Trial Outcomes & Findings for Open-label, Randomized Trial in Participants Undergoing TAVR to Determine Safety & Efficacy of Bivalirudin vs UFH (NCT NCT01651780)
NCT ID: NCT01651780
Last Updated: 2017-04-07
Results Overview
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.
Recruitment status
COMPLETED
Study phase
PHASE3
Target enrollment
803 participants
Primary outcome timeframe
at 48 hours or discharge, whichever occurs first
Results posted on
2017-04-07
Participant Flow
Participant milestones
| Measure |
Bivalirudin
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.
|
Unfractionated Heparin (UFH)
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.
|
|---|---|---|
|
Overall Study
STARTED
|
405
|
398
|
|
Overall Study
Intent-To-Treat (ITT) Population
|
404
|
398
|
|
Overall Study
Received at Least 1 Dose of Study Drug
|
393
|
394
|
|
Overall Study
BRAVO 2 Feasibility Cohort
|
65
|
0
|
|
Overall Study
COMPLETED
|
394
|
388
|
|
Overall Study
NOT COMPLETED
|
11
|
10
|
Reasons for withdrawal
| Measure |
Bivalirudin
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.
|
Unfractionated Heparin (UFH)
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.
|
|---|---|---|
|
Overall Study
Physician decision: No 30-day visit
|
2
|
1
|
|
Overall Study
Reason Not Specified: No 30-day visit
|
2
|
2
|
|
Overall Study
Withdrawal by Subject
|
2
|
0
|
|
Overall Study
Inclusion/Exclusion Criteria Not Met
|
3
|
0
|
|
Overall Study
Lost to Follow-up
|
1
|
2
|
|
Overall Study
Physician decision: Day 30 visit <23 day
|
1
|
5
|
Baseline Characteristics
Open-label, Randomized Trial in Participants Undergoing TAVR to Determine Safety & Efficacy of Bivalirudin vs UFH
Baseline characteristics by cohort
| Measure |
Bivalirudin
n=404 Participants
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.
|
Unfractionated Heparin (UFH)
n=398 Participants
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
n=802 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
82.3 years
STANDARD_DEVIATION 6.5 • n=93 Participants
|
82.3 years
STANDARD_DEVIATION 6.5 • n=4 Participants
|
82.3 years
STANDARD_DEVIATION 6.5 • n=27 Participants
|
|
Sex: Female, Male
Female
|
195 Participants
n=93 Participants
|
196 Participants
n=4 Participants
|
391 Participants
n=27 Participants
|
|
Sex: Female, Male
Male
|
209 Participants
n=93 Participants
|
202 Participants
n=4 Participants
|
411 Participants
n=27 Participants
|
|
Region of Enrollment
Canada
|
36 participants
n=93 Participants
|
38 participants
n=4 Participants
|
74 participants
n=27 Participants
|
|
Region of Enrollment
Netherlands
|
10 participants
n=93 Participants
|
10 participants
n=4 Participants
|
20 participants
n=27 Participants
|
|
Region of Enrollment
Italy
|
37 participants
n=93 Participants
|
39 participants
n=4 Participants
|
76 participants
n=27 Participants
|
|
Region of Enrollment
United Kingdom
|
8 participants
n=93 Participants
|
10 participants
n=4 Participants
|
18 participants
n=27 Participants
|
|
Region of Enrollment
France
|
108 participants
n=93 Participants
|
106 participants
n=4 Participants
|
214 participants
n=27 Participants
|
|
Region of Enrollment
Switzerland
|
25 participants
n=93 Participants
|
22 participants
n=4 Participants
|
47 participants
n=27 Participants
|
|
Region of Enrollment
Germany
|
180 participants
n=93 Participants
|
173 participants
n=4 Participants
|
353 participants
n=27 Participants
|
PRIMARY outcome
Timeframe: at 48 hours or discharge, whichever occurs firstPopulation: Participants in the ITT population.
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.
Outcome measures
| Measure |
Bivalirudin
n=404 Participants
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.
|
Unfractionated Heparin (UFH)
n=398 Participants
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.
|
UFH: First Half of Study Site's Enrolled Participants
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.
|
UFH: Second Half of Study Site's Enrolled Participants
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.
|
|---|---|---|---|---|
|
Major Bleeding (BARC ≥3b) at 48 Hours or Before Hospital Discharge
|
6.9 percentage of participants
|
9 percentage of participants
|
—
|
—
|
PRIMARY outcome
Timeframe: up to 30 days after procedurePopulation: Participants in the ITT population.
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.
Outcome measures
| Measure |
Bivalirudin
n=404 Participants
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.
|
Unfractionated Heparin (UFH)
n=398 Participants
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.
|
UFH: First Half of Study Site's Enrolled Participants
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.
|
UFH: Second Half of Study Site's Enrolled Participants
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.
|
|---|---|---|---|---|
|
Net Adverse Clinical Events (NACE) at up to 30 Days
|
14.4 percentage of participants
|
16.1 percentage of participants
|
—
|
—
|
SECONDARY outcome
Timeframe: at 48 hours or before hospital discharge, whichever occurred earlierPopulation: Participants in the ITT population.
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.
Outcome measures
| Measure |
Bivalirudin
n=404 Participants
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.
|
Unfractionated Heparin (UFH)
n=398 Participants
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.
|
UFH: First Half of Study Site's Enrolled Participants
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.
|
UFH: Second Half of Study Site's Enrolled Participants
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.
|
|---|---|---|---|---|
|
NACE at 48 Hours or Before Hospital Discharge
|
8.9 percentage of participants
|
12.6 percentage of participants
|
—
|
—
|
SECONDARY outcome
Timeframe: at 48 hours or before hospital discharge, whichever occurred earlier, and at up to 30 days (±7 days)Population: Participants in the ITT population.
The percentage of participants reporting a MACE overall and the individual components of MACE (including death, non-fatal MI, and stroke) are presented.
Outcome measures
| Measure |
Bivalirudin
n=404 Participants
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.
|
Unfractionated Heparin (UFH)
n=398 Participants
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.
|
UFH: First Half of Study Site's Enrolled Participants
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.
|
UFH: Second Half of Study Site's Enrolled Participants
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.
|
|---|---|---|---|---|
|
Major Adverse Cardiac Events (MACE) Including Death, Non-fatal MI, and Stroke
MI at 48 hours or before hospital discharge
|
0 percentage of participants
|
1.3 percentage of participants
|
—
|
—
|
|
Major Adverse Cardiac Events (MACE) Including Death, Non-fatal MI, and Stroke
Stroke at 48 hours or before hospital discharge
|
2 percentage of participants
|
2 percentage of participants
|
—
|
—
|
|
Major Adverse Cardiac Events (MACE) Including Death, Non-fatal MI, and Stroke
MACE at up to 30 days
|
7.7 percentage of participants
|
8 percentage of participants
|
—
|
—
|
|
Major Adverse Cardiac Events (MACE) Including Death, Non-fatal MI, and Stroke
Death at up to 30 days
|
4.7 percentage of participants
|
4.8 percentage of participants
|
—
|
—
|
|
Major Adverse Cardiac Events (MACE) Including Death, Non-fatal MI, and Stroke
MACE at 48 hours or before hospital discharge
|
3.5 percentage of participants
|
4.8 percentage of participants
|
—
|
—
|
|
Major Adverse Cardiac Events (MACE) Including Death, Non-fatal MI, and Stroke
Death at 48 hours or before hospital discharge
|
1.5 percentage of participants
|
1.8 percentage of participants
|
—
|
—
|
|
Major Adverse Cardiac Events (MACE) Including Death, Non-fatal MI, and Stroke
MI at up to 30 days
|
0.5 percentage of participants
|
1.8 percentage of participants
|
—
|
—
|
|
Major Adverse Cardiac Events (MACE) Including Death, Non-fatal MI, and Stroke
Stroke at up to 30 days
|
3.5 percentage of participants
|
2.8 percentage of participants
|
—
|
—
|
SECONDARY outcome
Timeframe: at 48 hours or hospital discharge, whichever occurred earlier, and at up to 30 days (±7 days) follow-upPopulation: Participants in the ITT population.
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
Outcome measures
| Measure |
Bivalirudin
n=404 Participants
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.
|
Unfractionated Heparin (UFH)
n=398 Participants
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.
|
UFH: First Half of Study Site's Enrolled Participants
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.
|
UFH: Second Half of Study Site's Enrolled Participants
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.
|
|---|---|---|---|---|
|
Major Bleeding According to Additional Scales (VARC, TIMI, GUSTO, ACUITY/HORIZONS)
GUSTO at 48 hours or hospital discharge
|
13.9 percentage of participants
|
11.6 percentage of participants
|
—
|
—
|
|
Major Bleeding According to Additional Scales (VARC, TIMI, GUSTO, ACUITY/HORIZONS)
ACUITY/HORIZONS at 48 hours or hospital discharge
|
26 percentage of participants
|
24.4 percentage of participants
|
—
|
—
|
|
Major Bleeding According to Additional Scales (VARC, TIMI, GUSTO, ACUITY/HORIZONS)
VARC at 30 days
|
26.5 percentage of participants
|
24.6 percentage of participants
|
—
|
—
|
|
Major Bleeding According to Additional Scales (VARC, TIMI, GUSTO, ACUITY/HORIZONS)
TIMI at 30 days
|
5.7 percentage of participants
|
7.3 percentage of participants
|
—
|
—
|
|
Major Bleeding According to Additional Scales (VARC, TIMI, GUSTO, ACUITY/HORIZONS)
ACUITY/HORIZONS at 30 days
|
33.4 percentage of participants
|
29.6 percentage of participants
|
—
|
—
|
|
Major Bleeding According to Additional Scales (VARC, TIMI, GUSTO, ACUITY/HORIZONS)
VARC at 48 hours or before hospital
|
21.8 percentage of participants
|
19.6 percentage of participants
|
—
|
—
|
|
Major Bleeding According to Additional Scales (VARC, TIMI, GUSTO, ACUITY/HORIZONS)
TIMI at 48 hours or before hospital
|
4 percentage of participants
|
6.5 percentage of participants
|
—
|
—
|
|
Major Bleeding According to Additional Scales (VARC, TIMI, GUSTO, ACUITY/HORIZONS)
GUSTO at 30 days
|
16.3 percentage of participants
|
14.6 percentage of participants
|
—
|
—
|
SECONDARY outcome
Timeframe: at 48 hours or before hospital discharge, whichever occurred earlier, and at up to 30 days (±7 days)Population: Participants in the ITT population.
The percentage of participants reporting transient ischemic attack is presented.
Outcome measures
| Measure |
Bivalirudin
n=404 Participants
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.
|
Unfractionated Heparin (UFH)
n=398 Participants
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.
|
UFH: First Half of Study Site's Enrolled Participants
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.
|
UFH: Second Half of Study Site's Enrolled Participants
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.
|
|---|---|---|---|---|
|
Transient Ischemic Attack
at 48 hours or before hospital discharge
|
0 percentage of participants
|
0 percentage of participants
|
—
|
—
|
|
Transient Ischemic Attack
at up to 30 days (±7 days) follow-up
|
0 percentage of participants
|
0 percentage of participants
|
—
|
—
|
SECONDARY outcome
Timeframe: at 48 hours or hospital discharge, whichever occurred earlier, and at up to 30 days (±7 days) follow-upPopulation: Participants in the ITT population.
The percentage of participants reporting acute kidney injury is presented.
Outcome measures
| Measure |
Bivalirudin
n=404 Participants
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.
|
Unfractionated Heparin (UFH)
n=398 Participants
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.
|
UFH: First Half of Study Site's Enrolled Participants
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.
|
UFH: Second Half of Study Site's Enrolled Participants
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.
|
|---|---|---|---|---|
|
Acute Kidney Injury
at 48 hours or before hospital discharge
|
10.9 percentage of participants
|
6.5 percentage of participants
|
—
|
—
|
|
Acute Kidney Injury
at up to 30 days (±7 days) follow-up
|
18.8 percentage of participants
|
13.8 percentage of participants
|
—
|
—
|
SECONDARY outcome
Timeframe: at 48 hours or before hospital discharge, whichever occurred earlier, and at up to 30 days (±7 days)Population: Participants in the ITT population.
The percentage of participants reporting a major vascular complications as defined by VARC is presented.
Outcome measures
| Measure |
Bivalirudin
n=404 Participants
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.
|
Unfractionated Heparin (UFH)
n=398 Participants
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.
|
UFH: First Half of Study Site's Enrolled Participants
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.
|
UFH: Second Half of Study Site's Enrolled Participants
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.
|
|---|---|---|---|---|
|
Major Vascular Complications
at 48 hours or before hospital discharge
|
8.7 percentage of participants
|
9 percentage of participants
|
—
|
—
|
|
Major Vascular Complications
at up to 30 days (±7 days) follow-up
|
9.2 percentage of participants
|
9.5 percentage of participants
|
—
|
—
|
SECONDARY outcome
Timeframe: at 48 hours or before hospital discharge, whichever occurred earlier, and at up to 30 days (±7 days)Population: Participants in the ITT population.
The percentage of participants reporting acquired thrombocytopenia is presented.
Outcome measures
| Measure |
Bivalirudin
n=404 Participants
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.
|
Unfractionated Heparin (UFH)
n=398 Participants
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.
|
UFH: First Half of Study Site's Enrolled Participants
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.
|
UFH: Second Half of Study Site's Enrolled Participants
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.
|
|---|---|---|---|---|
|
Acquired Thrombocytopenia
at up to 30 days (±7 days)
|
24 percentage of participants
|
23.1 percentage of participants
|
—
|
—
|
|
Acquired Thrombocytopenia
at 48 hours or before hospital discharge
|
16.6 percentage of participants
|
17.3 percentage of participants
|
—
|
—
|
SECONDARY outcome
Timeframe: at 48 hours or before hospital discharge, whichever occurred earlier, and at up to 30 days (±7 days)Population: Participants in the ITT population.
The percentage of participants reporting new onset atrial fibrillation/flutter is presented.
Outcome measures
| Measure |
Bivalirudin
n=404 Participants
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.
|
Unfractionated Heparin (UFH)
n=398 Participants
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.
|
UFH: First Half of Study Site's Enrolled Participants
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.
|
UFH: Second Half of Study Site's Enrolled Participants
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.
|
|---|---|---|---|---|
|
New Onset Atrial Fibrillation/Flutter
at 48 hours or before hospital discharge
|
3.2 percentage of participants
|
2.5 percentage of participants
|
—
|
—
|
|
New Onset Atrial Fibrillation/Flutter
at up to 30 days (±7 days) follow-up
|
5.4 percentage of participants
|
4 percentage of participants
|
—
|
—
|
SECONDARY outcome
Timeframe: Up to 48 hours after procedure or at hospital discharge (but also includes any subsequent hospitalizations)Population: 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.
The effect of timing on bleeding event rates (the percentage of participants with an incidence of major bleeding) is presented.
Outcome measures
| Measure |
Bivalirudin
n=173 Participants
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.
|
Unfractionated Heparin (UFH)
n=171 Participants
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.
|
UFH: First Half of Study Site's Enrolled Participants
n=173 Participants
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.
|
UFH: Second Half of Study Site's Enrolled Participants
n=165 Participants
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.
|
|---|---|---|---|---|
|
Timing Effect on Bleeding Event Rate up to 48 Hours or Hospital Discharge
|
6.4 percentage of participants
|
6.4 percentage of participants
|
11.6 percentage of participants
|
8.5 percentage of participants
|
SECONDARY outcome
Timeframe: at 48 hours or hospital discharge, whichever occurred earlier, and at up to 30 days (±7 days) follow-upPopulation: Participants in the ITT population.
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.
Outcome measures
| Measure |
Bivalirudin
n=404 Participants
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.
|
Unfractionated Heparin (UFH)
n=398 Participants
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.
|
UFH: First Half of Study Site's Enrolled Participants
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.
|
UFH: Second Half of Study Site's Enrolled Participants
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.
|
|---|---|---|---|---|
|
Bleeding BARC 3a, BARC Types 1 or 2, and TIMI Minor
BARC 3a at 48 hours or hospital discharge
|
15.6 percentage of participants
|
13.3 percentage of participants
|
—
|
—
|
|
Bleeding BARC 3a, BARC Types 1 or 2, and TIMI Minor
BARC types 1 and 2 at 48 hours or discharge
|
20.8 percentage of participants
|
21.1 percentage of participants
|
—
|
—
|
|
Bleeding BARC 3a, BARC Types 1 or 2, and TIMI Minor
TIMI minor at 48 hours or hospital discharge
|
16.6 percentage of participants
|
14.3 percentage of participants
|
—
|
—
|
|
Bleeding BARC 3a, BARC Types 1 or 2, and TIMI Minor
BARC 3a at 30 days
|
18.8 percentage of participants
|
17.3 percentage of participants
|
—
|
—
|
|
Bleeding BARC 3a, BARC Types 1 or 2, and TIMI Minor
BARC types 1 and 2 at 30 days
|
27.7 percentage of participants
|
25.6 percentage of participants
|
—
|
—
|
|
Bleeding BARC 3a, BARC Types 1 or 2, and TIMI Minor
TIMI minor at 30 days
|
21.3 percentage of participants
|
19.3 percentage of participants
|
—
|
—
|
Adverse Events
Bivalirudin
Serious events: 112 serious events
Other events: 73 other events
Deaths: 0 deaths
Unfractionated Heparin (UFH)
Serious events: 116 serious events
Other events: 70 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Bivalirudin
n=393 participants at risk
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.
|
Unfractionated Heparin (UFH)
n=394 participants at risk
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.
|
|---|---|---|
|
Vascular disorders
Hypotension
|
0.51%
2/393
|
0.25%
1/394
|
|
Vascular disorders
Peripheral ischaemia
|
0.00%
0/393
|
0.51%
2/394
|
|
Vascular disorders
Aortic dissection
|
0.25%
1/393
|
0.00%
0/394
|
|
Vascular disorders
Circulatory collapse
|
0.25%
1/393
|
0.00%
0/394
|
|
Vascular disorders
Femoral artery dissection
|
0.25%
1/393
|
0.00%
0/394
|
|
Vascular disorders
Haemodynamic instability
|
0.00%
0/393
|
0.25%
1/394
|
|
Vascular disorders
Hypertensive crisis
|
0.00%
0/393
|
0.25%
1/394
|
|
Vascular disorders
Peripheral arterial occlusive disease
|
0.25%
1/393
|
0.00%
0/394
|
|
Vascular disorders
Peripheral artery thrombosis
|
0.25%
1/393
|
0.00%
0/394
|
|
Vascular disorders
Phlebitis
|
0.25%
1/393
|
0.00%
0/394
|
|
Vascular disorders
Shock
|
0.00%
0/393
|
0.25%
1/394
|
|
Surgical and medical procedures
Intestinal anastomosis
|
0.25%
1/393
|
0.00%
0/394
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Colon cancer
|
0.00%
0/393
|
0.51%
2/394
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Bladder cancer
|
0.25%
1/393
|
0.00%
0/394
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Gastric cancer
|
0.00%
0/393
|
0.25%
1/394
|
|
Immune system disorders
Anaphylactic shock
|
0.25%
1/393
|
0.00%
0/394
|
|
General disorders
Death
|
0.25%
1/393
|
0.25%
1/394
|
|
General disorders
Device leakage
|
0.25%
1/393
|
0.25%
1/394
|
|
General disorders
Thrombosis in device
|
0.51%
2/393
|
0.00%
0/394
|
|
General disorders
Device dislocation
|
0.00%
0/393
|
0.25%
1/394
|
|
General disorders
General physical health deterioration
|
0.25%
1/393
|
0.00%
0/394
|
|
General disorders
Hyperthermia
|
0.25%
1/393
|
0.00%
0/394
|
|
General disorders
Multi-organ failure
|
0.00%
0/393
|
0.25%
1/394
|
|
General disorders
Non-cardiac chest pain
|
0.25%
1/393
|
0.00%
0/394
|
|
General disorders
Pyrexia
|
0.25%
1/393
|
0.00%
0/394
|
|
General disorders
Sudden death
|
0.25%
1/393
|
0.00%
0/394
|
|
Psychiatric disorders
Confusional state
|
0.25%
1/393
|
0.00%
0/394
|
|
Psychiatric disorders
Panic attack
|
0.00%
0/393
|
0.25%
1/394
|
|
Injury, poisoning and procedural complications
Cardiac valve replacement
|
0.76%
3/393
|
0.00%
0/394
|
|
Injury, poisoning and procedural complications
Cardiac valve rupture
|
0.00%
0/393
|
0.51%
2/394
|
|
Injury, poisoning and procedural complications
Fall
|
0.00%
0/393
|
0.51%
2/394
|
|
Injury, poisoning and procedural complications
Pneumothorax traumatic
|
0.25%
1/393
|
0.00%
0/394
|
|
Injury, poisoning and procedural complications
Vascular procedure complication
|
0.25%
1/393
|
0.00%
0/394
|
|
Cardiac disorders
Atrioventricular block complete
|
11.7%
46/393
|
8.6%
34/394
|
|
Cardiac disorders
Bundle branch block left
|
1.8%
7/393
|
2.5%
10/394
|
|
Cardiac disorders
Bradycardia
|
0.51%
2/393
|
1.8%
7/394
|
|
Cardiac disorders
Cardiac arrest
|
0.51%
2/393
|
1.8%
7/394
|
|
Cardiac disorders
Atrioventricular block second degree
|
0.51%
2/393
|
1.5%
6/394
|
|
Cardiac disorders
Atrioventricular block first degree
|
0.76%
3/393
|
1.0%
4/394
|
|
Cardiac disorders
Atrioventricular block
|
0.51%
2/393
|
1.0%
4/394
|
|
Cardiac disorders
Ventricular tachycardia
|
1.0%
4/393
|
0.25%
1/394
|
|
Cardiac disorders
Cardiac failure acute
|
0.25%
1/393
|
0.76%
3/394
|
|
Cardiac disorders
Aortic valve incompetence
|
0.25%
1/393
|
0.25%
1/394
|
|
Cardiac disorders
Cardiac tamponade
|
0.25%
1/393
|
0.25%
1/394
|
|
Cardiac disorders
Cardiogenic shock
|
0.00%
0/393
|
0.51%
2/394
|
|
Cardiac disorders
Coronary artery occlusion
|
0.00%
0/393
|
0.51%
2/394
|
|
Cardiac disorders
Ventricular fibrillation
|
0.25%
1/393
|
0.25%
1/394
|
|
Cardiac disorders
Ventricular tachyarrhythmia
|
0.25%
1/393
|
0.25%
1/394
|
|
Cardiac disorders
Bifascicular block
|
0.25%
1/393
|
0.00%
0/394
|
|
Cardiac disorders
Bradyarrhythmia
|
0.25%
1/393
|
0.00%
0/394
|
|
Cardiac disorders
Cardiac perforation
|
0.00%
0/393
|
0.25%
1/394
|
|
Cardiac disorders
Cardio-respiratory arrest
|
0.25%
1/393
|
0.00%
0/394
|
|
Cardiac disorders
Cardiopulmonary failure
|
0.25%
1/393
|
0.00%
0/394
|
|
Cardiac disorders
Coronary artery stenosis
|
0.00%
0/393
|
0.25%
1/394
|
|
Cardiac disorders
Ischaemic cardiomyopathy
|
0.00%
0/393
|
0.25%
1/394
|
|
Cardiac disorders
Low cardiac output syndrome
|
0.00%
0/393
|
0.25%
1/394
|
|
Cardiac disorders
Pericardial effusion
|
0.25%
1/393
|
0.00%
0/394
|
|
Cardiac disorders
Sick sinus syndrome
|
0.25%
1/393
|
0.00%
0/394
|
|
Cardiac disorders
Supraventricular tachycardia
|
0.25%
1/393
|
0.00%
0/394
|
|
Cardiac disorders
Bundle branch block
|
0.51%
2/393
|
0.00%
0/394
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnoea
|
0.51%
2/393
|
0.25%
1/394
|
|
Respiratory, thoracic and mediastinal disorders
Pleural effusion
|
0.51%
2/393
|
0.00%
0/394
|
|
Respiratory, thoracic and mediastinal disorders
Respiratory failure
|
0.25%
1/393
|
0.25%
1/394
|
|
Respiratory, thoracic and mediastinal disorders
Chronic obstructive pulmonary
|
0.25%
1/393
|
0.00%
0/394
|
|
Respiratory, thoracic and mediastinal disorders
Pleurisy
|
0.25%
1/393
|
0.00%
0/394
|
|
Respiratory, thoracic and mediastinal disorders
Pneumothorax
|
0.00%
0/393
|
0.25%
1/394
|
|
Respiratory, thoracic and mediastinal disorders
Pulmonary embolism
|
0.00%
0/393
|
0.25%
1/394
|
|
Nervous system disorders
Ischaemic stroke
|
0.76%
3/393
|
0.00%
0/394
|
|
Nervous system disorders
Carotid artery stenosis
|
0.00%
0/393
|
0.25%
1/394
|
|
Nervous system disorders
Cerebrovascular accident
|
0.00%
0/393
|
0.25%
1/394
|
|
Nervous system disorders
Cognitive disorder
|
0.00%
0/393
|
0.25%
1/394
|
|
Nervous system disorders
Haemorrhage intracranial
|
0.00%
0/393
|
0.25%
1/394
|
|
Nervous system disorders
Haemorrhagic stroke
|
0.25%
1/393
|
0.00%
0/394
|
|
Nervous system disorders
Loss of consciousness
|
0.00%
0/393
|
0.25%
1/394
|
|
Nervous system disorders
Myasthenia gravis
|
0.25%
1/393
|
0.00%
0/394
|
|
Nervous system disorders
Syncope
|
0.25%
1/393
|
0.00%
0/394
|
|
Gastrointestinal disorders
Retroperitoneal haemorrhage
|
0.25%
1/393
|
0.25%
1/394
|
|
Gastrointestinal disorders
Abdominal hernia
|
0.00%
0/393
|
0.25%
1/394
|
|
Gastrointestinal disorders
Abdominal pain
|
0.00%
0/393
|
0.25%
1/394
|
|
Gastrointestinal disorders
Gastric haemorrhage
|
0.25%
1/393
|
0.00%
0/394
|
|
Gastrointestinal disorders
Gastritis
|
0.00%
0/393
|
0.25%
1/394
|
|
Gastrointestinal disorders
Intestinal infarction
|
0.00%
0/393
|
0.25%
1/394
|
|
Gastrointestinal disorders
Intestinal ischaemia
|
0.25%
1/393
|
0.00%
0/394
|
|
Gastrointestinal disorders
Umbilical hernia, obstructive
|
0.25%
1/393
|
0.00%
0/394
|
|
Hepatobiliary disorders
Cholecystitis acute
|
0.00%
0/393
|
0.25%
1/394
|
|
Renal and urinary disorders
Renal failure acute
|
0.00%
0/393
|
0.51%
2/394
|
|
Metabolism and nutrition disorders
Diabetes mellitus inadequate control
|
0.00%
0/393
|
0.25%
1/394
|
|
Metabolism and nutrition disorders
Hyperglycaemia
|
0.25%
1/393
|
0.00%
0/394
|
|
Infections and infestations
Pneumonia
|
0.51%
2/393
|
0.51%
2/394
|
|
Infections and infestations
Bronchopneumonia
|
0.00%
0/393
|
0.51%
2/394
|
|
Infections and infestations
Sepsis
|
0.25%
1/393
|
0.25%
1/394
|
|
Infections and infestations
Bronchitis
|
0.00%
0/393
|
0.25%
1/394
|
|
Infections and infestations
Infection
|
0.00%
0/393
|
0.25%
1/394
|
|
Infections and infestations
Intervertebral discitis
|
0.25%
1/393
|
0.00%
0/394
|
|
Infections and infestations
Klebsiella infection
|
0.00%
0/393
|
0.25%
1/394
|
|
Infections and infestations
Pneumonia viral
|
0.25%
1/393
|
0.00%
0/394
|
|
Infections and infestations
Postoperative wound infection
|
0.00%
0/393
|
0.25%
1/394
|
|
Infections and infestations
Pseudomonas infection
|
0.25%
1/393
|
0.00%
0/394
|
|
Infections and infestations
Septic encephalopathy
|
0.25%
1/393
|
0.00%
0/394
|
|
Infections and infestations
Urinary tract infection
|
0.00%
0/393
|
0.25%
1/394
|
|
Cardiac disorders
Cardiac failure
|
1.5%
6/393
|
2.5%
10/394
|
Other adverse events
| Measure |
Bivalirudin
n=393 participants at risk
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.
|
Unfractionated Heparin (UFH)
n=394 participants at risk
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.
|
|---|---|---|
|
Vascular disorders
Hypertension
|
4.8%
19/393
|
4.1%
16/394
|
|
Cardiac disorders
Bundle branch block left
|
3.8%
15/393
|
4.1%
16/394
|
|
General disorders
Pyrexia
|
3.1%
12/393
|
4.8%
19/394
|
|
Psychiatric disorders
Confusional state
|
3.6%
14/393
|
2.5%
10/394
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
3.3%
13/393
|
2.3%
9/394
|
Additional Information
Global Health Science Center
The Medicines Company
Phone: 800-388-1183
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place