Short-term Endothelin A Receptor Blockade in Patients With On-pump CABG

NCT01658410 | Unknown Phase 2 DMC

• 1 other identifier: 2010-023552-90
• Study Type: interventional
• Target: 120
• Locations: 1 country
• Sites: 1

Brief Summary

Background: Although selected cardiac surgery can be performed off-pump, the vast majority of cardiac surgical procedures today are performed with the support of cardiopulmonary bypass (CPB). Blood cardioplegia is used to protect the heart during aortic cross-clamping. However, negative effects of myocardial hypoxia during surgery are often aggravated by ischemia/reperfusion injury. In addition, cardiopulmonary bypass leads to an inflammatory response including endothelial cell activation. Comparable to the reperfusion injury following acute myocardial infarction resolved by percutaneous coronary intervention, the microcirculatory impairment observed after cardiac surgery may be caused by endothelin 1 (ET-1). ET-1 is a potent vasoconstrictor peptide upregulated in myocardial ischemia-reperfusion injury. Short-term administration of the selective ETA receptor blocker BQ-123 was found safe in a pilot study including patients with acute myocardial infarction. Hypothesis: Acute local ETA receptor blockade by intracoronary administered BQ-123 reduces myocardial injury. Methods: BQ-123 will be administered in patients undergoing on-pump aorto-coronary bypass grafting to the left anterior descending coronary artery with the use a left inner mammary artery graft and at least one vein graft. Subjects will be randomized to receive the endothelin-A receptor blocker BQ-123 or placebo administered intracoronarily in combination with cardioplegia in a double-blind manner. The primary endpoint will be enzymatic infarct size. Clinical perspective: The implementation of BQ-123 as an add-on pharmacologic therapy in cardiac surgery performed with the use of cardiopulmonary bypass could lead to improved tissue reperfusion and reduced ischemia/reperfusion injury, potentially impacting clinical long-term outcome.

Conditions

Coronary Artery Disease; Aorto-coronary Bypass Grafting

Keywords

Coronary artery disease; bypass grafting

Outcome Measures

Primary Outcomes (1)

• enzymatic infarct size

  72h

Secondary Outcomes (3)

• Catecholamines

  5h

• Liver function

  72h

• catecholamine requirement

  72h

Study Arms (2)

BQ-123

ACTIVE COMPARATOR

Drug: BQ-123

NaCl

PLACEBO COMPARATOR

Drug: NaCl

Interventions

BQ-123 DRUG

BQ-123 (Clinalfa, Läufelfingen, Switzerland) Dosage: 15µmol in two equal amounts (7.5µmol); in the first and last cardioplegia Route: intracoronary

Also known as: Cyclo(-D-Trp-D-Asp-Pro-D-Val-Leu) sodium salt

BQ-123

NaCl DRUG

NaCl, Route: intracoronary

NaCl

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients undergoing on-pump coronary artery bypass grafting using the left mammary artery to the left anterior descendent artery and at least one vein graft due to coronary artery disease, aged 18 years and above.

You may not qualify if:

• Significant liver disease (Transaminases and/or gamma-GT \> 3 fold upper limit)
• Glomerular filtration rate \<40mL/h
• History of severe congestive heart failure (Left ventricular ejection fraction \<35%)
• Current atrial fibrillation
• Significant valvular heart disease requiring valve replacement Department of Cardiac Surgery
• Primary myocardial disease
• Acute coronary syndrome or cardiogenic shock (sRR \<90mmHg or need for inotropic support)
• Women with child-bearing potential
• Subjects with contraindications for CMR (cardiac magnetic resonance)
• Inability to read, understand and sign the informed consent
• Life expectancy \<1y
• Prior organ transplantation
• Participation in a clinical trial using an investigational medical product

Sponsors & Collaborators

• Medical University of Vienna: lead

Study Sites (1)

Medical University of Vienna

Vienna, Austria, 1090, Austria

Location

MeSH Terms

Conditions

Coronary Artery Disease

Interventions

cyclo(Trp-Asp-Pro-Val-Leu)

Condition Hierarchy (Ancestors)

Coronary Disease; Myocardial Ischemia; Heart Diseases; Cardiovascular Diseases; Arteriosclerosis; Arterial Occlusive Diseases; Vascular Diseases

Study Officials

• Alfred Kocher, MD

  Medical University of Vienna

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor, Principal Investigator

Study Record Dates

• First Submitted: July 26, 2012
• First Posted: August 7, 2012
• Study Start: July 1, 2012
• Primary Completion: December 1, 2015
• Study Completion: December 1, 2016
• Last Updated: August 7, 2012

Record last verified: 2012-08

Locations

AU (1)