Expired Study
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Saint Louis, Missouri 63110


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.


Study summary:

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


Criteria:

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]


NCT ID:

NCT00655980


Primary Contact:

Principal Investigator
Peter Nagele, MD
Washington University School of Medicine


Backup Contact:

N/A


Location Contact:

Saint Louis, Missouri 63110
United States



There is no listed contact information for this specific location.

Site Status: N/A


Data Source: ClinicalTrials.gov

Date Processed: March 16, 2018

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