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Trial record 22 of 228 for:    EDN1

Proteolytic Enzyme Induction Within the Human Myocardial Interstitium

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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)
Hide 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
Hide 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
Hide 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
Hide 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
Layout table for Results Point of Contact information
Name/Title: Francis G. Spinale
Organization: University of South Carolina SOM
Phone: 803-777-3964
EMail: cvctrc@uscmed.sc.edu
Layout table for additonal information
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