Stent Retriever Thrombectomy for Thrombus Burden Reduction in Patients With Acute Myocardial Infarction - RETRIEVE-AMI Study
Phase: NA
Conditions: Myocardial Infarction, Thrombus, Coronary Artery Disease
Sponsor: Oxford University Hospitals NHS Trust

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Trial Title:  STENT RETRIEVER THROMBECTOMY FOR THROMBUS BURDEN REDUCTION IN PATIENTS WITH 
ACUTE MYOCARDIAL INFARCTION – RETRIEVE – AMI study 
Short title: RETRIEVE-AMI 
Ethics Ref: 21/SC/0220 
IRAS Project ID:  294665 
Date and Version No: 22/04/2024 v4.0 
 
Chief Investigator: 
Dr Giovanni Luigi De Maria  
Department of Cardiology, John Radcliffe Hospital 
 
Investigators:  
 
 
 
 
 
 
 
 
 
 
Prof Adrian P Banning                                                     
Department of Cardiology, John Radcliffe Hospital  
Prof Keith M. Channon                                                  
Department of Cardiology, John Radcliffe Hospital 
Dr Rafail A. Kotronias  
Department of Cardiology, John Radcliffe Hospital 
Dr Jeremy P. Langrish  
Department of Cardiology, John Radcliffe Hospital 
Dr Mohammad Alkhalil 
The Newcastle upon Tyne Hospitals NHS Foundation Trust   
 
Sponsor:  
Oxford University Hospitals NHS Foundation Trust  
Research and Development Department 
Joint Research Office 
Oxford University Hospitals NHS Foundation Trust 
Second Floor, OUH Cowley 
Unipart House Business Centre 
Garsington Road 
Oxford OX4 2PG 
 

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Funder:  
Medtronic and Terumo Inc 
 
Chief Investigator Signature:  
 
Statistician Signature: 
 
Confidentiality Statement 
This document contains confidential information that must not be disclosed to anyone other than the 
Sponsor, the Investigator Team, HRA, host organisations, and members of the Research Ethics Committee 
and Regulatory Authorities unless authorised to do so. 
 

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1. Table of Contents 
2. 
KEY TRIAL CONTACTS ........................................................................................................ 6 
3. 
Lay Summary .................................................................................................................... 7 
4. 
SYNOPSIS .......................................................................................................................... 8 
5. 
ABBREVIATIONS ................................................................................................................ 9 
6. 
BACKGROUND AND RATIONALE ...................................................................................... 10 
7. 
HYPOTHESIS .................................................................................................................... 12 
8. 
OBJECTIVES AND OUTCOME MEASURES .......................................................................... 12 
9. 
TRIAL DESIGN .................................................................................................................. 13 
10. 
PARTICIPANT IDENTIFICATION ..................................................................................... 15 
 
Trial Participants .............................................................................................................. 15 
 
Inclusion Criteria .............................................................................................................. 15 
 
Exclusion Criteria .............................................................................................................. 15 
11. 
TRIAL PROCEDURES ..................................................................................................... 17 
 
Informed Consent ............................................................................................................. 17 
 
Discontinuation/Withdrawal of Participants from Trial Treatment ................................... 20 
 
Recruitment ..................................................................................................................... 21 
 
Randomisation ................................................................................................................. 21 
 
Blinding and code-breaking .............................................................................................. 23 
 
Study timeline .................................................................................................................. 23 
 
Trial Assessments ............................................................................................................. 25 
11.7.1. 
Data Collection, Patient Reported Outcomes and Clinical Outcomes ... Error! Bookmark not defined. 
11.7.2. 
Optical Coherence Tomography ........................................................................................................ 25 
11.7.3. 
Angiography-derived coronary physiology ........................................................................................ 26 
11.7.4. 
Extracted Thrombus Imaging ............................................................................................................ 26 
11.7.5. 
Electrocardiography (ECG) ................................................................................................................ 26 
 
Subsequent telephone follow-ups .................................................................................... 26 
 
Definition of End of Trial ................................................................................................... 26 
12. 
IDENTIFICATION & DESCRIPTION OF THE INVESTIGATIONAL DEVICE & COMPARATORS 28 
 
Investigational Device & Comparators .............................................................................. 28 
12.1.1. 
Standalone PCI (Arm 1) ..................................................................................................................... 28 
12.1.2. 
Aspiration thrombectomy and PCI (Arm 2) ....................................................................................... 28 
12.1.3. 
Investigational arm (Arm 3) ............................................................................................................... 28 
12.1.4. 
Masking (blinding) ............................................................................................................................. 29 
12.1.5. 
Storage of investigational devices ..................................................................................................... 29 
 
Retriever thrombectomy safety ........................................................................................ 29 
Deleted: 25

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Other Interventions .......................................................................................................... 31 
13. 
SAFETY REPORTING ..................................................................................................... 32 
 
Definitions ........................................................................................................................ 32 
 
Causality .......................................................................................................................... 35 
 
Procedures for Recording Adverse Events ......................................................................... 36 
 
Reporting Procedures for Serious Adverse Events ............................................................. 36 
 
Expectedness ................................................................................................................... 37 
 
Trial cessation rules .......................................................................................................... 37 
 
Safety Monitoring Committee – Trial Safety Group (TSG) ................................................. 37 
 
Safety of stent-retriever thrombectomy ........................................................................... 38 
 
Safety of intravascular imaging ......................................................................................... 38 
14. 
STATISTICS ................................................................................................................... 39 
 
Number of participants .................................................................................................... 39 
 
Analysis of Endpoints ....................................................................................................... 39 
 
Interim Safety Analysis ..................................................................................................... 40 
15. 
DATA MANAGEMENT .................................................................................................. 41 
 
Source Data ...................................................................................................................... 41 
 
Data recording and Record Keeping .................................................................................. 41 
 
Access to Data .................................................................................................................. 42 
 
Approval to share imaging data with third parties ............................................................ 42 
16. 
QUALITY ASSURANCE PROCEDURES ............................................................................. 44 
 
Risk assessment ............................................................................................................... 44 
 
Monitoring ....................................................................................................................... 44 
17. 
PROTOCOL DEVIATIONS ............................................................................................... 45 
18. 
SERIOUS BREACHES ..................................................................................................... 45 
19. 
ETHICAL AND REGULATORY CONSIDERATIONS ............................................................ 46 
 
Declaration of Helsinki ..................................................................................................... 46 
 
Guidelines for Good Clinical Practice ................................................................................ 46 
 
Medical Device Regulations .............................................................................................. 46 
 
Approvals ......................................................................................................................... 46 
 
Specific Ethical Considerations for participants in emergency situations ........................... 47 
 
Possible risks/discomfort to participants .......................................................................... 47 

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Collaboration and Partnership with Commercial Companies & Third parties .................... 48 
 
Feasibility ......................................................................................................................... 49 
 
Reporting ......................................................................................................................... 49 
 
Participant Confidentiality ................................................................................................ 49 
20. 
FINANCE AND INSURANCE ........................................................................................... 49 
 
Funding ............................................................................................................................ 49 
 
Insurance ......................................................................................................................... 50 
21. 
PUBLICATION POLICY ................................................................................................... 50 
22. 
DEVELOPMENT OF A NEW PRODUCT/ PROCESS OR THE GENERATION OF INTELLECTUAL 
PROPERTY .............................................................................................................................. 50 
23. 
REFERENCES ................................................................................................................ 51 
24. 
APPENDIX A: Trial flow chart ....................................................................................... 54 
25. 
APPENDIX B: Vessel reference diameters for device sizing ............................................ 55 
26. 
APPENDIX C: Schematic diagram of device operation .................................................. 56 
27. 
APPENDIX D:  Amendment history ............................................................................... 57 
 
 
 

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2. KEY TRIAL CONTACTS 
Chief Investigator 
Dr Giovanni Luigi De Maria 
Department of Cardiology 
John Radcliffe Hospital 
Headington, Oxford, OX3 9DU 
GiovanniLuigi.DeMaria@ouh.nhs.uk  
Tel:  07490707811 
Sponsor 
Oxford University Hospitals NHS Foundation Trust  
Research and Development Department 
Joint Research Office 
Oxford University Hospitals NHS Foundation Trust 
Second Floor, OUH Cowley 
Unipart House Business Centre 
Garsington Road 
Oxford OX4 2PG 
ouh.sponsorship@ouh.nhs.uk 
Funder(s) 
Medtronic and Terumo Inc 
 
Clinical Trials Unit 
Not applicable 
 
Statistician 
Dr Abhirup Banerjee 
Division of Cardiovascular Medicine  
Radcliffe Department of Medicine 
University of Oxford  
abhirup.banerjee@cardiov.ox.ac.uk 
Tel: +44 7448807087 
 
 
 

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3. Lay Summary 
 
Heart attacks are caused by the sudden formation of a clot inside a diseased coronary artery which 
reduces blood flow beyond the blockage site. During conventional treatment of the blockage with what is 
known as a stent; a stainless-steel tube that keeps the artery open, the clot that has formed is disrupted 
and is pushed further down leading to damage in smaller blood vessels supplying the heart muscle. This 
additional damage can lead to long-term heart muscle damage influencing recovery and wellbeing. The 
original concept that was tested to prevent this ‘clot shower’ was that of a suction device to withdraw the 
clot before stenting. However, this approach has not translated to patient benefit.  
Amongst the reasons put forward for the inefficacy of the suction device was that it does not remove 
the entire clot as it does not interact with it. A new device that physically interacts with the clot and traps 
it before pulling it out - the stent retriever - is now routinely used in stroke therapy to remove clots in the 
arteries supplying the brain. This device has been successfully used as a last resort to remove clots in a 
small number of heart attacks. We hypothesize that stent retriever therapy will be more effective in clot 
removal than the current standard of care; suction or stenting. To study this, we propose the RETRIEVE-
AMI randomised controlled trial.  
 
 

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4. SYNOPSIS 
Trial Title 
STENT RETRIEVER THROMBECTOMY FOR THROMBUS BURDEN 
REDUCTION IN PATIENTS WITH ACUTE MYOCARDIAL INFARCTION 
Internal ref. no. (or 
short title) 
RETRIEVE – AMI study 
Trial registration 
 NCT05307965 
Sponsor  
Oxford University Hospitals NHS Foundation Trust 
Funder  
Medtronic & Terumo Inc 
Clinical Phase  
Device Pilot 
Trial Design 
Randomised controlled trial 
Trial Participants 
ST elevation Myocardial Infarction Patients 
Sample Size 
n=81 
Planned Trial Period  
Start Date: 01/03/2022 
End Date: 30/09/2025 
Planned Recruitment 
period  
36 months  
 
Objectives 
Outcome Measures 
Timepoint(s)  
Primary 
 
Efficacy of thrombus 
burden reduction 
Thrombus volume (mm3)  
(OCT assessment)  
Pre-stent 
Co-primary 
Safety of retriever 
thrombectomy 
• 
Angiography-/OCT-defined 
device related target vessel 
complications, device 
deficiency 
• Rate of major adverse cardiac 
and cerebrovascular events 
(MACCE) 
Pre-stent 
In hospital 
30 days 
6 months 
Secondary 
 
Efficacy of thrombus 
burden reduction  
Thrombus area, flow area 
(mm2)  
(OCT assessment)  
Pre-stent 
Efficacy of 
thromboatheroma 
reduction 
Thromboatheroma area, flow 
area (mm2) 
(OCT assessment) 
Post-stent 
Efficacy of stent 
implantation 
Stent expansion & 
apposition 
(OCT assessment) 
Post-stent 
 
Angiographic success 
rate  
TIMI flow, Myocardial Blush 
Grade, Angiography derived 
coronary physiology indices 
Post-stent 
 
Intervention(s) 
• 
Other 
intervention(s)  
Percutaneous coronary intervention with adjunctive use of stent 
retriever thrombectomy 
Comparator  
Percutaneous Coronary Intervention alone or Percutaneous coronary 
intervention with adjunctive aspiration thrombectomy 
 
 

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5. ABBREVIATIONS 
 
AE 
Adverse event 
ADE 
Adverse device effect 
CI 
Chief Investigator 
CRF 
Case Report Form 
CTA 
Clinical Trials Authorisation 
CTRG 
Clinical Trials and Research Governance 
GCP 
Good Clinical Practice 
GP 
General Practitioner 
HRA 
Health Research Authority 
ICH 
International Conference on Harmonisation 
IRB 
Independent Review Board 
MACCE 
Major adverse cardiac and cerebrovascular event 
MHRA 
Medicines and Healthcare products Regulatory Agency 
NHS 
National Health Service 
RES 
 Research Ethics Service  
OCT 
Optical coherence tomography 
OXTREC 
Oxford Tropical Research Ethics Committee 
PCI 
Percutaneous coronary intervention 
pPCI 
Primary percutaneous coronary intervention 
PI 
Principal Investigator 
PIL 
Participant/ Patient Information Leaflet 
R&D 
NHS Trust R&D Department 
REC 
Research Ethics Committee 
RMP 
Registered Medical Practitioner 
SAE 
Serious Adverse Event 
SADE 
Serious Adverse Defice Effect 
SOP 
Standard Operating Procedure 
TIMI 
Thrombolysis in myocardial infarction 
TMF 
Trial Master File 
TSG 
Oxford University Hospitals NHS Foundation Trust Trials Safety Group 
 
 

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6. BACKGROUND AND RATIONALE 
Ischaemic heart disease remains the leading cause of death across the globe despite sustained reductions 
in mortality rates.1 However, cardiovascular morbidity following myocardial infarction remains a 
significant burden to healthcare systems.  Our attempts during the last decade have thus shifted towards 
reperfusion therapies that reduce the extent of the myocardial infarction.2  
Amongst the proposed adjuncts to angioplasty, aspiration thrombectomy has been proposed as a simple 
method of removing the in-situ clot prior to stent deployment. Aspiration thrombectomy was thought to 
reduce distal embolisation of athero/thrombotic debris, limiting the ensuing microvascular dysfunction 
and final infarct size.3,4 Early randomised controlled trials of aspiration thrombectomy supported its 
routine clinical use,5 but contemporary trials suggest no effect on mortality and a signal of increased 
stroke.6,7 Amongst the reasons put forward to explain the lack of benefit of aspiration thrombectomy is its 
inefficacy in removing thrombi.8 Indeed, the optical coherence tomography (OCT) sub-study of TOTAL 
suggested that there was no difference in pre-PCI thrombus volume in lesions treated with aspiration 
thrombectomy versus PCI alone.9  
One of the reasons why thrombus-aspiration catheters failed to remove thrombotic debris in STEMI can 
be related to the inability of the devices to actually interact with the clot. In the coronary artery the clot 
develops on top of an ulcerated/ruptured plaque, meaning that the bulk of the clot is often in an eccentric 
position, eventually protruding towards the centre of the lumen. An additional element that must be taken 
into account is the disproportion between the vessel lumen-cross-section-area (which can potentially be 
filled with thrombus) and the aspiration-opening area at tip of the aspiration catheter. If an average size 
coronary artery (diameter: 3.0 – 3.5 mm) is considered, the vessel lumen-cross-section-area can range 
from 7.06 to 9.61 mm2. Since the aspiration-opening area at tip of the aspiration catheter is on average 
0.9-1.0 mm2, that means that the thrombectomy device technically covers (on average) from 9.4 to 14.2% 
of the vessel lumen-cross-section-area. In a larger caliber vessel (for example large ectatic right coronary 
arteries) this ratio becomes even more unfavourable. As the caliber of the vessel increases, its 
“theoretical” ability to contain large thrombus-burden increases proportionally, meaning that 

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paradoxically the currently available aspiration devices become less effective in those cases when they 
would be required to work at their best. 
Another element to account for poor performance of the current aspiration-catheters is the “guidewire 
bias effect”. This is a direct consequence of 1) the coronary arteries not being straight tubes, but having 
bends and curves and 2) of the thrombectomy-catheter sliding over an angioplasty-guidewire during the 
procedure. In a curved tube, like the coronary artery, the position of the wire can actually bias the 
aspiration device away from the clot.  The “guidewire bias effect” can be minimally influenced by the 
operator. For this reason a clot-removal device that could interact with the whole vessel-lumen cross 
section area (and thus with the whole clot) and whose mode action is not affected by coronary artery 
caliber and by “guidewire bias effect” would be desirable and likely to be more effective in removing 
thrombus in STEMI patients. 
Stent-retriever thrombectomy technology has this property and not surprisingly it has revolutionised the 
treatment of acute ischaemic stroke improving recanalization rates and clinical outcomes significantly.10,11 
Stent-retriever technology has been proved to be safe with low rates of vascular perforations (~2.1%) and 
iatrogenic dissection (1.7%-3.5%) in acute ischaemic stroke treatment.10-14 
Isolated case reports of successful bailout stent-retriever thrombectomy in ST elevation myocardial 
infarction (STEMI) patients attest to the feasibility of a stent-retriever thrombectomy approach in 
STEMI.15,16 However whether a stent-retriever strategy is more effective that conventional thrombus 
aspiration in STEMI has to be proved. Recently, stent retriever thrombectomy with the NeVa (Vesalio) 
device was evaluated in STEMI patients with large thrombus burden.17 
We set out to study the efficacy and safety of retriever thrombectomy in a carefully selected cohort of 
patients with ST elevation myocardial infarction and compare it with current standard of care; standalone 
PCI or PCI with adjunctive thrombus aspiration. We expect that stent retriever thrombectomy will more 
effectively reduce the thrombotic burden when compared to the current standard of care (e.g. standalone 
PCI and/or PCI with adjunctive aspiration thrombectomy). 
 

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7. HYPOTHESIS 
 
We hypothesize that stent retriever thrombectomy will be more efficacious than aspiration or mechanical 
thrombectomy in thrombus burden reduction as assessed by OCT derived pre-stent thrombus volume 
(mm3).  
8. OBJECTIVES AND OUTCOME MEASURES 
Objectives 
Outcome Measures 
Timepoint(s) of evaluation 
of this outcome measure (if 
applicable) 
Primary Objectives 
 
 
Efficacy of thrombus burden 
reduction 
Thrombus volume (mm3) 
(OCT assessment)  
Pre-stent 
Safety of retriever 
thrombectomy 
• Angiography-/OCT-defined device 
related target vessel complications, 
device deficiency 
• Rate of major adverse cardiac and 
cerebrovascular events (MACCE) 
Pre-stent 
In hospital 
30 days 
6 months 
Secondary Objectives 
 
 
Efficacy of thrombus burden 
reduction  
Thrombus area, flow area (mm2) 
(OCT assessment)  
Pre-stent 
Efficacy of thromboatheroma 
reduction 
Thromboatheroma area, flow area 
(mm2) 
(OCT assessment) 
Post-stent 
Efficacy of stent implantation 
Stent expansion & apposition 
(OCT assessment) 
Post-stent 
Angiographic success rate 
TIMI flow, Myocardial Blush Grade, 
Angiography derived coronary 
physiology indices 
Post-stent 
 
 

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9. TRIAL DESIGN 
 
RETRIEVE AMI is an investigator-initiated, multi-centre, exploratory three arms, randomised controlled 
trial. Patients over the age of 18 admitted for primary PCI (pPCI) for ST elevation myocardial infarction and 
meeting the inclusion criteria laid out in section 10.2 will be 1:1:1 randomised to receive either standalone 
PCI (Arm 1), thrombus aspiration + PCI (Arm 2) or retriever thrombectomy + PCI (Arm 3). Recruitment is 
expected to last for 18 months with the study finishing when the last follow-up of the last recruited patient 
is completed and all data is entered into the study. Each participant is expected to remain in the study for 
6 months during which one telephone follow-up at 6 months will be arranged. (Figure 1, Appendix A) 
The RETRIEVE AMI will enrol specifically patients with  
- evidence of large thrombus burden on coronary angiography  
- with culprit lesion located in a relatively large caliber (diameter > 3.0 mm) coronary artery  
By only including a large caliber vessel, the retriever-stent will be tested in a setting where the currently 
available technology is perceived to be suboptimal as described in section 6. Our decision to expand 
recruitment to the left coronary system was driven by our experience with the device in this trial as well 
as from published reports of the systematic evaluation of the NeVa (Vesalio) stent retriever device. Indeed, 
the authors have shown that thrombectomy is safe in both the left and right coronary artery systems.17 
Procedurally, we are reducing the risk of a major interaction of the device by placing a coronary guidewire 
alongside the stent retriever allowing us to retain safe control of the vessel whilst the clot is retrieved.  

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Figure 1: Trial flow chart 

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10. PARTICIPANT IDENTIFICATION 
 
Trial Participants 
Patients over 18 years of age having pPCI for ST elevation myocardial infarction and meeting the inclusion 
criteria as listed below will be randomised to either retriever thrombectomy + PCI, or thrombus aspiration 
+ PCI, or standalone PCI. 
 
Inclusion Criteria 
• 
Male or Female, aged 18-90 years. 
• 
pPCI patient with ST elevation myocardial infarction. 
• 
Angiographic criteria: 
à 
TIMI 0/1 flow at presentation 
à 
Angiographic thrombus score ≥ 4 
à 
Vessel diameter at site of occlusion ≥ 3.0 mm (measured by quantitative coronary 
angiography) 
 
 
Exclusion Criteria 
The participant may not enter the trial if ANY of the following apply: 
• 
Female participant who is pregnant or lactating  
• 
Participant with known hypersensitivity to nickel-titanium 
• 
Unconscious at presentation 
• 
Late presenter (pain to wire time > 12 h) 
• 
Class Killip III/IV and/or profound bradycardia (HR < 40 bpm) 
• 
Known history of kidney failure 
• 
Ostial occlusion 

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• 
Highly tortuous vessel*  
• 
Highly calcified vessel 
• 
Suspected (angiographically) spontaneous coronary artery dissection  
• 
Stent thrombosis  
• 
Previous stent implanted proximal to the occlusion site 
• 
Previous CABG 
• 
Previous STEMI/TIA/Stroke 
• 
Known anaemia (Hb <9). 
 
*A highly tortuous vessel is defined by the presence of ≥3 consecutive curvatures of 90° to 180° measured at end-
diastole in a major epicardial coronary artery ≥2 mm in diameter.18 In our protocol tortuosity will lead to a 
participant’s exclusion if it is affecting the vessel at the target lesion or proximal to it. 
 
 

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11. TRIAL PROCEDURES 
 
Informed Consent 
Informed consent will be obtained, with the recruitment approach to the patient, as described below. 
11.1.1.  Waiver request for patients having emergency angioplasty procedure 
The clinical treatment of these patients is in the emergency context and delays to treatment are 
detrimental. It is necessary to administer prompt emergency treatment and it is not always possible to 
identify and approach a Consultee beforehand. Thus we would seek a waiver, as described in Section 
32(9) of the Mental Capacity Act, since  
a) 
the treatment needs to be given urgently,  
b) 
it is necessary to take the action for the purpose of the research urgently,  
but  
c) 
it is not reasonably practicable to consult prior to enrolling the patient.  
In this situation the Mental Capacity Act allows the participant to be enrolled with an agreement of a 
registered medical practitioner (RMP) not involved in the research or in accordance with a procedure 
agreed with the appropriate body (i.e. REC). Since this is only applicable for the duration of the 
emergency we will seek written informed consent as soon as reasonably practicable (see diagram and 
Section 11.1.1.2 below). This process includes an important role for a healthcare professional as a type 
of patient “advocate”. This is discussed in section 11.1.1.2 below.  We also seek approval from the REC 
for the waiver procedure. 
11.1.1.1. 
Verbal assent 
Because of the urgency of the situation it is not feasible to obtain fully informed written consent. Fully 
informed consent requires that the potential participant have time to read and reflect on a patient 
information sheet which in this context is clinically inadvisable. We therefore propose to obtain verbal 
assent so as to optimize the amount of appropriate information conveyed to potential participants 

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acutely and minimize the clinical risks involved with substantial delay. The research study will be 
discussed verbally with the patient and the risks and benefits explained.  
In detail the patient at the time of verbal assent process will be informed that the particular pattern of 
heart attack they are having would be suitable for recruitment in our research trial which investigates a 
new device to remove the blood clot that is causing the heart attack. We will explain that as part of the 
trial they will receive either standard of care procedures or the investigational device. We will also briefly 
mention that we will be obtaining some extra pictures from within the arteries, a sample of the clot and 
measurements of flow and resistance in the small net of capillaries feeding the heart. 
Participants will be reminded that they have the right to withdraw from the study at any stage and that 
this will not affect their treatment or human rights. The research and clinical team have extensive 
experience of patient assent, and the role of a Patient Advocate (see below), through the recruitment of 
approximately 500 participants undergoing emergency PCI for STEMI in the OxAMI [Ethics Ref 
11/SC0397] and OxAMI PICSO [Ethics Ref 15/SC0167] studies. Newcastle upon Tyne Hospitals NHS 
Foundation Trust is a participating site to the OxAMI Study.I 
Only conscious patients, able to provide verbal assent will be enrolled in the study. 
11.1.1.2. 
Patient Advocate  
Because of the urgency of the situation it is not feasible to obtain written informed consent from the 
patient prior to enrolment, so an RMP or patient “advocate” will be identified to act in accordance with 
section 32(9). The Patient Advocate will act as witness and documenter of the verbal assent process for 
all conscious potential participants and/or overseer of the waiver process as a whole. This RMP will be 
present at the time of emergency treatment, but is not part of the research team. The Advocate will 
ensure that the verbal assent process is undertaken, that the patient does not object (i.e. the patient 
“assents” rather than “dissents”), and that the researcher has taken practical steps to explain the study, 
risks and benefits, within the context of the emergency clinical situation, and in accordance with the 
clinical status of the patient.  The Advocate in this situation will be a healthcare professional such as a 
Commented [GS(O1]: I don’t think this is needed here? 
Commented [RK2R1]: It is as the assent relies on OxAMI 
advocates. 

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specialist nurse. Assessment of patients in this context is within their professional capacity and the role 
here will be to witness verbal assent.  
Most of the nursing staff at the Oxford Heart Centre has already attended a series of seminars to make 
them aware of their specific roles and responsibilities in this situation, and they have acted as patients’ 
advocates through the recruitment of approximately 500 participants undergoing emergency PCI for 
STEMI in the ongoing OxAMI and OxAMI PICSO studies. The seminars have been directed by an ethicist 
who is not directly involved with the research project. We will continue to provide this training and 
draw on the extensive experience of the members of the clinical team currently acting as a Patient 
Advocate. Staff training at the Newcastle upon Tyne University Hospitals NHS Foundation Trust is 
ongoing. 
 
11.1.1.3. 
Post-emergency phase 
Once the emergency phase is over and treatment has been delivered, we will seek full written informed 
consent as soon as practical. For most patients this means within 12 hours of admission. This consent 
will be a two parts process: 
a) We will seek consent to allow use of data already acquired during the emergency phase  
Figure 2: Informed consent in emergency research 

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b) We will seek consent for ongoing participation in the study.  
Written Informed Consent will be obtained by means of participant dated signature and dated 
signature of the person who presented and obtained the Informed Consent. The person who obtained 
the consent must be suitably qualified and experienced, and have been authorised to do so by the 
Chief/Principal Investigator. A copy of the signed Informed Consent will be given to the participant and 
another copy will. Be filed in their medical records. The original signed form will be retained at the trial 
site. 
If the participant elects to withdraw from the study at this point then we will present them with three 
withdrawal options as outlined in section 11.2.1. 
If a patient is unable to provide informed consent at this stage due to deterioration in clinical condition, 
then advice may be sought from a relative/carer/friend acting as a consultee. When reasonable steps 
have been taken to identify a consultee  and one is unavailable, then the researcher must nominate a 
person to act as in their stead. This person may be involved in the patient’s care in a professional capacity 
but they must have no connection with the research project. A suitable person who might act as a 
nominated consultee is an independent doctor working with the patient or nominated by the healthcare 
provider. Consent from the patient will be obtained directly, if they recover promptly, at the earliest 
opportunity.  
 Discontinuation/Withdrawal of Participants from Trial Treatment 
11.2.1. Study Withdrawal 
We anticipate and have made provision for withdrawal when the emergency exception period is 
complete; if a patient is assessed and has capacity then they may completely or partially withdraw at 
any time. This possibility will be made clear as a part of seeking of full written informed consent after 
the initial emergency procedure. Participants may have the following three options for withdrawal:  

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1) 
Participants may withdraw from active follow-up and further communication but allow the trial 
team to continue to write to their GP and access their medical records and any relevant hospital 
data that is recorded as part of routine standard of care; i.e., Radiology/diagnostic test, blood 
results and disease progression data etc.   
2) 
Participants can withdraw from the study but permit data obtained up until the point of 
withdrawal to be retained for use in the study analysis.  No further data would be collected after 
withdrawal.  
3) 
Participants can withdraw completely from the study and withdraw the data collected up until 
the point of withdrawal. The data already collected would not be used in the final study analysis.  
The type of withdrawal and reason for withdrawal will be recorded in the case report form (CRF). 
If the participant is withdrawn due to an adverse event, the Investigator will arrange for follow-up visits 
or telephone calls until the adverse event has resolved or stabilised. 
11.2.2. Participant death  
If the participant dies before giving full written consent then we propose to continue using the data 
obtained. We would not seek further ‘consent’ from relatives at the risk of causing undue distress.  
 Recruitment 
RETRIEVE-AMI is a multi centre study recruiting at the John Radcliffe Hospital and the Newcastle upon 
Tyne Hospitals NHS Foundation Trust sites. Participants will be identified as they are being admitted for 
primary PCI. They will be approached by a research team member (a primary PCI operator who is also 
a member of the clinical care team) who will verbally assent them as explained in section 11.1.1.1. Upon 
assent, participant will be randomised to one of the three study arms, by a system based on sealed 
Envelope system. Consent will be completed at the post-emergency phase as described in section 
11.1.1.3. 
 
Randomisation 

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Upon assent, participant will be randomised to one of the three study arms, by a system based on 
sealed envelopes. Randomization will take place in the cathlab once both inclusion and exclusion 
criteria are verified and assent provided. 
 

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Blinding and code-breaking 
Due to the interventional nature of the trial, masking and code-breaking procedures are not applicable. 
 
Study timeline 
Stage 1 – Screening, Assent & Randomisation 
Participant identification and assent will proceed as described in sections 10 and 11.1.1.1-11.1.1.2 
respectively.  
• 
Diagnostic angiography will be performed in the standard manner using appropriate catheters. 
Heparin will be administered as routinely used for PCI. Angiograms will be reviewed to ensure 
participation eligibility according to angiographic inclusion/exclusion criteria (section 10.3) 
• 
Once eligibility is confirmed patients will be assented and randomised. 
Stage 2 – Baseline assessments 
• 
Once the lesion has been crossed with a coronary guidewire, flow will be established with a 1.5mm 
semicompliant balloon predilation.  
• 
OCT measurements will be performed using a dedicated OCT catheter over the coronary guide wire in 
the usual manner for clinical OCT assessment. For Arm 1, the OCT measurements in the baseline 
assessment will be treated as the pre-stent measurements as thrombus modification will not be 
performed in this group.  
Stage 3 – Post-thrombus modification pre-stent assessments 
Patients randomised to Arm 2 (thrombus aspiration) or Arm 3 (thrombus retrieval) will undergo the 
assessments in this stage.  
• 
Thrombus aspiration (Arm 2) will proceed according to standard clinical practice. In brief, a thrombus 
aspiration device (i.e. Export Catheter) will be advanced over the coronary guidewire. Aspiration will 
then proceed.  

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• 
Retrieval thrombectomy (Arm 3) will proceed according to the manufacturer’s manual. In brief, a 
microcatheter (e.g. PhenomTM, MarksmanTM) is advanced over the guidewire. Once the microcatheter 
has traversed the thrombotic occlusion the SolitaireTM X revascularisation device is advanced through 
the microcatheter until the usable length of the stent extends past each side of the thrombus in the 
vessel. Then the microcatheter is retracted to the proximal radiopaque marker of the stent. As this 
retraction occurs the stent self-expands and entangles the thrombus. Next, the microcatheter and 
SolitaireTM X Revascularisation Device are withdrawn as a unit into the guide catheter under 
continuous aspiration (Appendix C). 
• 
OCT measurements will be performed using a dedicated OCT catheter over the coronary guide wire in 
the usual manner for clinical OCT assessment. 
• 
Angiography-derived coronary physiology measurements will be performed with up to two 
angiographic views (complementary and separated by an angle of at least 25 degrees) at a frame rate 
of 15 frames per second. Maximal hyperaemia will be achieved with an intravenous infusion of 
adenosine at a rate of at a rate of 140 mg/kg/min. Since stage 3 is the same as stage 2 for Arm 1 
participants, these measurements will be performed at Stage 2. 
• 
Extracted thrombus from aspiration/stent retriever at any stage of the procedure will be collected, 
and imaged ex-vivo. 
Stage 4 – PCI & post-PCI assessments 
• 
PCI will proceed according to clinical practice. Post-dilation will be performed at the operator’s 
discretion.  
• 
OCT measurements will be performed following a successful angiographic PCI result using a dedicated 
OCT catheter over the coronary guide wire in the usual manner for clinical OCT assessment. 
• 
Angiography-derived coronary physiology measurements will be performed with up to two 
angiographic views (complementary and separated by an angle of at least 25 degrees) at a frame rate 

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of 15 frames per second. Maximal hyperaemia will be achieved with an intravenous infusion of 
adenosine at a rate of at a rate of 140 mg/kg/min. 
Stage 5 – Consent & data collection 
Patients will be approached for consent according to procedures detailed in section 11.1.1.3. Once consent 
has been obtained in-hospital data collection will be completed (section 11.7.1.). ECGs will also be stored. 
Stage 6 – 6 month follow-up 
At 6 months patients will have a scheduled telephone follow-up to gather relevant clinical information as 
detailed in section 11.8. 
 
Trial Assessments 
11.7.1. Data Collection, Patient Reported Outcomes and Clinical Outcomes 
Data on the clinical procedures and any devices and/or imaging technologies used will be collected. 
Medical history will be taken from the patient once informed consent has been given and relevant sections 
of the medical notes and scans may be accessed by the study team. Clinical outcomes and MACCE will be 
ascertained at the 6-month telephone follow-up, by accessing relevant sections of the medical records or 
by contacting the GP if appropriate.  
11.7.2. Optical Coherence Tomography 
OCT is a high-resolution intravascular imaging modality that can accurately characterise coronary plaque 
morphology and quantify atherothrombotic burden.4,19 It also has the capability to accurately define the 
inner lumen of the native coronary artery allowing to measure the flow area and monitor the structural 
integrity of the artery. It is expected therefore to play a key role in identifying target vessel complications 
(e.g. dissection, intramural haematoma) and aspects of stent deployment (e.g. stent apposition, 
expansion, edge dissection).20 Finally, OCT has the advantage of having a fast acquisition frame rate and 
being relatively inexpensive. 

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11.7.3. Angiography-derived coronary physiology 
Coronary physiology measurements during emergency PCI can be used to assess the coronary 
microvascular function which is affected amongst other factors by the pre-stenting thrombotic burden and 
distal embolisation of atherothrombotic material during angioplasty.3 Indeed, coronary physiology 
measurements under adenosine-induced hyperaemia can be employed to characterise microvascular 
obstruction and predict the extent of myocardial infarction.21  
Contemporary work enables us to derive 
cardiac physiology indices such as quantitative flow ratio non-invasively using coronary angiograms.22,23  
11.7.4. Extracted Thrombus Imaging 
Intracoronary thrombus/plaque material obtained with the use of aspiration/stent-retriever 
thrombectomy as part of the procedure will be imaged ex-vivo. Images will be obtained in the 
catheterisation laboratory and stored in a pseudonymised format. The extracted thrombus will not be 
stored by the study team and will be discarded.  
11.7.5. Electrocardiography (ECG) 
ECG refers to the measurement of the electrical activity of the heart. It is a routine non-invasive 
assessment carried out in patients with suspected or known coronary artery disease. 
 
Subsequent telephone follow-ups 
Participants will have a scheduled telephone follow-up 6 months after their randomisation to the study. 
This telephone follow-up will gather information on concurrent medication therapy, patient reported 
outcomes, study outcomes and serve as an opportunity to log a participant’s recovery progress. 
 
Definition of End of Trial 
Recruitment to the trial will cease as soon as 81 participants have been randomised in the study and have 
completed follow-up at 6 months. The trial will end when the last patient exits the study. To ensure that 

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the scientific integrity of the trial is maintained, should the target recruitment not be reached by the pre-
specified study end-date we will seek an extension of the study  
 

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12. IDENTIFICATION & DESCRIPTION OF THE INVESTIGATIONAL DEVICE & COMPARATORS 
 
Investigational Device & Comparators 
12.1.1. Standalone PCI (Arm 1) 
Participants randomised to the standalone PCI arm of the RETRIEVE AMI trial will have standard of care 
treatment. Participants will undergo PCI with devices and techniques driven by clinical decision making at 
the patient level and institutional level, and carried out in accordance with local guidelines. 
12.1.2. Aspiration thrombectomy and PCI (Arm 2) 
Participants randomised to Arm 2 of the RETRIEVE AMI trial will have standard of care treatment with 
manual thrombectomy catheter and PCI. Participants will undergo PCI with devices and techniques driven 
by clinical decision making at the patient level and institutional level, and carried out in accordance with 
local guidelines. 
12.1.3. Investigational arm (Arm 3) 
Participants randomised to the stent-retriever thrombectomy arm of the 
RETRIEVE AMI trial will undergo stent-retriever thrombectomy with the 
SolitaireTM X Revascularisation Device (Figure 3). The SolitaireTM X 
revascularisation device has been clinically approved and CE marked for 
use in acute ischaemic stroke endovascular intervention.14 SolitaireTM X 
works by mechanically retrieving the thrombus and restoring blood flow 
to the area distal to the occlusion. The SolitaireTM X Revascularisation 
Device is a self-expanding stent designed for dynamic clot integration 
with radiopaque markers that enhance visualisation of the optimal 
working length.  Features including the range of stent diameters and 
usable lengths are presented in Appendix B. The device can be used in 
vessels with a diameter between 2.0mm and 5.5mm at the thrombotic occlusion site (Appendix B).  
Figure 3: SolitaireTM X device 
Commented [FK(O3]: This should be made applicable to both 
organisations so perhaps"carried out in accordance with the hospital 
department guidelines." 
Commented [RK4R3]: Thank you. Addressed. 
Commented [FK(O5]: This should be made applicable to both 
organisations so perhaps"carried out in accordance with the hospital 
department guidelines." 
Commented [RK6R5]: Addressed. 

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After a thrombotic occlusion has been identified and crossed with a guidewire, the stent-retriever 
thrombectomy proceeds as described below (see Appendix C for schematic diagram).15 A microcatheter 
(e.g. PhenomTM, MarksmanTM) is advanced  over the guidewire. Once the microcatheter has traversed the 
thrombotic occlusion the SolitaireTM X revascularisation device is advanced through the microcatheter until 
the usable length of the stent extends past each side of the thrombus in the vessel. Then the microcatheter 
is retracted to the proximal radiopaque marker of the stent. As this retraction occurs the stent self-expands 
and entangles the thrombus. Finally, the microcatheter and SolitaireTM X Revascularisation Device are 
withdrawn as a unit under continuous aspiration into the guide catheter. PCI will then proceed with devices 
and techniques driven by clinical decision making at the patient level and institutional level, and carried 
out in accordance with local guidelines. 
12.1.4.  Masking (blinding) 
Due to the interventional nature of the trial, masking is not applicable. 
12.1.5.   Storage of investigational devices 
The SolitaireTM X Revascularisation Device and Phenom microcatheters will be provided by Medtronic. The 
OFDI catheters will be provided by Terumo Inc. We will be documenting the number of devices, with their 
lot numbers, that will be shipped to the John Radcliffe Hospital and Newcastle Upon Tyne Hospitals NHS 
Foundation Trust. After their delivery, the kit will be stored in designated spaces at both sites and kept in 
a cool, dry place. We will document on the CRF the LOT number and expiry date for each device for each 
patient. 
 
Retriever thrombectomy safety 
Stent-retriever thrombectomy is clinically tested and licensed for endovascular intervention in acute 
ischaemic strokes with large vessel occlusions involving the internal carotid and the first segment of the 
middle cerebral artery.14,24 Our proposed pilot in acute coronary syndrome – STEMI patients would 
therefore represent an off-license application for the SolitaireTM X Revascularisation Device. Endovascular 
intervention for acute ischaemic stroke bears similarities to coronary intervention for acute myocardial 
Commented [FK(O7]: This should be made applicable to both 
organisations so perhaps"carried out in accordance with the hospital 
department guidelines." 
Commented [RK8R7]: Addressed. 

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infarction. Off license use of retriever thrombectomy in STEMI patients is reported twice in the literature 
with no reported complications and a successful recanalization outcome.15,16  
From an anatomical perspective, the SolitaireTM X revascularisation device is licensed for interventions in 
vessels with a minimum diameter of 2mm and a maximum of 5.5mm depending on the device model used 
(see appendix A). The diameter of internal carotid and middle cerebral arteries (arteries for which 
SolitaireTM X intervention is licensed) is reportedly 3.38±1.34mm and 2.45±0.85mm respectively.25 Our 
pilot study is designed to include patients with heart attack due to thrombotic occlusion of a “large caliber” 
coronary artery (diameter at the site of occlusion ≥ 3.0 mm). The size range of the target vessel is thus well 
within the safety range proposed by the manufacturer (e.g. between 2.0 and 5.5 mm).  
From a device perspective, in stroke patients SolitaireTM X revascularisation device failure was reported in 
one case (0.8%) in the two pivotal trials that examined this end-point with no significant sequelae.14,26 
Regarding device related complications in patients randomised to the SolitaireTM X revascularisation 
device, arterial dissection or perforation was reported in 5/211 (2.3%). Perforations, albeit in the 
coronaries are encountered in routine PCI practice in 0.37% of patients27, while edge dissections following 
stent deployment in 7.7% of patients.28 The relatively higher perforation with the SolitaireTM X device can 
be explained by the tortuosity of the intracerebral vessels that are treated as well as the early stage of the 
thrombectomy experience in the RCTs and the small sample size. To minimise the potential for coronary 
perforations in our trial, we will include patients with thrombotic occlusions involving the right coronary 
artery prior to the crux, e.g. in a vessel segment with minimal, if any, tortuosity. Nonetheless, in the event 
of a coronary perforation the treatment – angioplasty – is similar to the definitive treatment for the 
myocardial infarction. 
Finally, stroke in the context of pPCI is reported in 0.25% to 0.5% of STEMI cases29-31 and in ~0.8% of STEMI 
patients with aspiration thrombectomy and PCI.30 In the SolitaireTM X device trials, the rate of embolisation 
to vascular fields proximal to the target vessel is not reported. It is therefore not possible to estimate the 
risk of stroke for our trial. However, from a mechanistic perspective stent-retriever thrombectomy is based 

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on the concept of integration of the stent scaffold into the thrombus which in combination with the 
withdrawal of the stent into the microcatheter and the continuous aspiration on withdrawal renders 
embolisation of thrombotic material less likely. 
 
Other Interventions 
Not applicable 
 

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13. SAFETY REPORTING 
 
Definitions 
Adverse Event (AE) 
Any untoward medical occurrence, unintended disease or injury or any 
untoward clinical signs (including an abnormal laboratory findings) in 
participants, users or other persons whether or not related to the 
investigational medical device. This includes events related to the 
investigational device or comparator, events related to the procedures 
involved (any procedure in the protocol). For users or other persons 
this is restricted to events related to the investigational medical device. 
Adverse 
Device 
Effect 
(ADE) 
 
An adverse event related to the use of an investigational medical device. 
This definition includes any events resulting from insufficient or 
inadequate instructions for use, deployment, implantation, installation, 
or operation, or any malfunction of the investigational device. This 
definition also includes any event resulting from user error or form 
intentional misuse of the investigational device. 
Serious 
Adverse 
Event 
(SAE) 
Any untoward medical occurrence that: 
• 
Results in death 
• 
Is life-threatening, 
• 
Requires inpatient hospitalisation or prolongation of existing 
hospitalisation, 
• 
Results in persistent or significant disability/incapacity, or 
• 
Is a congenital anomaly/birth defect. 
• 
Other important medical events. 

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Included herein are device deficiencies that might have led to a serious 
adverse event if: 
a) suitable action had not been taken or 
b) intervention had not been made or 
c) circumstances had been less fortunate.  
These are handled under the SAE reporting system. 
Planned hospitalisation for a pre-existing condition, or a procedure 
required by the trial protocol, without serious deterioration in health, is 
not considered a serious adverse event. 
The term ‘life-threatening’ in the definition of ‘serious’ refers to an event 
in which the patient was at risk of death at the time of the event. It does 
not refer to an event that hypothetically might have caused death if it 
were more severe. 
Hospitalisation for a pre-existing condition, including elective 
procedures planned prior to study entry, which has not worsened, does 
not constitute a serious adverse event. 
Other events that may not result in death, are not life threatening, or do 
not require hospitalisation, may be considered a serious adverse event 
when, based upon appropriate medical judgement, the event may 
jeopardise the patient and may require medical or surgical intervention 
to prevent one of the outcomes listed above. 

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Serious Adverse Device 
Effect (SADE) 
Any untoward medical occurrence that can be attributed wholly or 
partly to the device, which resulted in any of the characteristics of a 
serious adverse event as described above. 
Unanticipated Serious Adverse Device Effects (USADE) 
Any serious adverse device effect which, by its nature, incidence, 
severity or outcome, has not been identified  
Device deficiency 
Inadequacy of a medical device with respect to its identity, quality, 
durability, reliability, safety or performance.  Device deficiencies include 
malfunctions, use errors and inadequate labelling. 
Device deficiencies that did not lead to an adverse event, but could have 
led to a medical occurrence if suitable action had not been taken, or 
intervention had not been made or if circumstances had been less 
fortunate 
User error 
Act or omission of an act that results in a different medical device 
response than intended by the manufacturer or expected by the user.  
Use error includes slips, lapses and mistakes.  An unexpected 
physiological response of the subject does not itself constitute a use 
error. 
 
Severity definitions 
The following definitions will be used to determine the severity rating for all adverse events: 
Mild: awareness of signs or symptoms, that does not interfere with the subject’s usual activity or is 
transient that resolved without treatment and with no sequelae. 

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Moderate: a sign or symptom, which interferes with the subject’s usual activity. 
Severe: incapacity with inability to do work or perform usual activities. 
Arterial injury classification scheme 
Coronary dissections and perforations will be classified according to the established NHLBI and Ellis 
classification schemes.32,33 A significant coronary dissection is defined as a dissection leading to coronary 
flow impairment or coronary occlusion. 
 
Causality 
The relationship of each adverse event to the trial device may be determined by the manufacturer and/or 
a medically qualified Investigator according to the following definitions:  
Not related: The event is clearly related to other factors such as the patients/participants clinical condition, 
therapeutic intervention, concomitant medication. 
Unlikely: The event is probably produced by other factors such as the patients/participants clinical 
condition, therapeutic intervention, concomitant medication and does not follow a known response 
pattern to the device 
Possibly: The event follows a reasonable temporal relationship form the time of placement/administration 
and/or follows a known response pattern to the device but could have been caused by other factors such 
as the patients/participants clinical condition, therapeutic intervention, concomitant medication. 
Most probable: The event follows a reasonable temporal relationship form the time of 
placement/administration and/or follows a known response pattern to the device and could not have been 
caused by other factors such as the patients/participants clinical condition, therapeutic intervention, 
concomitant medication. Further the event immediately follows the administration/placement of the 
device and improves on stopping or removing the device. 

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Procedures for Recording Adverse Events 
All adverse events (including ADEs) and device deficiencies occurring during the course of the study will be 
recorded on the CRF whether or not attributed to the trial device. The information recorded will include 
but not be limited to: 
• 
A description of the event 
• 
The dates of the onset and resolution 
• 
Action taken 
• 
Outcome 
• 
Assessment of relatedness to the device 
• 
Whether the AE is serious or not 
• 
Whether the AE arises from device deficiency 
• 
Whether the AE arises from user error 
The severity of events will be assessed on the following scale:  1 = mild, 2 = moderate, 3 = severe. 
The CI shall submit to Medtronic a report of AEs and ADEs that occur in Arm 3 of this study. AEs/ADEs 
considered related to the device as judged by a medically qualified investigator or the Sponsor will be 
followed either until resolution, or the event is considered stable.  
It will be left to the Investigator’s clinical judgment to decide whether or not an AE/ADE is of sufficient 
severity to require the participant’s removal from treatment.  A participant may also voluntarily withdraw 
from treatment due to what he or she perceives as an intolerable AE/ADE.  If either of these occurs, the 
participant must undergo an end of trial assessment and be given appropriate care under medical 
supervision until symptoms cease, or the condition becomes stable. 
 
Reporting Procedures for Serious Adverse Events 
Reporting of all Serious Adverse Events will be done in accordance with the European Commission 
Guidelines on Medical Devices Serious Adverse Event Reporting (MEDDEV 2.7/3; December 2010). 

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SAEs/SADEs that pose an immediate risk to patient health or safety will be reported to the trial 
TSG/Sponsor immediately or no later than 24 hours after the Investigator is aware and to the device 
manufacturer, the MHRA and the REC within 2 calendar days of the Chief Investigator becoming aware of 
the event. The SAE form should be emailed to ouhsae.reports@ouh.nhs.uk. 
All other reported SAEs/SADEs will be reported to the trial TSG, the Sponsor, device manufacturer and the 
MHRA within 7 calendar days of notification, if appropriate. This will not include SAEs that may be expected 
as part of the risks of routine care. Adverse device events (SADEs, USADEs) and device deficiencies will also 
be reported to the device manufacturer.  All SAEs will be followed up to resolution.   
SAEs/SADEs will be recorded for a time period starting from verbal assent/investigational device 
deployment to 30 days following the use of the device. 
 
Expectedness 
Expectedness will be determined according to the Manufacturers risk analysis report 
 
Trial cessation rules 
 
The trial will be halted early if any of the following occur: 
• 
>2 transient ischaemic attack /ischaemic stroke-related SADEs  
• 
>2 coronary perforation-related SADEs   
• 
> 2 significant coronary dissection-related SADEs 
 
 
Safety Monitoring Committee – Trial Safety Group (TSG) 
The Oxford University Hospitals Trust Trial Safety Group (TSG) will conduct a review of all SAEs/SADEs for 
the trial reported during the quarter and cumulatively. The aims of this committee include: 
• 
To pick up any trends, such as increases in un/expected events, and take appropriate action 
• 
To seek additional advice or information from investigators where required 

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• 
To evaluate the risk of the trial continuing and take appropriate action where necessary 
 
Safety of stent-retriever thrombectomy 
See Section 12.2. 
 
Safety of intravascular imaging 
Intravascular imaging using OCT is often performed during PCI to assist in the procedure. The utilization of 
this modality typically adds up to 5 minutes to the procedure duration. Use of any intra-coronary device 
including OCT can cause ischaemia, chest discomfort or, rarely, other local coronary complications during 
the PCI. However, this is in the context of a PCI procedure where significant interventions such as balloon 
expansion and stent deployment are already being carried out in the coronary artery, which themselves 
may cause ischaemia, chest pain that may require the use of analgesia, or other local coronary 
complications. 
 
 

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14. STATISTICS 
 
Number of participants 
Based on estimates from previously published work9,34 and our stipulation for inclusion of patients with high 
thrombotic burden, we anticipate a mean pre-stent thrombus volume of 9.6mm3 with a standard deviation 
estimate of 5.1 mm3 in the standard of care arms. Since this is the first pilot of stent retriever in acute 
coronary syndromes there is no previous published work that can inform on the expected pre-stent thrombus 
volume reduction with retriever thrombectomy. We have therefore hypothesised a 33% reduction in mean 
pre-stent thrombus volume. Using a 1-way pairwise ANOVA with a 2-sided equality, accounting for 2 
pairwise comparisons with an a of 0.05, a sample size of 72 patients would have 80% power to detect a 
33% reduction in pre-stent thrombus volume with retriever thrombectomy.35 The approach that was used 
accounts for two pairwise comparisons. Indeed, for one such comparison a sample size of n=48 (n=24 for 
Arm 1 and 24 for Arm 3) would maintain the desired a of 0.05 and b of 0.2. Given that aspiration 
thrombectomy was not shown to differ from no thrombus modification,9 a sample size of n=48 (n=24 for 
Arm 2 and n=24 for Arm 3) would maintain the desired a of 0.05 and b of 0.2 for this comparison. The 
overall sample size is therefore increased by a further n=24 patients for the aspiration thrombectomy group. 
This leads us to n=72 patients required to show a 33% reduction in pre-stent thrombus burden with a power 
of 80%. Assuming 12.5% of patients will not have analysable OCT imaging, we plan to enrol 81 patients 
(n=27 in each group) to ensure the study remains adequately powered.  
 Analysis of Endpoints  
In keeping with our usual practice, we will obtain expert statistical advice from the Centre for Statistics in 
Medicine (or equivalent) for each specific task. A flow diagram detailing number of participants screened 
and randomised will be provided. Analysis of the OCT-derived primary and secondary endpoints (including 
angiography-derived) will be conducted offline in a blinded fashion. Summary statistics, including means, 
medians, and variances, will be calculated at each time point and for each type of data and group (e.g. 
baseline characteristics, parameters derived from OCT, angiography-derived coronary physiology). The 
distribution of the levels will be described. For each parameter an analysis of variance will be carried out. 

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An analysis evaluating for a between group difference in pre-stent thrombus volume will first use an 1-way 
ANOVA with a 2-sided equality test to assess for an overall trend. Post-hoc analyses exploring the following 
hypotheses i) retriever thrombectomy (Arm 3) is different to no thrombus modification (arm 1) and ii) 
retriever thrombectomy (Arm 3) is different to aspiration thrombectomy (Arm 2) will be performed using 
the Dunnett test. Control of the Type I error at 5% two-sided significance level due to multiple testing will 
be achieved using Dunnett’s method.36 . Missing data for the primary analysis will be dealt with complete 
case analysis if data missingness is <10% (<3 cases per group). If missingness is higher, multiple imputation 
will be performed instead. Major adverse cardiac and cerebrovascular events will be analysed using 
proportions statistical testing (Fisher’s exact or c2 tests), yet they represent an exploratory analysis. 
 Interim Safety Analysis 
 
Based on the reported coronary perforation (0.37%), coronary dissection (7.7%) and transient ischaemic 
attack/ischaemic stroke (0.25-0.8%) rates in contemporary STEMI practice, in a 27-patient arm study, 1 
coronary perforation, 1 significant coronary dissection and 1 transient ischaemic attack/ischaemic stroke 
may be expected by chance. If >2 (>10%) coronary perforation-related SADEs or >2 significant coronary 
dissection-related SADEs or >2 transient ischaemic attack-/ischaemic stroke-related SADEs occur in the 
investigational device arm this will be considered too high. 
 

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15. DATA MANAGEMENT 
 
 Source Data 
Source documents are where data are first recorded, and from which participants’ CRF data are obtained. 
These include, but are not limited to, hospital records (from which medical history and previous and 
concurrent medication may be summarised into the CRF), ECGs, radiographic and OCT images and 
correspondence. Access to relevant source data will be sought for members of the research team. 
 
Data recording and Record Keeping 
The study will comply with the Data Protection Act, which requires data to be anonymised as soon as it is 
practical to do so. This will be achieved by assigning participants a unique trial ID number that will be used 
in case record forms (CRFs), ECGs, radiographs, OCT and extracted thrombus images (pseudonymisation). 
A contact record form linking a participant’s unique trial ID number with their personal identifiable data 
(name, hospital ID, personal address, emails or telephone numbers) will be used. This form will be kept in 
the code break folder, separate from other documents. This form is needed to perform the 6 months 
telephone follow-up and to ensure that in case of an emergency participants can be identified and 
contacted. The written informed consent form that contains personal data (name and signature) can not 
be anonymised, but will be kept in a separate folder to the pseudonymised data and stored securely at the 
Oxford University Hospitals NHS Foundation Trust and the Newcastle upon Tyne Hospitals NHS Foundation 
Trust. 
Study data will be entered into the CRFs by members of the research team after reviewing source data 
and/or seeking information from the patient. This data will then be securely stored in an on-site location 
with restricted access and will only be accessible by study staff and authorised personnel. Pseudonymised 
data from non-Oxford sites can be transferred using appropriately encrypted means  to Oxford University 
Hospitals NHS Foundation Trust. Source ECG data will be copied, identifiable data will be removed and 
subsequently labelled with the trial participant ID number. ECG’s will be securely stored alongside the 
Commented [GS(O9]: How will this be done? 
Commented [RK10R9]: Hi Steph, we typically use USB/hard 
drive/email but we don’t want to restrict ourselves in the protocol in 
case of other suitable encrypted ways for data transfer. 

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participant’s CRFs in an on-site location with restricted access and will only be accessible by study staff and 
authorised personnel. Radiographic and OCT imaging data will be de-identified using the unique trial 
participant ID number before downloading them on to encrypted electronic transfer media and 
transferred to be stored on to password protected NHS computers in an on-site location with restricted 
access. Pseudonymised data from non-Oxford sites can be transferred using appropriately encrypted 
means to Oxford University Hospitals NHS Foundation Trust. In Oxford, extracted thrombus imaging data 
will be stored in a de-identified format using the trial participant ID number on to password protected NHS 
computers in an on-site location with restricted access. 
Personal data (contact record form) will be stored for 12 months after the study has ended, while 
pseudonymised research data generated by the study and any research documents with personal 
information, such as the consent forms, will be stored for 10 years. All study data and documents will be 
stored securely in an on-site location with restricted access. Study data will only be accessed by study staff 
and authorised personnel. After analysis is completed, data will be archived in a secure location with 
restricted access. After the specified data storage period elapses, the data custodian will agree a date for 
destruction and data will be destroyed confidentially at that time. 
 
Access to Data 
Direct access will be granted to authorised representatives from the Sponsor, host institution and the 
regulatory authorities to permit trial-related monitoring, audits and inspections.  
 
Approval to share imaging data with third parties 
De-identified research data including imaging data may be shared with the University of Oxford or other 
specialised centers in partnership with RETRIEVE-AMI, according to the availability of specialist analysis 
techniques that may not be available to the local research team. Data transfer and storage should follow 
the processes described in 15.2. Participants will be informed in the information leaflet and sign in the 
consent form (if they approve) that their pseudonymised images may in the future be sent to third parties 

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for specialist processing. It will be clearly stated that no identifying information will be sent with these 
imaging data. 
 
 

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16. QUALITY ASSURANCE PROCEDURES 
 
Risk assessment 
The trial will be conducted in accordance with the current approved protocol, ICH GCP, relevant 
regulations and standard operating procedures. 
 
Monitoring 
Regular monitoring will be performed by the sponsor according to ICH GCP. Data will be evaluated for 
compliance with the protocol and accuracy in relation to source documents. The monitors will verify that 
the clinical trial is conducted and data are generated, documented and reported in compliance with the 
protocol, GCP and the applicable regulatory requirements. 
 

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17. PROTOCOL DEVIATIONS  
A trial related deviation is a departure from the ethically approved trial protocol or other trial document 
or process or from Good Clinical Practice (GCP) or any applicable regulatory requirements. Any deviations 
from the protocol will be documented in a protocol deviation form and filed in the trial master file. 
All deviations will be reported to the MHRA. 
18. SERIOUS BREACHES 
A serious breach is defined as “A breach of GCP or the trial protocol which is likely to affect to a significant 
degree -  
(a) the safety or physical or mental integrity of the subjects of the trial; or 
(b) the scientific value of the trial”. 
In the event that a serious breach is suspected the Sponsor must be contacted within 1 working day. In 
collaboration with the C.I., the serious breach will be reviewed by the Sponsor and, if appropriate, the 
Sponsor will report it to the REC committee, Regulatory authority and the NHS host organisation within 
seven calendar days. 
 

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19. ETHICAL AND REGULATORY CONSIDERATIONS 
 
Declaration of Helsinki 
The Investigator will ensure that this trial is conducted in accordance with the principles of the Declaration 
of Helsinki.  
 
Guidelines for Good Clinical Practice 
The Investigator will ensure that this trial is conducted in accordance with relevant regulations and with 
Good Clinical Practice. 
 
Medical Device Regulations 
The Investigator will ensure that this trial is conducted in full conformity with: 
• 
European Commission Medical Device Guidelines relating to the application of the EU Directives 
on Medical Devices 
• 
Guide to European Medical Device Trials and BS EN ISO 14155 
 
 
Approvals 
Following Sponsor approval the protocol, informed consent form and participant information sheet will be 
submitted to an appropriate Research Ethics Committee (REC), HRA (where required), regulatory 
authorities (MHRA in the UK), and host institution(s) for written approval. 
The Investigator will submit and, where necessary, obtain approval from the above parties for all 
substantial amendments to the original approved documents. 
 
 

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Specific Ethical Considerations for participants in emergency situations 
Research in emergency situations is ethically complex because of the urgent nature of the interventions 
and the often severely compromised capacity of the patient. The processes of enrolment and consent 
described above, including verbal assent and the involvement of the Advocate represents our attempt to 
develop a thorough, ethically justified process that both protects patients’ rights and interests and enables 
important research to be done. These processes have been developed in the light of and guided by the 
provisions laid out in the Mental Capacity Act with special reference to Section 32(9). 
 
Possible risks/discomfort to participants 
Patients referred for emergency cardiac catheterization and PCI will undergo this procedure as would 
routinely be performed. Patients will therefore be informed of the standard of care procedure and its 
associated risks. All local protocols will be adhered to and only fully trained staff will carry out procedure 
according to departmental SOPs.  
From a research perspective, the PCI procedure time may be lengthened by around 10 minutes to 
complete the selected study procedures (OCT acquisitions, angiography derived physiology & 
aspiration/stent retriever thrombectomy). In the context of a PCI procedure that typically lasts 
approximately 60 minutes. The additional time should not result in any clinically significant difference to 
the participants. Very occasionally this additional time can result in some back discomfort for patients 
having to lie on the angiography bed for the additional time period. 
Stent-retriever thrombectomy with the Solitaire X revascularisation device is clinically tested and licensed 
for endovascular intervention in acute ischaemic strokes. Device failure was reported in one case (0.8%) 
in the two trials that examined this endpoint with no significant sequelae. Device related complications 
such as arterial dissection or perforation was reported in 5/211 (2.3%) of ischaemic stroke patients 
randomised to stent-retriever thrombectomy with the Solitaire X revascularisation device. Perforations 
and edge dissections are encountered in routine PCI practice in 0.37% and 7.7% of patients and 
interventional cardiologists are familiar with their management. Coronary perforations and significant 

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dissections are usually treated with a stent which is the treatment these patients will eventually receive 
for their heart attack.  
Finally, stroke in the context of pPCI is reported in 0.25% to 0.5% of STEMI cases and in ~0.8% of STEMI 
patients with aspiration thrombectomy and PCI. In the Solitaire X device trials, the rate of embolisation to 
vascular fields proximal to the target vessel is not reported. From a mechanistic perspective, stent-
retriever thrombectomy is based on the concept of integration of the stent scaffold into the thrombus 
which in combination with the withdrawal of the stent into the microcatheter and the continuous 
aspiration on withdrawal renders embolisation of thrombotic material less likely.  
Patients having a heart attack have a higher risk of cardiac mortality, heart failure, periprocedural 
myocardial infarction and access-site complications (haematoma, bruising, discomfort) by virtue of the 
underlying condition and its treatment with PCI. Additionally, participants who have suffered a heart attack 
are frequently re-admitted for a pre-planned procedure to complete revascularisation of their coronary 
artery disease. We expect that some combination of these events will be noted in trial participants during 
the study follow-up period. Adverse event reporting will proceed as described in section 13. 
 
Collaboration and Partnership with Commercial Companies & Third parties 
The Oxford University Hospitals NHS Foundation Trust (OUHT), the Newcastle upon Tyne Hospitals NHS 
Foundation Trust and the RETRIEVE-AMI study receive support from, commercial companies who provide 
the devices and technologies related to PCI and other research investigations.  
To futureproof our study, we may also share research data, including imaging data, with the University of 
Oxford or other specialised centres (academic or commercial) in partnership with The Oxford University 
Hospitals Trust, the Newcastle upon Tyne Hospitals NHS Foundation Trust and the RETRIEVE-AMI study for 
specialist analysis techniques that may not be available to the local research team. We will ensure that 
participants are not identifiable from the shared research data.  
 

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Feasibility 
The Oxford Heart Centre is a state-of-the-art facility which incorporated services in cardiology and cardiac 
surgery. The cardiac catheter laboratories are fully equipped to support this study. The Newcastle upon 
Tyne Hospitals NHS Foundation Trust is a high volume institution with considerable experience in acute 
cardiology research. 
 
Reporting 
The CI shall submit once a year throughout the clinical trial, or on request, an Annual Progress Report to 
the REC, the HRA (where required), Medtronic, Terumo Inc, the host organisation, and the Sponsor. A 
progress report will also be submitted on a semi-annual basis to Medtronic and Terumo Inc. In addition, 
an End of Trial notification and final report will be submitted to the MHRA, the REC, host organisation and 
Sponsor. The CI shall make the generated results available to Medtronic and Terumo Inc up to 14 days 
before publication or dissemination to the public. 
 
Participant Confidentiality 
The study will comply with the General Data Protection Regulation (GDPR) and Data Protection Act 2018, 
which require data to be de-identified as soon as it is practical to do so. The processing of the personal 
data of participants will be minimised by making use of a unique participant study number only on all study 
documents and any electronic database(s), with the exceptions of i) the contact record and ii) consent 
forms.  All documents will be stored securely and only accessible by study staff and authorised personnel. 
The study staff will safeguard the privacy of participants’ personal data. Data management is described in 
detail in section 15.  
20. FINANCE AND INSURANCE 
 
Funding 

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RETRIEVE AMI will be supported in kind by Medtronic (Minnesota, US) through the provision of medical 
devices and assistance with the MHRA application process. RETRIEVE AMI will also be supported in kind by 
Terumo corporation (Tokyo, Japan) through the provision of OFDI (second generation OCT) catheters.  
 
Insurance 
NHS bodies are legally liable for the negligent acts and omissions of their employees. If participants are 
harmed whilst taking part in a clinical trial as a result of negligence on the part of a member of the trial 
team this liability cover would apply. 
Non-negligent harm is not covered by the NHS indemnity scheme. The Oxford University NHS Foundation 
Trust, therefore, cannot agree in advance to pay compensation in these circumstances. 
In exceptional circumstances an ex-gratia payment may be offered. 
21. PUBLICATION POLICY 
Data will be owned and supervised by the trust. The Investigators will be involved in reviewing drafts of 
the manuscripts, abstracts, press releases and any other publications arising from the study.  Authors will 
acknowledge that the study was funded by Medtronic and Terumo. Authorship will be determined in 
accordance with the ICMJE guidelines and other contributors will be acknowledged. Copies of any 
publications connected to this study are available on request from the RETRIEVE-AMI investigators. 
22. DEVELOPMENT OF A NEW PRODUCT/ PROCESS OR THE GENERATION OF INTELLECTUAL 
PROPERTY  
Not applicable 
 

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23. REFERENCES 
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15. 
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Saver JL, Jahan R, Levy EI, et al. Solitaire flow restoration device versus the Merci Retriever in 
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Kinnaird T, Kwok CS, Davies R, et al. Coronary perforation complicating percutaneous coronary 
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28. 
Kobayashi N, Mintz GS, Witzenbichler B, et al. Prevalence, Features, and Prognostic Importance of 
Edge Dissection After Drug-Eluting Stent Implantation: An ADAPT-DES Intravascular Ultrasound Substudy. 
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Myint PK, Kwok CS, Roffe C, et al. Determinants and Outcomes of Stroke Following Percutaneous 
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Jolly SS, James S, Dzavik V, et al. Thrombus Aspiration in ST-Segment-Elevation Myocardial 
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Shoji S, Kohsaka S, Kumamaru H, et al. Stroke After Percutaneous Coronary Intervention in the Era 
of Transradial Intervention. Circulation: Cardiovascular Interventions 2018; 11(12): e006761. 
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34. 
Amabile N, Hammas S, Fradi S, et al. Intra-coronary thrombus evolution during acute coronary 
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Chow S-C, Shao J, Wang H, Lokhnygina Y. Sample size calculations in clinical research: chapman 
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Journal of the American Statistical Association 1955; 50(272): 1096-121. 
 
 

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24. APPENDIX A: Trial flow chart 
 
 
 

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25. APPENDIX B: Vessel reference diameters for device sizing 
 
 
 

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26. APPENDIX C: Schematic diagram of device operation 
 
Schematic diagram of device operation15 
 

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27. APPENDIX D:  Amendment history 
 
Amendment 
No. 
Protocol 
Version No. 
Date issued 
Author(s) 
of 
changes 
Details of Changes made 
1 
V1.3 
21/01/2022 
Rafail A Kotronias 
Giovanni 
L 
De 
Maria 
Sample size increase 
2 
V2 
21/12/2022 
Rafail A Kotronias 
Giovanni 
L 
De 
Maria 
Changes in inclusion and exclusion 
criteria 
3 
v3.0 
02/10/2023 
Rafail A Kotronias 
Giovanni 
L 
De 
Maria 
Inclusion of an additional site 
Extension of recruitment period