MACE. Overall event rates will be 

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presented as well as the HRs and 95% confidence intervals. Patients will be censored 
based on the last known follow-up. The assumption of proportional hazards will first 
be tested by plotting the log-negative-log survival curves vs the log of survival time for 
each level of treatment group. If it is determined that the proportional hazard 
assumption is violated, then a logistic regression will be performed adjusting for time 
of follow-up in each group. The primary analysis set for this analysis is the FAS analysis 
set. 
 
Both unadjusted and covariate adjusted analyses will be performed. The primary 
analysis is specified as the adjusted analysis. 
 
16.6.2  
 MAJOR SECONDARY ENDPOINT ANALYSIS  
The major secondary endpoint in PROSPECT II is NC-MACE on a lesion level. Cox 
proportional hazards model will be used to test the relationship between high-risk lesion 
characteristics and NC-MACE. Lesions will be censored based on the last known 
follow-up for the patient. Other analysis details are as described above. 
 
For this secondary analysis, the Wei-Lin-Weissfeld method will be used. A robust 
sandwich covariance matrix estimate will be used to account for the within-patient 
dependencies (correlations of lesions within each patient). 
16.6.3 
SENSITIVITY ANALYSIS 
Sensitivity analyses for the primary endpoint and major secondary endpoints will be 
described in the Statistical Analysis Plan. 
16.6.4 
ADDITIONAL SECONDARY ANALYSES 
Secondary endpoints including clinical and imaging, will be analyzed in a similar way 
as the primary and major secondary endpoints above, or, as applicable, as described in 
the General Methods section. The univariate and multivariate analyses will be 
performed, in general, for all study time points at patient level, vessel level, and lesion 
level, as applicable and detailed in the SAP. 
 
An additional analysis of the primary endpoint will be performed removing the patients 
who had a single vulnerable plaque treated by Absorb BVS and who had no other 
vulnerable plaque lesions. 
 
PB, maxLCBI4mm, MLA, and other covariates will also be analyzed as continuous 
variables in the Cox regression model. 
 
MACE will also be analyzed (culprit-lesion related, NC-MACE, or indeterminate) in 
univariate and multivariate analyses, performed for all study time points at the patient 
level, vessel level, and lesion level. 
 
The correlation of the PB, maxLCBI4mm, MLA, and other continuous variables will be 
explored and reported. 

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An ROC analysis will be conducted to additionally report the “optimal” cutoff for PB, 
maxLCBI4mm, MLA and other continuous variables based on the current data. 
 
16.6.5 
SAFETY ANALYSIS 
The analysis set for this analysis is the SA analysis set. 
 
The primary safety endpoint in PROSPECT II is major complications of IVUS/NIRS 
imaging 
of 
3 
vessels, 
defined 
as 
imaging-related 
death, 
or 
vessel 
dissection/perforation/spasm or other complication requiring percutaneous or surgical 
treatment (including pericardiocentesis), during the hospitalization in which the 
imaging was performed, as assessed by the ACL . The number and percent of 
complications will be presented on a patient level for the entire study, not broken down 
by imaging risk group.  
 
Other safety endpoint analyses:  
 In-hospital (index culprit-lesion PCI-related) MACE 
 
Note: For patients who undergo planned staged procedures, adverse events from both 
procedures will add to the categorical measurement of imaging-related and culprit-
lesion PCI-related in-hospital event rates. All other event rates are determined in time-
to-first event analyses from the time of enrollment. 
16.6.7 
ANALYSIS WINDOW 
Clinical follow-up for the primary endpoints should occur at 24 months ± 14 days, prior 
to the imaging follow-up for those patients in the PROSPECT ABSORB cohort. For 
clinical endpoints, a year is defined as 365 days. Analyses up to 24 months will include 
all data/events occurring up to and including 730 days. 
16.6.8 
HANDLING OF DROPOUTS AND MISSING DATA 
For the primary safety endpoint of NC-MACE all available data will be used and 
dropouts will be censored at their last known status time. 
16.7 
STATISTICAL ANALYSIS FOR PROSPECT 
ABSORB (RANDOMIZED TRIAL) 
Baseline demographic, clinical, angiographic, grayscale IVUS, and outcome variables 
(including follow-up imaging data) for the randomized cohort (300 patients) will be 
summarized for Absorb BVS + GDMT versus GDMT alone as well as the overall 
population. These analyses will be conducted in the FASA and PPA analysis sets. 
Safety analyses will be conducted on SAA. 

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16.7.1  
 PRIMARY EFFICACY ENDPOINT ANALYSIS 
The primary efficacy endpoint is the IVUS MLA at 25 months in the randomized 
lesions. The mean MLA in each group will be presented along with the difference 
between groups and 95% confidence intervals and compared via analysis of covariance, 
adjusted for baseline MLA. 
 
The analysis set for the primary endpoint is the ITT analysis set. Imaging results will 
be reported from the IVUS analysis set. 
16.7.2  
SENSITIVITY ANALYSIS 
As a sensitivity analysis, the primary analysis of the primary efficacy endpoint, will be 
conducted including images obtained outside the pre-defined window. 
 
To assess the impact of missing values from patients with insufficient follow-up on the 
primary study endpoint, the primary analysis of the primary efficacy endpoint will be 
repeated where, in the FAS, patients with insufficient follow-up will have their data 
imputed via multiple imputation by the MCMC algorithm. The resulting estimates and 
confidence intervals will be presented 
16.7.3  
 SECONDARY EFFICACY ENDPOINTS ANALYSIS 
Secondary endpoints including clinical and imaging, will be analyzed in a similar way 
as the primary and major secondary efficacy endpoints above. The univariate and 
multivariate analyses will be performed, in general, for all study time points at patient 
level, vessel level, and lesion level, as applicable and detailed in the SAP. 
 
Study lesion (randomized)-level endpoints and patient-level endpoints related to the 
randomized lesion and vessel will be analyzed between the treatment groups, stratified 
by severity of LRP (NIRS) at baseline (by maxLCBI4mm and LCBI in separate models).  
 
A NC-MACE bivariate analysis will be performed by treatment for all PROSPECT II 
covariates, at study time points, and at patient level, vessel level, and lesion level.  
16.7.4  
SAFETY ENDPOINT ANALYSIS 
The analysis set for the safety endpoints is the Safety Analysis set (SAA). 
 
The primary safety endpoint is TLF (cardiac death, target-vessel myocardial infarction, 
or ischemia-driven TLR) up to 24 months (prior to routine imaging follow-up). Patients 
will be censored at the time of their 24-month clinical follow-up, or if this did not occur, 
just prior to the time of the routine imaging follow-up, or at their last known status time. 
 
Other safety endpoint analyses: 
 TLF measured at 1 month, 6 months, 12 months, 24 months, and possibly yearly 
through 15 years will be analyzed in the same way as for the primary TLF time 
point. 

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 Periprocedural (Absorb BVS procedure-related) MACE will be analyzed in a 
Cox proportional hazards model, by treatment, with only maxLCBI4mm and, 
respectively, LCBI as covariates, at lesion level, vessel level, and patient level. 
 
Scaffold thrombosis (definite or probable per ARC definition) as per CEC and 
Core Lab adjudication measured at 1 month, 6 months, 12 months, 24 months, 
and possibly yearly through 15 years 
- 
Temporal classification: 
- 
All 
- 
Acute (0 to 24 hours after stent implantation) 
- 
Subacute (>24 hours to 30 days after stent implantation) 
- 
Late (>30 days to 1 year after stent implantation) 
- 
Very late (>1 year after stent implantation) 
 Complications of IVUS/NIRS imaging during PCI will be analyzed in a 
similar way with the primary safety endpoint: 
o Core lab assessed and adjudicated 
o Site assessed 
16.7.5 
ANALYSIS WINDOW 
Imaging follow-up for patients in PROSPECT ABOSRB should occur at 25 
months (from 24.5 months to28 months); 25-month angiographic follow-up 
will not be required in PROSPECT-ABSORB randomized patients who either 
a) have had scaffold thrombosis or in-scaffold restenosis (DS>50% as 
determined by the angiographic core laboratory) at any time point prior to 25 
months, OR b) have had a repeat angiogram ≥12 months after enrollment and 
in whom IVUS/NIRS of the randomized target lesion was performed. The 
imaging data from such patients will be included in the primary analysis dataset. 
These exceptions notwithstanding, a sensitivity analysis will be conducted including 
images obtained outside the window for the primary efficacy endpoint. 
 
Clinical follow-up for the primary safety endpoint should occur at 24 months ± 2 weeks, 
prior to the imaging follow-up. For clinical endpoints, a year is defined as 365 days. 
Analyses up to 24 months will include all data/events occurring up to and including 730 
days.  
 
See Study Flow Chart in Appendix II. 
16.7.6 
HANDLING OF DROPOUTS AND MISSING DATA 
For the primary safety endpoint of NC-MACE all available data will be used and 
dropouts will be censored at their last known status time. 
 
For the primary efficacy endpoint of MLA, all available data will be used. In addition, 
as a sensitivity analysis in the FAS group, in order to assess the impact of missing values 
from patients with insufficient follow-up on the primary study endpoint, patients with 
insufficient follow-up will have their data imputed via multiple imputation by the 
MCMC algorithm. The resulting estimates and confidence intervals will be presented. 
 

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For all other analyses, only available data will be analyzed. 
16.8 
SUBGROUP ANALYSIS 
For PROSPECT II, subgroup analysis will be performed for the primary and major 
secondary endpoints by age, sex, the presence of medically treated or insulin-treated 
diabetes mellitus, metabolic syndrome status, prior history of MI, prior PCI, clinical 
presentation (STEMI versus NSTEMI), maxLCBI4mm (cutoffs defined as: the upper 
quartile of observed NCL values, median of observed NCL values, ≥400 versus <400, 
categorized into 3 groups: ≥ upper quartile versus < upper quartile and ≥ lower quartile 
versus < lower quartile, and categorized into 3 groups: ≥400 versus ≥100 and <400 
versus <100), plaque burden (cutoffs defined as: ≥70% versus <70%, <40% versus 
≥40% to <50% versus ≥50% to 60% versus ≥60% to 70% versus ≥70% to <80% versus 
>80%, and median of observed NCL values), MLA (cutoff defined as: ≤4 versus >4 
mm2, and median of observed NCL values), remodeling index (positive remodeling is 
defined as remodeling index >1.0, negative remodeling is defined as remodeling index 
<0.88, intermediate remodeling is defined as remodeling index ≥0.88 and ≤1.0), lesion 
length by IVUS (cutoff defined as the median of observed NCL values), distance from 
ostium to the MLA by IVUS (cutoff defined as the median of observed NCL values), 
renal insufficiency (calculated creatinine clearance <60 versus ≥60 mL/min), white 
blood cell count (cutoff defined as the median of observed values, use of aggressive 
lipid lowering agents at baseline, and baseline levels of LDL, HDL, and hs-CRP 
(cutoffs defined as the median of observed values). Other subgroups and endpoints may 
be analyzed. Forest plots for all primary endpoints will be constructed. Periprocedural 
(Absorb BVS PCI procedure) MACE will be analyzed by levels of maxLCBI4mm (cutoff 
defined as the upper quartile of observed values). 
 
For PROSPECT ABSORB, the major subgroup of interest will be for the safety results 
(patient level) and efficacy results (lesion level), for the primary endpoint of MLA at 
25-month IVUS follow-up, according to whether the baseline maxLCBI4mm was greater 
than or equal to versus less than the upper quartile of observed values; greater than or 
equal to versus less than the median of observed values; or greater than or equal to 
versus less than 400. Additional subgroups and endpoints, as in the PROSPECT II 
analysis, may also be analyzed, including using PB and MLA as covariates. Other 
covariates for the primary endpoint will be reference vessel area by IVUS (cutoff 
defined as the median of observed values), the presence of calcification by IVUS (cutoff 
defined as <180 versus ≥180 degrees)). 
16.9  
DEVIATIONS FROM PROTOCOL ANALYSIS PLAN 
Details of the statistical analysis will be outlined in a study-specific SAP. Any changes 
to analyses planned in the final version of the protocol will be described and justified 
in the SAP and noted in the final study report.  
16.10  
INTERIM ANALYSIS AND STOPPING RULES 
There are no planned formal interim analyses in this study. If the pooled event rate is 
lower than expected, and/or the 24-month clinical results are of sufficient interest and 
import to warrant additional follow-up, patient follow-up in PROSPECT 

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II/PROSPECT ABSORB may be extended beyond 2 years to a maximum of 15 years 
to collect additional events. 
 
There will be an independent DSMB assigned to review data during the course of the 
study. Details and any potential stopping rules suggested by this committee will be 
described in the DSMB Charter. See also section 10.6. 
 
17 
MONITORING PLAN 
Monitoring will be performed by the Sponsor or its designee in accordance with the 
principles of International Conference on Harmonisation (ICH) GCP, the EN ISO 
14155, and Sponsor SOPs. During the study, the monitor will have regular contacts 
with the study sites, including visits, where necessary, to ensure that the study is 
conducted and documented properly.  
The extent of monitoring will be described in the monitoring plan prepared by the 
Sponsor. The monitor will ensure that accountability of investigational products is 
performed and will review source documents for verification of consistency (source 
data verification) with the data recorded in the eCRFs. The monitor will also provide 
information and support to the investigator sites.  
 
18 
CRITERIA FOR TERMINATION OF THE STUDY 
The Executive Committee reserves the right to discontinue the study prior to inclusion 
of the intended number of subjects, but intends to exercise this right only for valid 
scientific or administrative reasons. After such a decision, all delivered unused study 
device and other study-related materials must be collected without delay and eCRFs 
must be completed as far as possible. 
The study could be prematurely discontinued in the following cases (examples): 
 New findings about the study device(s) that changes the benefit/risk ratio. 
 Investigational plan is difficult to cope with. 
 Recruitment of eligible subjects is far too low. 
 Unacceptable low Investigator, Academic Sponsor or subject compliance. 
 Critical change in personnel, administrative, or scientific standards at either the 
coordinating academic research organizations or at the study site(s). 
 
19 
QUALITY ASSURANCE 
The Regulatory Sponsor representative or designee may request access to all study 
records, including source documentation, for inspection and duplication during a 
quality assurance audit. In the event that an investigator is contacted by a regulatory 
agency in relation to this study, the Investigator will notify UCR immediately. The 
Investigator and Research Coordinator must be available to respond to reasonable 

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requests and audit queries made during the audit process. The Investigator must provide 
the Sponsor with copies of all correspondence that may affect the review of the current 
study. The Regulatory Sponsor may provide any needed assistance in responding to 
regulatory audits. 
 
20 
CONFIDENTIALITY 
Patients providing a signed informed consent are agreeing to allow the Sponsor and/or 
the coordinating academic research organizations access to pertinent information in 
their medical records concerning their participation in this study. This information will 
be shared with regulatory bodies. This Investigational Plan, documentation data, and 
all other information generated will be held in strict confidence by the Investigator and 
their representatives. No information concerning the study or the data will be released 
to any unauthorized third party without prior written approval by the Sponsor. 
 
21 
COMPLIANCE TO STANDARDS AND REGULATIONS 
The study will be conducted in accordance with the Investigational Plan, applicable 
regulatory requirements, ICH GCP, EN ISO 14155, and the ethical principles of the 
Declaration of Helsinki as adopted by the 18th World Medical Assembly in Helsinki, 
Finland, in 1964 and subsequent versions. 
22 
INSURANCE 
Study patients are insured by Local Country Patient Insurances of Sweden, Denmark, 
and Norway. Appropriate product insurances are held by InfraReDx Inc and Abbott 
Vascular for their respective products in the study.  
 
23 
PUBLICATION POLICY 
All information not previously published concerning the investigational product, 
including patent applications, manufacturing processes, basic scientific data, etc, is 
considered as confidential and should remain the sole property of the manufacturing 
company. The Investigator agrees to use this information only in connection with this 
study and will not use it for other purposes without written permission from the 
Sponsor.  
The coordinating academic research organizations will each maintain a copy of the 
complete final and locked dataset to facilitate joint academic projects. After completion 
of the study, statistical analyses will be performed by CRF and the Sponsor in 
collaboration with the Coordinating Principal Investigators, and the results will be 
presented to the funding manufacturers Based on these data, a clinical study report will 
be prepared and the data will be presented at one or more major international medical 
congresses, and at least two manuscripts (PROSPECT II and PROSPECT ABSORB) 
intended for publication in major medical/scientific journals will be prepared. These 

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presentations and publications will report the combined results from all centers. No 
presentations or publications from individual sites are permitted until publication of 
these two joint manuscripts. Before public presentation or publication of the results, the 
funding manufacturers will be given the opportunity to review and to provide non-
binding comments on the presentations/manuscripts. The publication procedure for the 
principal and subsequent presentations and publications will be defined in more detail 
in a Publication Charter. 
 
24 
COMMITTEES 
24.1 
DATA SAFETY MONITORING BOARD (DSMB) 
The DSMB will comprise at least three members. The DSMB members will not have 
any affiliation with CRF, the Sponsor, the Coordinating Principal Investigators, the core 
labs, or the clinical investigation sites. The DSMB will be responsible for making 
recommendations to the Executive Committee regarding any potentially significant 
safety-related observations. 
24.2 
CLINICAL ENDPOINT CLASSIFICATION (CEC) 
The independent CEC group at UCR will be composed of interventional and/or non-
interventional cardiologists who are not participants in the study and are independent 
from the study. The CEC group will review and adjudicate all potential MACE events. 
In parallel, the ACL at CRF will be responsible for reviewing and analyzing all repeat 
angiograms to determine lesion progression and if an event was related to the culprit 
lesion or NCL or the randomized BVS lesion and if revascularization was performed. 
All details of the CEC and ACL process are specified in the CEC and ACL charter 
respectively.   
24.3 
OPERATIONS COMMITTEE (OC) 
The Operations Committee (OC) is a Regulatory Sponsor-designated team comprising 
the Coordinating Principal Investigators, the Sponsor, and CRF representatives and 
coordinated by the Regulatory Sponsor PM. Representatives from the funding 
companies are represented as appropriate. The OC will be responsible for the day-to-
day administrative management of the study. This OC will monitor patient enrollment, 
clinical site progress, and Investigational Plan compliance. The OC will provide 
assistance to the sites with study management issues, including compliance with 
specific record keeping and reporting requirements. 
24.4 
STEERING COMMITTEE (SC) 
The Steering Committee (SC) is responsible for overseeing the operational progress of 
the study. The SC comprises the Study Chairs/Coordinating Principal Investigators, the 
National Coordinators, and representatives of the Sponsor and the coordinating 
academic research organizations. The funding companies will be represented as 
appropriate. This SC will meet regularly to discuss patient accrual, the Investigational 

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Plan and amendments, actions upon recommendations of the DSMB, etc. SC members 
are listed in a separate document 
24.5 
EXECUTIVE COMMITTEE (EC) 
The Executive Committee (EC) is responsible for overseeing the administrative 
progress of the investigational plan. The EC comprises the Study Chairs, and 
representative(s) from the Coordinating Academic Research Organizations. Other 
representatives may participate in the EC meeting if appropriate. This committee will 
meet regularly to monitor patient accrual, non-compliance with the Investigational Plan 
at individual centers, to review and act upon recommendations of the DSMB, and to 
determine policy regarding any publications arising from data generated from the 
performance of the study. EC members are listed in a separate document. 
 
25 
STUDY ADMINISTRATIVE STRUCTURE  
A separate document as part of the Trial Master File/Investigator File will specify the 
study administrative structure including Sponsor representatives, responsible 
collaborative parties, the EC, SC, and OC, and the study sites. This document will be 
updated regularly as needed and distributed as appropriate. 
 
 

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26 
REFERENCES  
1. 
Organization WH. The global burden of disease: 2004 update. Geneva, 
Switzerland: WHO Press, 2008. 
2. 
White HD, Chew DP. Acute myocardial infarction. Lancet 2008;372:570-84. 
3. 
Virmani R, Kolodgie FD, Burke AP, Farb A, Schwartz SM. Lessons from 
sudden coronary death: a comprehensive morphological classification scheme 
for atherosclerotic lesions. Arterioscler Thromb Vasc Biol 2000;20:1262-75. 
4. 
Muller JE, Tofler GH, Stone PH. Circadian variation and triggers of onset of 
acute cardiovascular disease. Circulation 1989;79:733-43. 
5. 
Stone GW, Maehara A, Lansky AJ, et al. A prospective natural-history study of 
coronary atherosclerosis. N Engl J Med 2011;364:226-35. 
6. 
Calvert PA, Obaid DR, O'Sullivan M, et al. Association between IVUS findings 
and adverse outcomes in patients with coronary artery disease: the VIVA (VH-
IVUS in Vulnerable Atherosclerosis) Study. JACC Cardiovasc Imaging 
2011;4:894-901. 
7. 
Stone PH, Saito S, Takahashi S, et al. Prediction of progression of coronary 
artery disease and clinical outcomes using vascular profiling of endothelial 
shear stress and arterial plaque characteristics: the PREDICTION Study. 
Circulation 2012;126:172-81. 
8. 
Gardner CM, Tan H, Hull EL, et al. Detection of lipid core coronary plaques in 
autopsy specimens with a novel catheter-based near-infrared spectroscopy 
system. JACC Cardiovasc Imaging 2008;1:638-48. 
9. 
Madder RD, Goldstein JA, Madden SP, et al. Detection by near-infrared 
spectroscopy of large lipid core plaques at culprit sites in patients with acute 
ST-segment elevation myocardial infarction. JACC Cardiovasc Interv 
2013;6:838-46. 
10. 
Erlinge D, Muller JE, Puri R. Validation of a near-infrared spectroscopic 
signature of lipid located at culprit lesions in ST-segment elevation myocardial 
infarction. 81st Congress of the European Atherosclerosis Society. Lyon, 
France, 2013. 
11. 
Brugaletta S, Radu MD, Garcia-Garcia HM, et al. Circumferential evaluation of 
the neointima by optical coherence tomography after ABSORB bioresorbable 
vascular scaffold implantation: can the scaffold cap the plaque? Atherosclerosis 
2012;221:106-12. 
12. 
Zhao Z, Witzenbichler B, Mintz GS, et al. Dynamic nature of nonculprit 
coronary artery lesion morphology in STEMI: a serial IVUS analysis from the 
HORIZONS-AMI trial. JACC Cardiovasc Imaging 2013;6:86-95. 
13. 
Muramatsu T, Onuma Y, van Geuns RJ, et al. 1-year clinical outcomes of 
diabetic patients treated with everolimus-eluting bioresorbable vascular 
scaffolds: a pooled analysis of the ABSORB and the SPIRIT trials. JACC 
Cardiovasc Interv 2014;7:482-93. 

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27  
LIST OF APPENDICES 
 
Appendix I. 
Acronyms and Abbreviations 
 
Appendix II. 
Study Flow Chart/Schedule of Procedures 
 
Appendix III. 
Angiography Guidelines 
 
Appendix IV. IVUS/NIRS Guidelines 
 
Appendix V: 
Endpoint Definitions (Copied from CEC Charter) 
 
 

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APPENDIX I  
ACRONYMS AND ABBREVIATIONS 
ACC 
American College of Cardiology 
ACL 
Angiographic Core Laboratory 
ACS 
Acute Coronary Syndromes 
AHA 
American Heart Association 
BVS 
Bioresorbable vascular Scaffold 
CABG 
Coronary artery bypass graft 
CASS 
Coronary Artery Surgery Study 
CE 
Conformité Européenne 
CEC 
Clinical endpoint classification 
CK-MB 
Creatine kinase – myocardial band isoenzyme 
CRF 
Cardiovascular Research Foundation 
eCRF 
Electronic case report form 
DCF 
Data clarification form 
DES 
Drug-eluting stent 
DMP 
Data management plan 
DS 
Diameter stenosis 
DSMB 
Data safety monitoring board 
DVP 
Data validation plan 
EC 
Executive committee 
ECG 
Electrocardiogram 
EEM 
External elastic membrane 
ESC 
European Society of Cardiology 
FAS 
Full analysis set 
FASA 
Full analysis set – PROSPECT ABSORB 
FFR 
Fractional flow reserve 
GDMT 
Guideline-directed medical therapy 
GCMP 
Good clinical manufacturing practice 
GCP 
Good clinical practice 
HbA1c 
Glycosylated hemoglobin 
HDL 
High-density lipoprotein 
HR 
Hazard ratio 
hs-CRP 
high-sensitivity C-reactive protein 
ICH 
International Conference on Harmonisation 
IEC 
Independent ethics committee 
iFR 
Instantaneous wave-free ratio 
IFU 
Instructions for use 
IRB 
Investigational review board 
IVUS 
Intravascular ultrasound 
LAD 
Left anterior descending coronary artery 
LCBI 
Lipid core burden index 
LCP 
Lipid core plaque 
LCX 
Left circumflex coronary artery 
LDL 
Low-density lipoprotein 
LRP 
Lipid-rich plaque 
MACE 
Major adverse Cardiac event 

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maxLCBI4mm Maximum lipid core burden index over a 4-mm length 
MI 
Myocardial infarction 
MLA 
Minimum lumen area 
MLD 
Minimum lumen diameter 
NCL 
Non-culprit lesion 
NC-MACE 
Non-culprit major adverse cardiac event 
NIRS 
Near-infrared spectroscopy 
NSTEMI 
Non–ST-segment elevation myocardial infarction 
OC 
Operations Committee 
PB 
Plaque burden 
PCI 
Percutaneous coronary intervention 
PDLLA 
Polymer poly (D,L-lactide) 
PLA 
Polyactic acid 
PLLA 
Polymer poly (L-lactide) 
PPA 
Per protocol – PROSPECT ABSORB 
QCA 
Quantitative coronary angiography 
OCT 
Optical coherence tomography 
RCA 
Right coronary artery 
RVD 
Reference Vascular Diameter 
SA 
Safety analysis set 
SAA 
Safety analysis set – PROSPECT ABSORB 
SADE 
Serious adverse device effect 
SAE 
Serious adverse event 
SAP 
Statistical analysis plan 
SC 
Steering Committee 
SCAI 
Society for Cardiac Angiography and Interventions 
STEMI 
ST-segment elevation myocardial infarction 
TCFA 
Thin-cap fibroatheroma 
TIMI 
Thrombolysis In Myocardial Infarction 
TLF 
Target lesion failure 
TLR 
Target lesion revascularization 
UCR 
Uppsala Clinical Research Center 
USADE 
Unanticipated serious adverse device effect 
VH-IVUS 
Virtual histology-intravascular ultrasound 
VH-TCFA 
Virtual 
histology 
intravascular 
ultrasound- 
derived 
thin-cap 
fibroatheroma 
 
 

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APPENDIX II 
STUDY FLOW CHART/SCHEDULE OF PROCEDURE 
 
 

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Schedule of Procedure 
 
 
 
 
 
 
 
 
PROSPECT II/ 
PROSPECT 
ABSORB  
All Patients 
Telephone Follow-up 
(All patients) 
 
PROSPECT Absorb 
(Randomized trial) 
Unexpected Visits 
up to 24 months 
follow-up 
Optional Telephone FU 
Yearly FU 
Years 3-158 
Schedule of Procedures 
Baseline/enrollment 
1 month 
(30 
days) 
± 7 days 
 
6 months 
(180 
days) 
± 14 days 
12 
months 
± 30 days  
24 months7 
± 14 days 
25 months 
(range 24.5 – 28 
months) 
 
 
 
Eligibility criteria1 
x 
 
 
 
 
 
 
 
Informed consent 
x 
 
 
 
 
 
 
 
Coronary angiogram2 
x 
 
 
 
 
X10 
X  
 
IVUS&NIRS imaging of 
target lesions (if possible) 
x 
 
 
 
 
X10 
 
 
PCI of culprit 
x 
 
 
 
 
 
X  
 
IVUS& NIRS imaging for 
all 3 coronary vessels1,2 
x 
 
 
 
 
X10 
X  
 
Check for possible 
randomization to 
PROSPECT ABSORB 
(Randomized trial)3 
x 
 
 
 
 
 
 
 
PROSPECT ABSORB: 
IVUS& NIRS imaging of 
BVS treated lesion2 
x 
 
 
 
 
 
 
 
Concomitant medication4 
x 
x 
x 
x 
x 
X 
X 
X8 
Safety laboratory5  
x 
 
 
 
 
 
 
 
Biobank samples6 
x 
 
 
 
 
 
 
 
Adverse Event/Adverse 
Device Event 
x 
X9 
X9 
X9 
X9 
X 
X9 
 
Events for Adjudication 
(CEC) 
x 
x 
x 
x 
x 
X 
X 
X8 

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1. Patient is enrolled in PROSPECT II if the catheter is advanced out of the guide catheter. If the imaging catheter passed into a coronary artery for 
imaging a non-culprit segment of the coronary tree and no non-culprit segment imaging data is obtained (e.g. the catheter fails and a second catheter 
is not used), the patient will be disenrolled (discontinued) from the study, and only be followed up for safety purposes for 30 days. 
2. All films will be transferred to the Core Lab according to Study Manual of Operations 
3. If PB (plaque burden) ≥ 65% in non-flow obstructing stenosis patient is eligible for randomization to PROSPECT ABSORB (Randomized Trial) 
4. All prescribed cardiac medications will be recorded at the admission, during the catheterization and hospitalization, at discharge and at the schedule 
follow-ups. See protocol section 9.6 
5. Hemoglobin, WBC, platelet count, creatinine, HgbA1C, cholesterol, LDL, HDL, triglycerides, p-glucose, hs-Troponin  (before and after PCI)  and hs-
CRP at local laboratory  
6. Samples for cardiac biomarker/genetic analysis should be taken from the arterial sheath after diagnostic angiogram and before the PCI is performed. 
See protocol section 9.7.2 
7. For patients in PROSPECT ABSORB clinical (telephone) follow-up at 24 months must occur PRIOR to 25 months angiogram/IVUS/NIRS.  
8. Contingent on approval by the Executive Committee 
9. Only SADEs will be reported. See protocol section 10.5. 
10. 25-month angiographic follow-up will not be required in PROSPECT-ABSORB randomized patients who either a) have had scaffold thrombosis or 
in-scaffold restenosis (DS>50% as determined by the angiographic core laboratory) at any time point prior to 25 months, OR b) have had a repeat 
angiogram ≥12 months after enrollment and in whom IVUS/NIRS of the randomized target lesion was performed.  

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APPENDIX III 
ANGIOGRAPHY GUIDELINES 
Angiographic Core Laboratory 
Angiographic Protocol 
 
PROSPECT II 
Instruction to the sites 
 
1) Use ≥ 5 Fr diagnostic or guiding catheters, and provide documentation stating the 
size of the catheter 
2) Administer 100-200 mcg IC nitroglycerin and record in the Case Report Form 
before the baseline, final (post intervention) and follow-up angiograms, unless 
judged inappropriate by the investigator. 
3) Provide 2 matched orthogonal views of the lesion at baseline, after final 
intervention and at follow-up.  
4) Ensure the catheter is visible in all frames. 
5) Avoid overlapping of vessel, superposition with diaphragm, and the presence of 
foreign body in the angiogram (e.g. EKG leads). 
6) Film as much detail of the intervention as possible (pre and post stent placement, 
intraprocedural images, complications etc…). Film all intraprocedural adverse 
events – e.g. side branch closure, new thrombus, dissection, distal embolization, 
decreased flow, etc. 
7) Film all stent deployments so that we can accurately assess areas of stent overlap / 
gap. 
8) Make sure that you image at least 3 cardiac cycles of the culprit vessel at baseline, 
final intervention, and at follow-up for assessment of TIMI flow. Make sure that 
the entire vessel, including the distal vasculature, is fully imaged. 
9) Make sure that you remove the wire for the final view (post intervention)/ 
10)  At follow-up (angiographic sub-study or for clinical events requiring angiography) 
please provide the same 2 orthogonal views as at baseline intervention. 
11)  Use a DICOM CD-R or DVD for pre, final, follow-up and event angiograms if 
not otherwise specified in the study manual of operations. 
12)  For DICOM CD-R or DVD labels must include your site ID, the patient ID, the 
procedure date, and the procedure type (baseline, follow-up or event). 
 
Shipping Instruction  
 
Shipping of Baseline Procedural Angiogram and Follow-up or Event Angiogram to the core 
lab is specified in the study manual of operations. 
 

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APPENDIX IV  
IVUS/NIRS GUIDELINES 
(See also the Study Manual of Operations.) 
 
Imaging: Pre-intervention in the culprit vessel and post-intervention in all three 
vessels 
 
1. Anticoagulation with either heparin or bivalirudin should be administered prior 
to IVUS/NIRS imaging. ACT should be monitored and should be above 250 
seconds (and 200 seconds with heparin and concomitant glycoprotein 2b/3a 
use). 
2. Make sure that the IVUS catheter is properly flushed at least 3 times.  
3. Administer 100-200 µg (200 µg is recommended) of intracoronary nitroglycerine 
before all NIRS/IVUS examinations. 
4. Place the tip of NIRS/IVUS catheter as distally as possible in the coronary artery 
(minimum 6 cm if possible). 
5. Disengaging the guiding catheter before imaging is recommended. 
6. Start automatic pullback until the ostium of each vessel is reached and imaged. 
 
IVUS analysis at site to determine eligibility and lesion selection for PROSPECT-
ABSORB: 
 
1. Non-culprit lesion can be located in the culprit vessel as well as non-culprit 
vessel, but must be at least 10mm apart from the edge of a previous PCI 
(Figure1). 
2. Non-culprit lesion is defined as a segment 2mm in length which has 40% 
plaque burden in at least 3 slices. 
3. Non-culprit lesions are considered separate if there is a ≥5mm-long normal 
segment with <40% plaque burden between them (Figure2). 
4. Once you recognize a non-culprit lesion, look around the minimum lumen area 
(MLA) site which usually co-locates to the maximum plaque burden site. 
5. Contour both lumen and vessel area for 2-3 potential slices (Figure2).  
6. If the largest plaque burden ≥65%, this non-culprit lesion qualifies for 
randomization. 
7. In cases that have multiple non-culprit lesions with plaque burden ≥65%, the 
more proximal lesion should be randomized to PROSPECT ABSORB 
(example: NC lesion 1 should be randomized, Figure1). 
 
 
 

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APPENDIX V:  ENDPOINT DEFINITIONS (COPIED FROM CEC   
CHARTER) 
 
Death 
All deaths reported post-randomization will be recorded and adjudicated. 
Deaths will be sub-classified by CV and non-CV primary cause. CV death includes 
sudden cardiac death, death due to acute MI, death due to heart failure, death due to a 
cerebrovascular event, death due to other CV causes (e.g., pulmonary embolism, 
aortic disease, CV intervention), and deaths for which there was no clearly 
documented non-CV cause (presumed CV death).  
 
Cardiovascular Death 
Cardiovascular death includes sudden cardiac death, death due to acute myocardial 
infarction, death due to heart failure, death due to a cerebrovascular event, and death 
due to other cardiovascular causes, as follows: 
1.   Sudden Cardiac Death: refers to death that occurs unexpectedly and includes any 
of the following deaths: 
a.   Death witnessed and instantaneous without new or worsening symptoms 
b.   Death witnessed within 60 minutes of the onset of new or worsening cardiac 
symptoms  
c.   Death witnessed and attributed to an identified arrhythmia (e.g., captured on an 
electrocardiographic (ECG) recording or witnessed on a monitor by either a medic or 
paramedic) 
d.   Death after unsuccessful resuscitation from cardiac arrest or successfully 
resuscitated from cardiac arrest but who die within 24 hours without identification of 
a non-cardiac etiology 
e.   Death > 24hrs after a patient has been successfully resuscitated from cardiac arrest 
and without identification of a non-cardiovascular etiology 
f. Unwitnessed death or other causes of death (information regarding the patient’s 
clinical status within the week preceding death should be provided if available) 
 
2.   Death due to Acute Myocardial Infarction (MI): refers to a death within 30 days 
after a myocardial infarction (MI) related to consequences seen immediately after the 
myocardial infarction, such as progressive congestive heart failure (CHF), inadequate 
cardiac output, or refractory arrhythmia. If these events occur after a “break” (e.g., a 
CHF and arrhythmia free period), they should be designated by the immediate cause. 
The acute MI should be verified by the diagnostic criteria outlined for acute MI 
(including autopsy findings showing recent MI or recent coronary thrombus) and 
there should be no conclusive evidence of another cause of death. 
Sudden, unexpected cardiac death, involving cardiac arrest, often with symptoms 
suggestive of myocardial ischemia, and accompanied by presumably new ST 
elevation, or new LBBB and/or evidence of fresh thrombus by coronary angiography 
and/or at autopsy, but death occurring before blood samples could be obtained, or at a 
time before the appearance of cardiac biomarkers in the blood should be considered 
death due to acute myocardial infarction. Death resulting from a procedure to treat 
myocardial ischemia or to treat a complication resulting from myocardial infarction 
should also be considered death due to acute MI. If death occurs before biochemical 

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confirmation of myocardial necrosis can be obtained, adjudication should be based on 
clinical presentation and ECG evidence. Death due to a myocardial infarction that 
occurs as a direct consequence of a cardiovascular investigation/procedure/operation 
will be classified as death due to other cardiovascular cause. 
3.   Death due to Heart Failure or Cardiogenic Shock: refers to death occurring in the 
context of clinically worsening symptoms and/or signs of heart failure not in the 
context of an acute MI and without evidence of another cause of death. New or 
worsening signs and/or symptoms of congestive heart failure (CHF) include any of 
the following: 
a.   New or increasing symptoms and/or signs of heart failure requiring the initiation 
of, or an increase in, treatment directed at heart failure or occurring in a patient 
already receiving maximal therapy for heart failure. 
b.   Heart failure symptoms or signs requiring continuous intravenous drug therapy or 
oxygen administration 
c.   Confinement to bed predominantly due to heart failure symptoms 
d.   Pulmonary edema sufficient to cause tachypnea and distress not occurring in the 
context of an acute myocardial infarction or as the consequence of an arrhythmia 
occurring in the absence of worsening heart failure 
e.   Cardiogenic shock not occurring in the context of an acute MI or as the 
consequence of an arrhythmia occurring in the absence of worsening heart failure. 
Cardiogenic shock is defined as systolic blood pressure (SBP) < 90 mm Hg for 
greater than 1 hour, not responsive to fluid resuscitation and/or heart rate correction, 
and felt to be secondary to cardiac dysfunction and associated with at least one of the 
following signs of hypoperfusion: 
• Cool, clammy skin or 
• Oliguria (urine output < 30 mL/hour) or 
• Altered sensorium or 
• Cardiac index < 2.2 L/min/m2 
Cardiogenic shock can also be defined as SBP ≥ 90 mm Hg as a result of positive 
inotropic or vasopressor agents alone and/or with mechanical support in less than 1 
hour. This category will include sudden death occurring during an admission for 
worsening heart failure. 
4.   Death due to Cerebrovascular Event (intracranial hemorrhage or non-
hemorrhagic stroke). Refers to cerebrovascular event and/or the sequelae of which 
lead to death, generally within 30 days. The cerebrovascular event should be verified 
by the diagnostic criteria outlined for cerebrovascular events (including autopsy 
findings) and there should be no conclusive evidence of another cause of death. 
5.   Death due to Other Cardiovascular Causes: death must be due to a fully 
documented cardiovascular cause not included in the above categories (e.g. 
pulmonary embolism, aortic disease (dissection or rupture), pericardial tamponade, or 
cardiovascular intervention). 
6.   Presumed cardiovascular death: All deaths not attributed to the categories of 
cardiovascular death and not attributed to a non-cardiovascular cause, are presumed 
cardiovascular deaths and as such are part of the cardiovascular mortality endpoint. 
Of note, Coronary Heart Disease death will include the following categories; Sudden 
Cardiac Death, Death due to Acute MI, and the subset of Death due to other 
Cardiovascular Causes that are secondary to a coronary revascularization procedure. 
 

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Cardiac death 
The composite of sudden cardiac death, death due to acute myocardial infarction, 
death due to heart failure, death due to arrhythmia, or death not due to known vascular 
or non-CV causes. 
 
Non-Cardiovascular Death 
Non-cardiovascular death is defined as any death not covered by cardiovascular death 
and falling into one of the following categories: 
 Pulmonary failure 
 Renal failure 
 Gastrointestinal causes 
 Hepatobiliary 
 Pancreatic 
 Infection (includes sepsis) 
 Non-infectious (e.g. SIRS) 
 Hemorrhage that is neither CV bleeding or stroke  
 Non-CV procedure or surgery 
 Trauma 
 Suicide 
 Non-prescription drug reaction or overdose 
 Prescription drug reaction or overdose 
 Neurological (non-cardiovascular) 
 Malignancy  
 Other, please specify. 
 
 
Definition of Myocardial Infarction 
 
The Third Universal MI definition (Thygesen et al. Eur Heart J 2012;33:2551-67) will 
be used as the study specific MI criteria during adjudication of spontaneous and 
demand ischemia MI and MI resulting in death when biomarkers are not available 
(Type I, II, III). For PCI related MI (Type 4a) and CABG related MI (type 5) the 
SCAI criteria will be used for primary endpoint adjudication with the Third Universal 
MI definition used as a secondary analysis. 
 
Criteria for acute myocardial infarction 
The term acute MI should be used when there is evidence of myocardial necrosis in a 
clinical setting consistent with acute myocardial ischemia. Under these conditions any 
one of the following criteria meets the diagnosis for MI: 
 
Detection of a rise and/or fall of cardiac biomarker values (preferably 
cardiac troponin [cTn]) with at least one value above the 99th percentile 
upper reference limit (URL) and with at least one of the following: 
 
Symptoms of ischaemia 
 
New or presumed new significant ST-segment–T wave (ST–T) 
changes or new left bundle branch block (LBBB) 

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 
Development of pathological Q waves in the ECG 
 
Imaging evidence of new loss of viable myocardium or new regional 
wall motion abnormality 
 
Identification of an intracoronary thrombus by angiography or autopsy 
 
Cardiac death with symptoms suggestive of myocardial ischaemia and 
presumed new ischaemic ECG changes or new LBBB, but death occurred 
before cardiac biomarkers were obtained, or before cardiac biomarker 
values would be increased 
 
PCI-related MI is defined based on biomarker elevation measured within 
48 hrs of the PCI as well as additional criteria as delineated below as per 
the SCAI definitions. In addition, the CEC will adjudicate to the alternative 
3rd Universal Definition of MI.  
 
Stent thrombosis associated with MI when detected by coronary 
angiography or autopsy in the setting of myocardial ischaemia and with a 
rise and/or fall of cardiac biomarker values with at least one value above 
the 99th percentile URL 
 
CABG-related MI is defined by elevation of cardiac biomarker values as 
measured within 48 hrs after the procedure as well as ECG changes and 
clinical presentation as defined by the SCAI criteria (see below). In 
addition the CEC will adjudicate to the alternative 3rd Universal Definition 
of MI (see below).  
Criteria for prior myocardial infarction 
Any one of the following criteria meets the diagnosis for prior MI: 
 
Pathological Q waves with or without symptoms in the absence of non-
ischaemic causes 
 
Imaging evidence of a region of loss of viable myocardium that is thinned 
and fails to contract, in the absence of a non-ischaemic cause 
 
Pathological findings of a prior MI 
Third Universal Classification of MI 
The following classification will be used by the CEC for classification of MI and will 
not be captured in the eCRFs. 
 
Type 1: Spontaneous MI 
Spontaneous myocardial infarction related to atherosclerotic plaque 
rupture, ulceration, fissuring, erosion, or dissection with resulting 
intraluminal thrombus in one or more of the coronary arteries leading to 
decreased myocardial blood flow or distal platelet emboli with ensuing 

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myocyte necrosis. The patient may have underlying severe CAD but on 
occasion non-obstructive or no CAD 
 
Type 2: Myocardial infarction secondary to an ischaemic imbalance 
In instances of myocardial injury with necrosis where a condition other 
than CAD contributes to an imbalance between myocardial oxygen supply 
and/or demand, e.g. coronary endothelial dysfunction, coronary artery 
spasm, coronary embolism, tachy-/brady-arrhythmias, anaemia, respiratory 
failure, hypotension, and hypertension with or without left ventricular 
hypertrophy 
 
Type 3: Myocardial infarction resulting in death when biomarker values are 
unavailable 
Cardiac death with symptoms suggestive of myocardial ischemia and 
presumed new ischaemic ECG changes or new LBBB, but death occurring 
before blood samples could be obtained, before cardiac biomarker could 
rise, or in rare cases cardiac biomarkers were not collected 
 
Type 4a: Myocardial infarction related to percutaneous coronary 
intervention (PCI) 
Myocardial infarction associated with PCI is arbitrarily defined by 
elevation of cTn values >5 x 99th percentile ULN in patients with normal 
baseline values (<99th percentile URL) or a rise of cTn values >20% if the 
baseline values are elevated and are stable or falling. In addition, either (i) 
symptoms suggestive of myocardial ischaemia, or (ii) new ischaemic ECG 
changes or new LBBB, or (iii) angiographic loss of patency of a major 
coronary artery or a side branch or persistent slow- or no-flow or 
embolization, or (iv) imaging demonstration of new loss of viable 
myocardium or new regional wall motion abnormality are required. 
 
Type 4b: Myocardial infarction related to stent thrombosis 
Myocardial infarction associated with stent thrombosis is detected by 
coronary angiography or autopsy in the setting of myocardial ischaemia 
and with a rise and/ or fall of cardiac biomarkers values with at least one 
value above the 99th percentile URL. Definitions according to ARC will be 
used. see below. 
 
Type 5: Myocardial infarction related to coronary artery bypass grafting 
(CABG) 
Myocardial infarction associated with CABG is arbitrarily defined by 
elevation of cardiac biomarker values >10 x 99th percentile URL in 
patients with normal baseline cTn values (<99th percentile URL). In 
addition, either (i) new pathological Q waves or new LBBB, or (ii) 
angiographic documented new graft or new native coronary artery 

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occlusion, or (iii) imaging evidence of new loss of viable myocardium or 
new regional wall motion abnormality. 
Post-PCI (Type 4a) and post-CABG (Periprocedural) MIs (Type 5):  
Periprocedural “clinically relevant” MIs for post-PCI and post-CABG events will be 
primarily defined based on the SCAI definitions [2] as follows: 
1) 
In patients with normal baseline cTn, a cTn (I or T) level measured within 
48 hours of the PCI, the peak Troponin rises to ≥70x the local laboratory 
ULN, or ≥35x ULN with new pathologic Q-waves in ≥2 contiguous leads or 
new persistent LBBB. In the absence of troponins, the peak CK-MB 
measured within 48 hours of the procedure rises to ≥10x the local laboratory 
ULN, or to ≥5x ULN with new pathologic Q-waves in ≥2 contiguous leads 
or new persistent LBBB, 
2) 
In patients with elevated baseline cTn (or CK-MB) in whom the biomarker 
levels are stable or falling: The cTn (or CK-MB) rises by an absolute 
increment equal to those levels recommended above from the most recent 
pre-procedure level. 
3) 
In patients with elevated cTn (or CK-MB) in whom the biomarker levels 
have not been shown to be stable or falling: The cTn (or CK-MB) rises by 
an absolute increment equal to those levels recommended above plus new 
ST-segment elevation or depression plus signs consistent with a clinically 
relevant MI, such as new onset or worsening heart failure or sustained 
hypotension. 
1 Thygesen, K, et al. Third universal definition of myocardial infarction. J Am Coll Cardiol, 2012. 
60(16): p. 1581-98. 
2 Moussa, ID, et al. Consideration of a new definition of clinically relevant myocardial infarction after 
coronary revascularization an expert consensus document from the society for cardiovascular 
angiography and interventions (SCAI). JACC 2013;62: 1563-1570.  
 
Unstable Angina 
The diagnosis of unstable angina will require ischemic chest pain (or equivalent) at 
rest considered to be myocardial ischemia upon final diagnosis and without elevation 
in cardiac biomarkers of necrosis, and the presence of objective evidence of ischemia 
as defined by at least 1 of the following criteria: 
1. 
New or worsening ST or T wave changes in 2 anatomically contiguous 
leads on a resting ECG (in the absence of LVH and LBBB): 
a) transient (<20 minutes) ST elevation at the J point ≥ 0.2 mV in men (> 
0.25 mV in men < 40 years old) or  0.15 mV in women in leads V2-V3 
and/or  0.1 mV in other leads, or 
b) horizontal or down-sloping ST depression ≥ 0.10 mV, or 
c) T-wave inversion ≥ 0.2 mV 
 
2. 
Definite evidence of myocardial ischemia on myocardial scintigraphy (clear 
reversible perfusion defect), stress echocardiography (reversible wall 

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motion abnormality), or MRI (myocardial perfusion deficit under 
pharmacologic stress), or during physiologic lesion testing during cardiac 
catheterization (e.g. positive FFR or iFR) that is believed to be responsible 
for the myocardial ischemic symptoms/signs. 
 
3. 
Angiographic evidence of ≥70% lesion and/or thrombus in an epicardial 
coronary artery that is believed to be responsible for the myocardial 
ischemic symptoms/signs. 
 
Progressive angina 
The diagnosis of progressive angina will require increase in angina class or CEC-
adjudicated angina equivalent symptoms (e.g. dyspnea on exertion) compared with 
the most recent stable period considered to be due to myocardial ischemia based on 
ECG changes, non-invasive testing, FFR/iFR, prompting unplanned angiography, not 
meeting criteria for myocardial infarction or unstable angina, with one of both of the 
following. 
a. Requiring PCI or CABG, or  
b. With angiographic rapid lesion progression 
 
Rapid lesion progression is defined as = angiographic core laboratory-determined 
QCA ≥10% increase + absolute diameter stenosis (DS) ≥50% OR new thrombosis or 
ulceration or aneurysm or intimal flap (regardless of DS progression or absolute 
value) 
 
Definition of Stent Thrombosis 
Stent thrombosis will be classified as per the definite or probable Academic Research 
Consortium Definitions (Cutlip DE et al. Circulation 2007;115:2344-2351). The CEC 
adjudication result will be compared with the outcome of the ACL angiographic 
evaluation. Any disagreements will be reconciled between the two parties by regular 
meetings, see 7.5. 
 
Definite Stent Thrombosis – is considered to have occurred by either angiographic 
or pathological confirmation. 
 The presence of thrombus that originates in the stent or in the segment 5 mm 
proximal or distal to the stent and presence of at least 1 of the following 
criteria within a 48-hour window (The incidental angiographic documentation 
of stent occlusion in the absence of clinical signs or symptoms is not 
considered a confirmed stent thrombosis {silent occlusion}): 
o Acute onset of ischemic symptoms at rest 
o New ischemic ECG changes that suggest acute ischemia 
o Typical rise and fall in cardiac biomarkers that represent a spontaneous 
MI  
o Non-occlusive Thrombus: Intracoronary thrombus defined as a 
(spheric, ovoid, or irregular) noncalcified filling defect or lucency 

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surrounded by contrast material (on 3 sides or within a coronary 
stenosis) seen in multiple projections, or persistence of contrast 
material within the lumen, or visible embolization of intraluminal 
material downstream. 
o Occlusive Thrombus: TIMI 0 or TIMI 1 intrastent or proximal to a 
stent up to the most adjacent proximal side branch or main branch (if 
originates from the side branch) 
 Evidence of recent thrombus within the stent determined at autopsy or via 
examination of tissue retrieved following thrombectomy. 
Probable Stent Thrombosis – Clinical definition of probable stent thrombosis is 
considered to have occurred after intracoronary stenting in the following cases: 
 Any unexplained death within the first 30 days  
 Irrespective of the time after the index procedure, any MI that is related to 
documented acute ischemia in the territory of the implanted stent without 
angiographic confirmation of stent thrombosis and in the absence of any other 
obvious cause