Myocardial Infarction, Thrombus, Coronary Artery Disease
Conditions
Keywords
Myocardial Infarction, Percutaneous coronary intervention, Stent Retriever, Thrombus Aspiration
Brief 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 tub 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. The investigators hypothesize that stent retriever therapy will be more effective in clot removal than the current standard of care; suction or stenting. To study this, the investigators propose the RETRIEVE-AMI randomised controlled trial.
Interventions
DEVICERetriever Thrombectomy
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. After a thrombotic occlusion has been identified and crossed with a guidewire, the stent-retriever thrombectomy proceeds. A microcatheter (e.g., PhenomTM, MarksmanTM) is advanced over the guidewire and once it has traversed the thrombotic occlusion, the SolitaireTM X device is advanced through the microcatheter until the usable length of the stent extends past each side of the thrombus in the vessel. As the microcatheter is retracted to the proximal radiopaque marker of the stent, the stent self-expands and entangles the thrombus. The microcatheter and SolitaireTM X Revascularisation Device are withdrawn as a unit into the guide catheter under continuous aspiration. PCI then proceeds driven by clinical decision making and department guidelines.
PROCEDUREPercutaneous Coronary Intervention
Standard of care
PROCEDUREThrombus Aspiration
Standard of care treatment with manual thrombectomy catheter
Sponsors
Medtronic
Terumo Corporation
Oxford University Hospitals NHS Trust
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
SINGLE (Outcomes Assessor)
Masking description
Due to the interventional nature of the trial, masking is not feasible for operators, the clinical care team and participants. However, analysis of the OCT-derived primary and secondary end-points will be conducted offline in a blinded fashion.
Intervention model description
The study will consist of 3 arms. Eligible participants will be 1:1:1 randomised to receive either standalone percutaneous coronary intervention (PCI) (Arm 1), thrombus aspiration + PCI (Arm 2) or retriever thrombectomy + PCI (Arm 3).
Eligibility
Sex/Gender
ALL
Age
18 Years to 90 Years
Healthy volunteers
No
Inclusion criteria
* Primary PCI patient with ST elevation myocardial infarction (STEMI) * TIMI 0/1 flow at presentation * Angiographic thrombus score ≥ 4 * Vessel diameter at site of occlusion ≥ 3.0 mm (measured by quantitative coronary angiography)
Exclusion criteria
* 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 (Heart rate \< 40 bpm) * Known history of kidney failure * Ostial occlusion * Highly tortuous vessel * Highly calcified vessel * Suspected (angiographically) spontaneous coronary artery dissection * Stent thrombosis * Previous stent implanted proximal to the occlusion site * Previous coronary artery bypass graft surgery (CABG) * Previous STEMI/Transient Ischemic Attack/Stroke * Known anaemia (Hemoglobin \<9)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Thrombus Volume (mm^3) | During PCI prior to stent implantation (typically 30 min from start of procedure) | Assessed with Optical Coherence Tomography \[OCT\] |
| Device-related Target Vessel Complications | During PCI prior to stent implantation (typically 30 min from start of procedure) | Assessed with angiography and/or OCT |
| Device Deficiency | During PCI prior to stent implantation (typically 30 min from start of procedure) | Assessed with angiography and/or OCT |
| Major Adverse Cardiac and Cerebrovascular Events (MACCE) | Up to 30 days after PCI | — |
| MACCE | At 6 months after PCI | — |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Flow Volume (mm^3) | During PCI prior to stent implantation (typically 30 min from start of procedure) | Assessed with OCT |
| Angiograpicy Derived Index of Microcirculatory Resistance | Post-stent implantation during PCI (typically 60 min after procedure start) | The angiography derived index of microcirculatory resistance is a continuous variable that measures microcirculatory resistance. No formal minimum and maximum values exist. The higher the value, the worse the angiographic perfusion. A value over 40U confers an adverse prognosis. |
| Thromboatheroma Volume (mm^3) | Post-stent implantation during PCI (typically 50 min after procedure start) | Assessed with OCT |
| Number of Participants With Stent Underexpansion & Malapposition | Post-stent implantation during PCI (typically 50 min after procedure start) | Assessed with OCT according to established international consensus criteria. |
| Thrombolysis in Myocardial Infarction (TIMI) Flow | Post-stent implantation during PCI (typically 60 min after procedure start) | Assessed with angiography according to the TIMI Flow criteria |
| Number of Participants With Myocardial Blush Grade (MBG) < 3 | Post-stent implantation during PCI (typically 60 min after procedure start) | Assessed angiographically according to the TIMI Myocardial Blush Grade Score Criteria. The scale goes from 0-3. Myocardial blush grade (MGB) of 0, 1 and 2 indicates angiographic malperfusion, whilst a Myocardial blush grade (MGB) score of 3 indicates normal perfusion. |
Countries
United Kingdom
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Standalone Percutaneous Coronary Intervention Participants will have standard of care treatment. They 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 the Oxford University Hospitals NHS Foundation Trust department guidelines.
Percutaneous Coronary Intervention: Standard of care | 27 |
| Percutaneous Coronary Intervention and Thrombus Aspiration Participants will have standard of care treatment with manual thrombectomy catheter and PCI. They 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 the Oxford University Hospitals NHS Foundation Trust department guidelines.
Percutaneous Coronary Intervention: Standard of care
Thrombus Aspiration: Standard of care treatment with manual thrombectomy catheter | 27 |
| Percutaneous Coronary Intervention and Retriever Thrombectomy Participants randomised to the stent-retriever thrombectomy arm of the RETRIEVE AMI trial will undergo stent-retriever thrombectomy with the SolitaireTM X Revascularisation Device.
Retriever Thrombectomy: 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. After a thrombotic occlusion has been identified and crossed with a guidewire, the stent-retriever thrombectomy proceeds. A microcatheter (e.g., PhenomTM, MarksmanTM) is advanced over the guidewire and once it has traversed the thrombotic occlusion, the SolitaireTM X device is advanced through the microcatheter until the usable length of the stent extends past each side of the thrombus in the vessel. As the microcatheter is retracted to the proximal radiopaque marker of the stent, the stent self-expands and entangles the thrombus. The microcatheter and SolitaireTM X Revascularisation Device are withdrawn as a unit into the guide catheter under continuous aspiration. PCI then proceeds driven by clinical decision making and department guidelines.
Percutaneous Coronary Intervention: Standard of care | 27 |
| Total | 81 |
Baseline characteristics
| Characteristic | Percutaneous Coronary Intervention and Thrombus Aspiration | Percutaneous Coronary Intervention and Retriever Thrombectomy | Total | Standalone Percutaneous Coronary Intervention |
|---|---|---|---|---|
| Age, Continuous | 63 years STANDARD_DEVIATION 12 | 63 years STANDARD_DEVIATION 13 | 64 years STANDARD_DEVIATION 12 | 67 years STANDARD_DEVIATION 12 |
| Race and Ethnicity Not Collected | — | — | 0 Participants | — |
| Region of Enrollment United Kingdom | 27 participants | 27 participants | 81 participants | 27 participants |
| Sex: Female, Male Female | 5 Participants | 4 Participants | 12 Participants | 3 Participants |
| Sex: Female, Male Male | 22 Participants | 23 Participants | 69 Participants | 24 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 2 / 27 | 1 / 27 | 0 / 27 |
| other Total, other adverse events | 0 / 27 | 2 / 27 | 4 / 27 |
| serious Total, serious adverse events | 5 / 27 | 4 / 27 | 1 / 27 |
Outcome results
Primary
Device Deficiency
Assessed with angiography and/or OCT
Time frame: During PCI prior to stent implantation (typically 30 min from start of procedure)
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Standalone Percutaneous Coronary Intervention | Device Deficiency | 0 Participants |
| Percutaneous Coronary Intervention and Thrombus Aspiration | Device Deficiency | 0 Participants |
| Percutaneous Coronary Intervention and Retriever Thrombectomy | Device Deficiency | 0 Participants |
Primary
Device-related Target Vessel Complications
Assessed with angiography and/or OCT
Time frame: During PCI prior to stent implantation (typically 30 min from start of procedure)
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Standalone Percutaneous Coronary Intervention | Device-related Target Vessel Complications | 0 Participants |
| Percutaneous Coronary Intervention and Thrombus Aspiration | Device-related Target Vessel Complications | 0 Participants |
| Percutaneous Coronary Intervention and Retriever Thrombectomy | Device-related Target Vessel Complications | 0 Participants |
Primary
MACCE
Time frame: At 6 months after PCI
Population: MACCE not available to all participants as two withdrew their consent for participation.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Standalone Percutaneous Coronary Intervention | MACCE | 5 Participants |
| Percutaneous Coronary Intervention and Thrombus Aspiration | MACCE | 4 Participants |
| Percutaneous Coronary Intervention and Retriever Thrombectomy | MACCE | 0 Participants |
Primary
Major Adverse Cardiac and Cerebrovascular Events (MACCE)
Time frame: Up to 30 days after PCI
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Standalone Percutaneous Coronary Intervention | Major Adverse Cardiac and Cerebrovascular Events (MACCE) | 2 Participants |
| Percutaneous Coronary Intervention and Thrombus Aspiration | Major Adverse Cardiac and Cerebrovascular Events (MACCE) | 4 Participants |
| Percutaneous Coronary Intervention and Retriever Thrombectomy | Major Adverse Cardiac and Cerebrovascular Events (MACCE) | 0 Participants |
Primary
Thrombus Volume (mm^3)
Assessed with Optical Coherence Tomography \[OCT\]
Time frame: During PCI prior to stent implantation (typically 30 min from start of procedure)
Population: The OCT run for one patient was not analysable due to slow flow precluding good blood clearance for a reliable measurement.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Standalone Percutaneous Coronary Intervention | Thrombus Volume (mm^3) | 9.8 mm^3 |
| Percutaneous Coronary Intervention and Thrombus Aspiration | Thrombus Volume (mm^3) | 4.8 mm^3 |
| Percutaneous Coronary Intervention and Retriever Thrombectomy | Thrombus Volume (mm^3) | 7.7 mm^3 |
Secondary
Angiograpicy Derived Index of Microcirculatory Resistance
The angiography derived index of microcirculatory resistance is a continuous variable that measures microcirculatory resistance. No formal minimum and maximum values exist. The higher the value, the worse the angiographic perfusion. A value over 40U confers an adverse prognosis.
Time frame: Post-stent implantation during PCI (typically 60 min after procedure start)
Population: The measurement was secondary and to the discretion of the treating physician.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Standalone Percutaneous Coronary Intervention | Angiograpicy Derived Index of Microcirculatory Resistance | 50.0 units |
| Percutaneous Coronary Intervention and Thrombus Aspiration | Angiograpicy Derived Index of Microcirculatory Resistance | 41 units |
| Percutaneous Coronary Intervention and Retriever Thrombectomy | Angiograpicy Derived Index of Microcirculatory Resistance | 40.6 units |
Secondary
Flow Volume (mm^3)
Assessed with OCT
Time frame: Post-stent implantation during PCI (typically 50 min after procedure start)
Population: One patient was crossed over to direct stent implantation due to radial spasm precluding stent retriever thrombectomy. The OCT runs for some patients were not analysable due to slow flow precluding good blood clearance for a reliable measurement.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Standalone Percutaneous Coronary Intervention | Flow Volume (mm^3) | 5.9 mm^3 |
| Percutaneous Coronary Intervention and Thrombus Aspiration | Flow Volume (mm^3) | 6.3 mm^3 |
| Percutaneous Coronary Intervention and Retriever Thrombectomy | Flow Volume (mm^3) | 7.2 mm^3 |
Secondary
Flow Volume (mm^3)
Assessed with OCT
Time frame: During PCI prior to stent implantation (typically 30 min from start of procedure)
Population: The OCT run for one patient was not analysable due to slow flow precluding good blood clearance for a reliable measurement.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Standalone Percutaneous Coronary Intervention | Flow Volume (mm^3) | 30.6 mm^3 |
| Percutaneous Coronary Intervention and Thrombus Aspiration | Flow Volume (mm^3) | 35.9 mm^3 |
| Percutaneous Coronary Intervention and Retriever Thrombectomy | Flow Volume (mm^3) | 66.5 mm^3 |
Secondary
Number of Participants With Myocardial Blush Grade (MBG) < 3
Assessed angiographically according to the TIMI Myocardial Blush Grade Score Criteria. The scale goes from 0-3. Myocardial blush grade (MGB) of 0, 1 and 2 indicates angiographic malperfusion, whilst a Myocardial blush grade (MGB) score of 3 indicates normal perfusion.
Time frame: Post-stent implantation during PCI (typically 60 min after procedure start)
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Standalone Percutaneous Coronary Intervention | Number of Participants With Myocardial Blush Grade (MBG) < 3 | 14 Participants |
| Percutaneous Coronary Intervention and Thrombus Aspiration | Number of Participants With Myocardial Blush Grade (MBG) < 3 | 6 Participants |
| Percutaneous Coronary Intervention and Retriever Thrombectomy | Number of Participants With Myocardial Blush Grade (MBG) < 3 | 6 Participants |
Secondary
Number of Participants With Stent Underexpansion & Malapposition
Assessed with OCT according to established international consensus criteria.
Time frame: Post-stent implantation during PCI (typically 50 min after procedure start)
Population: One patient was crossed over to direct stent implantation due to radial spasm precluding stent retriever thrombectomy. The OCT runs for some patients were not analysable due to slow flow precluding good blood clearance for a reliable measurement.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Standalone Percutaneous Coronary Intervention | Number of Participants With Stent Underexpansion & Malapposition | 5 Participants |
| Percutaneous Coronary Intervention and Thrombus Aspiration | Number of Participants With Stent Underexpansion & Malapposition | 3 Participants |
| Percutaneous Coronary Intervention and Retriever Thrombectomy | Number of Participants With Stent Underexpansion & Malapposition | 2 Participants |
Secondary
Thromboatheroma Volume (mm^3)
Assessed with OCT
Time frame: Post-stent implantation during PCI (typically 50 min after procedure start)
Population: One patient was crossed over to direct stent implantation due to radial spasm precluding stent retriever thrombectomy. The OCT runs for some patients were not analysable due to slow flow precluding good blood clearance for a reliable measurement.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Standalone Percutaneous Coronary Intervention | Thromboatheroma Volume (mm^3) | 3.4 mm^3 |
| Percutaneous Coronary Intervention and Thrombus Aspiration | Thromboatheroma Volume (mm^3) | 1.8 mm^3 |
| Percutaneous Coronary Intervention and Retriever Thrombectomy | Thromboatheroma Volume (mm^3) | 0.5 mm^3 |
Secondary
Thrombolysis in Myocardial Infarction (TIMI) Flow
Assessed with angiography according to the TIMI Flow criteria
Time frame: Post-stent implantation during PCI (typically 60 min after procedure start)
Population: TIMI less than 3
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Standalone Percutaneous Coronary Intervention | Thrombolysis in Myocardial Infarction (TIMI) Flow | 10 Participants |
| Percutaneous Coronary Intervention and Thrombus Aspiration | Thrombolysis in Myocardial Infarction (TIMI) Flow | 5 Participants |
| Percutaneous Coronary Intervention and Retriever Thrombectomy | Thrombolysis in Myocardial Infarction (TIMI) Flow | 5 Participants |