Coronary Artery Bypass SurgeryPhase 2NCT01098409
Nitrite Mediated Cardioprotection During Coronary Artery Bypass Surgery
A Phase 2 study testing sodium nitrite and 0.9% sodium chloride in people with Coronary Artery Bypass Surgery, run by University Hospital Birmingham NHS Foundation Trust at 1 site in United Kingdom.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 80 years
- Conditions the study is for
- Coronary Artery Bypass Surgery
- What is being tested?
- sodium nitrite and 0.9% sodium chloride
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 50 participants
- Where
- 1 siteUnited Kingdom
- Study dates
- Feb 2010to Jul 2012
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Patients undergoing elective first time multi-vessel coronary artery bypass surgery
- Older than 18 years of age
Who cannot join
- 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
Show all 9Show fewer
- Diabetes Mellitus
- Intended heart valve or additional surgery
- Episodes of angina or ischemia within 48hours prior to the procedure
Trial locations and contacts
1 site in 1 country.
United Kingdom1 site, 1 recruiting
- Recruiting
University Hospitals Birmingham NHS Trust
Birmingham, B15 2TH
Sayqa Arif, MBChB, 0044(1)214145916, s.arif@bham.ac.uk
Sayqa Arif, MBChB
About this study
Official title: 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.
Read the 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.
- Conditions
- Coronary Artery Bypass Surgery
- Being tested
- sodium nitrite, 0.9% sodium chloride
- Keywords
- sodium nitrite, coronary artery bypass surgery, cardioprotection, myocardial injury
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
sodium nitriteDrug
0.2mcg/kg/min or 1mcg/kg/min intravenous for 30minutes at 1ml/min
0.9% sodium chlorideDrug
intravenous 0.9% sodium chloride over 30minutes at 1ml/min
| Study group | Role | What they receive |
|---|---|---|
| sodium nitrite 24 hours before | Experimental | Not described Receives: Drug: sodium nitrite |
| sodium nitrite during surgery | Experimental | Not described Receives: Drug: sodium nitrite |
| 0.9% sodium chloride | Placebo comparator | Not described Receives: Drug: 0.9% sodium chloride |
What is being measured
The primary outcome is the main question the study is designed to answer.
Troponin T
Biochemical marker of myocardial injury
Measured: 72 hours post release of aortic cross clamp
Secondary outcomes (18)
Troponin T
Measured: 6 hours post release of aortic cross clamp
troponin T
Measured: 12 hours post release of aortic cross clamp
Troponin T
Measured: 24 hours post release of aortic cross clamp
Troponin T
Measured: 48 hours post release of aortic cross clamp
Creatinine Kinase myocardial Fraction (CKMB)
Measured: 6 hours post release of aortic cross clamp
Creatinine Kinase myocardial Fraction (CKMB)
Measured: 12 hours post release of aortic cross clamp
Creatinine Kinase myocardial Fraction (CKMB)
Measured: 24 hours post release of aortic cross clamp
Creatinine Kinase myocardial Fraction (CKMB)
Measured: 48 hours post release of aortic cross clamp
Creatinine Kinase myocardial Fraction (CKMB)
Measured: 72 hours post release of aortic cross clamp
venous methemoglobinaemia
study drug means both sodium nitrite and placebo
Measured: immediately before infusion of study drug
plasma 8-isoprostane
Measured: before aortic cross clamp administration
Nitric oxide metabolites in cardiac tissue
Measured: before aortic cross clamp application
Cardiac output studies
Measured: upto 12 hours after release of aortic cross clamp
inotrope usage
Measured: 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.
Measured: immediately after infusion of study drug.
Nitric oxide metabolites in cardiac tissue
Measured: before release of aortic cross clamp
Nitric oxide metabolites in cardiac tissue
Measured: 10minutes after release of aortic cross clamp
Plasma 8 isoprostane levels
Measured: 5minutes after discontinuation of cardiopulmonary bypass
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted2 Apr 2010 (estimated)
- Study startFeb 2010
- Primary completionJan 2012 (estimated)
- Study completionJul 2012 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Coronary Artery Bypass SurgeryStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Outcomes assessor
- Enrolment
- 50 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University Hospital Birmingham NHS Foundation Trust
- Sponsor type
- University, hospital or other
- Investigators
- Michael P Frenneaux, MD, Principal investigator, University of Aberdeen
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01098409
- Sponsor's protocol ID
- RRK3719
- Other IDs
- RG/04/005/14168, 09/H1207/7
- Status last verified
- Jan 2010
- First submitted
- 30 Mar 2010
- Last updated
- 2 Apr 2010
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 2 Apr 2010. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Mechanisms of Nitrite Mediated Cardioprotection in Coronary Artery Bypass Surgery
- ClinicalTrials.gov ID
- NCT01098409
- Acronym / sponsor ID
- RRK3719
- Conditions
- Coronary Artery Bypass Surgery
- Keywords
- sodium nitrite, coronary artery bypass surgery, cardioprotection, myocardial injury
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 50 participants (estimated)
- Lead sponsor
- University Hospital Birmingham NHS Foundation TrustUniversity, hospital or other
- Study start
- Feb 2010
- Primary completion
- Jan 2012 (estimated)
- Study completion
- Jul 2012 (estimated)
- First posted
- 2 Apr 2010 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, outcomes assessor)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| sodium nitrite 24 hours before | Experimental | Drug: sodium nitrite |
| sodium nitrite during surgery | Experimental | Drug: sodium nitrite |
| 0.9% sodium chloride | Placebo comparator | Drug: 0.9% sodium chloride |
Who may qualify
- Ages
- 18 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (2 listed)
- Patients undergoing elective first time multi-vessel coronary artery bypass surgery
- Older than 18 years of age
Key exclusion criteria (9 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| sodium nitrite0.2mcg/kg/min or 1mcg/kg/min intravenous for 30minutes at 1ml/min | Drug | sodium nitrite 24 hours before, sodium nitrite during surgery |
| 0.9% sodium chlorideintravenous 0.9% sodium chloride over 30minutes at 1ml/min | Drug | 0.9% sodium chloride |
Primary outcome
Troponin T
Time frame: 72 hours post release of aortic cross clamp
Biochemical marker of myocardial injury
18 secondary outcomes
Troponin T
Time frame: 6 hours post release of aortic cross clamp
troponin T
Time frame: 12 hours post release of aortic cross clamp
Troponin T
Time frame: 24 hours post release of aortic cross clamp
Troponin T
Time frame: 48 hours post release of aortic cross clamp
Creatinine Kinase myocardial Fraction (CKMB)
Time frame: 6 hours post release of aortic cross clamp
Creatinine Kinase myocardial Fraction (CKMB)
Time frame: 12 hours post release of aortic cross clamp
Creatinine Kinase myocardial Fraction (CKMB)
Time frame: 24 hours post release of aortic cross clamp
Creatinine Kinase myocardial Fraction (CKMB)
Time frame: 48 hours post release of aortic cross clamp
Creatinine Kinase myocardial Fraction (CKMB)
Time frame: 72 hours post release of aortic cross clamp
venous methemoglobinaemia
Time frame: immediately before infusion of study drug
plasma 8-isoprostane
Time frame: before aortic cross clamp administration
Nitric oxide metabolites in cardiac tissue
Time frame: before aortic cross clamp application
Cardiac output studies
Time frame: upto 12 hours after release of aortic cross clamp
inotrope usage
Time frame: up to 12 hours after release of aortic cross clamp
venous methemoglobinemia
Time frame: immediately after infusion of study drug.
Nitric oxide metabolites in cardiac tissue
Time frame: before release of aortic cross clamp
Nitric oxide metabolites in cardiac tissue
Time frame: 10minutes after release of aortic cross clamp
Plasma 8 isoprostane levels
Time frame: 5minutes after discontinuation of cardiopulmonary bypass
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 2 Apr 2010.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Michael P Frenneaux, MD principal investigator
University of Aberdeen
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing sodium nitrite and 0.9% sodium chloride in people with Coronary Artery Bypass Surgery, run by University Hospital Birmingham NHS Foundation Trust at 1 site in United Kingdom.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 2 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 2 Apr 2010. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Sayqa Arif, MBChB (0044(1)214145916, s.arif@bham.ac.uk), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Troponin T (time frame: 72 hours post release of aortic cross clamp). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 2 Apr 2010.