Trial Outcomes & Findings for Bradykinin Receptor Antagonism During Cardiopulmonary Bypass (NCT NCT00223704)
NCT ID: NCT00223704
Last Updated: 2013-11-25
Results Overview
Blood product transfusion during hospitalization that included packed red blood cells, plasma, platelets and cryoprecipitate.
Recruitment status
COMPLETED
Study phase
PHASE2/PHASE3
Target enrollment
150 participants
Primary outcome timeframe
Patients were followed for the duration of hospital stay, an average of 6 days
Results posted on
2013-11-25
Participant Flow
Patients were enrolled by the research nurse at the time of the preoperative evaluation for surgery. All patients provided written informed consent. The study period was from June 2007 until June 2012.
One hundred and fifty patients consented to participate in the study. Of these patients, 13 were excluded,12 withdrew before randomization, 4 had their surgeries canceled, 3 had their surgery dates changed, and 3 patients did not proceed with the study for other reasons. The remaining 115 patients were randomly assigned to one of three groups.
Participant milestones
| Measure |
Placebo Group
Normal saline (placebo) was started in the operating room after induction of anesthesia and before heparinization, continued throughout the bypass period, and discontinued at the end of surgery.
|
Aminocaproic Acid Group
Aminocaproic acid (an antifibrinolytic drug) was started in the operating room after induction of anesthesia and before heparinization, continued throughout the bypass period, and discontinued at the end of surgery. Aminocaproic acid was given as an intravenous bolus of 100 mg/kg over one-half hour followed by an infusion of 30 mg/kg/hr.
|
HOE 140 Group
HOE 140 (a bradykinin B2 receptor antagonist) was started in the operating room after induction of anesthesia and before heparinization, continued throughout the bypass period, and discontinued at the end of surgery. HOE 140 was given as an intravenous bolus of 22 µg/kg over one-half hour followed by an infusion of 18 µg/kg/hr.
|
|---|---|---|---|
|
Overall Study
STARTED
|
38
|
37
|
40
|
|
Overall Study
COMPLETED
|
38
|
37
|
40
|
|
Overall Study
NOT COMPLETED
|
0
|
0
|
0
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
Bradykinin Receptor Antagonism During Cardiopulmonary Bypass
Baseline characteristics by cohort
| Measure |
Placebo Group
n=38 Participants
Placebo was normal saline
|
Aminocaproic Acid Group
n=37 Participants
Aminocaproic acid is an antifibrinolytic drug
|
HOE 140 Group
n=40 Participants
Bradykinin B2 receptor antagonist
|
Total
n=115 Participants
Total of all reporting groups
|
|---|---|---|---|---|
|
Age, Categorical
<=18 years
|
0 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
0 Participants
n=206 Participants
|
0 Participants
n=7 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
25 Participants
n=99 Participants
|
23 Participants
n=107 Participants
|
24 Participants
n=206 Participants
|
72 Participants
n=7 Participants
|
|
Age, Categorical
>=65 years
|
13 Participants
n=99 Participants
|
14 Participants
n=107 Participants
|
16 Participants
n=206 Participants
|
43 Participants
n=7 Participants
|
|
Age Continuous
|
60.1 years
STANDARD_DEVIATION 10.8 • n=99 Participants
|
58.5 years
STANDARD_DEVIATION 12.0 • n=107 Participants
|
61.0 years
STANDARD_DEVIATION 12.8 • n=206 Participants
|
59.9 years
STANDARD_DEVIATION 11.8 • n=7 Participants
|
|
Sex: Female, Male
Female
|
12 Participants
n=99 Participants
|
18 Participants
n=107 Participants
|
18 Participants
n=206 Participants
|
48 Participants
n=7 Participants
|
|
Sex: Female, Male
Male
|
26 Participants
n=99 Participants
|
19 Participants
n=107 Participants
|
22 Participants
n=206 Participants
|
67 Participants
n=7 Participants
|
|
Region of Enrollment
United States
|
38 participants
n=99 Participants
|
37 participants
n=107 Participants
|
40 participants
n=206 Participants
|
115 participants
n=7 Participants
|
PRIMARY outcome
Timeframe: Patients were followed for the duration of hospital stay, an average of 6 daysBlood product transfusion during hospitalization that included packed red blood cells, plasma, platelets and cryoprecipitate.
Outcome measures
| Measure |
Placebo Group
n=38 Participants
Normal saline (placebo) was started in the operating room after induction of anesthesia and before heparinization, continued throughout the bypass period, and discontinued at the end of surgery.
|
Aminocaproic Acid Group
n=37 Participants
Aminocaproic acid (an antifibrinolytic drug) was started in the operating room after induction of anesthesia and before heparinization, continued throughout the bypass period, and discontinued at the end of surgery. Aminocaproic acid was given as an intravenous bolus of 100 mg/kg over one-half hour followed by an infusion of 30 mg/kg/hr.
|
HOE 140 Group
n=40 Participants
HOE 140 (a bradykinin B2 receptor antagonist) was started in the operating room after induction of anesthesia and before heparinization, continued throughout the bypass period, and discontinued at the end of surgery. HOE 140 was given as an intravenous bolus of 22 µg/kg over one-half hour followed by an infusion of 18 µg/kg/hr.
|
|---|---|---|---|
|
Allogenic Blood Product Transfusion Risk
Received any transfusion
|
47.4 percentage of participants
|
56.8 percentage of participants
|
52.5 percentage of participants
|
|
Allogenic Blood Product Transfusion Risk
Received packed red blood cells
|
36.8 percentage of participants
|
48.6 percentage of participants
|
47.5 percentage of participants
|
|
Allogenic Blood Product Transfusion Risk
Received plasma
|
31.6 percentage of participants
|
24.3 percentage of participants
|
17.5 percentage of participants
|
|
Allogenic Blood Product Transfusion Risk
Received platelets
|
23.7 percentage of participants
|
16.2 percentage of participants
|
17.5 percentage of participants
|
|
Allogenic Blood Product Transfusion Risk
Received cryoprecipitate
|
10.5 percentage of participants
|
2.7 percentage of participants
|
5.0 percentage of participants
|
SECONDARY outcome
Timeframe: Patients were followed for the duration of hospital stay, an average of 6 daysUnits of Packed Red Blood Cells Transfused
Outcome measures
| Measure |
Placebo Group
n=38 Participants
Normal saline (placebo) was started in the operating room after induction of anesthesia and before heparinization, continued throughout the bypass period, and discontinued at the end of surgery.
|
Aminocaproic Acid Group
n=37 Participants
Aminocaproic acid (an antifibrinolytic drug) was started in the operating room after induction of anesthesia and before heparinization, continued throughout the bypass period, and discontinued at the end of surgery. Aminocaproic acid was given as an intravenous bolus of 100 mg/kg over one-half hour followed by an infusion of 30 mg/kg/hr.
|
HOE 140 Group
n=40 Participants
HOE 140 (a bradykinin B2 receptor antagonist) was started in the operating room after induction of anesthesia and before heparinization, continued throughout the bypass period, and discontinued at the end of surgery. HOE 140 was given as an intravenous bolus of 22 µg/kg over one-half hour followed by an infusion of 18 µg/kg/hr.
|
|---|---|---|---|
|
Units of Packed Red Blood Cells Transfused During Hospitalization
|
1.97 units
Standard Error 0.61
|
1.41 units
Standard Error 0.30
|
1.45 units
Standard Error 0.34
|
SECONDARY outcome
Timeframe: Patients were followed for the duration of hospital stay, an average of 6 daysUnits of plasma transfused
Outcome measures
| Measure |
Placebo Group
n=38 Participants
Normal saline (placebo) was started in the operating room after induction of anesthesia and before heparinization, continued throughout the bypass period, and discontinued at the end of surgery.
|
Aminocaproic Acid Group
n=37 Participants
Aminocaproic acid (an antifibrinolytic drug) was started in the operating room after induction of anesthesia and before heparinization, continued throughout the bypass period, and discontinued at the end of surgery. Aminocaproic acid was given as an intravenous bolus of 100 mg/kg over one-half hour followed by an infusion of 30 mg/kg/hr.
|
HOE 140 Group
n=40 Participants
HOE 140 (a bradykinin B2 receptor antagonist) was started in the operating room after induction of anesthesia and before heparinization, continued throughout the bypass period, and discontinued at the end of surgery. HOE 140 was given as an intravenous bolus of 22 µg/kg over one-half hour followed by an infusion of 18 µg/kg/hr.
|
|---|---|---|---|
|
Units of Plasma Transfused During Hospitalization
|
1.08 units
Standard Error 0.37
|
0.68 units
Standard Error 0.25
|
0.82 units
Standard Error 0.36
|
SECONDARY outcome
Timeframe: Patients were followed from the start of surgery until postoperative day 2Interleukin-6 was measured at baseline, post-bypass and on postoperative day 1 and 2.
Outcome measures
| Measure |
Placebo Group
n=38 Participants
Normal saline (placebo) was started in the operating room after induction of anesthesia and before heparinization, continued throughout the bypass period, and discontinued at the end of surgery.
|
Aminocaproic Acid Group
n=37 Participants
Aminocaproic acid (an antifibrinolytic drug) was started in the operating room after induction of anesthesia and before heparinization, continued throughout the bypass period, and discontinued at the end of surgery. Aminocaproic acid was given as an intravenous bolus of 100 mg/kg over one-half hour followed by an infusion of 30 mg/kg/hr.
|
HOE 140 Group
n=40 Participants
HOE 140 (a bradykinin B2 receptor antagonist) was started in the operating room after induction of anesthesia and before heparinization, continued throughout the bypass period, and discontinued at the end of surgery. HOE 140 was given as an intravenous bolus of 22 µg/kg over one-half hour followed by an infusion of 18 µg/kg/hr.
|
|---|---|---|---|
|
Inflammatory Response as Measured by Interleukin-6
Baseline
|
4.98 pg/ml
Standard Error 0.77
|
6.58 pg/ml
Standard Error 1.50
|
4.80 pg/ml
Standard Error 0.64
|
|
Inflammatory Response as Measured by Interleukin-6
Post-bypass
|
68.8 pg/ml
Standard Error 17.49
|
64.65 pg/ml
Standard Error 12.24
|
142.02 pg/ml
Standard Error 85.28
|
|
Inflammatory Response as Measured by Interleukin-6
Postoperative day 1
|
118.8 pg/ml
Standard Error 19.15
|
161.91 pg/ml
Standard Error 28.19
|
166.27 pg/ml
Standard Error 49.44
|
|
Inflammatory Response as Measured by Interleukin-6
Postoperative day 2
|
201.5 pg/ml
Standard Error 95.29
|
122.88 pg/ml
Standard Error 19.54
|
86.54 pg/ml
Standard Error 15.84
|
SECONDARY outcome
Timeframe: Patients were followed from the start of surgery until postoperative day 1D-dimer concentrations were measured at baseline, 30min and 60min of bypass, post-bypass and postoperative day 1
Outcome measures
| Measure |
Placebo Group
n=38 Participants
Normal saline (placebo) was started in the operating room after induction of anesthesia and before heparinization, continued throughout the bypass period, and discontinued at the end of surgery.
|
Aminocaproic Acid Group
n=37 Participants
Aminocaproic acid (an antifibrinolytic drug) was started in the operating room after induction of anesthesia and before heparinization, continued throughout the bypass period, and discontinued at the end of surgery. Aminocaproic acid was given as an intravenous bolus of 100 mg/kg over one-half hour followed by an infusion of 30 mg/kg/hr.
|
HOE 140 Group
n=40 Participants
HOE 140 (a bradykinin B2 receptor antagonist) was started in the operating room after induction of anesthesia and before heparinization, continued throughout the bypass period, and discontinued at the end of surgery. HOE 140 was given as an intravenous bolus of 22 µg/kg over one-half hour followed by an infusion of 18 µg/kg/hr.
|
|---|---|---|---|
|
Fibrinolytic Response as Measured by D-dimer
Baseline
|
95.5 ng/ml
Standard Error 12.0
|
103.0 ng/ml
Standard Error 18.8
|
88.1 ng/ml
Standard Error 9.6
|
|
Fibrinolytic Response as Measured by D-dimer
30min of bypass
|
150.6 ng/ml
Standard Error 17.5
|
131.9 ng/ml
Standard Error 19.7
|
209.0 ng/ml
Standard Error 49.4
|
|
Fibrinolytic Response as Measured by D-dimer
60min of bypass
|
287.6 ng/ml
Standard Error 51.1
|
154.3 ng/ml
Standard Error 24.7
|
363.3 ng/ml
Standard Error 74.4
|
|
Fibrinolytic Response as Measured by D-dimer
Post-bypass
|
589.8 ng/ml
Standard Error 104.5
|
168.9 ng/ml
Standard Error 22.4
|
858.5 ng/ml
Standard Error 182.5
|
|
Fibrinolytic Response as Measured by D-dimer
Postoperative day 1
|
390.4 ng/ml
Standard Error 73.2
|
269.5 ng/ml
Standard Error 51.3
|
337.3 ng/ml
Standard Error 36.4
|
Adverse Events
Placebo Group
Serious events: 1 serious events
Other events: 15 other events
Deaths: 0 deaths
Aminocaproic Acid Group
Serious events: 1 serious events
Other events: 11 other events
Deaths: 0 deaths
HOE 140 Group
Serious events: 1 serious events
Other events: 18 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Placebo Group
n=38 participants at risk
Placebo was normal saline
|
Aminocaproic Acid Group
n=37 participants at risk
Aminocaproic acid is an antifibrinolytic drug
|
HOE 140 Group
n=40 participants at risk
Bradykinin B2 receptor antagonist
|
|---|---|---|---|
|
Blood and lymphatic system disorders
Re-exploration for bleeding
|
2.6%
1/38 • Number of events 1 • Hospitalization
|
2.7%
1/37 • Number of events 1 • Hospitalization
|
2.5%
1/40 • Number of events 1 • Hospitalization
|
Other adverse events
| Measure |
Placebo Group
n=38 participants at risk
Placebo was normal saline
|
Aminocaproic Acid Group
n=37 participants at risk
Aminocaproic acid is an antifibrinolytic drug
|
HOE 140 Group
n=40 participants at risk
Bradykinin B2 receptor antagonist
|
|---|---|---|---|
|
Renal and urinary disorders
Acute kidney injury
|
18.4%
7/38 • Number of events 7 • Hospitalization
|
10.8%
4/37 • Number of events 4 • Hospitalization
|
15.0%
6/40 • Number of events 6 • Hospitalization
|
|
Cardiac disorders
New onset postoperative atrial fibrillation
|
13.2%
5/38 • Number of events 5 • Hospitalization
|
13.5%
5/37 • Number of events 5 • Hospitalization
|
22.5%
9/40 • Number of events 9 • Hospitalization
|
|
Cardiac disorders
Placement of permanent pacemaker
|
5.3%
2/38 • Number of events 2 • Hospitalization
|
5.4%
2/37 • Number of events 2 • Hospitalization
|
7.5%
3/40 • Number of events 3 • Hospitalization
|
|
Respiratory, thoracic and mediastinal disorders
Prolonged Mechanical Ventilation (>24 hours)
|
10.5%
4/38 • Number of events 4 • Hospitalization
|
2.7%
1/37 • Number of events 1 • Hospitalization
|
7.5%
3/40 • Number of events 3 • Hospitalization
|
Additional Information
Mias Pretorius, Associate Professor of Anesthesiology and Clinical Pharmacology
Vanderbilt University
Phone: 615-8757402
Email: [email protected]
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place