Trial Outcomes & Findings for Bivalirudin Infusion for Ventricular Infarction Limitation (NCT NCT02565147)
NCT ID: NCT02565147
Last Updated: 2018-10-05
Results Overview
Size of cardiac infarct, expressed as grams, as assessed by CMR. The use of CMR has dramatically improved the ability for accurate infarct size estimations and is therefore currently considered the gold standard. The number of participants and their mean reported infarct size, as grams, at Day 5 are presented.
TERMINATED
PHASE3
78 participants
5 days post PPCI
2018-10-05
Participant Flow
Enrolled participants who underwent successful primary percutaneous coronary intervention (PPCI) defined as thrombolysis in myocardial infarction (TIMI) Flow of 2 or 3, underwent cardiac magnetic resonance imaging (CMR) at 5 days, and were without major protocol deviations were included in the per-protocol population (primary/secondary analyses).
Participant milestones
| Measure |
PPCI With Bivalirudin
Bivalirudin was administered as a bolus (0.75 milligrams \[mg\]/kilogram \[kg\]) and an infusion (1.75 mg/kg/hours \[h\]) for the duration of the PPCI and continued for the first 4 h after completion of the procedure.
|
PPCI With Heparin
Unfractionated heparin (UFH) was administered as a bolus according to standard of care for completion of PPCI per site. An activated clotting time (ACT) ≥250 seconds (s) at the end of the procedure was recommended.
|
|---|---|---|
|
Overall Study
STARTED
|
38
|
40
|
|
Overall Study
Received Study Drug
|
38
|
40
|
|
Overall Study
Per-Protocol Population
|
28
|
36
|
|
Overall Study
COMPLETED
|
32
|
37
|
|
Overall Study
NOT COMPLETED
|
6
|
3
|
Reasons for withdrawal
| Measure |
PPCI With Bivalirudin
Bivalirudin was administered as a bolus (0.75 milligrams \[mg\]/kilogram \[kg\]) and an infusion (1.75 mg/kg/hours \[h\]) for the duration of the PPCI and continued for the first 4 h after completion of the procedure.
|
PPCI With Heparin
Unfractionated heparin (UFH) was administered as a bolus according to standard of care for completion of PPCI per site. An activated clotting time (ACT) ≥250 seconds (s) at the end of the procedure was recommended.
|
|---|---|---|
|
Overall Study
Withdrawal by Subject
|
5
|
1
|
|
Overall Study
Lost to Follow-up
|
0
|
1
|
|
Overall Study
Death
|
1
|
1
|
Baseline Characteristics
Race and Ethnicity were not collected from any participant.
Baseline characteristics by cohort
| Measure |
PPCI With Bivalirudin
n=38 Participants
Bivalirudin was administered as a bolus (0.75 mg/kg) and an infusion (1.75 mg/kg/h) for the duration of the PPCI and continued for the first 4 h after completion of the procedure.
|
PPCI With Heparin
n=40 Participants
UFH was administered as a bolus according to standard of care for completion of PPCI per site. An ACT ≥250 s at the end of the procedure was recommended.
|
Total
n=78 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
63.6 Years
STANDARD_DEVIATION 11.4 • n=38 Participants
|
61.2 Years
STANDARD_DEVIATION 13.2 • n=40 Participants
|
62.4 Years
STANDARD_DEVIATION 12.3 • n=78 Participants
|
|
Sex: Female, Male
Female
|
10 Participants
n=38 Participants
|
6 Participants
n=40 Participants
|
16 Participants
n=78 Participants
|
|
Sex: Female, Male
Male
|
28 Participants
n=38 Participants
|
34 Participants
n=40 Participants
|
62 Participants
n=78 Participants
|
|
Race and Ethnicity Not Collected
|
—
|
—
|
0 Participants
Race and Ethnicity were not collected from any participant.
|
|
Region of Enrollment
Netherlands
|
21 Participants
n=38 Participants
|
22 Participants
n=40 Participants
|
43 Participants
n=78 Participants
|
|
Region of Enrollment
France
|
17 Participants
n=38 Participants
|
18 Participants
n=40 Participants
|
35 Participants
n=78 Participants
|
PRIMARY outcome
Timeframe: 5 days post PPCIPopulation: All enrolled participants who underwent successful PPCI and CMR without major protocol deviations (Per-Protocol Population).
Size of cardiac infarct, expressed as grams, as assessed by CMR. The use of CMR has dramatically improved the ability for accurate infarct size estimations and is therefore currently considered the gold standard. The number of participants and their mean reported infarct size, as grams, at Day 5 are presented.
Outcome measures
| Measure |
PPCI With Bivalirudin
n=28 Participants
Bivalirudin was administered as a bolus (0.75 mg/kg) and an infusion (1.75 mg/kg/h) for the duration of the PPCI and continued for the first 4 h after completion of the procedure.
|
PPCI With Heparin
n=36 Participants
UFH was administered as a bolus according to standard of care for completion of PPCI per site. An ACT ≥250 s at the end of the procedure was recommended.
|
|---|---|---|
|
CMR Assessment Of Infarct Size At Day 5
|
25.0 Grams
Standard Deviation 19.7
|
27.1 Grams
Standard Deviation 20.7
|
SECONDARY outcome
Timeframe: 5 days post PPCIPopulation: All enrolled participants who underwent successful PPCI and CMR without major protocol deviations (Per-Protocol Population) and participants with a successful CMR assessment of MSI.
MSI is a CMR-derived parameter of myocardial recovery and treatment efficacy that allows comparisons among infarcts of different sizes. MSI is calculated as the difference between the area at risk (AAR) and the final infarct size, divided by the AAR, and it is expressed as a percentage of AAR. An MSI of 100% indicates maximum treatment success, whereas an MSI of 0% indicates no treatment benefit. The number of participants and their mean-reported MSI at Day 5 are presented.
Outcome measures
| Measure |
PPCI With Bivalirudin
n=12 Participants
Bivalirudin was administered as a bolus (0.75 mg/kg) and an infusion (1.75 mg/kg/h) for the duration of the PPCI and continued for the first 4 h after completion of the procedure.
|
PPCI With Heparin
n=15 Participants
UFH was administered as a bolus according to standard of care for completion of PPCI per site. An ACT ≥250 s at the end of the procedure was recommended.
|
|---|---|---|
|
CMR Assessment Of Myocardial Salvage Index (MSI) At Day 5
|
39.4 Percentage of AAR
Standard Deviation 19.3
|
51.2 Percentage of AAR
Standard Deviation 21.7
|
SECONDARY outcome
Timeframe: 5 days post PPCIPopulation: All enrolled participants who underwent successful PPCI and CMR without major protocol deviations (Per-Protocol Population) and participants with a successful CMR assessment of MVO.
Early and late assessment of MVO, expressed as grams, as assessed by CMR. MVO is an established complication of coronary reperfusion therapy for acute myocardial infarction. MVO occurs in the setting of reperfusion following prolonged myocardial ischemia and provides incremental prognostic information beyond infarct size, to which it is related. Early MVO is a prolonged (approximately 60 s) perfusion deficit in dynamic gadolinium (Gd) first-pass images that is determined within 2 minutes (min) of administration of the Gd-based contrast agent. Late MVO is usually assessed as a hypointense infarct core on late-Gd-enhancement images acquired 10 min after contrast administration. The number of participants and their mean reported early and late MVO, as grams, at Day 5 are presented.
Outcome measures
| Measure |
PPCI With Bivalirudin
n=28 Participants
Bivalirudin was administered as a bolus (0.75 mg/kg) and an infusion (1.75 mg/kg/h) for the duration of the PPCI and continued for the first 4 h after completion of the procedure.
|
PPCI With Heparin
n=36 Participants
UFH was administered as a bolus according to standard of care for completion of PPCI per site. An ACT ≥250 s at the end of the procedure was recommended.
|
|---|---|---|
|
CMR Assessment Of Micro-vascular Obstruction (MVO) At Day 5
CMR Early MVO Assessment
|
5.3 Grams
Standard Deviation 5.8
|
7.7 Grams
Standard Deviation 6.3
|
|
CMR Assessment Of Micro-vascular Obstruction (MVO) At Day 5
CMR Late MVO Assessment
|
3.7 Grams
Standard Deviation 5.7
|
4.2 Grams
Standard Deviation 4.5
|
SECONDARY outcome
Timeframe: 5 days post PPCIPopulation: All enrolled participants who underwent successful PPCI and CMR without major protocol deviations (Per-Protocol Population).
Percentage of cardiac LVEF as assessed by CMR. LVEF is a measurement of the percentage of blood ejected out of the left ventricle with each contraction. The number of participants and their mean reported LVEF, as a percentage of blood, at Day 5 are presented.
Outcome measures
| Measure |
PPCI With Bivalirudin
n=28 Participants
Bivalirudin was administered as a bolus (0.75 mg/kg) and an infusion (1.75 mg/kg/h) for the duration of the PPCI and continued for the first 4 h after completion of the procedure.
|
PPCI With Heparin
n=36 Participants
UFH was administered as a bolus according to standard of care for completion of PPCI per site. An ACT ≥250 s at the end of the procedure was recommended.
|
|---|---|---|
|
CMR Assessment Of Left Ventricular Ejection Fraction (LVEF) At Day 5
|
48.5 Percentage of Blood
Standard Deviation 11.0
|
48.6 Percentage of Blood
Standard Deviation 10.9
|
SECONDARY outcome
Timeframe: 90 days post PPCIPopulation: All enrolled participants who underwent successful PPCI and CMR without major protocol deviations (Per-Protocol Population) and participants with a successful CMR assessment of LVEF at Day 90.
Percentage of cardiac LVEF as assessed by CMR. LVEF is a measurement of the percentage of blood ejected out of the left ventricle with each contraction. The number of participants and their mean reported LVEF, as a percentage of blood, at Day 90 are presented.
Outcome measures
| Measure |
PPCI With Bivalirudin
n=22 Participants
Bivalirudin was administered as a bolus (0.75 mg/kg) and an infusion (1.75 mg/kg/h) for the duration of the PPCI and continued for the first 4 h after completion of the procedure.
|
PPCI With Heparin
n=29 Participants
UFH was administered as a bolus according to standard of care for completion of PPCI per site. An ACT ≥250 s at the end of the procedure was recommended.
|
|---|---|---|
|
CMR Assessment Of LVEF At Day 90
|
54.6 Percentage of Blood
Standard Deviation 12.0
|
49.1 Percentage of Blood
Standard Deviation 12.1
|
SECONDARY outcome
Timeframe: 1 day (end of PPCI)Population: All enrolled participants who underwent successful PPCI and CMR without major protocol deviations (Per-Protocol Population) and participants with a detectable TIMI Flow and MBG at the end of PPCI.
TIMI flow (grade 0-3) is an angiographic determination of briskness of epicardial coronary blood flow: TIMI 0 flow (no perfusion); TIMI 1 flow (penetration without perfusion); TIMI 2 flow (partial reperfusion); TIMI 3 flow (complete perfusion/normal flow). MBG (grade 0-3) is an angiographic method for determination of blood flow in the distal myocardial vascular bed. Blush grades: 0 = failure of dye to enter the micro-vasculature; 1 = dye slowly enters but fails to exit the micro-vasculature; 2 = delayed entry and exit of dye from the micro-vasculature; 3 = normal entry and exit of dye from the micro-vasculature. Blush that is only mildly intense throughout the washout phase, but fades minimally, is also classified as grade 3. The number of participants and their mean reported TIMI flow and MBG grades at the end of PPCI are presented.
Outcome measures
| Measure |
PPCI With Bivalirudin
n=28 Participants
Bivalirudin was administered as a bolus (0.75 mg/kg) and an infusion (1.75 mg/kg/h) for the duration of the PPCI and continued for the first 4 h after completion of the procedure.
|
PPCI With Heparin
n=36 Participants
UFH was administered as a bolus according to standard of care for completion of PPCI per site. An ACT ≥250 s at the end of the procedure was recommended.
|
|---|---|---|
|
TIMI Flow And Myocardial Blush Grade (MBG) At End Of PPCI
TIMI Flow Grade
|
2.8 Units on a Scale
Standard Deviation 0.4
|
2.8 Units on a Scale
Standard Deviation 0.4
|
|
TIMI Flow And Myocardial Blush Grade (MBG) At End Of PPCI
MBG
|
1.8 Units on a Scale
Standard Deviation 1.2
|
1.5 Units on a Scale
Standard Deviation 1.2
|
SECONDARY outcome
Timeframe: 5 days post PPCI or at discharge, whichever occurs firstPopulation: All enrolled participants who underwent successful PPCI and CMR without major protocol deviations (Per-Protocol Population).
The NACE at 5 days is the composite of major bleeding (Bleeding Academic Research Consortium Type 3 or greater \[BARC type ≥3\]), death, re-infarction, and ischaemia driven revascularization (IDR). In brief, BARC ≥3 includes: Type 3a-3c, clinical, laboratory, and/or imaging evidence of bleeding; Type 4, coronary artery bypass grafting-related bleeding; Type 5, fatal bleeding that directly results in death that is either clinically suspicious or is confirmed as the cause of death. A participant was defined to have a composite event if the participant experienced at least 1 of the components. If the participant did not have any of the components, then he or she did not have the composite endpoint. If a participant had more than 1 of the components, he or she was only counted once in the determination of the total number of participants experiencing the composite endpoint. The percentage of participants with in-hospital NACE up to Day 5 is presented.
Outcome measures
| Measure |
PPCI With Bivalirudin
n=28 Participants
Bivalirudin was administered as a bolus (0.75 mg/kg) and an infusion (1.75 mg/kg/h) for the duration of the PPCI and continued for the first 4 h after completion of the procedure.
|
PPCI With Heparin
n=36 Participants
UFH was administered as a bolus according to standard of care for completion of PPCI per site. An ACT ≥250 s at the end of the procedure was recommended.
|
|---|---|---|
|
Percentage of Participants With In-Hospital Net Adverse Cardiac Events (NACE) At Day 5
|
7.1 Percentage of Participants
|
8.3 Percentage of Participants
|
SECONDARY outcome
Timeframe: 90 days post PPCIPopulation: All enrolled participants who underwent successful PPCI and CMR without major protocol deviations (Per-Protocol Population).
Participant survival during the clinical follow-up period is presented as the number of participants with reported death at 90 days post PPCI.
Outcome measures
| Measure |
PPCI With Bivalirudin
n=28 Participants
Bivalirudin was administered as a bolus (0.75 mg/kg) and an infusion (1.75 mg/kg/h) for the duration of the PPCI and continued for the first 4 h after completion of the procedure.
|
PPCI With Heparin
n=36 Participants
UFH was administered as a bolus according to standard of care for completion of PPCI per site. An ACT ≥250 s at the end of the procedure was recommended.
|
|---|---|---|
|
Death At Day 90
|
0 Participants
|
1 Participants
|
OTHER_PRE_SPECIFIED outcome
Timeframe: 1 day (end of PPCI)Population: All participants enrolled into the randomized trial (Intent-to-treat \[ITT\] Population) who took part in the IMR sub study (IMR-ITT).
IMR, a predictor of clinical outcome, is a readily available, quantitative, and reproducible method for invasively assessing coronary microvascular function. It is measured using the thermodilution technique and defined as mean distal coronary pressure, expressed in millimeters (mm) of mercury (Hg), multiplied by the mean hyperemic transit time (s) (mmHg\*s). Higher IMR values indicate poorer microcirculation and are associated with a worse clinical outcome. A cutoff point of 32 (associated with better clinical outcomes) was selected as the threshold. Only participants at study locations with previous experience in IMR measurements participated in this sub study. The number of participants and their mean reported IMR at the end of PPCI are presented.
Outcome measures
| Measure |
PPCI With Bivalirudin
n=25 Participants
Bivalirudin was administered as a bolus (0.75 mg/kg) and an infusion (1.75 mg/kg/h) for the duration of the PPCI and continued for the first 4 h after completion of the procedure.
|
PPCI With Heparin
n=25 Participants
UFH was administered as a bolus according to standard of care for completion of PPCI per site. An ACT ≥250 s at the end of the procedure was recommended.
|
|---|---|---|
|
Index Of Microcirculatory Resistance (IMR)
|
43.49 mmHg*s
Standard Deviation 21.62
|
68.66 mmHg*s
Standard Deviation 35.77
|
Adverse Events
PPCI With Bivalirudin
PPCI With Heparin
Serious adverse events
| Measure |
PPCI With Bivalirudin
n=38 participants at risk
Bivalirudin was administered as a bolus (0.75 mg/kg) and an infusion (1.75 mg/kg/h) for the duration of the PPCI and continued for the first 4 h after completion of the procedure.
|
PPCI With Heparin
n=40 participants at risk
UFH was administered as a bolus according to standard of care for completion of PPCI per site. An ACT ≥250 s at the end of the procedure was recommended.
|
|---|---|---|
|
Cardiac disorders
Cardiac arrest
|
0.00%
0/38 • Up to 5 days (±36 h) post randomization/discharge
|
5.0%
2/40 • Up to 5 days (±36 h) post randomization/discharge
|
|
Cardiac disorders
Cardiac asthma
|
0.00%
0/38 • Up to 5 days (±36 h) post randomization/discharge
|
2.5%
1/40 • Up to 5 days (±36 h) post randomization/discharge
|
|
Cardiac disorders
Cardiac failure
|
0.00%
0/38 • Up to 5 days (±36 h) post randomization/discharge
|
2.5%
1/40 • Up to 5 days (±36 h) post randomization/discharge
|
|
Cardiac disorders
Cardiac tamponade
|
2.6%
1/38 • Up to 5 days (±36 h) post randomization/discharge
|
0.00%
0/40 • Up to 5 days (±36 h) post randomization/discharge
|
|
Cardiac disorders
Cardiac ventricular thrombosis
|
0.00%
0/38 • Up to 5 days (±36 h) post randomization/discharge
|
2.5%
1/40 • Up to 5 days (±36 h) post randomization/discharge
|
|
Cardiac disorders
Cardiogenic shock
|
5.3%
2/38 • Up to 5 days (±36 h) post randomization/discharge
|
0.00%
0/40 • Up to 5 days (±36 h) post randomization/discharge
|
|
Cardiac disorders
Coronary artery perforation
|
2.6%
1/38 • Up to 5 days (±36 h) post randomization/discharge
|
0.00%
0/40 • Up to 5 days (±36 h) post randomization/discharge
|
|
Cardiac disorders
Myocardial rupture
|
2.6%
1/38 • Up to 5 days (±36 h) post randomization/discharge
|
0.00%
0/40 • Up to 5 days (±36 h) post randomization/discharge
|
|
Cardiac disorders
Ventricular fibrillation
|
2.6%
1/38 • Up to 5 days (±36 h) post randomization/discharge
|
0.00%
0/40 • Up to 5 days (±36 h) post randomization/discharge
|
|
Nervous system disorders
Transient ischaemic attack
|
2.6%
1/38 • Up to 5 days (±36 h) post randomization/discharge
|
0.00%
0/40 • Up to 5 days (±36 h) post randomization/discharge
|
|
Psychiatric disorders
Delirium
|
0.00%
0/38 • Up to 5 days (±36 h) post randomization/discharge
|
2.5%
1/40 • Up to 5 days (±36 h) post randomization/discharge
|
|
Respiratory, thoracic and mediastinal disorders
Lung disorder
|
0.00%
0/38 • Up to 5 days (±36 h) post randomization/discharge
|
2.5%
1/40 • Up to 5 days (±36 h) post randomization/discharge
|
Other adverse events
| Measure |
PPCI With Bivalirudin
n=38 participants at risk
Bivalirudin was administered as a bolus (0.75 mg/kg) and an infusion (1.75 mg/kg/h) for the duration of the PPCI and continued for the first 4 h after completion of the procedure.
|
PPCI With Heparin
n=40 participants at risk
UFH was administered as a bolus according to standard of care for completion of PPCI per site. An ACT ≥250 s at the end of the procedure was recommended.
|
|---|---|---|
|
Cardiac disorders
Atrial fibrillation
|
5.3%
2/38 • Up to 5 days (±36 h) post randomization/discharge
|
2.5%
1/40 • Up to 5 days (±36 h) post randomization/discharge
|
|
Cardiac disorders
Cardiac ventricular thrombosis
|
2.6%
1/38 • Up to 5 days (±36 h) post randomization/discharge
|
0.00%
0/40 • Up to 5 days (±36 h) post randomization/discharge
|
|
Cardiac disorders
Ventricular tachycardia
|
5.3%
2/38 • Up to 5 days (±36 h) post randomization/discharge
|
0.00%
0/40 • Up to 5 days (±36 h) post randomization/discharge
|
|
Cardiac disorders
Bradycardia
|
0.00%
0/38 • Up to 5 days (±36 h) post randomization/discharge
|
2.5%
1/40 • Up to 5 days (±36 h) post randomization/discharge
|
|
Cardiac disorders
Ventricular arrhythmia
|
2.6%
1/38 • Up to 5 days (±36 h) post randomization/discharge
|
0.00%
0/40 • Up to 5 days (±36 h) post randomization/discharge
|
|
Renal and urinary disorders
Nephropathy toxic
|
0.00%
0/38 • Up to 5 days (±36 h) post randomization/discharge
|
2.5%
1/40 • Up to 5 days (±36 h) post randomization/discharge
|
|
Renal and urinary disorders
Renal failure
|
2.6%
1/38 • Up to 5 days (±36 h) post randomization/discharge
|
0.00%
0/40 • Up to 5 days (±36 h) post randomization/discharge
|
|
Renal and urinary disorders
Urinary retention
|
0.00%
0/38 • Up to 5 days (±36 h) post randomization/discharge
|
2.5%
1/40 • Up to 5 days (±36 h) post randomization/discharge
|
|
Vascular disorders
Hypotension
|
2.6%
1/38 • Up to 5 days (±36 h) post randomization/discharge
|
2.5%
1/40 • Up to 5 days (±36 h) post randomization/discharge
|
|
Vascular disorders
Phlebitis
|
2.6%
1/38 • Up to 5 days (±36 h) post randomization/discharge
|
0.00%
0/40 • Up to 5 days (±36 h) post randomization/discharge
|
|
Gastrointestinal disorders
Constipation
|
2.6%
1/38 • Up to 5 days (±36 h) post randomization/discharge
|
0.00%
0/40 • Up to 5 days (±36 h) post randomization/discharge
|
|
Gastrointestinal disorders
Vomiting
|
0.00%
0/38 • Up to 5 days (±36 h) post randomization/discharge
|
2.5%
1/40 • Up to 5 days (±36 h) post randomization/discharge
|
|
Psychiatric disorders
Delirium
|
0.00%
0/38 • Up to 5 days (±36 h) post randomization/discharge
|
2.5%
1/40 • Up to 5 days (±36 h) post randomization/discharge
|
|
Respiratory, thoracic and mediastinal disorders
Chronic obstructive pulmonary disease
|
0.00%
0/38 • Up to 5 days (±36 h) post randomization/discharge
|
2.5%
1/40 • Up to 5 days (±36 h) post randomization/discharge
|
|
Respiratory, thoracic and mediastinal disorders
Lung disorder
|
2.6%
1/38 • Up to 5 days (±36 h) post randomization/discharge
|
2.5%
1/40 • Up to 5 days (±36 h) post randomization/discharge
|
|
Immune system disorders
Drug hypersensitivity
|
2.6%
1/38 • Up to 5 days (±36 h) post randomization/discharge
|
0.00%
0/40 • Up to 5 days (±36 h) post randomization/discharge
|
|
Infections and infestations
Pneumonia
|
2.6%
1/38 • Up to 5 days (±36 h) post randomization/discharge
|
0.00%
0/40 • Up to 5 days (±36 h) post randomization/discharge
|
|
Metabolism and nutrition disorders
Type 2 diabetes mellitus
|
0.00%
0/38 • Up to 5 days (±36 h) post randomization/discharge
|
2.5%
1/40 • Up to 5 days (±36 h) post randomization/discharge
|
|
Skin and subcutaneous tissue disorders
Rash
|
2.6%
1/38 • Up to 5 days (±36 h) post randomization/discharge
|
0.00%
0/40 • Up to 5 days (±36 h) post randomization/discharge
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place
Restriction type: GT60