The primary objective of the study is to demonstrate that among subjects undergoing primary PCI for anterior STEMI treated with a bivalirudin monotherapy anticoagulation strategy, the intracoronary infusion of an abciximab bolus with or without…
ID
Source
Brief title
Condition
- Coronary artery disorders
- Arteriosclerosis, stenosis, vascular insufficiency and necrosis
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Infarct size (percentage of total LV mass) at 30 days (range -7 days/+14 days;
i.e., between 23 to 44 days) measured by cardiac MRI, comparing the pooled
randomized active (abciximab) infusion (with or without thrombus aspiration) to
the pooled non infusion arms (with or without thrombus aspiration).
Secondary outcome
Major Secondary Endpoint:
Infarct size (percentage of total LV mass) at 30 days (range -7 days/+14 days)
measured by cardiac MRI, comparing the pooled randomized aspiration arms (with
or without local infusion of abciximab) to the pooled no aspiration arms (with
or without local infusion of abciximab). Formal interaction testing between the
infusion and aspiration randomizations will also be performed.
Other Secondary Endpoints:
The following secondary endpoints will be examined across both pooled,
randomized arms:
* Incidence of complete ST segment resolution (defined as >= 70% ST resolution)
60 ± 30 minutes after last angiogram;
* Incidence of final TIMI 3 flow and corrected TIMI frame counts;
* Final myocardial perfusion measured by angiographic myocardial blush grade;
* Composite angiographic complications at any time during the procedure (new
thrombus, formation, transient or sustained no reflow or slow flow, distal
embolization, side branch loss, acute closure), and requirement for bail-out
nitroprusside, calcium channel blocker or adenosine administration, or
unplanned use of thrombectomy, aspiration or distal protection devices;
* Thrombus area after infusion or aspiration before stent implantation;
* Stent thrombosis (ARC definite and/or probable) within 24 hours of stent
implantation, in-hospital, at 30 days and 12 months post index procedure;
* Major or minor bleeding in-hospital, at 30 days and 12 months post index
procedure (HORIZONS scale, TIMI scale, GUSTO scale, thrombocytopenia,
transfusions);
* Major Adverse Cardiac and Cerebrovascular Events (MACCE) in-hospital, at 30
days and 12 months post index procedure. MACCE is defined as composite of all
cause death, reinfarction (Q-Wave and non-Q Wave), ischemia driven target
vessel revascularization, or stroke;
* Net Adverse Clinical Events (NACE) in-hospital, at 30 days and 12 months
post index procedure (NACE is defined as composite of MACCE (as defined above)
or major bleeding);
* New onset severe heart failure;
* Rehospitalization for heart failure;
* Major Adverse Cardiac Events (MACE). MACE is defined as composite of death,
reinfarction, new onset severe heart failure or rehospitalization for heart
failure. Refer to Appendix I for definition of severe heart failure;
* Acute success (clinical device and clinical procedure).
Background summary
Primary mechanical reperfusion with either PTCA or stenting for the treatment
of patients with acute myocardial infarction results in lower rates of death,
reinfarction and stroke. These benefits of primary angioplasty are primarily
due to higher rates of establishing normal myocardial perfusion in the early
stages of AMI.
Aspiration devices have been shown to improve ST segment resolution and reduce
MACE in the setting of STEMI. The Thrombus Aspiration during Percutaneous
coronary intervention in Acute myocardial infarction Study (TAPAS) was a single
center randomized trial of 1071 patients. Patients randomized to aspiration
with the Export® Aspiration Catheter (Medtronic, Inc., California), resulted in
improved myocardial perfusion after intervention. Whether these results can be
reproduced in a multicenter trial to confirm the benefit of thrombus aspiration
remains unknown. Moreover, two other studies have examined the potential of an
aspiration catheter to reduce infarct size; in one study infarct size was
paradoxically increased with aspiration, whereas in a second smaller study
there was a non significant trend toward a reduction in infarct size with
aspiration.
A number of clinical studies have been performed that support the intracoronary
use of abciximab in the setting of STEMI, demonstrating improvements in post
procedural coronary flow, myocardial salvage, and left ventricular function
compared to systemic administration or placebo. However, the systemic
administration of GP IIb/IIIa receptor inhibitors in patients with STEMI
undergoing PCI and stenting of native vessels has shown mixed results in the
RAPPORT, Munich, ADMIRAL, and the CADILLAC trials. The increased rates of
bleeding and thrombocytopenia in patients treated with abciximab may in part
diminish the efficacy of this agent.
Preliminary clinical studies suggest that delivering the abciximab bolus
directly into the coronary artery rather than intravenously may improve
clinical outcomes and reduce infarct size.
This investigation will evaluate the different treatments in order to improve
the treatment of acute myocardial infarction.
Study objective
The primary objective of the study is to demonstrate that among subjects
undergoing primary PCI for anterior STEMI treated with a bivalirudin
monotherapy anticoagulation strategy, the intracoronary infusion of an
abciximab bolus with or without thrombus aspiration prior to stent
implantation, compared to no infusion with or without thrombus aspiration
(standard of care), results in 1) reduced infarct size measured by cardiac MRI
at 30 days (range -7 days/+14 days; i.e., between 23 and 44 days), 2) reduce
microvascular obstruction (MVO) by cardiac MRI at 5 + 2 days (i.e., between 3
and 7 days), 3) enhanced ST-segment resolution, 4) improved myocardial
perfusion, 5) reduced thrombus burden and angiographic complications, and 6) no
increase in major and minor bleeding.
Study design
This is a multicenter, open-label, controlled, single-blind, randomized study
with up to 452 subjects enrolled in up to 50 US and European sites
Intervention
Next to the standard treatment, patients will be randomized to:
1. Local infusion of abciximab following thrombus aspiration
2. Local infusion of abciximab and no thrombus aspiration
3. No local infusion and thrombus aspiration
4. No local infusion and no thrombus aspiration
Study burden and risks
Patients will return after 5 days and again after 30 days for the MRI
assessment (and ECG).
After 12 months, patients will be contacted by phone to evaluate the overall
health status.
5 Wentworth Drive
Hudson, New Hampshire 03051
US
5 Wentworth Drive
Hudson, New Hampshire 03051
US
Listed location countries
Age
Inclusion criteria
- >= 18 years of age;
- Anterior MI with ECG showing at least 1 mm of ST-segment elevation in 2 or more contiguous leads in V1-V4, or new (or presumably new) left bundle branch block;
- Anticipated symptom onset to balloon or aspiration time of <= 5 hours;
- Infarct artery located in the proximal or mid left anterior descending coronary artery, with TIMI 0, 1 or 2 flow at the time of initial diagnostic angiography (prior to wire passage);
- Based on coronary anatomy, PCI is indicated for revascularization;
- Only one epicardial coronary artery will be treated;
- Expected ability to deliver a ClearWay* RX Infusion Catheter to the infarct lesion (absence of excessive tortuosity, diffuse disease or moderate/heavy calcification).
Exclusion criteria
- Prior myocardial infarction, or known prior systolic dysfunction (known ejection fraction <40% by any prior measure or regional wall motion abnormalities);
- An elective surgical procedure is planned that would necessitate interruption of anti-platelet agents during the first twelve months post enrollment;
- Subjects who previously underwent coronary stent implantation and in whom coronary angiography demonstrates stent thrombosis to be the cause of the AMI;
- Subject has previously undergone an angioplasty or stenting procedure in the left anterior descending artery;
- Any contraindication to undergo MRI imaging.
- Coronary anatomy such that coronary artery bypass graft surgery will possibly be required within 30 days;
- Multivessel intervention required during the index procedure
- Severe vessel tortuosity, diffuse disease or severe calcification is present which may impede successful delivery of the Clearway Catheter
- Subjects who have prior history of bypass surgery (CABG);
- MI is due to thrombosis within or adjacent to a previously implanted stent;
- Left ventriculography demonstrates severe mitral regurgitation or a VSD;
- Unprotected left main stenosis >40% or that will require intervention;
- Subject has received >5000 units of unfractionated heparin within the preceding 24 hours prior to presenting to the catheterization laboratory, or any subject who receives heparin after arrival in the cardiac catheterization laboratory prior to randomization.
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| EudraCT | EUCTR2009-013425-42-NL |
| CCMO | NL28608.060.09 |