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Nitrite Mediated Cardioprotection During Coronary Artery Bypass Surgery

The recruitment status of this study is unknown because the information has not been verified recently.
Verified January 2010 by University Hospital Birmingham NHS Foundation Trust.
Recruitment status was  Recruiting
Sponsor:
Information provided by:
University Hospital Birmingham NHS Foundation Trust
ClinicalTrials.gov Identifier:
NCT01098409
First received: March 30, 2010
Last updated: April 1, 2010
Last verified: January 2010

March 30, 2010
April 1, 2010
February 2010
January 2012   (final data collection date for primary outcome measure)
Troponin T [ Time Frame: 72 hours post release of aortic cross clamp ] [ Designated as safety issue: No ]
Biochemical marker of myocardial injury
Same as current
Complete list of historical versions of study NCT01098409 on ClinicalTrials.gov Archive Site
  • Troponin T [ Time Frame: 6 hours post release of aortic cross clamp ] [ Designated as safety issue: No ]
  • troponin T [ Time Frame: 12 hours post release of aortic cross clamp ] [ Designated as safety issue: No ]
  • Troponin T [ Time Frame: 24 hours post release of aortic cross clamp ] [ Designated as safety issue: No ]
  • Troponin T [ Time Frame: 48 hours post release of aortic cross clamp ] [ Designated as safety issue: No ]
  • Creatinine Kinase myocardial Fraction (CKMB) [ Time Frame: 6 hours post release of aortic cross clamp ] [ Designated as safety issue: No ]
  • Creatinine Kinase myocardial Fraction (CKMB) [ Time Frame: 12 hours post release of aortic cross clamp ] [ Designated as safety issue: No ]
  • Creatinine Kinase myocardial Fraction (CKMB) [ Time Frame: 24 hours post release of aortic cross clamp ] [ Designated as safety issue: No ]
  • Creatinine Kinase myocardial Fraction (CKMB) [ Time Frame: 48 hours post release of aortic cross clamp ] [ Designated as safety issue: No ]
  • Creatinine Kinase myocardial Fraction (CKMB) [ Time Frame: 72 hours post release of aortic cross clamp ] [ Designated as safety issue: No ]
  • venous methemoglobinaemia [ Time Frame: immediately before infusion of study drug ] [ Designated as safety issue: Yes ]
    study drug means both sodium nitrite and placebo
  • plasma 8-isoprostane [ Time Frame: before aortic cross clamp administration ] [ Designated as safety issue: No ]
  • Nitric oxide metabolites in cardiac tissue [ Time Frame: before aortic cross clamp application ] [ Designated as safety issue: No ]
  • Cardiac output studies [ Time Frame: upto 12 hours after release of aortic cross clamp ] [ Designated as safety issue: No ]
  • inotrope usage [ Time Frame: up to 12 hours after release of aortic cross clamp ] [ Designated as safety issue: No ]
  • venous methemoglobinemia [ Time Frame: immediately after infusion of study drug. ] [ Designated as safety issue: Yes ]
    Study drug could be sodium nitrite or placebo and each infusion last 30minutes.
  • Nitric oxide metabolites in cardiac tissue [ Time Frame: before release of aortic cross clamp ] [ Designated as safety issue: No ]
  • Nitric oxide metabolites in cardiac tissue [ Time Frame: 10minutes after release of aortic cross clamp ] [ Designated as safety issue: No ]
  • Plasma 8 isoprostane levels [ Time Frame: 5minutes after discontinuation of cardiopulmonary bypass ] [ Designated as safety issue: No ]
Same as current
Not Provided
Not Provided
 
Nitrite Mediated Cardioprotection During Coronary Artery Bypass Surgery
Mechanisms of Nitrite Mediated Cardioprotection in Coronary Artery Bypass Surgery

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.

Interventional
Phase 2
Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Outcomes Assessor)
Primary Purpose: Treatment
Coronary Artery Bypass Surgery
  • Drug: sodium nitrite
    0.2mcg/kg/min or 1mcg/kg/min intravenous for 30minutes at 1ml/min
  • Drug: 0.9% sodium chloride
    intravenous 0.9% sodium chloride over 30minutes at 1ml/min
  • Experimental: sodium nitrite 24 hours before
    Intervention: Drug: sodium nitrite
  • Experimental: sodium nitrite during surgery
    Intervention: Drug: sodium nitrite
  • Placebo Comparator: 0.9% sodium chloride
    Intervention: Drug: 0.9% sodium chloride
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruiting
50
July 2012
January 2012   (final data collection date for primary outcome measure)

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
Both
18 Years to 80 Years
No
Contact: Sayqa Arif, MBChB 0044(1)214145916 s.arif@bham.ac.uk
Contact: Robert Bonser, MD 0044(1)214721311 robert.bonser@uhb.nhs.uk
United Kingdom
 
NCT01098409
RRK3719, RG/04/005/14168, 09/H1207/7
No
Professor Robert Bonser, University Hospitals Birmingham NHS Trust
University Hospital Birmingham NHS Foundation Trust
Not Provided
Principal Investigator: Michael P Frenneaux, MD University of Aberdeen
University Hospital Birmingham NHS Foundation Trust
January 2010

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP