Vitamins in Nitrous Oxide Study (VINO)
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Purpose
In this study, we want to find out if laughing gas (nitrous oxide) leads to a higher rate of cardiac complications after surgery in patients with a specific genetic profile (mutations in the MTHFR gene) and if this risk can be prevented by giving patients vitamin B12 and folate during surgery.
| Condition | Intervention |
|---|---|
|
Major Surgery Coronary Artery Disease |
Drug: Vitamin B12 and folic acid |
| Study Type: | Interventional |
| Study Design: | Allocation: Randomized Endpoint Classification: Safety Study Intervention Model: Factorial Assignment Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor) Primary Purpose: Diagnostic |
| Official Title: | Pharmacogenetics of Adverse Outcomes After Nitrous Oxide Anesthesia |
- Myocardial ischemia [ Time Frame: first 3 postoperative days ] [ Designated as safety issue: No ]Measured by serial troponin and ECG
- Composite endpoint of 30-day mortality and major cardiac morbidity (non-fatal MI) [ Time Frame: 30 day postoperative ] [ Designated as safety issue: No ]
| Estimated Enrollment: | 625 |
| Study Start Date: | February 2008 |
| Estimated Study Completion Date: | July 2012 |
| Primary Completion Date: | December 2011 (Final data collection date for primary outcome measure) |
| Arms | Assigned Interventions |
|---|---|
|
Experimental: 1
Patients receive N2O during surgery and B-vitamin before and after anesthesia
|
Drug: Vitamin B12 and folic acid
1 mg vitamin B12 IV 5 mg folic acid IV in 100 ml NS infusion
|
|
Placebo Comparator: 2
Patients receive N2O during surgery but receive NO B-vitamins but a "placebo" ( normal saline 100ml)
|
Drug: Vitamin B12 and folic acid
1 mg vitamin B12 IV 5 mg folic acid IV in 100 ml NS infusion
|
|
No Intervention: 3
Patients receive no N2O and no B-vitamins. Patients in this control group will be concurrently enrolled, not randomized, but will meet the identical inclusion and exclusion criteria
|
Detailed Description:
Background and significance: Recent studies have shown that nitrous oxide (N2O) anesthesia may be associated with an increased risk of adverse cardiovascular outcomes. It is well-known that N2O inhibits vitamin B12-dependent enzymes and as a result increases plasma homocysteine concentrations. Homocysteine has been identified as risk factor for cardiovascular disease. Therefore elevations in homocysteine after N2O may be a causative factor in N2O toxicity. In a previous investigation, we found that patients who carry a homozygous mutation in the MTHFR gene develop higher homocysteine levels after N2O anesthesia than non-carriers. These patients might be at higher risk for adverse cardiac outcomes from N2O. Thus, there may be a pharmacogenetic mechanism to account for the adverse cardiac outcomes from N2O. Moreover, prevention of N2O-increased homocysteine concentrations in these high risk patients by perioperative vitamin B12 and folate supplementation might decrease the incidence of adverse cardiac outcomes.
Hypothesis: Patients carrying a homozygous MTHFR 677C>T or 1298 A>C variant allele will have a higher incidence rate of postoperative myocardial ischemia after N2O anesthesia [detected by serial TnI measurements] due to elevated homocysteine levels than normal "wild-type" non-carriers, and that the incidence rate will be reduced if they receive perioperative vitamin B12/folate supplementation.
Primary outcome: Myocardial ischemia in the first 72 hours after surgery (measured by serial troponin and ECGs).
Secondary outcome: Composite endpoint of 30-day mortality and major cardiac morbidity (non-fatal MI)
Design: Randomized controlled trial. 500 patients will receive N2O during surgery and will be randomized to receive B-vitamins or placebo. 125 patients will receive no N2O and no B-vitamins (control arm). Mendelian randomization of MTHFR genotype.
Intervention: IV vitamin B12 (1 mg) and folate (5 mg) pre- and postoperatively
Study setting: Barnes-Jewish-Hospital, St. Louis, MO
Patients: Patients scheduled for major surgery with or at risk for coronary artery disease
Eligibility| Ages Eligible for Study: | 18 Years and older |
| Genders Eligible for Study: | Both |
| Accepts Healthy Volunteers: | No |
Inclusion Criteria:
- Adult patients; age >18 yrs, ASA III-IV
- Previously diagnosed coronary artery disease or at risk for coronary artery disease
- Scheduled for major surgery (>2 hrs)
Exclusion Criteria:
- Patients not expected to live past 24 hours (ASA 5)
- Patients with significant pulmonary disease requiring supplemental oxygen
- Patients taking supplemental vitamin B12 or folate
- Contraindication against N2O (pneumothorax, mechanical bowel obstruction, middle ear occlusion, laparoscopic surgery, raised intracranial pressure)
- Hypersensitivity to cobalamins
- Leber's disease (hereditary optic nerve atrophy) [vitamin B12 interaction]
- Seizure disorder [folate interference]
Contacts and Locations| United States, Missouri | |
| Barnes-Jewish Hospital | |
| St. Louis, Missouri, United States, 63110 | |
| Principal Investigator: | Peter Nagele, MD | Washington University School of Medicine |
More Information
No publications provided
| Responsible Party: | Peter Nagele, Assistant Professor of Anesthesiology, Washington University School of Medicine |
| ClinicalTrials.gov Identifier: | NCT00655980 History of Changes |
| Other Study ID Numbers: | HSC 07-0592 |
| Study First Received: | April 4, 2008 |
| Last Updated: | April 11, 2012 |
| Health Authority: | United States: Institutional Review Board |
Additional relevant MeSH terms:
|
Coronary Artery Disease Myocardial Ischemia Coronary Disease Heart Diseases Cardiovascular Diseases Arteriosclerosis Arterial Occlusive Diseases Vascular Diseases Folic Acid Vitamin B Complex Vitamin B 12 Hydroxocobalamin Vitamins Nitrous Oxide Micronutrients |
Growth Substances Physiological Effects of Drugs Pharmacologic Actions Hematinics Hematologic Agents Therapeutic Uses Analgesics, Non-Narcotic Analgesics Sensory System Agents Peripheral Nervous System Agents Central Nervous System Agents Anesthetics, Inhalation Anesthetics, General Anesthetics Central Nervous System Depressants |
ClinicalTrials.gov processed this record on May 19, 2013