ClinicalTrials.gov
ClinicalTrials.gov Menu

Proteolytic Enzyme Induction Within the Human Myocardial Interstitium

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT00744211
Recruitment Status : Completed
First Posted : August 29, 2008
Results First Posted : November 9, 2017
Last Update Posted : November 9, 2017
Sponsor:
Collaborator:
Medical University of South Carolina
Information provided by (Responsible Party):
VA Office of Research and Development

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Double (Participant, Investigator);   Primary Purpose: Other
Condition Heart Disease
Interventions Drug: 1mg/kg sitaxsentan sodium
Drug: 2mg/kg sitaxsentan sodium
Other: Vehicle
Enrollment 29

Recruitment Details Prospective randomization in a blinded fashion, at the time of elective coronary revascularization or valve replacement requiring cardiopulmonary bypass.
Pre-assignment Details  
Arm/Group Title Vehicle ET-ARA 1mg/kg ET-ARA 2mg/kg
Hide Arm/Group Description Saline intravenous bolus 1mg/kg sitaxsentan sodium intravenous bolus 2mg/kg sitaxsentan sodium intravenous bolus
Period Title: Baseline
Started 10 9 10
Completed 10 9 10
Not Completed 0 0 0
Period Title: 0.5 Hours After Cardiopulmonary Bypass
Started 10 9 10
Completed 10 9 10
Not Completed 0 0 0
Period Title: 6 Hours After Cardiopulmonary Bypass
Started 10 9 10
Completed 10 9 10
Not Completed 0 0 0
Period Title: 12 Hours After Cardiopulmonary Bypass
Started 10 9 10
Completed 10 9 10
Not Completed 0 0 0
Period Title: 24 Hours After Cardiopulmonary Bypass
Started 10 9 10
Completed 10 9 10
Not Completed 0 0 0
Arm/Group Title Vehicle ET-ARA 1mg/kg ET-ARA 2mg/kg Total
Hide Arm/Group Description Saline, intravenous bolus 1mg/kg sitaxsentan sodium 2mg/kg sitaxsentan sodium Total of all reporting groups
Overall Number of Baseline Participants 10 9 10 29
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 10 participants 9 participants 10 participants 29 participants
67  (2) 62  (3) 68  (3) 66  (2)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 10 participants 9 participants 10 participants 29 participants
Female
1
  10.0%
2
  22.2%
0
   0.0%
3
  10.3%
Male
9
  90.0%
7
  77.8%
10
 100.0%
26
  89.7%
Left Ventricular Ejection Fraction (LVEF)  
Mean (Standard Deviation)
Unit of measure:  Percent
Number Analyzed 10 participants 9 participants 10 participants 29 participants
35  (3) 38  (2) 37  (3) 37  (2)
Plasma Endothelin  
Mean (Standard Deviation)
Unit of measure:  fmol/mL
Number Analyzed 10 participants 9 participants 10 participants 29 participants
3.9  (0.4) 3.7  (0.3) 4.3  (0.7) 4.0  (0.3)
Systemic vascular resistance  
Mean (Standard Deviation)
Unit of measure:  Dyne*second/centimeter˄5
Number Analyzed 10 participants 9 participants 10 participants 29 participants
1408  (119) 1359  (210) 1307  (112) 1358  (83)
Pulmonary vascular resistance  
Mean (Standard Deviation)
Unit of measure:  Dyne*second/centimeter˄5
Number Analyzed 10 participants 9 participants 10 participants 29 participants
153.8  (19.9) 213.0  (65.3) 174.6  (28.4) 180  (23)
1.Primary Outcome
Title Pulmonary Vascular Resistance
Hide Description Pulmonary Vascular Resistance (d.s.cm-5)
Time Frame Baseline, 0, 6, 12 and 24 hours post-cardiopulmonary bypass (CPB)
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Vehicle 1mg/kg ET-ARA 2mg/kg ET-ARA
Hide Arm/Group Description:
Vehicle group
1 mg/kg ET-ARA
2 mg/kg ET-ARA
Overall Number of Participants Analyzed 10 9 10
Mean (Standard Deviation)
Unit of Measure: dyne*second/centimeter˄5
Baseline 153.8  (19.9) 213.0  (65.3) 174.6  (28.4)
0 hours post-CPB 123.5  (20.7) 125.3  (24.8) 175.8  (26.6)
6 hours post-CPB 138.7  (28.0) 144.6  (15.2) 132.7  (17.6)
12 hours post-CPB 146.8  (21.6) 132.7  (12.7) 136.6  (17.5)
24 hours post-CPB 163.3  (26.6) 125.5  (22.3) 138.7  (20.0)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Vehicle, 1mg/kg ET-ARA, 2mg/kg ET-ARA
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.05
Comments p<0.05; Pairwise tests of individual groups means were compared by adjusted probabilities (Bonferroni method).
Method ANOVA
Comments [Not Specified]
2.Secondary Outcome
Title Plasma Endothelin-1
Hide Description Plasma Endothelin-1 (fmol/mL)
Time Frame Baseline, 0, 6, 12 and 24 hours post-CPB
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Vehicle 1mg/kg ET-ARA 2mg/kg ET-ARA
Hide Arm/Group Description:
Vehicle Group
1 mg/kg ET-ARA
2 mg/kg ET-ARA
Overall Number of Participants Analyzed 10 9 10
Mean (Standard Deviation)
Unit of Measure: fmol/mL
Baseline 3.9  (0.4) 3.7  (0.3) 4.3  (0.7)
0 hours post-CPB 5.5  (0.8) 4.7  (0.5) 4.1  (0.5)
6 hours post-CPB 8.2  (1.1) 7.2  (1.3) 7.6  (1.2)
12 hours post-CPB 8.6  (1.1) 8.8  (1.7) 10.4  (1.6)
24 hours post-CPB 8.0  (1.0) 8.3  (1.0) 8.6  (1.4)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Vehicle, 1mg/kg ET-ARA, 2mg/kg ET-ARA
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.001
Comments Pairwise tests of individual groups means were compared by adjusted probabilities (Bonferroni method).
Method ANOVA
Comments [Not Specified]
3.Other Pre-specified Outcome
Title Sitaxsentan Levels
Hide Description Sitaxsentan levels (microg/mL)
Time Frame 0, 6, 12 and 24 hours post-CPB
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title 1mg/kg ET-ARA 2mg/kg ET-ARA
Hide Arm/Group Description:
1 mg/kg ET-ARA
2 mg/kg ET-ARA
Overall Number of Participants Analyzed 9 10
Mean (Standard Deviation)
Unit of Measure: microg/mL
0 hours post-CPB 7.35  (0.83) 11.78  (1.17)
6 hours post-CPB 0.06  (0.01) 2.24  (2.13)
12 hours post-CPB 1.88  (1.26) 8.63  (3.24)
24 hours post-CPB 0.06  (0.01) 0.09  (0.01)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection 1mg/kg ET-ARA, 2mg/kg ET-ARA
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.05
Comments [Not Specified]
Method ANOVA
Comments [Not Specified]
4.Other Pre-specified Outcome
Title Number of Other Adverse Events By Type
Hide Description Other (non-serious) Adverse Events (reported by arm/group)
Time Frame up to 24-hours post-CPB
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Vehicle 1mg/kg ET-ARA 2mg/kg ET-ARA
Hide Arm/Group Description:
Vehicle group
1 mg/kg ET-ARA
2 mg/kg ET-ARA
Overall Number of Participants Analyzed 10 9 10
Measure Type: Number
Unit of Measure: events
Cardiovascular 12 20 17
Pulmonary 3 4 8
Neurological 2 0 0
Urinary 2 0 3
Gastrointestinal 9 8 8
Hepatic 0 3 1
Musculoskeletal 1 7 5
Genitourinary/Gynecological 0 0 0
Endocrine/Metabolic 1 1 5
Immunological/Allergic 0 1 0
Hematological/Lymphatic 1 4 10
Psychological/Behavioral 3 4 7
HEENT 1 0 0
Infection 3 0 2
Fever 0 3 4
Dermatological 0 3 2
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Vehicle, 1mg/kg ET-ARA, 2mg/kg ET-ARA
Comments [Not Specified]
Type of Statistical Test Equivalence
Comments Chi-square tests for differences between groups.
Statistical Test of Hypothesis P-Value 0.015
Comments P-value is associated with the hematological/lymphatic adverse event.
Method Chi-squared
Comments [Not Specified]
Time Frame Post-operative period, reported up to 30+ days post CPB
Adverse Event Reporting Description 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.
 
Arm/Group Title Vehicle ET-ARA 1mg/kg ET-ARA 2mg/kg
Hide Arm/Group Description Vehicle Group ET - ARA 1 mg / kg ET - ARA 2 mg / kg
All-Cause Mortality
Vehicle ET-ARA 1mg/kg ET-ARA 2mg/kg
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   --/--      --/--      --/--    
Show Serious Adverse Events Hide Serious Adverse Events
Vehicle ET-ARA 1mg/kg ET-ARA 2mg/kg
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   6/10 (60.00%)      6/9 (66.67%)      6/10 (60.00%)    
Blood and lymphatic system disorders       
Thrombo-embolic event  [1]  1/10 (10.00%)  1 4/9 (44.44%)  4 3/10 (30.00%)  3
Cardiac disorders       
Death  [2]  0/10 (0.00%)  0 2/9 (22.22%)  2 1/10 (10.00%)  1
Gastrointestinal disorders       
Gastrointestinal (ischemic bowel)  [1]  1/10 (10.00%)  1 0/9 (0.00%)  0 0/10 (0.00%)  0
Infections and infestations       
Pulmonary/infection  [1]  4/10 (40.00%)  4 0/9 (0.00%)  0 2/10 (20.00%)  2
Indicates events were collected by systematic assessment
[1]
When all SAE's were considered as a composite, there were no significant differences between treatment groups (Chi-square 1.59; p=0.452).
[2]
Following adjudication, all 3 deaths were determined to be unrelated to ET-ARA treatment.
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 0%
Vehicle ET-ARA 1mg/kg ET-ARA 2mg/kg
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   0/0      0/0      0/0    
Small sample size, which in turn can result in a disproportionate number of patients with greater pre-operative risk profiles randomized to one treatment group.
Certain Agreements
All Principal Investigators ARE employed by the organization sponsoring the study.
Results Point of Contact
Name/Title: Francis G. Spinale
Organization: University of South Carolina SOM
Phone: 803-777-3964
Responsible Party: VA Office of Research and Development
ClinicalTrials.gov Identifier: NCT00744211     History of Changes
Other Study ID Numbers: SURG-001-07F
First Submitted: August 27, 2008
First Posted: August 29, 2008
Results First Submitted: November 7, 2014
Results First Posted: November 9, 2017
Last Update Posted: November 9, 2017