Clinical trial NCT01098409: Nitrite Mediated Cardioprotection During Coronary Artery Bypass Surgery
Official title: Mechanisms of Nitrite Mediated Cardioprotection in Coronary Artery Bypass Surgery
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE2
Conditions: Coronary Artery Bypass Surgery
Keywords: sodium nitrite
coronary artery bypass surgery
cardioprotection
myocardial injury
Lead sponsor: University Hospital Birmingham NHS Foundation Trust
Sponsor class: OTHER
First posted: 2010-04-02
Enrollment: 50
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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.

Detailed 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.

Eligibility criteria: 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

Primary outcomes:
measure: Troponin T
timeFrame: 72 hours post release of aortic cross clamp
Secondary outcomes:
measure: Troponin T
timeFrame: 6 hours post release of aortic cross clamp
measure: troponin T
timeFrame: 12 hours post release of aortic cross clamp
measure: Troponin T
timeFrame: 24 hours post release of aortic cross clamp
measure: Troponin T
timeFrame: 48 hours post release of aortic cross clamp
measure: Creatinine Kinase myocardial Fraction (CKMB)
timeFrame: 6 hours post release of aortic cross clamp
measure: Creatinine Kinase myocardial Fraction (CKMB)
timeFrame: 12 hours post release of aortic cross clamp
measure: Creatinine Kinase myocardial Fraction (CKMB)
timeFrame: 24 hours post release of aortic cross clamp
measure: Creatinine Kinase myocardial Fraction (CKMB)
timeFrame: 48 hours post release of aortic cross clamp
measure: Creatinine Kinase myocardial Fraction (CKMB)
timeFrame: 72 hours post release of aortic cross clamp
measure: venous methemoglobinaemia
timeFrame: immediately before infusion of study drug
measure: plasma 8-isoprostane
timeFrame: before aortic cross clamp administration
measure: Nitric oxide metabolites in cardiac tissue
timeFrame: before aortic cross clamp application
measure: Cardiac output studies
timeFrame: upto 12 hours after release of aortic cross clamp
measure: inotrope usage
timeFrame: up to 12 hours after release of aortic cross clamp
measure: venous methemoglobinemia
timeFrame: immediately after infusion of study drug.
measure: Nitric oxide metabolites in cardiac tissue
timeFrame: before release of aortic cross clamp
measure: Nitric oxide metabolites in cardiac tissue
timeFrame: 10minutes after release of aortic cross clamp
measure: Plasma 8 isoprostane levels
timeFrame: 5minutes after discontinuation of cardiopulmonary bypass
Other outcomes:
Locations:
city: Birmingham
country: United Kingdom
facility: University Hospitals Birmingham NHS Trust
Study officials:
affiliation: University of Aberdeen
name: Michael P Frenneaux, MD
role: PRINCIPAL_INVESTIGATOR
References: