Trial Outcomes & Findings for Proteolytic Enzyme Induction Within the Human Myocardial Interstitium (NCT NCT00744211)
NCT ID: NCT00744211
Last Updated: 2017-11-09
Results Overview
Pulmonary Vascular Resistance (d.s.cm-5)
Recruitment status
COMPLETED
Study phase
NA
Target enrollment
29 participants
Primary outcome timeframe
Baseline, 0, 6, 12 and 24 hours post-cardiopulmonary bypass (CPB)
Results posted on
2017-11-09
Participant Flow
Prospective randomization in a blinded fashion, at the time of elective coronary revascularization or valve replacement requiring cardiopulmonary bypass.
Participant milestones
| Measure |
Vehicle
Saline intravenous bolus
|
ET-ARA 1mg/kg
1mg/kg sitaxsentan sodium intravenous bolus
|
ET-ARA 2mg/kg
2mg/kg sitaxsentan sodium intravenous bolus
|
|---|---|---|---|
|
Baseline
STARTED
|
10
|
9
|
10
|
|
Baseline
COMPLETED
|
10
|
9
|
10
|
|
Baseline
NOT COMPLETED
|
0
|
0
|
0
|
|
0.5 Hours After Cardiopulmonary Bypass
STARTED
|
10
|
9
|
10
|
|
0.5 Hours After Cardiopulmonary Bypass
COMPLETED
|
10
|
9
|
10
|
|
0.5 Hours After Cardiopulmonary Bypass
NOT COMPLETED
|
0
|
0
|
0
|
|
6 Hours After Cardiopulmonary Bypass
STARTED
|
10
|
9
|
10
|
|
6 Hours After Cardiopulmonary Bypass
COMPLETED
|
10
|
9
|
10
|
|
6 Hours After Cardiopulmonary Bypass
NOT COMPLETED
|
0
|
0
|
0
|
|
12 Hours After Cardiopulmonary Bypass
STARTED
|
10
|
9
|
10
|
|
12 Hours After Cardiopulmonary Bypass
COMPLETED
|
10
|
9
|
10
|
|
12 Hours After Cardiopulmonary Bypass
NOT COMPLETED
|
0
|
0
|
0
|
|
24 Hours After Cardiopulmonary Bypass
STARTED
|
10
|
9
|
10
|
|
24 Hours After Cardiopulmonary Bypass
COMPLETED
|
10
|
9
|
10
|
|
24 Hours After Cardiopulmonary Bypass
NOT COMPLETED
|
0
|
0
|
0
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
Proteolytic Enzyme Induction Within the Human Myocardial Interstitium
Baseline characteristics by cohort
| Measure |
Vehicle
n=10 Participants
Saline, intravenous bolus
|
ET-ARA 1mg/kg
n=9 Participants
1mg/kg sitaxsentan sodium
|
ET-ARA 2mg/kg
n=10 Participants
2mg/kg sitaxsentan sodium
|
Total
n=29 Participants
Total of all reporting groups
|
|---|---|---|---|---|
|
Age, Continuous
|
67 years
STANDARD_DEVIATION 2 • n=93 Participants
|
62 years
STANDARD_DEVIATION 3 • n=4 Participants
|
68 years
STANDARD_DEVIATION 3 • n=27 Participants
|
66 years
STANDARD_DEVIATION 2 • n=483 Participants
|
|
Sex: Female, Male
Female
|
1 Participants
n=93 Participants
|
2 Participants
n=4 Participants
|
0 Participants
n=27 Participants
|
3 Participants
n=483 Participants
|
|
Sex: Female, Male
Male
|
9 Participants
n=93 Participants
|
7 Participants
n=4 Participants
|
10 Participants
n=27 Participants
|
26 Participants
n=483 Participants
|
|
Left Ventricular Ejection Fraction (LVEF)
|
35 percent
STANDARD_DEVIATION 3 • n=93 Participants
|
38 percent
STANDARD_DEVIATION 2 • n=4 Participants
|
37 percent
STANDARD_DEVIATION 3 • n=27 Participants
|
37 percent
STANDARD_DEVIATION 2 • n=483 Participants
|
|
Plasma Endothelin
|
3.9 fmol/mL
STANDARD_DEVIATION 0.4 • n=93 Participants
|
3.7 fmol/mL
STANDARD_DEVIATION 0.3 • n=4 Participants
|
4.3 fmol/mL
STANDARD_DEVIATION 0.7 • n=27 Participants
|
4.0 fmol/mL
STANDARD_DEVIATION 0.3 • n=483 Participants
|
|
Systemic vascular resistance
|
1408 dyne*second/centimeter˄5
STANDARD_DEVIATION 119 • n=93 Participants
|
1359 dyne*second/centimeter˄5
STANDARD_DEVIATION 210 • n=4 Participants
|
1307 dyne*second/centimeter˄5
STANDARD_DEVIATION 112 • n=27 Participants
|
1358 dyne*second/centimeter˄5
STANDARD_DEVIATION 83 • n=483 Participants
|
|
Pulmonary vascular resistance
|
153.8 dyne*second/centimeter˄5
STANDARD_DEVIATION 19.9 • n=93 Participants
|
213.0 dyne*second/centimeter˄5
STANDARD_DEVIATION 65.3 • n=4 Participants
|
174.6 dyne*second/centimeter˄5
STANDARD_DEVIATION 28.4 • n=27 Participants
|
180 dyne*second/centimeter˄5
STANDARD_DEVIATION 23 • n=483 Participants
|
PRIMARY outcome
Timeframe: Baseline, 0, 6, 12 and 24 hours post-cardiopulmonary bypass (CPB)Pulmonary Vascular Resistance (d.s.cm-5)
Outcome measures
| Measure |
Vehicle
n=10 Participants
Vehicle group
|
1mg/kg ET-ARA
n=9 Participants
1 mg/kg ET-ARA
|
2mg/kg ET-ARA
n=10 Participants
2 mg/kg ET-ARA
|
|---|---|---|---|
|
Pulmonary Vascular Resistance
Baseline
|
153.8 dyne*second/centimeter˄5
Standard Deviation 19.9
|
213.0 dyne*second/centimeter˄5
Standard Deviation 65.3
|
174.6 dyne*second/centimeter˄5
Standard Deviation 28.4
|
|
Pulmonary Vascular Resistance
0 hours post-CPB
|
123.5 dyne*second/centimeter˄5
Standard Deviation 20.7
|
125.3 dyne*second/centimeter˄5
Standard Deviation 24.8
|
175.8 dyne*second/centimeter˄5
Standard Deviation 26.6
|
|
Pulmonary Vascular Resistance
6 hours post-CPB
|
138.7 dyne*second/centimeter˄5
Standard Deviation 28.0
|
144.6 dyne*second/centimeter˄5
Standard Deviation 15.2
|
132.7 dyne*second/centimeter˄5
Standard Deviation 17.6
|
|
Pulmonary Vascular Resistance
12 hours post-CPB
|
146.8 dyne*second/centimeter˄5
Standard Deviation 21.6
|
132.7 dyne*second/centimeter˄5
Standard Deviation 12.7
|
136.6 dyne*second/centimeter˄5
Standard Deviation 17.5
|
|
Pulmonary Vascular Resistance
24 hours post-CPB
|
163.3 dyne*second/centimeter˄5
Standard Deviation 26.6
|
125.5 dyne*second/centimeter˄5
Standard Deviation 22.3
|
138.7 dyne*second/centimeter˄5
Standard Deviation 20.0
|
SECONDARY outcome
Timeframe: Baseline, 0, 6, 12 and 24 hours post-CPBPlasma Endothelin-1 (fmol/mL)
Outcome measures
| Measure |
Vehicle
n=10 Participants
Vehicle group
|
1mg/kg ET-ARA
n=9 Participants
1 mg/kg ET-ARA
|
2mg/kg ET-ARA
n=10 Participants
2 mg/kg ET-ARA
|
|---|---|---|---|
|
Plasma Endothelin-1
Baseline
|
3.9 fmol/mL
Standard Deviation 0.4
|
3.7 fmol/mL
Standard Deviation 0.3
|
4.3 fmol/mL
Standard Deviation 0.7
|
|
Plasma Endothelin-1
0 hours post-CPB
|
5.5 fmol/mL
Standard Deviation 0.8
|
4.7 fmol/mL
Standard Deviation 0.5
|
4.1 fmol/mL
Standard Deviation 0.5
|
|
Plasma Endothelin-1
6 hours post-CPB
|
8.2 fmol/mL
Standard Deviation 1.1
|
7.2 fmol/mL
Standard Deviation 1.3
|
7.6 fmol/mL
Standard Deviation 1.2
|
|
Plasma Endothelin-1
12 hours post-CPB
|
8.6 fmol/mL
Standard Deviation 1.1
|
8.8 fmol/mL
Standard Deviation 1.7
|
10.4 fmol/mL
Standard Deviation 1.6
|
|
Plasma Endothelin-1
24 hours post-CPB
|
8.0 fmol/mL
Standard Deviation 1.0
|
8.3 fmol/mL
Standard Deviation 1.0
|
8.6 fmol/mL
Standard Deviation 1.4
|
OTHER_PRE_SPECIFIED outcome
Timeframe: 0, 6, 12 and 24 hours post-CPBSitaxsentan levels (microg/mL)
Outcome measures
| Measure |
Vehicle
n=9 Participants
Vehicle group
|
1mg/kg ET-ARA
n=10 Participants
1 mg/kg ET-ARA
|
2mg/kg ET-ARA
2 mg/kg ET-ARA
|
|---|---|---|---|
|
Sitaxsentan Levels
0 hours post-CPB
|
7.35 microg/mL
Standard Deviation 0.83
|
11.78 microg/mL
Standard Deviation 1.17
|
—
|
|
Sitaxsentan Levels
6 hours post-CPB
|
0.06 microg/mL
Standard Deviation 0.01
|
2.24 microg/mL
Standard Deviation 2.13
|
—
|
|
Sitaxsentan Levels
12 hours post-CPB
|
1.88 microg/mL
Standard Deviation 1.26
|
8.63 microg/mL
Standard Deviation 3.24
|
—
|
|
Sitaxsentan Levels
24 hours post-CPB
|
0.06 microg/mL
Standard Deviation 0.01
|
0.09 microg/mL
Standard Deviation 0.01
|
—
|
OTHER_PRE_SPECIFIED outcome
Timeframe: up to 24-hours post-CPBOther (non-serious) Adverse Events (reported by arm/group)
Outcome measures
| Measure |
Vehicle
n=10 Participants
Vehicle group
|
1mg/kg ET-ARA
n=9 Participants
1 mg/kg ET-ARA
|
2mg/kg ET-ARA
n=10 Participants
2 mg/kg ET-ARA
|
|---|---|---|---|
|
Number of Other Adverse Events By Type
Endocrine/Metabolic
|
1 events
|
1 events
|
5 events
|
|
Number of Other Adverse Events By Type
Cardiovascular
|
12 events
|
20 events
|
17 events
|
|
Number of Other Adverse Events By Type
Pulmonary
|
3 events
|
4 events
|
8 events
|
|
Number of Other Adverse Events By Type
Neurological
|
2 events
|
0 events
|
0 events
|
|
Number of Other Adverse Events By Type
Urinary
|
2 events
|
0 events
|
3 events
|
|
Number of Other Adverse Events By Type
Gastrointestinal
|
9 events
|
8 events
|
8 events
|
|
Number of Other Adverse Events By Type
Hepatic
|
0 events
|
3 events
|
1 events
|
|
Number of Other Adverse Events By Type
Musculoskeletal
|
1 events
|
7 events
|
5 events
|
|
Number of Other Adverse Events By Type
Genitourinary/Gynecological
|
0 events
|
0 events
|
0 events
|
|
Number of Other Adverse Events By Type
Immunological/Allergic
|
0 events
|
1 events
|
0 events
|
|
Number of Other Adverse Events By Type
Hematological/Lymphatic
|
1 events
|
4 events
|
10 events
|
|
Number of Other Adverse Events By Type
Psychological/Behavioral
|
3 events
|
4 events
|
7 events
|
|
Number of Other Adverse Events By Type
HEENT
|
1 events
|
0 events
|
0 events
|
|
Number of Other Adverse Events By Type
Infection
|
3 events
|
0 events
|
2 events
|
|
Number of Other Adverse Events By Type
Fever
|
0 events
|
3 events
|
4 events
|
|
Number of Other Adverse Events By Type
Dermatological
|
0 events
|
3 events
|
2 events
|
Adverse Events
Vehicle
Serious events: 6 serious events
Other events: 0 other events
Deaths: 0 deaths
ET-ARA 1mg/kg
Serious events: 6 serious events
Other events: 0 other events
Deaths: 0 deaths
ET-ARA 2mg/kg
Serious events: 6 serious events
Other events: 0 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Vehicle
n=10 participants at risk
Vehicle Group
|
ET-ARA 1mg/kg
n=9 participants at risk
ET - ARA 1 mg / kg
|
ET-ARA 2mg/kg
n=10 participants at risk
ET - ARA 2 mg / kg
|
|---|---|---|---|
|
Cardiac disorders
Death
|
0.00%
0/10 • Post-operative period, reported up to 30+ days post CPB
Data for the Number of Participants Affected with Other Adverse Events is no longer available. Other Adverse Event Data is only available as a count of occurrences of AE's by Arm/Group.
|
22.2%
2/9 • Number of events 2 • Post-operative period, reported up to 30+ days post CPB
Data for the Number of Participants Affected with Other Adverse Events is no longer available. Other Adverse Event Data is only available as a count of occurrences of AE's by Arm/Group.
|
10.0%
1/10 • Number of events 1 • Post-operative period, reported up to 30+ days post CPB
Data for the Number of Participants Affected with Other Adverse Events is no longer available. Other Adverse Event Data is only available as a count of occurrences of AE's by Arm/Group.
|
|
Blood and lymphatic system disorders
Thrombo-embolic event
|
10.0%
1/10 • Number of events 1 • Post-operative period, reported up to 30+ days post CPB
Data for the Number of Participants Affected with Other Adverse Events is no longer available. Other Adverse Event Data is only available as a count of occurrences of AE's by Arm/Group.
|
44.4%
4/9 • Number of events 4 • Post-operative period, reported up to 30+ days post CPB
Data for the Number of Participants Affected with Other Adverse Events is no longer available. Other Adverse Event Data is only available as a count of occurrences of AE's by Arm/Group.
|
30.0%
3/10 • Number of events 3 • Post-operative period, reported up to 30+ days post CPB
Data for the Number of Participants Affected with Other Adverse Events is no longer available. Other Adverse Event Data is only available as a count of occurrences of AE's by Arm/Group.
|
|
Infections and infestations
Pulmonary/infection
|
40.0%
4/10 • Number of events 4 • Post-operative period, reported up to 30+ days post CPB
Data for the Number of Participants Affected with Other Adverse Events is no longer available. Other Adverse Event Data is only available as a count of occurrences of AE's by Arm/Group.
|
0.00%
0/9 • Post-operative period, reported up to 30+ days post CPB
Data for the Number of Participants Affected with Other Adverse Events is no longer available. Other Adverse Event Data is only available as a count of occurrences of AE's by Arm/Group.
|
20.0%
2/10 • Number of events 2 • Post-operative period, reported up to 30+ days post CPB
Data for the Number of Participants Affected with Other Adverse Events is no longer available. Other Adverse Event Data is only available as a count of occurrences of AE's by Arm/Group.
|
|
Gastrointestinal disorders
Gastrointestinal (ischemic bowel)
|
10.0%
1/10 • Number of events 1 • Post-operative period, reported up to 30+ days post CPB
Data for the Number of Participants Affected with Other Adverse Events is no longer available. Other Adverse Event Data is only available as a count of occurrences of AE's by Arm/Group.
|
0.00%
0/9 • Post-operative period, reported up to 30+ days post CPB
Data for the Number of Participants Affected with Other Adverse Events is no longer available. Other Adverse Event Data is only available as a count of occurrences of AE's by Arm/Group.
|
0.00%
0/10 • Post-operative period, reported up to 30+ days post CPB
Data for the Number of Participants Affected with Other Adverse Events is no longer available. Other Adverse Event Data is only available as a count of occurrences of AE's by Arm/Group.
|
Other adverse events
Adverse event data not reported
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place