Vitamins in Nitrous Oxide Study (VINO)
|Major Surgery Coronary Artery Disease||Drug: Vitamin B12 and folic acid Drug: Nitrous oxide and placebo Other: standard of care|
|Study Design:||Allocation: Randomized
Intervention Model: Factorial Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Diagnostic
|Official Title:||Pharmacogenetics of Adverse Outcomes After Nitrous Oxide Anesthesia|
- Myocardial ischemia [ Time Frame: first 3 postoperative days ]Measured by serial troponin and ECG
- Composite endpoint of 30-day mortality and major cardiac morbidity (non-fatal MI) [ Time Frame: 30 day postoperative ]
|Study Start Date:||February 2008|
|Study Completion Date:||December 2016|
|Primary Completion Date:||December 2016 (Final data collection date for primary outcome measure)|
Vitamin B12 and folic acid
Drug: Vitamin B12 and folic acid
1 mg vitamin B12 IV 5 mg folic acid IV in 100 ml NS infusion
Placebo Comparator: Comparator
Nitrous oxide and placebo
|Drug: Nitrous oxide and placebo|
Standard of care
standard of care
|Other: standard of care|
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
Please refer to this study by its ClinicalTrials.gov identifier: NCT00655980
|United States, Missouri|
|Saint Louis, Missouri, United States, 63110|
|Principal Investigator:||Peter Nagele, MD||Washington University School of Medicine|