Nitrite Mediated Cardioprotection During Coronary Artery Bypass Surgery

April 1, 2010 updated by: University Hospital Birmingham NHS Foundation Trust

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.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Unknown

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

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 Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Anticipated)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
50

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.

Study Contact Backup

Study Locations

  • United Kingdom
      • Birmingham, United Kingdom, B15 2TH
        • Recruiting
        • University Hospitals Birmingham NHS Trust
        • Contact:
        • Sub-Investigator:
          • Sayqa Arif, MBChB
        • Principal Investigator:
          • Robert S Bonser, MD

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years to 80 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Double

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
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

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Troponin T
Time Frame: 72 hours post release of aortic cross clamp
Biochemical marker of myocardial injury
72 hours post release of aortic cross clamp

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Troponin T
Time Frame: 6 hours post release of aortic cross clamp
6 hours post release of aortic cross clamp
troponin T
Time Frame: 12 hours post release of aortic cross clamp
12 hours post release of aortic cross clamp
Troponin T
Time Frame: 24 hours post release of aortic cross clamp
24 hours post release of aortic cross clamp
Troponin T
Time Frame: 48 hours post release of aortic cross clamp
48 hours post release of aortic cross clamp
Creatinine Kinase myocardial Fraction (CKMB)
Time Frame: 6 hours post release of aortic cross clamp
6 hours post release of aortic cross clamp
Creatinine Kinase myocardial Fraction (CKMB)
Time Frame: 12 hours post release of aortic cross clamp
12 hours post release of aortic cross clamp
Creatinine Kinase myocardial Fraction (CKMB)
Time Frame: 24 hours post release of aortic cross clamp
24 hours post release of aortic cross clamp
Creatinine Kinase myocardial Fraction (CKMB)
Time Frame: 48 hours post release of aortic cross clamp
48 hours post release of aortic cross clamp
Creatinine Kinase myocardial Fraction (CKMB)
Time Frame: 72 hours post release of aortic cross clamp
72 hours post release of aortic cross clamp
venous methemoglobinaemia
Time Frame: immediately before infusion of study drug
study drug means both sodium nitrite and placebo
immediately before infusion of study drug
plasma 8-isoprostane
Time Frame: before aortic cross clamp administration
before aortic cross clamp administration
Nitric oxide metabolites in cardiac tissue
Time Frame: before aortic cross clamp application
before aortic cross clamp application
Cardiac output studies
Time Frame: upto 12 hours after release of aortic cross clamp
upto 12 hours after release of aortic cross clamp
inotrope usage
Time Frame: up to 12 hours after release of aortic cross clamp
up to 12 hours after release of aortic cross clamp
venous methemoglobinemia
Time Frame: immediately after infusion of study drug.
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
Time Frame: before release of aortic cross clamp
before release of aortic cross clamp
Nitric oxide metabolites in cardiac tissue
Time Frame: 10minutes after release of aortic cross clamp
10minutes after release of aortic cross clamp
Plasma 8 isoprostane levels
Time Frame: 5minutes after discontinuation of cardiopulmonary bypass
5minutes after discontinuation of cardiopulmonary bypass

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
University Hospital Birmingham NHS Foundation Trust

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Michael P Frenneaux, MD, University of Aberdeen

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
February 1, 2010

Primary Completion (Anticipated)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
January 1, 2012

Study Completion (Anticipated)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
July 1, 2012

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
March 30, 2010

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
April 1, 2010

First Posted (Estimate)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
April 2, 2010

Study Record Updates

Last Update Posted (Estimate)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
April 2, 2010

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
April 1, 2010

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
January 1, 2010

More Information

Terms related to this study

Keywords

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • RRK3719
  • RG/04/005/14168 (Other Grant/Funding Number: British Heart Foundation)
  • 09/H1207/7 (Other Identifier: South Birmingham Research and Ethics Committee)

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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