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

Brief Summary:
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.

Condition or disease Intervention/treatment Phase
Heart Disease Drug: 1mg/kg sitaxsentan sodium Drug: 2mg/kg sitaxsentan sodium Other: Vehicle Not Applicable

Detailed Description:
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.

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 29 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Other
Official Title: Proteolytic Enzyme Induction Within the Human Myocardial Interstitium
Study Start Date : July 2008
Actual Primary Completion Date : June 2011
Actual Study Completion Date : April 2013

Arm Intervention/treatment
Placebo Comparator: Vehicle
Vehicle Group
Other: Vehicle
Intravenous bolus performed immediately before separation from cardiopulmonary bypass and again at 12 hours after cardiopulmonary bypass.
Other Name: Saline

Experimental: ET-ARA 1mg/kg
ET-ARA 1 mg/kg
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

Experimental: ET-ARA 2mg/kg
ET-ARA 2 mg/kg
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




Primary Outcome Measures :
  1. Pulmonary Vascular Resistance [ Time Frame: Baseline, 0, 6, 12 and 24 hours post-cardiopulmonary bypass (CPB) ]
    Pulmonary Vascular Resistance (d.s.cm-5)


Secondary Outcome Measures :
  1. Plasma Endothelin-1 [ Time Frame: Baseline, 0, 6, 12 and 24 hours post-CPB ]
    Plasma Endothelin-1 (fmol/mL)


Other Outcome Measures:
  1. Sitaxsentan Levels [ Time Frame: 0, 6, 12 and 24 hours post-CPB ]
    Sitaxsentan levels (microg/mL)

  2. Number of Other Adverse Events By Type [ Time Frame: up to 24-hours post-CPB ]
    Other (non-serious) Adverse Events (reported by arm/group)



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Ages Eligible for Study:   60 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00744211


Locations
United States, South Carolina
Ralph H. Johnson VA Medical Center, Charleston, SC
Charleston, South Carolina, United States, 29401-5799
Sponsors and Collaborators
VA Office of Research and Development
Medical University of South Carolina
Investigators
Principal Investigator: Francis Spinale, MD PhD Wm. Jennings Bryan Dorn VA Medical Center, Columbia, SC

Publications of Results:
Responsible Party: VA Office of Research and Development
ClinicalTrials.gov Identifier: NCT00744211     History of Changes
Other Study ID Numbers: SURG-001-07F
First Posted: August 29, 2008    Key Record Dates
Results First Posted: November 9, 2017
Last Update Posted: November 9, 2017
Last Verified: November 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Additional relevant MeSH terms:
Heart Diseases
Cardiovascular Diseases
Sitaxsentan
Endothelin Receptor Antagonists
Molecular Mechanisms of Pharmacological Action