Nitrite Mediated Cardioprotection During Coronary Artery Bypass Surgery

University Hospital Birmingham NHS Foundation Trust

Status and phase: Unknown; Phase 2

Conditions: Coronary Artery Bypass Surgery

Treatments: Drug: 0.9% sodium chloride; Drug: sodium nitrite

Study type: Interventional

Funder types: Other

Identifiers

NCT01098409

RG/04/005/14168 (Other Grant/Funding Number)

09/H1207/7 (Other Identifier)

RRK3719

Details and patient eligibility

About

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.

Full 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.

Enrollment: 50 estimated patients

Sex: All

Ages: 18 to 80 years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

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50 participants in 3 patient groups, including a placebo group

sodium nitrite 24 hours before

Experimental group

Treatment:

Drug: sodium nitrite

sodium nitrite during surgery

Experimental group

Treatment:

Drug: sodium nitrite

0.9% sodium chloride

Placebo Comparator group

Treatment:

Drug: 0.9% sodium chloride