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Trial record 17 of 172 for:    "Heart Disease" | "Heparin"

Open-label, Randomized Trial in Participants Undergoing TAVR to Determine Safety & Efficacy of Bivalirudin vs UFH (BRAVO 2/3)

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ClinicalTrials.gov Identifier: NCT01651780
Recruitment Status : Completed
First Posted : July 27, 2012
Results First Posted : February 27, 2017
Last Update Posted : April 7, 2017
Sponsor:
Information provided by (Responsible Party):
The Medicines Company

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Conditions Severe Aortic Stenosis
Transcatheter Aortic Valve Replacement
Aortic Valve Replacement
Interventions Drug: Bivalirudin
Drug: Unfractionated Heparin
Enrollment 803
Recruitment Details  
Pre-assignment Details  
Arm/Group Title Bivalirudin Unfractionated Heparin (UFH)
Hide Arm/Group Description Bivalirudin administered as a bolus and intravenous (IV) infusion during transcatheter aortic valve replacement (TAVR). It was recommended that the bolus (0.75 milligrams per kilogram [mg/kg]) be directly administered through the valve delivery sheath immediately following its successful delivery via percutaneous femoral access. Systemic IV administration of the bolus dose was also acceptable. The bivalirudin IV infusion was initiated immediately after the bolus administration. All wires, catheters, and sheaths were to be flushed with heparinized saline. The dose of UFH adhered to the standard institutional practice. An activated clotting time (ACT) target ≥250 seconds was recommended. All wires, catheters, and sheaths were to be flushed with heparinized saline.
Period Title: Overall Study
Started 405 398
Intent-To-Treat (ITT) Population 404 398
Received at Least 1 Dose of Study Drug 393 [1] 394
BRAVO 2 Feasibility Cohort 65 [2] 0 [2]
Completed 394 388
Not Completed 11 10
Reason Not Completed
Physician decision: No 30-day visit             2             1
Reason Not Specified: No 30-day visit             2             2
Withdrawal by Subject             2             0
Inclusion/Exclusion Criteria Not Met             3             0
Lost to Follow-up             1             2
Physician decision: Day 30 visit <23 day             1             5
[1]
All but 1 participant in the bivalirudin group (withdrew consent) comprised the ITT population.
[2]
1st 2 participants/site made up the bivalirudin feasibility cohort (BRAVO2) and analyzed separately.
Arm/Group Title Bivalirudin Unfractionated Heparin (UFH) Total
Hide Arm/Group Description Bivalirudin administered as a bolus and intravenous (IV) infusion during TAVR. It was recommended that the bolus (0.75 milligrams per kilogram [mg/kg]) be directly administered through the valve delivery sheath immediately following its successful delivery via percutaneous femoral access. Systemic IV administration of the bolus dose was also acceptable. The bivalirudin IV infusion was initiated immediately after the bolus administration. All wires, catheters, and sheaths were to be flushed with heparinized saline. The dose of UFH adhered to the standard institutional practice. An ACT target ≥250 seconds was recommended. All wires, catheters, and sheaths were to be flushed with heparinized saline. Total of all reporting groups
Overall Number of Baseline Participants 404 398 802
Hide Baseline Analysis Population Description
Participants in the ITT population.
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 404 participants 398 participants 802 participants
82.3  (6.5) 82.3  (6.5) 82.3  (6.5)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 404 participants 398 participants 802 participants
Female
195
  48.3%
196
  49.2%
391
  48.8%
Male
209
  51.7%
202
  50.8%
411
  51.2%
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 404 participants 398 participants 802 participants
Canada 36 38 74
Netherlands 10 10 20
Italy 37 39 76
United Kingdom 8 10 18
France 108 106 214
Switzerland 25 22 47
Germany 180 173 353
1.Primary Outcome
Title Major Bleeding (BARC ≥3b) at 48 Hours or Before Hospital Discharge
Hide Description

Major bleeding (Bleeding Academic Research Consortium [BARC] type ≥3b) was defined as follows:

  • Bleeds that were evident clinically, or by laboratory or imaging results, which resulted in surgical intervention or administration of IV vasoactive drugs; overt bleeds with a hemoglobin drop of at least 5 grams per deciliter (g/dL); and bleeding that caused cardiac tamponade.
  • BARC 3c includes intracranial or intraocular bleeds that compromised vision.
  • BARC type 4 (Coronary Artery Bypass Grafting [CABG]-related bleeding) includes perioperative intracranial bleeding within 48 hours, bleeds that result in reoperation following closure of sternotomy for the purpose of controlling bleeding, bleeds that result in treatment with transfusion of ≥5 units of whole blood or packed red blood cells within a 48 hour period; and chest tube output ≥2 liters (L) within a 24-hour period.
  • BARC type 5, fatal bleeding, describes bleeds that directly result in death with no other cause.
Time Frame at 48 hours or discharge, whichever occurs first
Hide Outcome Measure Data
Hide Analysis Population Description
Participants in the ITT population.
Arm/Group Title Bivalirudin Unfractionated Heparin (UFH)
Hide Arm/Group Description:
Bivalirudin administered as a bolus and intravenous (IV) infusion during TAVR. It was recommended that the bolus (0.75 milligrams per kilogram [mg/kg]) be directly administered through the valve delivery sheath immediately following its successful delivery via percutaneous femoral access. Systemic IV administration of the bolus dose was also acceptable. The bivalirudin IV infusion was initiated immediately after the bolus administration. All wires, catheters, and sheaths were to be flushed with heparinized saline.
The dose of UFH adhered to the standard institutional practice. An ACT target ≥250 seconds was recommended. All wires, catheters, and sheaths were to be flushed with heparinized saline.
Overall Number of Participants Analyzed 404 398
Measure Type: Number
Unit of Measure: percentage of participants
6.9 9
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Bivalirudin, Unfractionated Heparin (UFH)
Comments [Not Specified]
Type of Statistical Test Non-Inferiority or Equivalence
Comments If non-inferiority was confirmed, then superiority analysis was pursued.
Statistical Test of Hypothesis P-Value 0.2692
Comments [Not Specified]
Method Chi-squared
Comments [Not Specified]
Method of Estimation Estimation Parameter Relative Risk
Estimated Value 0.77
Confidence Interval (2-Sided) 95%
0.48 to 1.23
Estimation Comments [Not Specified]
2.Primary Outcome
Title Net Adverse Clinical Events (NACE) at up to 30 Days
Hide Description The net adverse cardiac events (NACE) at 30 days is the composite of major adverse cardiovascular events (MACE) + major bleeding (BARC type ≥3b). The composite of MACE is defined as all-cause mortality, myocardial infarction (MI), and stroke. 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.
Time Frame up to 30 days after procedure
Hide Outcome Measure Data
Hide Analysis Population Description
Participants in the ITT population.
Arm/Group Title Bivalirudin Unfractionated Heparin (UFH)
Hide Arm/Group Description:
Bivalirudin administered as a bolus and intravenous (IV) infusion during TAVR. It was recommended that the bolus (0.75 milligrams per kilogram [mg/kg]) be directly administered through the valve delivery sheath immediately following its successful delivery via percutaneous femoral access. Systemic IV administration of the bolus dose was also acceptable. The bivalirudin IV infusion was initiated immediately after the bolus administration. All wires, catheters, and sheaths were to be flushed with heparinized saline.
The dose of UFH adhered to the standard institutional practice. An ACT target ≥250 seconds was recommended. All wires, catheters, and sheaths were to be flushed with heparinized saline.
Overall Number of Participants Analyzed 404 398
Measure Type: Number
Unit of Measure: percentage of participants
14.4 16.1
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Bivalirudin, Unfractionated Heparin (UFH)
Comments [Not Specified]
Type of Statistical Test Non-Inferiority or Equivalence
Comments If non-inferiority was confirmed, then superiority analysis was pursued.
Statistical Test of Hypothesis P-Value 0.4967
Comments [Not Specified]
Method Chi-squared
Comments [Not Specified]
Method of Estimation Estimation Parameter Relative Risk
Estimated Value 0.89
Confidence Interval (2-Sided) 95%
0.64 to 1.24
Estimation Comments [Not Specified]
3.Secondary Outcome
Title NACE at 48 Hours or Before Hospital Discharge
Hide Description NACE at 48 hours or before hospital discharge is the composite of major adverse cardiovascular events (MACE) + major bleeding (BARC type ≥3b). The composite of MACE is defined as all-cause mortality, MI, and stroke. 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.
Time Frame at 48 hours or before hospital discharge, whichever occurred earlier
Hide Outcome Measure Data
Hide Analysis Population Description
Participants in the ITT population.
Arm/Group Title Bivalirudin Unfractionated Heparin (UFH)
Hide Arm/Group Description:
Bivalirudin administered as a bolus and intravenous (IV) infusion during TAVR. It was recommended that the bolus (0.75 milligrams per kilogram [mg/kg]) be directly administered through the valve delivery sheath immediately following its successful delivery via percutaneous femoral access. Systemic IV administration of the bolus dose was also acceptable. The bivalirudin IV infusion was initiated immediately after the bolus administration. All wires, catheters, and sheaths were to be flushed with heparinized saline.
The dose of UFH adhered to the standard institutional practice. An ACT target ≥250 seconds was recommended. All wires, catheters, and sheaths were to be flushed with heparinized saline.
Overall Number of Participants Analyzed 404 398
Measure Type: Number
Unit of Measure: percentage of participants
8.9 12.6
4.Secondary Outcome
Title Major Adverse Cardiac Events (MACE) Including Death, Non-fatal MI, and Stroke
Hide Description The percentage of participants reporting a MACE overall and the individual components of MACE (including death, non-fatal MI, and stroke) are presented.
Time Frame at 48 hours or before hospital discharge, whichever occurred earlier, and at up to 30 days (±7 days)
Hide Outcome Measure Data
Hide Analysis Population Description
Participants in the ITT population.
Arm/Group Title Bivalirudin Unfractionated Heparin (UFH)
Hide Arm/Group Description:
Bivalirudin administered as a bolus and intravenous (IV) infusion during TAVR. It was recommended that the bolus (0.75 milligrams per kilogram [mg/kg]) be directly administered through the valve delivery sheath immediately following its successful delivery via percutaneous femoral access. Systemic IV administration of the bolus dose was also acceptable. The bivalirudin IV infusion was initiated immediately after the bolus administration. All wires, catheters, and sheaths were to be flushed with heparinized saline.
The dose of UFH adhered to the standard institutional practice. An ACT target ≥250 seconds was recommended. All wires, catheters, and sheaths were to be flushed with heparinized saline.
Overall Number of Participants Analyzed 404 398
Measure Type: Number
Unit of Measure: percentage of participants
MACE at 48 hours or before hospital discharge 3.5 4.8
Death at 48 hours or before hospital discharge 1.5 1.8
MI at 48 hours or before hospital discharge 0 1.3
Stroke at 48 hours or before hospital discharge 2 2
MACE at up to 30 days 7.7 8
Death at up to 30 days 4.7 4.8
MI at up to 30 days 0.5 1.8
Stroke at up to 30 days 3.5 2.8
5.Secondary Outcome
Title Major Bleeding According to Additional Scales (VARC, TIMI, GUSTO, ACUITY/HORIZONS)
Hide Description

Percentage of participants with major bleeding according to the following scales:

  • Valve Academic Research Consortium (VARC)=life threatening, disabling bleeding, or major bleeding
  • Thrombolysis in Myocardial Infarction (TIMI)=major bleeding
  • Global Use of Strategies to Open Occluded Coronary Arteries (GUSTO)=severe or moderate
  • Acute Catheterization and Urgent Intervention Triage StrategY (ACUITY)/Harmonizing Outcomes with RevasculariZatiON and Stents (HORIZONS)=major bleeding
Time Frame at 48 hours or hospital discharge, whichever occurred earlier, and at up to 30 days (±7 days) follow-up
Hide Outcome Measure Data
Hide Analysis Population Description
Participants in the ITT population.
Arm/Group Title Bivalirudin Unfractionated Heparin (UFH)
Hide Arm/Group Description:
Bivalirudin administered as a bolus and intravenous (IV) infusion during TAVR. It was recommended that the bolus (0.75 milligrams per kilogram [mg/kg]) be directly administered through the valve delivery sheath immediately following its successful delivery via percutaneous femoral access. Systemic IV administration of the bolus dose was also acceptable. The bivalirudin IV infusion was initiated immediately after the bolus administration. All wires, catheters, and sheaths were to be flushed with heparinized saline.
The dose of UFH adhered to the standard institutional practice. An ACT target ≥250 seconds was recommended. All wires, catheters, and sheaths were to be flushed with heparinized saline.
Overall Number of Participants Analyzed 404 398
Measure Type: Number
Unit of Measure: percentage of participants
VARC at 48 hours or before hospital 21.8 19.6
TIMI at 48 hours or before hospital 4 6.5
GUSTO at 48 hours or hospital discharge 13.9 11.6
ACUITY/HORIZONS at 48 hours or hospital discharge 26 24.4
VARC at 30 days 26.5 24.6
TIMI at 30 days 5.7 7.3
GUSTO at 30 days 16.3 14.6
ACUITY/HORIZONS at 30 days 33.4 29.6
6.Secondary Outcome
Title Transient Ischemic Attack
Hide Description The percentage of participants reporting transient ischemic attack is presented.
Time Frame at 48 hours or before hospital discharge, whichever occurred earlier, and at up to 30 days (±7 days)
Hide Outcome Measure Data
Hide Analysis Population Description
Participants in the ITT population.
Arm/Group Title Bivalirudin Unfractionated Heparin (UFH)
Hide Arm/Group Description:
Bivalirudin administered as a bolus and intravenous (IV) infusion during TAVR. It was recommended that the bolus (0.75 milligrams per kilogram [mg/kg]) be directly administered through the valve delivery sheath immediately following its successful delivery via percutaneous femoral access. Systemic IV administration of the bolus dose was also acceptable. The bivalirudin IV infusion was initiated immediately after the bolus administration. All wires, catheters, and sheaths were to be flushed with heparinized saline.
The dose of UFH adhered to the standard institutional practice. An ACT target ≥250 seconds was recommended. All wires, catheters, and sheaths were to be flushed with heparinized saline.
Overall Number of Participants Analyzed 404 398
Measure Type: Number
Unit of Measure: percentage of participants
at 48 hours or before hospital discharge 0 0
at up to 30 days (±7 days) follow-up 0 0
7.Secondary Outcome
Title Acute Kidney Injury
Hide Description The percentage of participants reporting acute kidney injury is presented.
Time Frame at 48 hours or hospital discharge, whichever occurred earlier, and at up to 30 days (±7 days) follow-up
Hide Outcome Measure Data
Hide Analysis Population Description
Participants in the ITT population.
Arm/Group Title Bivalirudin Unfractionated Heparin (UFH)
Hide Arm/Group Description:
Bivalirudin administered as a bolus and intravenous (IV) infusion during TAVR. It was recommended that the bolus (0.75 milligrams per kilogram [mg/kg]) be directly administered through the valve delivery sheath immediately following its successful delivery via percutaneous femoral access. Systemic IV administration of the bolus dose was also acceptable. The bivalirudin IV infusion was initiated immediately after the bolus administration. All wires, catheters, and sheaths were to be flushed with heparinized saline.
The dose of UFH adhered to the standard institutional practice. An ACT target ≥250 seconds was recommended. All wires, catheters, and sheaths were to be flushed with heparinized saline.
Overall Number of Participants Analyzed 404 398
Measure Type: Number
Unit of Measure: percentage of participants
at 48 hours or before hospital discharge 10.9 6.5
at up to 30 days (±7 days) follow-up 18.8 13.8
8.Secondary Outcome
Title Major Vascular Complications
Hide Description The percentage of participants reporting a major vascular complications as defined by VARC is presented.
Time Frame at 48 hours or before hospital discharge, whichever occurred earlier, and at up to 30 days (±7 days)
Hide Outcome Measure Data
Hide Analysis Population Description
Participants in the ITT population.
Arm/Group Title Bivalirudin Unfractionated Heparin (UFH)
Hide Arm/Group Description:
Bivalirudin administered as a bolus and intravenous (IV) infusion during TAVR. It was recommended that the bolus (0.75 milligrams per kilogram [mg/kg]) be directly administered through the valve delivery sheath immediately following its successful delivery via percutaneous femoral access. Systemic IV administration of the bolus dose was also acceptable. The bivalirudin IV infusion was initiated immediately after the bolus administration. All wires, catheters, and sheaths were to be flushed with heparinized saline.
The dose of UFH adhered to the standard institutional practice. An ACT target ≥250 seconds was recommended. All wires, catheters, and sheaths were to be flushed with heparinized saline.
Overall Number of Participants Analyzed 404 398
Measure Type: Number
Unit of Measure: percentage of participants
at 48 hours or before hospital discharge 8.7 9
at up to 30 days (±7 days) follow-up 9.2 9.5
9.Secondary Outcome
Title Acquired Thrombocytopenia
Hide Description The percentage of participants reporting acquired thrombocytopenia is presented.
Time Frame at 48 hours or before hospital discharge, whichever occurred earlier, and at up to 30 days (±7 days)
Hide Outcome Measure Data
Hide Analysis Population Description
Participants in the ITT population.
Arm/Group Title Bivalirudin Unfractionated Heparin (UFH)
Hide Arm/Group Description:
Bivalirudin administered as a bolus and intravenous (IV) infusion during TAVR. It was recommended that the bolus (0.75 milligrams per kilogram [mg/kg]) be directly administered through the valve delivery sheath immediately following its successful delivery via percutaneous femoral access. Systemic IV administration of the bolus dose was also acceptable. The bivalirudin IV infusion was initiated immediately after the bolus administration. All wires, catheters, and sheaths were to be flushed with heparinized saline.
The dose of UFH adhered to the standard institutional practice. An ACT target ≥250 seconds was recommended. All wires, catheters, and sheaths were to be flushed with heparinized saline.
Overall Number of Participants Analyzed 404 398
Measure Type: Number
Unit of Measure: percentage of participants
at 48 hours or before hospital discharge 16.6 17.3
at up to 30 days (±7 days) 24 23.1
10.Secondary Outcome
Title New Onset Atrial Fibrillation/Flutter
Hide Description The percentage of participants reporting new onset atrial fibrillation/flutter is presented.
Time Frame at 48 hours or before hospital discharge, whichever occurred earlier, and at up to 30 days (±7 days)
Hide Outcome Measure Data
Hide Analysis Population Description
Participants in the ITT population.
Arm/Group Title Bivalirudin Unfractionated Heparin (UFH)
Hide Arm/Group Description:
Bivalirudin administered as a bolus and intravenous (IV) infusion during TAVR. It was recommended that the bolus (0.75 milligrams per kilogram [mg/kg]) be directly administered through the valve delivery sheath immediately following its successful delivery via percutaneous femoral access. Systemic IV administration of the bolus dose was also acceptable. The bivalirudin IV infusion was initiated immediately after the bolus administration. All wires, catheters, and sheaths were to be flushed with heparinized saline.
The dose of UFH adhered to the standard institutional practice. An ACT target ≥250 seconds was recommended. All wires, catheters, and sheaths were to be flushed with heparinized saline.
Overall Number of Participants Analyzed 404 398
Measure Type: Number
Unit of Measure: percentage of participants
at 48 hours or before hospital discharge 3.2 2.5
at up to 30 days (±7 days) follow-up 5.4 4
11.Secondary Outcome
Title Timing Effect on Bleeding Event Rate up to 48 Hours or Hospital Discharge
Hide Description The effect of timing on bleeding event rates (the percentage of participants with an incidence of major bleeding) is presented.
Time Frame Up to 48 hours after procedure or at hospital discharge (but also includes any subsequent hospitalizations)
Hide Outcome Measure Data
Hide Analysis Population Description
Participants in the ITT population with an incidence of major bleeding. Participants were categorized as "First half of study site's enrolled participants" (Bivalirudin, N=173; UFH, N=173) and "Second half of study site's enrolled participants" (Bivalirudin, N=171; UFH, N=165). Only sites with >20 participants are included in this analysis.
Arm/Group Title Bivalirudin: First Half of Study Site's Enrolled Participants Bivalirudin: Second Half of Study Site's Enrolled Participants UFH: First Half of Study Site's Enrolled Participants UFH: Second Half of Study Site's Enrolled Participants
Hide Arm/Group Description:
Bivalirudin administered as a bolus and intravenous (IV) infusion during TAVR. It was recommended that the bolus (0.75 milligrams per kilogram [mg/kg]) be directly administered through the valve delivery sheath immediately following its successful delivery via percutaneous femoral access. Systemic IV administration of the bolus dose was also acceptable. The bivalirudin IV infusion was initiated immediately after the bolus administration. All wires, catheters, and sheaths were to be flushed with heparinized saline. This includes the first half of the site’s enrolled participants, and only sites with more than 20 participants are included in this analysis.
Bivalirudin administered as a bolus and intravenous (IV) infusion during TAVR. It was recommended that the bolus (0.75 milligrams per kilogram [mg/kg]) be directly administered through the valve delivery sheath immediately following its successful delivery via percutaneous femoral access. Systemic IV administration of the bolus dose was also acceptable. The bivalirudin IV infusion was initiated immediately after the bolus administration. All wires, catheters, and sheaths were to be flushed with heparinized saline. This includes the second half of the site’s enrolled participants, and only sites with more than 20 participants are included in this analysis.
The dose of UFH adhered to the standard institutional practice. An ACT target ≥250 seconds was recommended. All wires, catheters, and sheaths were to be flushed with heparinized saline. This includes the first half of the site’s enrolled participants, and only sites with more than 20 participants are included in this analysis.
The dose of UFH adhered to the standard institutional practice. An ACT target ≥250 seconds was recommended. All wires, catheters, and sheaths were to be flushed with heparinized saline. This includes the second half of the site’s enrolled participants, and only sites with more than 20 participants are included in this analysis.
Overall Number of Participants Analyzed 173 171 173 165
Measure Type: Number
Unit of Measure: percentage of participants
6.4 6.4 11.6 8.5
12.Secondary Outcome
Title Bleeding BARC 3a, BARC Types 1 or 2, and TIMI Minor
Hide Description The percentage of participants with moderate bleeding as defined by BARC 3a and minor bleeding as defined as BARC type 1 and 2 and TIMI minor is presented.
Time Frame at 48 hours or hospital discharge, whichever occurred earlier, and at up to 30 days (±7 days) follow-up
Hide Outcome Measure Data
Hide Analysis Population Description
Participants in the ITT population.
Arm/Group Title Bivalirudin Unfractionated Heparin (UFH)
Hide Arm/Group Description:
Bivalirudin administered as a bolus and intravenous (IV) infusion during TAVR. It was recommended that the bolus (0.75 milligrams per kilogram [mg/kg]) be directly administered through the valve delivery sheath immediately following its successful delivery via percutaneous femoral access. Systemic IV administration of the bolus dose was also acceptable. The bivalirudin IV infusion was initiated immediately after the bolus administration. All wires, catheters, and sheaths were to be flushed with heparinized saline.
The dose of UFH adhered to the standard institutional practice. An ACT target ≥250 seconds was recommended. All wires, catheters, and sheaths were to be flushed with heparinized saline.
Overall Number of Participants Analyzed 404 398
Measure Type: Number
Unit of Measure: percentage of participants
BARC 3a at 48 hours or hospital discharge 15.6 13.3
BARC types 1 and 2 at 48 hours or discharge 20.8 21.1
TIMI minor at 48 hours or hospital discharge 16.6 14.3
BARC 3a at 30 days 18.8 17.3
BARC types 1 and 2 at 30 days 27.7 25.6
TIMI minor at 30 days 21.3 19.3
Time Frame [Not Specified]
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Bivalirudin Unfractionated Heparin (UFH)
Hide Arm/Group Description Bivalirudin administered as a bolus and intravenous (IV) infusion during TAVR. It was recommended that the bolus (0.75 milligrams per kilogram [mg/kg]) be directly administered through the valve delivery sheath immediately following its successful delivery via percutaneous femoral access. Systemic IV administration of the bolus dose was also acceptable. The bivalirudin IV infusion was initiated immediately after the bolus administration. All wires, catheters, and sheaths were to be flushed with heparinized saline. The dose of UFH adhered to the standard institutional practice. An ACT target ≥250 seconds was recommended. All wires, catheters, and sheaths were to be flushed with heparinized saline.
All-Cause Mortality
Bivalirudin Unfractionated Heparin (UFH)
Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/-- 
Show Serious Adverse Events Hide Serious Adverse Events
Bivalirudin Unfractionated Heparin (UFH)
Affected / at Risk (%) Affected / at Risk (%)
Total   112/393 (28.50%)   116/394 (29.44%) 
Cardiac disorders     
Atrioventricular block complete  1  46/393 (11.70%)  34/394 (8.63%) 
Bundle branch block left  1  7/393 (1.78%)  10/394 (2.54%) 
Bradycardia  1  2/393 (0.51%)  7/394 (1.78%) 
Cardiac arrest  1  2/393 (0.51%)  7/394 (1.78%) 
Atrioventricular block second degree  1  2/393 (0.51%)  6/394 (1.52%) 
Atrioventricular block first degree  1  3/393 (0.76%)  4/394 (1.02%) 
Atrioventricular block  1  2/393 (0.51%)  4/394 (1.02%) 
Ventricular tachycardia  1  4/393 (1.02%)  1/394 (0.25%) 
Cardiac failure acute  1  1/393 (0.25%)  3/394 (0.76%) 
Aortic valve incompetence  1  1/393 (0.25%)  1/394 (0.25%) 
Cardiac tamponade  1  1/393 (0.25%)  1/394 (0.25%) 
Cardiogenic shock  1  0/393 (0.00%)  2/394 (0.51%) 
Coronary artery occlusion  1  0/393 (0.00%)  2/394 (0.51%) 
Ventricular fibrillation  1  1/393 (0.25%)  1/394 (0.25%) 
Ventricular tachyarrhythmia  1  1/393 (0.25%)  1/394 (0.25%) 
Bifascicular block  1  1/393 (0.25%)  0/394 (0.00%) 
Bradyarrhythmia  1  1/393 (0.25%)  0/394 (0.00%) 
Cardiac perforation  1  0/393 (0.00%)  1/394 (0.25%) 
Cardio-respiratory arrest  1  1/393 (0.25%)  0/394 (0.00%) 
Cardiopulmonary failure  1  1/393 (0.25%)  0/394 (0.00%) 
Coronary artery stenosis  1  0/393 (0.00%)  1/394 (0.25%) 
Ischaemic cardiomyopathy  1  0/393 (0.00%)  1/394 (0.25%) 
Low cardiac output syndrome  1  0/393 (0.00%)  1/394 (0.25%) 
Pericardial effusion  1  1/393 (0.25%)  0/394 (0.00%) 
Sick sinus syndrome  1  1/393 (0.25%)  0/394 (0.00%) 
Supraventricular tachycardia  1  1/393 (0.25%)  0/394 (0.00%) 
Bundle branch block  1  2/393 (0.51%)  0/394 (0.00%) 
Cardiac failure  1  6/393 (1.53%)  10/394 (2.54%) 
Gastrointestinal disorders     
Retroperitoneal haemorrhage  1  1/393 (0.25%)  1/394 (0.25%) 
Abdominal hernia  1  0/393 (0.00%)  1/394 (0.25%) 
Abdominal pain  1  0/393 (0.00%)  1/394 (0.25%) 
Gastric haemorrhage  1  1/393 (0.25%)  0/394 (0.00%) 
Gastritis  1  0/393 (0.00%)  1/394 (0.25%) 
Intestinal infarction  1  0/393 (0.00%)  1/394 (0.25%) 
Intestinal ischaemia  1  1/393 (0.25%)  0/394 (0.00%) 
Umbilical hernia, obstructive  1  1/393 (0.25%)  0/394 (0.00%) 
General disorders     
Death  1 [1]  1/393 (0.25%)  1/394 (0.25%) 
Device leakage  1 [1]  1/393 (0.25%)  1/394 (0.25%) 
Thrombosis in device  1 [1]  2/393 (0.51%)  0/394 (0.00%) 
Device dislocation  1 [1]  0/393 (0.00%)  1/394 (0.25%) 
General physical health deterioration  1 [1]  1/393 (0.25%)  0/394 (0.00%) 
Hyperthermia  1 [1]  1/393 (0.25%)  0/394 (0.00%) 
Multi-organ failure  1 [1]  0/393 (0.00%)  1/394 (0.25%) 
Non-cardiac chest pain  1 [1]  1/393 (0.25%)  0/394 (0.00%) 
Pyrexia  1 [1]  1/393 (0.25%)  0/394 (0.00%) 
Sudden death  1 [1]  1/393 (0.25%)  0/394 (0.00%) 
Hepatobiliary disorders     
Cholecystitis acute  1  0/393 (0.00%)  1/394 (0.25%) 
Immune system disorders     
Anaphylactic shock  1  1/393 (0.25%)  0/394 (0.00%) 
Infections and infestations     
Pneumonia  1  2/393 (0.51%)  2/394 (0.51%) 
Bronchopneumonia  1  0/393 (0.00%)  2/394 (0.51%) 
Sepsis  1  1/393 (0.25%)  1/394 (0.25%) 
Bronchitis  1  0/393 (0.00%)  1/394 (0.25%) 
Infection  1  0/393 (0.00%)  1/394 (0.25%) 
Intervertebral discitis  1  1/393 (0.25%)  0/394 (0.00%) 
Klebsiella infection  1  0/393 (0.00%)  1/394 (0.25%) 
Pneumonia viral  1  1/393 (0.25%)  0/394 (0.00%) 
Postoperative wound infection  1  0/393 (0.00%)  1/394 (0.25%) 
Pseudomonas infection  1  1/393 (0.25%)  0/394 (0.00%) 
Septic encephalopathy  1  1/393 (0.25%)  0/394 (0.00%) 
Urinary tract infection  1  0/393 (0.00%)  1/394 (0.25%) 
Injury, poisoning and procedural complications     
Cardiac valve replacement  1  3/393 (0.76%)  0/394 (0.00%) 
Cardiac valve rupture  1  0/393 (0.00%)  2/394 (0.51%) 
Fall  1  0/393 (0.00%)  2/394 (0.51%) 
Pneumothorax traumatic  1  1/393 (0.25%)  0/394 (0.00%) 
Vascular procedure complication  1  1/393 (0.25%)  0/394 (0.00%) 
Metabolism and nutrition disorders     
Diabetes mellitus inadequate control  1  0/393 (0.00%)  1/394 (0.25%) 
Hyperglycaemia  1  1/393 (0.25%)  0/394 (0.00%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)     
Colon cancer  1  0/393 (0.00%)  2/394 (0.51%) 
Bladder cancer  1  1/393 (0.25%)  0/394 (0.00%) 
Gastric cancer  1  0/393 (0.00%)  1/394 (0.25%) 
Nervous system disorders     
Ischaemic stroke  1  3/393 (0.76%)  0/394 (0.00%) 
Carotid artery stenosis  1  0/393 (0.00%)  1/394 (0.25%) 
Cerebrovascular accident  1  0/393 (0.00%)  1/394 (0.25%) 
Cognitive disorder  1  0/393 (0.00%)  1/394 (0.25%) 
Haemorrhage intracranial  1  0/393 (0.00%)  1/394 (0.25%) 
Haemorrhagic stroke  1  1/393 (0.25%)  0/394 (0.00%) 
Loss of consciousness  1  0/393 (0.00%)  1/394 (0.25%) 
Myasthenia gravis  1  1/393 (0.25%)  0/394 (0.00%) 
Syncope  1  1/393 (0.25%)  0/394 (0.00%) 
Psychiatric disorders     
Confusional state  1  1/393 (0.25%)  0/394 (0.00%) 
Panic attack  1  0/393 (0.00%)  1/394 (0.25%) 
Renal and urinary disorders     
Renal failure acute  1  0/393 (0.00%)  2/394 (0.51%) 
Respiratory, thoracic and mediastinal disorders     
Dyspnoea  1  2/393 (0.51%)  1/394 (0.25%) 
Pleural effusion  1  2/393 (0.51%)  0/394 (0.00%) 
Respiratory failure  1  1/393 (0.25%)  1/394 (0.25%) 
Chronic obstructive pulmonary  1  1/393 (0.25%)  0/394 (0.00%) 
Pleurisy  1  1/393 (0.25%)  0/394 (0.00%) 
Pneumothorax  1  0/393 (0.00%)  1/394 (0.25%) 
Pulmonary embolism  1  0/393 (0.00%)  1/394 (0.25%) 
Surgical and medical procedures     
Intestinal anastomosis  1  1/393 (0.25%)  0/394 (0.00%) 
Vascular disorders     
Hypotension  1  2/393 (0.51%)  1/394 (0.25%) 
Peripheral ischaemia  1  0/393 (0.00%)  2/394 (0.51%) 
Aortic dissection  1  1/393 (0.25%)  0/394 (0.00%) 
Circulatory collapse  1  1/393 (0.25%)  0/394 (0.00%) 
Femoral artery dissection  1  1/393 (0.25%)  0/394 (0.00%) 
Haemodynamic instability  1  0/393 (0.00%)  1/394 (0.25%) 
Hypertensive crisis  1  0/393 (0.00%)  1/394 (0.25%) 
Peripheral arterial occlusive disease  1  1/393 (0.25%)  0/394 (0.00%) 
Peripheral artery thrombosis  1  1/393 (0.25%)  0/394 (0.00%) 
Phlebitis  1  1/393 (0.25%)  0/394 (0.00%) 
Shock  1  0/393 (0.00%)  1/394 (0.25%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 15.1
[1]
Organ system includes administration site conditions.
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 3%
Bivalirudin Unfractionated Heparin (UFH)
Affected / at Risk (%) Affected / at Risk (%)
Total   73/393 (18.58%)   70/394 (17.77%) 
Cardiac disorders     
Bundle branch block left  1  15/393 (3.82%)  16/394 (4.06%) 
General disorders     
Pyrexia  1 [1]  12/393 (3.05%)  19/394 (4.82%) 
Musculoskeletal and connective tissue disorders     
Back pain  1  13/393 (3.31%)  9/394 (2.28%) 
Psychiatric disorders     
Confusional state  1  14/393 (3.56%)  10/394 (2.54%) 
Vascular disorders     
Hypertension  1  19/393 (4.83%)  16/394 (4.06%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 15.1
[1]
Organ system includes administration site conditions.
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There is NOT 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: 800-388-1183
Layout table for additonal information
Responsible Party: The Medicines Company
ClinicalTrials.gov Identifier: NCT01651780     History of Changes
Other Study ID Numbers: TMC-BIV-11-02
2012‐000632‐26 ( EudraCT Number )
First Submitted: July 24, 2012
First Posted: July 27, 2012
Results First Submitted: January 9, 2017
Results First Posted: February 27, 2017
Last Update Posted: April 7, 2017