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Nitrite Mediated Cardioprotection During Coronary Artery Bypass Surgery

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ClinicalTrials.gov Identifier: NCT01098409
Recruitment Status : Unknown
Verified January 2010 by University Hospital Birmingham NHS Foundation Trust.
Recruitment status was:  Recruiting
First Posted : April 2, 2010
Last Update Posted : April 2, 2010
Sponsor:
Information provided by:
University Hospital Birmingham NHS Foundation Trust

Study Description
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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.

Condition or disease Intervention/treatment Phase
Coronary Artery Bypass Surgery Drug: sodium nitrite Drug: 0.9% sodium chloride Phase 2

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.

Study Design
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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 50 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Mechanisms of Nitrite Mediated Cardioprotection in Coronary Artery Bypass Surgery
Study Start Date : February 2010
Estimated Primary Completion Date : January 2012
Estimated Study Completion Date : July 2012

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Arms and Interventions
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Arm Intervention/treatment
Experimental: sodium nitrite 24 hours before Drug: sodium nitrite
0.2mcg/kg/min or 1mcg/kg/min intravenous for 30minutes at 1ml/min
Experimental: sodium nitrite during surgery Drug: sodium nitrite
0.2mcg/kg/min or 1mcg/kg/min intravenous for 30minutes at 1ml/min
Placebo Comparator: 0.9% sodium chloride Drug: 0.9% sodium chloride
intravenous 0.9% sodium chloride over 30minutes at 1ml/min


Outcome Measures
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Primary Outcome Measures :
  1. Troponin T [ Time Frame: 72 hours post release of aortic cross clamp ]
    Biochemical marker of myocardial injury


Secondary Outcome Measures :
  1. Troponin T [ Time Frame: 6 hours post release of aortic cross clamp ]
  2. troponin T [ Time Frame: 12 hours post release of aortic cross clamp ]
  3. Troponin T [ Time Frame: 24 hours post release of aortic cross clamp ]
  4. Troponin T [ Time Frame: 48 hours post release of aortic cross clamp ]
  5. Creatinine Kinase myocardial Fraction (CKMB) [ Time Frame: 6 hours post release of aortic cross clamp ]
  6. Creatinine Kinase myocardial Fraction (CKMB) [ Time Frame: 12 hours post release of aortic cross clamp ]
  7. Creatinine Kinase myocardial Fraction (CKMB) [ Time Frame: 24 hours post release of aortic cross clamp ]
  8. Creatinine Kinase myocardial Fraction (CKMB) [ Time Frame: 48 hours post release of aortic cross clamp ]
  9. Creatinine Kinase myocardial Fraction (CKMB) [ Time Frame: 72 hours post release of aortic cross clamp ]
  10. venous methemoglobinaemia [ Time Frame: immediately before infusion of study drug ]
    study drug means both sodium nitrite and placebo

  11. plasma 8-isoprostane [ Time Frame: before aortic cross clamp administration ]
  12. Nitric oxide metabolites in cardiac tissue [ Time Frame: before aortic cross clamp application ]
  13. Cardiac output studies [ Time Frame: upto 12 hours after release of aortic cross clamp ]
  14. inotrope usage [ Time Frame: up to 12 hours after release of aortic cross clamp ]
  15. venous methemoglobinemia [ Time Frame: immediately after infusion of study drug. ]
    Study drug could be sodium nitrite or placebo and each infusion last 30minutes.

  16. Nitric oxide metabolites in cardiac tissue [ Time Frame: before release of aortic cross clamp ]
  17. Nitric oxide metabolites in cardiac tissue [ Time Frame: 10minutes after release of aortic cross clamp ]
  18. Plasma 8 isoprostane levels [ Time Frame: 5minutes after discontinuation of cardiopulmonary bypass ]

Eligibility Criteria
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Ages Eligible for Study:   18 Years to 80 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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
Contacts and Locations
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To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01098409


Contacts
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Contact: Sayqa Arif, MBChB 0044(1)214145916 s.arif@bham.ac.uk
Contact: Robert Bonser, MD 0044(1)214721311 robert.bonser@uhb.nhs.uk

Locations
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United Kingdom
University Hospitals Birmingham NHS Trust Recruiting
Birmingham, United Kingdom, B15 2TH
Contact: Sayqa Arif, MBChB    0044(1)214145916    s.arif@bham.ac.uk   
Sub-Investigator: Sayqa Arif, MBChB         
Principal Investigator: Robert S Bonser, MD         
Sponsors and Collaborators
University Hospital Birmingham NHS Foundation Trust
Investigators
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Principal Investigator: Michael P Frenneaux, MD University of Aberdeen
More Information
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Responsible Party: Professor Robert Bonser, University Hospitals Birmingham NHS Trust
ClinicalTrials.gov Identifier: NCT01098409    
Other Study ID Numbers: RRK3719
RG/04/005/14168 ( Other Grant/Funding Number: British Heart Foundation )
09/H1207/7 ( Other Identifier: South Birmingham Research and Ethics Committee )
First Posted: April 2, 2010    Key Record Dates
Last Update Posted: April 2, 2010
Last Verified: January 2010
Keywords provided by University Hospital Birmingham NHS Foundation Trust:
sodium nitrite
coronary artery bypass surgery
cardioprotection
myocardial injury