Vitamins in Nitrous Oxide Study
This trial is active, not recruiting.
|Conditions||major surgery, coronary artery disease|
|Treatment||vitamin b12 and folic acid|
|Sponsor||Washington University School of Medicine|
|Collaborator||National Institute of General Medical Sciences (NIGMS)|
|Start date||February 2008|
|End date||December 2011|
|Trial size||625 participants|
|Trial identifier||NCT00655980, HSC 07-0592|
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.
|Endpoint classification||safety study|
|Intervention model||factorial assignment|
|Masking||double blind (subject, caregiver, investigator, outcomes assessor)|
time frame: first 3 postoperative days
Composite endpoint of 30-day mortality and major cardiac morbidity (non-fatal MI)
time frame: 30 day postoperative
Male or female participants at least 18 years old.
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]
|Official title||Pharmacogenetics of Adverse Outcomes After Nitrous Oxide Anesthesia|
|Principal investigator||Peter Nagele, MD|
|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|
Call for more information