We are updating the design of this site. Learn more.
Show more
ClinicalTrials.gov
ClinicalTrials.gov Menu

Proteolytic Enzyme Induction Within the Human Myocardial Interstitium

This study has been completed.
Sponsor:
ClinicalTrials.gov Identifier:
NCT00744211
First Posted: August 29, 2008
Last Update Posted: November 9, 2017
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.
Collaborator:
Medical University of South Carolina
Information provided by (Responsible Party):
VA Office of Research and Development
August 27, 2008
August 29, 2008
November 7, 2014
November 9, 2017
November 9, 2017
July 2008
June 2011   (Final data collection date for primary outcome measure)
Pulmonary Vascular Resistance [ Time Frame: Baseline, 0, 6, 12 and 24 hours post-cardiopulmonary bypass (CPB) ]
Pulmonary Vascular Resistance (d.s.cm-5)
Changes in Interstitial Metalloproteinase Activity From Pre-Bypass Levels [ Time Frame: 2 hours ]
Complete list of historical versions of study NCT00744211 on ClinicalTrials.gov Archive Site
Plasma Endothelin-1 [ Time Frame: Baseline, 0, 6, 12 and 24 hours post-CPB ]
Plasma Endothelin-1 (fmol/mL)
Not Provided
  • Sitaxsentan Levels [ Time Frame: 0, 6, 12 and 24 hours post-CPB ]
    Sitaxsentan levels (microg/mL)
  • Number of Other Adverse Events By Type [ Time Frame: up to 24-hours post-CPB ]
    Other (non-serious) Adverse Events (reported by arm/group)
Not Provided
 
Proteolytic Enzyme Induction Within the Human Myocardial Interstitium
Proteolytic Enzyme Induction Within the Human Myocardial Interstitium
A robust release of endothelin-1-1 (ET) with subsequent ETA subtype receptor (ET-AR) activation occurs in patients following cardiac surgery requiring cardiopulmonary bypass (CPB). Increased ET-AR activation has been identified in patients with poor left ventricular (LV) function (reduced ejection fraction; EF). Accordingly, this study tested the hypothesis that a selective ET-AR antagonist (ET-ARA) administered peri-operatively would favorably affect post-CPB hemodynamic profiles in patients with a pre-existing poor LVEF.
Patients with a reduced LVEF were prospectively randomized, in a blinded fashion, at the time of elective coronary revascularization and/or valve replacement requiring CPB, to infusion of the highly-selective and potent ET-ARA, sitaxsentan at 1 or 2 mg/kg (IV bolus) or vehicle (saline). Infusion of the ET-ARA/vehicle was performed immediately prior to separation from CPB and again at 12 hrs post-CPB. ET and hemodynamic measurements were performed at baseline, at separation from CPB (Time 0) and at 0.5, 6, 12, 24 hrs post-CPB.
Interventional
Not Provided
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Other
Heart Disease
  • Drug: 1mg/kg sitaxsentan sodium
    1mg/kg sitaxsentan sodium (intravenous bolus) performed immediately before separation from cardiopulmonary bypass and again at 12 hours after cardiopulmonary bypass.
    Other Name: TBC11251Na
  • Drug: 2mg/kg sitaxsentan sodium
    2mg/kg sitaxsentan sodium (intravenous bolus) performed immediately before separation from cardiopulmonary bypass and again at 12 hours after cardiopulmonary bypass.
    Other Name: TBC11251Na
  • Other: Vehicle
    Intravenous bolus performed immediately before separation from cardiopulmonary bypass and again at 12 hours after cardiopulmonary bypass.
    Other Name: Saline
  • Placebo Comparator: Vehicle
    Vehicle Group
    Intervention: Other: Vehicle
  • Experimental: ET-ARA 1mg/kg
    ET-ARA 1 mg/kg
    Intervention: Drug: 1mg/kg sitaxsentan sodium
  • Experimental: ET-ARA 2mg/kg
    ET-ARA 2 mg/kg
    Intervention: Drug: 2mg/kg sitaxsentan sodium

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
29
April 2013
June 2011   (Final data collection date for primary outcome measure)

Inclusion Criteria:

  • >60 years of age
  • Body mass index <40 kg/m2
  • Left ventricular ejection fraction less than or equal to 50% documented by a pre-operative echocardiogram
  • Patients undergoing coronary artery bypass (CABG), aortic and/or mitral valve replacement or combined CABG and valve procedures requiring CPB.
  • If diabetic, be under proper control, (fasting glucose <350 mg/dL or recent hemoglobin A1c [HgbA1c] <9%).
  • If hypertensive, be on a stable medical regimen with no significant changes over the past 30 days.
  • Female of child bearing potential with a negative pregnancy test, or post-menopausal for at least 2 years
  • The patient is an appropriate study candidate as determined by the Investigator on the basis of medical history and physical examination

Exclusion Criteria:

  • Emergent revascularization
  • Previous stroke or thrombo-embolic event in the 3 months prior to study entry
  • A previous myocardial infarction within the last 7 days
  • Documented coagulopathy
  • Hepatic dysfunction as defined by aspartate transaminase (AST) or alanine transaminase (ALT) > 1.5 times the upper limit of normal
  • Patient is pregnant or breastfeeding
Sexes Eligible for Study: All
60 Years and older   (Adult, Senior)
No
Contact information is only displayed when the study is recruiting subjects
United States
 
 
NCT00744211
SURG-001-07F
Yes
Not Provided
Plan to Share IPD: No
VA Office of Research and Development
VA Office of Research and Development
Medical University of South Carolina
Principal Investigator: Francis Spinale, MD PhD Wm. Jennings Bryan Dorn VA Medical Center, Columbia, SC
VA Office of Research and Development
November 2017

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP