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Trial record 86 of 172 for:    "Heart Disease" | "Heparin"

Bivalirudin Infusion for Ventricular Infarction Limitation (BIVAL)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02565147
Recruitment Status : Terminated (Futility at the interim analysis.)
First Posted : October 1, 2015
Results First Posted : October 5, 2018
Last Update Posted : October 5, 2018
Sponsor:
Information provided by (Responsible Party):
The Medicines Company

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Single (Outcomes Assessor);   Primary Purpose: Treatment
Condition Acute Myocardial Infarction
Interventions Procedure: PPCI
Drug: Bivalirudin
Drug: Heparin
Enrollment 78
Recruitment Details  
Pre-assignment Details 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).
Arm/Group Title PPCI With Bivalirudin PPCI With Heparin
Hide Arm/Group Description 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. 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.
Period Title: Overall Study
Started 38 40
Received Study Drug [1] 38 40
Per-Protocol Population [2] 28 36
Completed 32 37
Not Completed 6 3
Reason Not Completed
Withdrawal by Subject             5             1
Lost to Follow-up             0             1
Death             1             1
[1]
Safety Population included all enrolled participants who received either bivalirudin or UFH.
[2]
Enrolled participants who underwent successful PPCI and Day-5 CMR without major protocol deviations.
Arm/Group Title PPCI With Bivalirudin PPCI With Heparin Total
Hide Arm/Group Description 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. 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 of all reporting groups
Overall Number of Baseline Participants 38 40 78
Hide Baseline Analysis Population Description
Safety Population included all enrolled participants who received either bivalirudin or UFH.
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 38 participants 40 participants 78 participants
63.6  (11.4) 61.2  (13.2) 62.4  (12.3)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 38 participants 40 participants 78 participants
Female
10
  26.3%
6
  15.0%
16
  20.5%
Male
28
  73.7%
34
  85.0%
62
  79.5%
Race and Ethnicity Not Collected   [1] 
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 0 participants 0 participants 0 participants
0
[1]
Measure Analysis Population Description: Race and Ethnicity were not collected from any participant.
Region of Enrollment  
Measure Type: Count of Participants
Unit of measure:  Participants
Netherlands Number Analyzed 38 participants 40 participants 78 participants
21
  55.3%
22
  55.0%
43
  55.1%
France Number Analyzed 38 participants 40 participants 78 participants
17
  44.7%
18
  45.0%
35
  44.9%
1.Primary Outcome
Title CMR Assessment Of Infarct Size At Day 5
Hide Description 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.
Time Frame 5 days post PPCI
Hide Outcome Measure Data
Hide Analysis Population Description
All enrolled participants who underwent successful PPCI and CMR without major protocol deviations (Per-Protocol Population).
Arm/Group Title PPCI With Bivalirudin PPCI With Heparin
Hide Arm/Group Description:
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.
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.
Overall Number of Participants Analyzed 28 36
Mean (Standard Deviation)
Unit of Measure: Grams
25.0  (19.7) 27.1  (20.7)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection PPCI With Bivalirudin, PPCI With Heparin
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.7505
Comments [Not Specified]
Method Wilcoxon Rank Sum Test
Comments [Not Specified]
2.Secondary Outcome
Title CMR Assessment Of Myocardial Salvage Index (MSI) At Day 5
Hide Description 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.
Time Frame 5 days post PPCI
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title PPCI With Bivalirudin PPCI With Heparin
Hide Arm/Group Description:
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.
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.
Overall Number of Participants Analyzed 12 15
Mean (Standard Deviation)
Unit of Measure: Percentage of AAR
39.4  (19.3) 51.2  (21.7)
3.Secondary Outcome
Title CMR Assessment Of Micro-vascular Obstruction (MVO) At Day 5
Hide Description

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.

Time Frame 5 days post PPCI
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title PPCI With Bivalirudin PPCI With Heparin
Hide Arm/Group Description:
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.
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.
Overall Number of Participants Analyzed 28 36
Mean (Standard Deviation)
Unit of Measure: Grams
CMR Early MVO Assessment Number Analyzed 23 participants 28 participants
5.3  (5.8) 7.7  (6.3)
CMR Late MVO Assessment Number Analyzed 27 participants 35 participants
3.7  (5.7) 4.2  (4.5)
4.Secondary Outcome
Title CMR Assessment Of Left Ventricular Ejection Fraction (LVEF) At Day 5
Hide Description 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.
Time Frame 5 days post PPCI
Hide Outcome Measure Data
Hide Analysis Population Description
All enrolled participants who underwent successful PPCI and CMR without major protocol deviations (Per-Protocol Population).
Arm/Group Title PPCI With Bivalirudin PPCI With Heparin
Hide Arm/Group Description:
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.
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.
Overall Number of Participants Analyzed 28 36
Mean (Standard Deviation)
Unit of Measure: Percentage of Blood
48.5  (11.0) 48.6  (10.9)
5.Secondary Outcome
Title CMR Assessment Of LVEF At Day 90
Hide Description 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.
Time Frame 90 days post PPCI
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title PPCI With Bivalirudin PPCI With Heparin
Hide Arm/Group Description:
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.
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.
Overall Number of Participants Analyzed 22 29
Mean (Standard Deviation)
Unit of Measure: Percentage of Blood
54.6  (12.0) 49.1  (12.1)
6.Secondary Outcome
Title TIMI Flow And Myocardial Blush Grade (MBG) At End Of PPCI
Hide Description

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.

Time Frame 1 day (end of PPCI)
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title PPCI With Bivalirudin PPCI With Heparin
Hide Arm/Group Description:
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.
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.
Overall Number of Participants Analyzed 28 36
Mean (Standard Deviation)
Unit of Measure: Units on a Scale
TIMI Flow Grade Number Analyzed 28 participants 36 participants
2.8  (0.4) 2.8  (0.4)
MBG Number Analyzed 22 participants 29 participants
1.8  (1.2) 1.5  (1.2)
7.Secondary Outcome
Title Percentage of Participants With In-Hospital Net Adverse Cardiac Events (NACE) At Day 5
Hide Description

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.

Time Frame 5 days post PPCI or at discharge, whichever occurs first
Hide Outcome Measure Data
Hide Analysis Population Description
All enrolled participants who underwent successful PPCI and CMR without major protocol deviations (Per-Protocol Population).
Arm/Group Title PPCI With Bivalirudin PPCI With Heparin
Hide Arm/Group Description:
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.
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.
Overall Number of Participants Analyzed 28 36
Measure Type: Number
Unit of Measure: Percentage of Participants
7.1 8.3
8.Secondary Outcome
Title Death At Day 90
Hide Description Participant survival during the clinical follow-up period is presented as the number of participants with reported death at 90 days post PPCI.
Time Frame 90 days post PPCI
Hide Outcome Measure Data
Hide Analysis Population Description
All enrolled participants who underwent successful PPCI and CMR without major protocol deviations (Per-Protocol Population).
Arm/Group Title PPCI With Bivalirudin PPCI With Heparin
Hide Arm/Group Description:
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.
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.
Overall Number of Participants Analyzed 28 36
Measure Type: Number
Unit of Measure: Participants
0 1
9.Other Pre-specified Outcome
Title Index Of Microcirculatory Resistance (IMR)
Hide Description

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.

Time Frame 1 day (end of PPCI)
Hide Outcome Measure Data
Hide Analysis Population Description
All participants enrolled into the randomized trial (Intent-to-treat [ITT] Population) who took part in the IMR sub study (IMR-ITT).
Arm/Group Title PPCI With Bivalirudin PPCI With Heparin
Hide Arm/Group Description:
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.
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.
Overall Number of Participants Analyzed 25 25
Mean (Standard Deviation)
Unit of Measure: mmHg*s
43.49  (21.62) 68.66  (35.77)
Time Frame Up to 5 days (±36 h) post randomization/discharge
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title PPCI With Bivalirudin PPCI With Heparin
Hide Arm/Group Description 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. 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.
All-Cause Mortality
PPCI With Bivalirudin PPCI With Heparin
Affected / at Risk (%) Affected / at Risk (%)
Total   1/38 (2.63%)   1/40 (2.50%) 
Show Serious Adverse Events Hide Serious Adverse Events
PPCI With Bivalirudin PPCI With Heparin
Affected / at Risk (%) Affected / at Risk (%)
Total   6/38 (15.79%)   7/40 (17.50%) 
Cardiac disorders     
Cardiac arrest  1  0/38 (0.00%)  2/40 (5.00%) 
Cardiac asthma  1  0/38 (0.00%)  1/40 (2.50%) 
Cardiac failure  1  0/38 (0.00%)  1/40 (2.50%) 
Cardiac tamponade  1  1/38 (2.63%)  0/40 (0.00%) 
Cardiac ventricular thrombosis  1  0/38 (0.00%)  1/40 (2.50%) 
Cardiogenic shock  1  2/38 (5.26%)  0/40 (0.00%) 
Coronary artery perforation  1  1/38 (2.63%)  0/40 (0.00%) 
Myocardial rupture  1  1/38 (2.63%)  0/40 (0.00%) 
Ventricular fibrillation  1  1/38 (2.63%)  0/40 (0.00%) 
Nervous system disorders     
Transient ischaemic attack  1  1/38 (2.63%)  0/40 (0.00%) 
Psychiatric disorders     
Delirium  1  0/38 (0.00%)  1/40 (2.50%) 
Respiratory, thoracic and mediastinal disorders     
Lung disorder  1  0/38 (0.00%)  1/40 (2.50%) 
1
Term from vocabulary, MedDRA (15.0)
Indicates events were collected by systematic assessment
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 1%
PPCI With Bivalirudin PPCI With Heparin
Affected / at Risk (%) Affected / at Risk (%)
Total   11/38 (28.95%)   6/40 (15.00%) 
Cardiac disorders     
Atrial fibrillation  1  2/38 (5.26%)  1/40 (2.50%) 
Cardiac ventricular thrombosis  1  1/38 (2.63%)  0/40 (0.00%) 
Ventricular tachycardia  1  2/38 (5.26%)  0/40 (0.00%) 
Bradycardia  1  0/38 (0.00%)  1/40 (2.50%) 
Ventricular arrhythmia  1  1/38 (2.63%)  0/40 (0.00%) 
Gastrointestinal disorders     
Constipation  1  1/38 (2.63%)  0/40 (0.00%) 
Vomiting  1  0/38 (0.00%)  1/40 (2.50%) 
Immune system disorders     
Drug hypersensitivity  1  1/38 (2.63%)  0/40 (0.00%) 
Infections and infestations     
Pneumonia  1  1/38 (2.63%)  0/40 (0.00%) 
Metabolism and nutrition disorders     
Type 2 diabetes mellitus  1  0/38 (0.00%)  1/40 (2.50%) 
Psychiatric disorders     
Delirium  1  0/38 (0.00%)  1/40 (2.50%) 
Renal and urinary disorders     
Nephropathy toxic  1  0/38 (0.00%)  1/40 (2.50%) 
Renal failure  1  1/38 (2.63%)  0/40 (0.00%) 
Urinary retention  1  0/38 (0.00%)  1/40 (2.50%) 
Respiratory, thoracic and mediastinal disorders     
Chronic obstructive pulmonary disease  1  0/38 (0.00%)  1/40 (2.50%) 
Lung disorder  1  1/38 (2.63%)  1/40 (2.50%) 
Skin and subcutaneous tissue disorders     
Rash  1  1/38 (2.63%)  0/40 (0.00%) 
Vascular disorders     
Hypotension  1  1/38 (2.63%)  1/40 (2.50%) 
Phlebitis  1  1/38 (2.63%)  0/40 (0.00%) 
1
Term from vocabulary, MedDRA (15.0)
Indicates events were collected by systematic assessment
Since the measured difference in infarct size at Day 5 (by CMR) was <18%, the study was terminated for futility at the interim analysis as pre-defined in the protocol.
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Global Health Science Center
Organization: The Medicines Company
Phone: 1.888.977.6326
EMail: medical.information@themedco.com
Publications:
Alderman EL, Stadius M. The angiographic definitions of the Bypass Angioplasty Revascularization Investigation. Coronary Artery Disease 1992;3: 1189-1207
Layout table for additonal information
Responsible Party: The Medicines Company
ClinicalTrials.gov Identifier: NCT02565147     History of Changes
Other Study ID Numbers: MDCO-BIV-12-02
2012-002314-39 ( EudraCT Number )
First Submitted: December 5, 2014
First Posted: October 1, 2015
Results First Submitted: May 23, 2017
Results First Posted: October 5, 2018
Last Update Posted: October 5, 2018