Vitamins in Nitrous Oxide Study (VINO)
|The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.|
|ClinicalTrials.gov Identifier: NCT00655980|
Recruitment Status : Completed
First Posted : April 10, 2008
Last Update Posted : December 18, 2017
|Condition or disease||Intervention/treatment||Phase|
|Major Surgery Coronary Artery Disease||Drug: Vitamin B12 and folic acid Drug: Nitrous oxide and placebo Other: standard of care||Not Applicable|
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
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||625 participants|
|Intervention Model:||Factorial Assignment|
|Masking:||Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)|
|Official Title:||Pharmacogenetics of Adverse Outcomes After Nitrous Oxide Anesthesia|
|Study Start Date :||February 2008|
|Actual Primary Completion Date :||December 2016|
|Actual Study Completion Date :||December 2016|
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|
- 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 ]
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00655980
|United States, Missouri|
|Saint Louis, Missouri, United States, 63110|
|Principal Investigator:||Peter Nagele, MD||Washington University School of Medicine|