Nitrite Mediated Cardioprotection During Coronary Artery Bypass Surgery

Coronary Artery Bypass Surgery Clinical Trial

Official title:

Mechanisms of Nitrite Mediated Cardioprotection in Coronary Artery Bypass Surgery

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT01098409
• Other study ID #: RRK3719
• Secondary ID: RG/04/005/141680
• Status: Recruiting
• Phase: Phase 2
• First received: March 30, 2010
• Last updated: April 1, 2010
• Start date: February 2010
• Est. completion date: July 2012

Study information

• Verified date: January 2010
• Source: University Hospital Birmingham NHS Foundation Trust
• Contact: Sayqa Arif, MBChB
• Phone: 0044(1)214145916
• Email: s.arif[@]bham.ac.uk
• Is FDA regulated: No
• Health authority: United Kingdom: National Health Service
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to determine whether sodium nitrite administration 24 hours prior to or during coronary artery bypass surgery protects the heart better from lack of blood flow which occurs as part of this type of operation. The study will also determine what the mechanisms of this cardioprotection are.

Description:

In recent years, there has been much interest in sodium nitrite as a cytoprotective agent in in vitro and animal models. A recent study undertaken in a canine model of myocardial infarction demonstrated a 50% reduction in myocardial injury following the administration of sodium nitrite prior to the ischemic event. In humans, the setting of coronary artery bypass surgery lends itself well to study potential cytoprotective agents. During cardiac surgery, the heart undergoes a period of ischemia allowing the surgeons to operate on the heart. This is followed by a period of reperfusion which in itself can add to cellular injury. Such injury can hinder post-operative myocardial recovery.

The aim of this pilot study is to determine whether the cardioprotective effects of sodium nitrite demonstrated in animal models are translated in humans and to determine the exact underlying mechanisms of this cytoprotection. Patients undergoing coronary artery bypass grafting surgery who give written, informed consent will receive sodium nitrite 24 hours prior to surgery, during cardiac surgery or placebo. Myocardial injury will be assessed through the measurement of biochemical markers such as troponin T. Cardiac biopsy samples will be obtained to determine underlying molecular mechanisms of this cardioprotection. The other aim of this pilot study is to determine what dose of sodium nitrite (i.e. 0.2mcg/kg/min or 1mcg/kg/min) is optimal for cardioprotection. This study will form pilot data also for a larger clinical trial with clinical endpoints.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 50
• Est. completion date: July 2012
• Est. primary completion date: January 2012
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 80 Years

Eligibility

Inclusion Criteria:

• Patients undergoing elective first time multi-vessel coronary artery bypass surgery

• Older than 18 years of age

Exclusion Criteria:

• Significant psychiatric /neurological impairment that might prevent adherence to the requirements of the protocol or the ability to give informed consent

• Inability to read the Information Sheet.

• Redo operation

• Age >80 years

• Pregnancy

• Renal Impairment requiring pre-operative renal support

• Diabetes Mellitus

• Intended heart valve or additional surgery

• Episodes of angina or ischemia within 48hours prior to the procedure

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Coronary Artery Bypass Surgery

Intervention

Drug:
• sodium nitrite
0.2mcg/kg/min or 1mcg/kg/min intravenous for 30minutes at 1ml/min
• 0.9% sodium chloride
intravenous 0.9% sodium chloride over 30minutes at 1ml/min

Locations

Country	Name	City	State
United Kingdom	University Hospitals Birmingham NHS Trust	Birmingham

Sponsors (1)

Lead Sponsor	Collaborator
University Hospital Birmingham NHS Foundation Trust

Country where clinical trial is conducted

United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Troponin T	Biochemical marker of myocardial injury	72 hours post release of aortic cross clamp	No
Secondary	Troponin T		6 hours post release of aortic cross clamp	No
Secondary	troponin T		12 hours post release of aortic cross clamp	No
Secondary	Troponin T		24 hours post release of aortic cross clamp	No
Secondary	Troponin T		48 hours post release of aortic cross clamp	No
Secondary	Creatinine Kinase myocardial Fraction (CKMB)		6 hours post release of aortic cross clamp	No
Secondary	Creatinine Kinase myocardial Fraction (CKMB)		12 hours post release of aortic cross clamp	No
Secondary	Creatinine Kinase myocardial Fraction (CKMB)		24 hours post release of aortic cross clamp	No
Secondary	Creatinine Kinase myocardial Fraction (CKMB)		48 hours post release of aortic cross clamp	No
Secondary	Creatinine Kinase myocardial Fraction (CKMB)		72 hours post release of aortic cross clamp	No
Secondary	venous methemoglobinaemia	study drug means both sodium nitrite and placebo	immediately before infusion of study drug	Yes
Secondary	plasma 8-isoprostane		before aortic cross clamp administration	No
Secondary	Nitric oxide metabolites in cardiac tissue		before aortic cross clamp application	No
Secondary	Cardiac output studies		upto 12 hours after release of aortic cross clamp	No
Secondary	inotrope usage		up to 12 hours after release of aortic cross clamp	No
Secondary	venous methemoglobinemia	Study drug could be sodium nitrite or placebo and each infusion last 30minutes.	immediately after infusion of study drug.	Yes
Secondary	Nitric oxide metabolites in cardiac tissue		before release of aortic cross clamp	No
Secondary	Nitric oxide metabolites in cardiac tissue		10minutes after release of aortic cross clamp	No
Secondary	Plasma 8 isoprostane levels		5minutes after discontinuation of cardiopulmonary bypass	No