Not provided
| ID | Type | Description | Link |
|---|---|---|---|
| RG/04/005/14168 | Other Grant/Funding Number | British Heart Foundation | |
| 09/H1207/7 | Other Identifier | South Birmingham Research and Ethics Committee |
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
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.
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.
Not provided
Not provided
Not provided
Not provided
| Label | Type | Description | Intervention Names |
|---|---|---|---|
| sodium nitrite 24 hours before | Experimental |
| |
| sodium nitrite during surgery | Experimental |
| |
| 0.9% sodium chloride | Placebo Comparator |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| sodium nitrite | Drug | 0.2mcg/kg/min or 1mcg/kg/min intravenous for 30minutes at 1ml/min |
|
| Measure | Description | Time Frame |
|---|---|---|
| Troponin T | Biochemical marker of myocardial injury | 72 hours post release of aortic cross clamp |
| Measure | Description | Time Frame |
|---|---|---|
| Troponin T | 6 hours post release of aortic cross clamp | |
| troponin T | 12 hours post release of aortic cross clamp | |
| Troponin T |
Not provided
Inclusion Criteria:
Exclusion Criteria:
Not provided
Not provided
Not provided
Not provided
| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Sayqa Arif, MBChB | Contact | 0044(1)214145916 | s.arif@bham.ac.uk | |
| Robert Bonser, MD | Contact | 0044(1)214721311 | robert.bonser@uhb.nhs.uk |
| Name | Affiliation | Role |
|---|---|---|
| Michael P Frenneaux, MD | University of Aberdeen | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| University Hospitals Birmingham NHS Trust | Recruiting | Birmingham | B15 2TH | United Kingdom |
Not provided
| ID | Term |
|---|---|
| D012977 | Sodium Nitrite |
| D012965 | Sodium Chloride |
| ID | Term |
|---|---|
| D009573 | Nitrites |
| D009608 | Nitrous Acid |
| D017672 | Nitrogen Compounds |
| D007287 | Inorganic Chemicals |
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| 0.9% sodium chloride | Drug | intravenous 0.9% sodium chloride over 30minutes at 1ml/min |
|
| 24 hours post release of aortic cross clamp |
| Troponin T | 48 hours post release of aortic cross clamp |
| Creatinine Kinase myocardial Fraction (CKMB) | 6 hours post release of aortic cross clamp |
| Creatinine Kinase myocardial Fraction (CKMB) | 12 hours post release of aortic cross clamp |
| Creatinine Kinase myocardial Fraction (CKMB) | 24 hours post release of aortic cross clamp |
| Creatinine Kinase myocardial Fraction (CKMB) | 48 hours post release of aortic cross clamp |
| Creatinine Kinase myocardial Fraction (CKMB) | 72 hours post release of aortic cross clamp |
| venous methemoglobinaemia | study drug means both sodium nitrite and placebo | immediately before infusion of study drug |
| plasma 8-isoprostane | before aortic cross clamp administration |
| Nitric oxide metabolites in cardiac tissue | before aortic cross clamp application |
| Cardiac output studies | upto 12 hours after release of aortic cross clamp |
| inotrope usage | up to 12 hours after release of aortic cross clamp |
| venous methemoglobinemia | Study drug could be sodium nitrite or placebo and each infusion last 30minutes. | immediately after infusion of study drug. |
| Nitric oxide metabolites in cardiac tissue | before release of aortic cross clamp |
| Nitric oxide metabolites in cardiac tissue | 10minutes after release of aortic cross clamp |
| Plasma 8 isoprostane levels | 5minutes after discontinuation of cardiopulmonary bypass |
| D017670 |
| Sodium Compounds |
| D002712 | Chlorides |
| D006851 | Hydrochloric Acid |
| D017606 | Chlorine Compounds |