Myocardial Infarction
Conditions
Keywords
Myocardial infarction, percutaneous coronary intervention, abciximab, reteplase, safety and efficacy
Brief summary
The purpose of this study is to determine whether abciximab given in combination with reteplase, before patients have a coronary intervention (a standard treatment where a catheter is inserted into the heart artery to get blood flowing past the clot), is safe and effective in the treatment of heart attacks compared to only abciximab given during coronary intervention.
Detailed description
The purpose of this medical research study is to determine whether abciximab given in combination with reteplase, before patients have a coronary intervention (a standard treatment where a catheter is inserted into the heart artery to get blood flowing past the clot), is safe and effective in the treatment of heart attacks compared to only abciximab given during coronary intervention. This medical research study will also help determine if the combination of abciximab and reduced dose reteplase will decrease the risk of death, and reduce complications of a heart attack at 90 days compared to abciximab alone which is a standard treatment. Patients will receive either abciximab and reteplease or abciximab alone. Safety evaluations will be performed at specified intervals throughout the study and will consist of laboratory tests, vital signs (such as blood pressure), physical examinations and the occurrence and severity of adverse events as well as other study specific procedures. Patients will receive either abciximab and reteplease or abciximab and placebo into a vein in their arm for up to 12 hours.
Interventions
DRUGabciximab placebo; reteplase placebo, abciximab, abciximab
placebo bolus; 1-2 placebo bolus; 0.25 mg/kg bolus; 0.125 ¼g/kg/min, max 10 ¼g/min infusion x 12h
DRUGAbciximab; reteplase; abciximab placebo; abciximab
0.25 mg/kg bolus; 1-2, 5 unit boluses; placebo bolus; 0.125 ¼g/kg/min, max 10 ¼g/min infusion x 12h
DRUGabciximab; reteplase placebo; abciximab placebo; abciximab
0.25 mg/kg bolus; 1-2 placebo boluses; placebo bolus; 0.125 ¼g/kg/min, max 10 ¼g/min infusion x 12h
Sponsors
Eli Lilly and Company
Centocor, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
21 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Patients who have prolonged, continuous (lasting at least 20 minutes) signs and symptoms of A heart attack not eliminated with nitrates and onset within 6 hours of randomization,and confirmation by Electrocardiogram
Exclusion criteria
* Low risk clinical presentation * patients who will not be undergoing a catherization within 4 hours of the qualifying Electrocardiogram
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| The Composite of All-Cause Mortality or Complications of MI at 90 Days. | 90 days | Occurs within 90 days and is composite of all-cause mortality or complications of myocardial infarction (MI) (rehospitalization or emergency department visit for congestive heart failure (CHF), cardiogenic shock, or resuscitated ventricular fibrillation occurring \> 48 hours after randomization). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Complications of MI as Defined in the Primary Outcome Measure Through 90 Days | 90 Days | The complications of myocardial infarction (MI) is defined as any event of rehospitalization or emergency department visit for CHF, cardiogenic shock, or resuscitated ventricular fibrillation occurring \> 48 hours after randomization. |
| All-Cause Mortality Through 90 Days | 90 days | All cause mortality occurred through 90 days from randomization. |
| Subjects With ST-Segment Resolution > 70% From Baseline at 60 to 90 Minutes Following Randomization | 60 to 90 minutes | — |
| All-Cause Mortality Through 1 Year | 1 year | All-cause mortality through 1 year from randomization. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Subjects With Intracranial Hemorrhage (Including Hemorrhagic Transformation) Through Discharge/Day 7 | Discharge/Day 7 | All cases of cerebrovascular event were confirmed by a CEC (Clinical Endpoints Committee). |
| Subjects With Non Intracranial Thrombolysis In Myocardial Infarction (TIMI) Bleeding Events Through Discharge/Day 7 | Discharge/Day 7 | Subjects with nonintracranial TIMI bleeding (either major or minor) through discharge/day 7, originating from vascular instrumentation sites, non-instrument related bleeding, as well as overall, were examined. |
| Subjects With Severe Thrombocytopenia Through Discharge/Day 7 | Discharge/Day 7 | Severe thrombocytopenia is defined as platelet count \< 50,000 cells/μL. |
| Subjects With Any Investigator Reported Bleeding Events Through Discharge/Day 7 | Discharge/Day 7 | — |
| Subjects With Pre-Specified Complications of Index Myocardial Infarction Through Discharge/Day 7 | Discharge/Day 7 | Number of subjects with one or more of the following: 2nd or 3rd Degree AVB, Asystole, Sustained V Tach, A Fib/Flutter, EMD/Pulseless Electrical Activity, Heart Failure, Tamponade, Myocardial Rupture, Papillary Muscle Rupture, Ventricular Septal Defect, Pulmonary Embolism, Systemic Arterial Embolism and/or Pericarditis/Pericardial Effusion. |
Countries
Argentina, Austria, Belgium, Bulgaria, Canada, Czechia, Denmark, France, Germany, Israel, Netherlands, Poland, Romania, South Africa, Spain, Sweden, Switzerland, United Kingdom, United States
Participant flow
Recruitment details
The study was conducted in 20 countries. The FINESSE (Facilitated INtervention with Enhanced Reperfusion Speed to Stop Events) study began enrollment in August 2002. It was planned that approximately 3,000 subjects would be enrolled. Because of enrollment difficulty, subject enrollment was stopped on 30 Dec 2006.
Pre-assignment details
A total of 2,461 subjects were enrolled in the study according to the sponsor's clinical trial management system. Out of 2461 subjects, 2,452 subjects were randomly assigned to the 3 treatment groups.
Participants by arm
| Arm | Count |
|---|---|
| Primary PCI Group Abciximab (bolus + 12 hr infusion) initiated just prior to primary percutaneous coronary intervention (PCI) | 806 |
| Abciximab Facilitated PCI Group Abciximab (bolus) administered as soon as possible after randomization, 12 hour infusion initiated prior to PCI | 818 |
| Reteplase/Abciximab Facilitated PCI Group Abciximab (bolus) + reteplase (5 U + 5 U double bolus for subjects \< 75 years of age; 5 U single bolus for subjects ≥ 75 years of age), abciximab 12 hour infusion initiated prior to PCI | 828 |
| Total | 2,452 |
Baseline characteristics
| Characteristic | Primary PCI Group | Abciximab Facilitated PCI Group | Reteplase/Abciximab Facilitated PCI Group | Total |
|---|---|---|---|---|
| Age, Continuous | 62.5 years STANDARD_DEVIATION 11.4 | 61.9 years STANDARD_DEVIATION 11.8 | 62.6 years STANDARD_DEVIATION 11.4 | 62.4 years STANDARD_DEVIATION 11.5 |
| Sex: Female, Male Female | 207 Participants | 216 Participants | 219 Participants | 642 Participants |
| Sex: Female, Male Male | 599 Participants | 602 Participants | 609 Participants | 1810 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 0 / 795 | 0 / 805 | 0 / 814 |
| serious Total, serious adverse events | 159 / 795 | 182 / 805 | 175 / 814 |
Outcome results
Primary
The Composite of All-Cause Mortality or Complications of MI at 90 Days.
Occurs within 90 days and is composite of all-cause mortality or complications of myocardial infarction (MI) (rehospitalization or emergency department visit for congestive heart failure (CHF), cardiogenic shock, or resuscitated ventricular fibrillation occurring \> 48 hours after randomization).
Time frame: 90 days
Population: Population is the intent-to-treat subjects. The intent-to-treat population is defined as all subjects randomly assigned to a treatment group and classified according to the randomization assignment.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Primary PCI Group | The Composite of All-Cause Mortality or Complications of MI at 90 Days. | 86 participants |
| Abciximab Facilitated PCI Group | The Composite of All-Cause Mortality or Complications of MI at 90 Days. | 86 participants |
| Reteplase/Abciximab Facilitated PCI Group | The Composite of All-Cause Mortality or Complications of MI at 90 Days. | 81 participants |
Comparison: The null hypothesis is if reteplase/abciximab facilitated PCI is the same as the primary PCI in terms of the primary efficacy outcome. Assuming the relative risk reduction for the reteplase/abciximab facilitated PCI group versus the Primary PCI group is 15% in lower risk, 25% in medium risk, and 35% in high risk, the power of this comparison (1,000 subjects per group) is 83.4 %.p-value: 0.55195% CI: [0.67, 1.23]Log Rank
Comparison: The null hypothesis is if abciximab facilitated PCI is the same as the primary PCI in terms of the primary efficacy outcome. Assuming the relative risk reduction for the Abciximab facilitated PCI versus the Primary PCI group is 12.7%, in lower risk, 17.9% in medium risk, and 25.0% in high risk, the power of this comparison (1000 subjects per group) is 54.1%p-value: 0.85895% CI: [0.72, 1.31]Log Rank
Comparison: The null hypothesis is if reteplase/abciximab facilitated PCI is the same as the abciximab facilitated PCI in terms of the primary efficacy outcome. Assuming the relative risk reduction for the reteplase/abciximab facilitated PCI versus the abciximab facilitated PCI group is 2.6% in lower risk, 8.7% in medium risk, and 13.3% in high risk, the power of this comparison (1,000 subjects per group) is 13.5%.p-value: 0.67695% CI: [0.69, 1.27]Log Rank
Secondary
All-Cause Mortality Through 1 Year
All-cause mortality through 1 year from randomization.
Time frame: 1 year
Population: Population is the intent-to-treat subjects. The intent-to-treat population is defined as all randomized subjects classified according to the randomization assignment.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Primary PCI Group | All-Cause Mortality Through 1 Year | 56 participants |
| Abciximab Facilitated PCI Group | All-Cause Mortality Through 1 Year | 60 participants |
| Reteplase/Abciximab Facilitated PCI Group | All-Cause Mortality Through 1 Year | 52 participants |
p-value: 0.60395% CI: [0.62, 1.32]Log Rank
p-value: 0.76595% CI: [0.73, 1.52]Log Rank
p-value: 0.41595% CI: [0.59, 1.24]Log Rank
Secondary
All-Cause Mortality Through 90 Days
All cause mortality occurred through 90 days from randomization.
Time frame: 90 days
Population: Population is the intent-to-treat subjects. The intent-to-treat population is defined as all randomized subjects classified according to the randomization assignment.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Primary PCI Group | All-Cause Mortality Through 90 Days | 36 participants |
| Abciximab Facilitated PCI Group | All-Cause Mortality Through 90 Days | 45 participants |
| Reteplase/Abciximab Facilitated PCI Group | All-Cause Mortality Through 90 Days | 43 participants |
Comparison: The null hypothesis is if retaplase/abciximab facilitated PCI is the same as the primary PCI in 90-day all cause mortality.p-value: 0.49495% CI: [0.74, 1.84]Chi-squared
Comparison: The null hypothesis is if abciximab facilitated PCI is the same as the primary PCI in 90-day all cause mortality.p-value: 0.33895% CI: [0.79, 1.95]Chi-squared
Comparison: The null hypothesis is if retaplase/abciximab facilitated PCI is the same as the abciximab facilitated PCI in 90-day all cause mortality.p-value: 0.78195% CI: [0.61, 1.45]Chi-squared
Secondary
Complications of MI as Defined in the Primary Outcome Measure Through 90 Days
The complications of myocardial infarction (MI) is defined as any event of rehospitalization or emergency department visit for CHF, cardiogenic shock, or resuscitated ventricular fibrillation occurring \> 48 hours after randomization.
Time frame: 90 Days
Population: Population is the intent-to-treat subjects. The intent-to-treat population is defined as all subjects that have been randomly assigned to a treatment group and classified according to the randomization assignment.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Primary PCI Group | Complications of MI as Defined in the Primary Outcome Measure Through 90 Days | 72 participants |
| Abciximab Facilitated PCI Group | Complications of MI as Defined in the Primary Outcome Measure Through 90 Days | 61 participants |
| Reteplase/Abciximab Facilitated PCI Group | Complications of MI as Defined in the Primary Outcome Measure Through 90 Days | 61 participants |
Comparison: The null hypothesis is if reteplase/abciximab facilitated PCI is the same as the primary PCI in complications of MI within 90 days.p-value: 0.24795% CI: [0.57, 1.16]Chi-squared
Comparison: The null hypothesis is if abciximab facilitated PCI is the same as the primary PCI in complications of MI within 90 days.p-value: 0.27895% CI: [0.58, 1.17]Chi-squared
Comparison: The null hypothesis is if reteplase/abciximab facilitated PCI is the same as the abciximab facilitated PCI in complications of MI within 90 days.p-value: 0.94495% CI: [0.68, 1.43]Chi-squared
Secondary
Subjects With ST-Segment Resolution > 70% From Baseline at 60 to 90 Minutes Following Randomization
Time frame: 60 to 90 minutes
Population: Population is the intent-to-treat subjects who were selected for evaluation by electrocardiogram (ECG) core laboratory.Subjects, who were not evaluable for a 60-90 minute ECG, were considered not having a ST segment resolution.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Primary PCI Group | Subjects With ST-Segment Resolution > 70% From Baseline at 60 to 90 Minutes Following Randomization | 75 participants |
| Abciximab Facilitated PCI Group | Subjects With ST-Segment Resolution > 70% From Baseline at 60 to 90 Minutes Following Randomization | 85 participants |
| Reteplase/Abciximab Facilitated PCI Group | Subjects With ST-Segment Resolution > 70% From Baseline at 60 to 90 Minutes Following Randomization | 108 participants |
Comparison: The null hypothesis is if retaplase/abciximab facilitated PCI is the same as the primary PCI in ST-segment resolution \>70% from baseline.p-value: 0.01695% CI: [1.08, 2.1]Chi-squared
Comparison: The null hypothesis is if abciximab facilitated PCI is the same as the primary PCI in ST-segment resolution \>70% from baseline.p-value: 0.6795% CI: [0.76, 1.52]Chi-squared
Comparison: The null hypothesis is if retaplase/abciximab facilitated PCI is the same as the abciximab facilitated PCI in ST-segment resolution \>70% from baseline.p-value: 0.04295% CI: [1.01, 1.93]Chi-squared
Other Pre-specified
Subjects With Any Investigator Reported Bleeding Events Through Discharge/Day 7
Time frame: Discharge/Day 7
Population: The population was defined as all subjects who were randomized and treated with any study agent, including those who discontinued for any reasons. Subjects randomized and treated was classified according to the study drug(s) received.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Primary PCI Group | Subjects With Any Investigator Reported Bleeding Events Through Discharge/Day 7 | 139 participants |
| Abciximab Facilitated PCI Group | Subjects With Any Investigator Reported Bleeding Events Through Discharge/Day 7 | 178 participants |
| Reteplase/Abciximab Facilitated PCI Group | Subjects With Any Investigator Reported Bleeding Events Through Discharge/Day 7 | 271 participants |
p-value: <0.001Fisher Exact
p-value: 0.02Fisher Exact
p-value: <0.001Fisher Exact
Other Pre-specified
Subjects With Intracranial Hemorrhage (Including Hemorrhagic Transformation) Through Discharge/Day 7
All cases of cerebrovascular event were confirmed by a CEC (Clinical Endpoints Committee).
Time frame: Discharge/Day 7
Population: The population was defined as all subjects who were randomized and treated with any study agent, including those who discontinued for any reasons. Subjects randomized and treated was classified according to the study drug(s) received.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Primary PCI Group | Subjects With Intracranial Hemorrhage (Including Hemorrhagic Transformation) Through Discharge/Day 7 | 1 participants |
| Abciximab Facilitated PCI Group | Subjects With Intracranial Hemorrhage (Including Hemorrhagic Transformation) Through Discharge/Day 7 | 0 participants |
| Reteplase/Abciximab Facilitated PCI Group | Subjects With Intracranial Hemorrhage (Including Hemorrhagic Transformation) Through Discharge/Day 7 | 5 participants |
Comparison: The null hypothesis is if reteplase/abciximab facilitated PCI is the same as the primary PCI in the risk of ICH.p-value: 0.218Fisher Exact
Comparison: The null hypothesis is if abciximab facilitated PCI is the same as the primary PCI in the risk of ICH.p-value: 0.497Fisher Exact
Comparison: The null hypothesis is if reteplase/abciximab facilitated PCI is the same as the abciximab facilitated PCI in the risk of ICH.p-value: 0.062Fisher Exact
Other Pre-specified
Subjects With Non Intracranial Thrombolysis In Myocardial Infarction (TIMI) Bleeding Events Through Discharge/Day 7
Subjects with nonintracranial TIMI bleeding (either major or minor) through discharge/day 7, originating from vascular instrumentation sites, non-instrument related bleeding, as well as overall, were examined.
Time frame: Discharge/Day 7
Population: The population was defined as all subjects who were randomized and treated with any study agent, including those who discontinued for any reasons. Subjects randomized and treated was classified according to the study drug(s) received.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Primary PCI Group | Subjects With Non Intracranial Thrombolysis In Myocardial Infarction (TIMI) Bleeding Events Through Discharge/Day 7 | 55 participant |
| Abciximab Facilitated PCI Group | Subjects With Non Intracranial Thrombolysis In Myocardial Infarction (TIMI) Bleeding Events Through Discharge/Day 7 | 81 participant |
| Reteplase/Abciximab Facilitated PCI Group | Subjects With Non Intracranial Thrombolysis In Myocardial Infarction (TIMI) Bleeding Events Through Discharge/Day 7 | 118 participant |
Comparison: The null hypothesis is if reteplase/abciximab facilitated PCI is the same as the primary PCI in the risk of non-ICH TIMI bleeding events.p-value: <0.00195% CI: [1.63, 3.19]Fisher Exact
Comparison: The null hypothesis is if abciximab facilitated PCI is the same as the primary PCI in the risk of non-ICH TIMI bleeding events.p-value: 0.02595% CI: [1.05, 2.15]Fisher Exact
Comparison: The null hypothesis is if reteplase/abciximab facilitated PCI is the same as the abciximab facilitated PCI in the risk of non-ICH TIMI bleeding events.p-value: 0.00895% CI: [1.12, 2.05]Fisher Exact
Other Pre-specified
Subjects With Pre-Specified Complications of Index Myocardial Infarction Through Discharge/Day 7
Number of subjects with one or more of the following: 2nd or 3rd Degree AVB, Asystole, Sustained V Tach, A Fib/Flutter, EMD/Pulseless Electrical Activity, Heart Failure, Tamponade, Myocardial Rupture, Papillary Muscle Rupture, Ventricular Septal Defect, Pulmonary Embolism, Systemic Arterial Embolism and/or Pericarditis/Pericardial Effusion.
Time frame: Discharge/Day 7
Population: Population is the intent-to-treat subjects. The intent-to-treat population is defined as all randomized subjects classified according to the randomization assignment.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Primary PCI Group | Subjects With Pre-Specified Complications of Index Myocardial Infarction Through Discharge/Day 7 | 128 participants |
| Abciximab Facilitated PCI Group | Subjects With Pre-Specified Complications of Index Myocardial Infarction Through Discharge/Day 7 | 122 participants |
| Reteplase/Abciximab Facilitated PCI Group | Subjects With Pre-Specified Complications of Index Myocardial Infarction Through Discharge/Day 7 | 120 participants |
p-value: 0.43495% CI: [0.69, 1.18]Chi-squared
p-value: 0.58995% CI: [0.71, 1.22]Chi-squared
p-value: 0.80995% CI: [0.74, 1.27]Chi-squared
Other Pre-specified
Subjects With Severe Thrombocytopenia Through Discharge/Day 7
Severe thrombocytopenia is defined as platelet count \< 50,000 cells/μL.
Time frame: Discharge/Day 7
Population: The population was defined as all subjects who were randomized and treated with any study agent, including those who discontinued for any reasons. Subjects randomized and treated was classified according to the study drug(s) received.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Primary PCI Group | Subjects With Severe Thrombocytopenia Through Discharge/Day 7 | 11 participants |
| Abciximab Facilitated PCI Group | Subjects With Severe Thrombocytopenia Through Discharge/Day 7 | 16 participants |
| Reteplase/Abciximab Facilitated PCI Group | Subjects With Severe Thrombocytopenia Through Discharge/Day 7 | 16 participants |
p-value: 0.439Fisher Exact
p-value: 0.438Fisher Exact
p-value: 1Fisher Exact