WENBIT - Western Norway B Vitamin Intervention Trial
Status:
Completed
Trial end date:
2008-02-01
Target enrollment:
Participant gender:
Summary
PURPOSE OF STUDY Observational studies have demonstrated that elevated levels of plasma total
homocysteine is a risk factor for cardiovascular disease. The purpose of this trial is to
evaluate the clinical effects of homocysteine lowering treatment with B vitamins during 3-5
years follow-up of patients undergoing cardiac catheterization for suspected coronary artery
disease (CAD). Special attention will be given to complication rates among patients needing
subsequent percutaneous transluminal coronary angioplasty (PCI) or coronary artery by-pass
grafting (CABG).
HYPOTHESIS The primary hypothesis of this study is that, among patients with CAD, a daily
supplement with B vitamins will reduce the risk for cardiovascular mortality and serious
cardiovascular events with at least 20%. The secondary hypothesis of this study is that,
among patients with CAD, a daily supplement with B vitamins will reduce the risk for total
mortality, coronary events, cerebrovascular events and other cardiovascular events. The
hypothesis will be tested for an effect of any of the treatments (folic acid / vitamin B12 or
B6), and the effect will be evaluated according to initial total homocysteine levels and B
vitamin levels as well as to the change in these levels after 1 and 6 months. The sample size
has been calculated to 3088 patients using a two-sided chi-square test with significance 0.05
and at an 80% power level, presumed event rate of 22% over 4 years, and event rate reduction
of 20%, adjusted for non-compliance/drop-out of 20%.
STUDY DESIGN This is a controlled, double-blind two-centre trial with 3090 included men and
women who underwent coronary angiography at Haukeland University Hospital or Stavanger
University Hospital between April 1999 and April 2004. At baseline about 1300 patients
underwent PCI and 600 underwent CABG. The patients were randomized into 4 groups in a 2 x 2
factorial design to receive one of the following four treatments: A, folic acid 0.8 mg plus
vitamin B12 0.4 mg and vitamin B6 40 mg per day; B, folic acid 0.8 mg plus vitamin B12 0.4 mg
per day; C, vitamin B6 40 mg per day; D, placebo. The active drug and the placebo tablets had
identical appearance and taste. Treatment was started as soon as the patients were randomized
after the coronary angiography procedure. The patients have been undergoing interviews,
clinical examination and blood-sampling at baseline, at follow-up after 1 month and 1 year,
and at a final study visit. In addition, information on dietary habits was obtained from 2400
patients at baseline. Among 350 patients that have undergone PCI at baseline, a full clinical
examination, blood sampling and repeat coronary angiography to assess re-stenosis has been
performed about 9 (6-12) months after the PCI procedure. For these patients, angiograms
suitable for quantitative coronary angiography (QCA) analysis have been obtained at the
baseline and follow-up invasive procedures.
The follow-up was terminated ahead of schedule in October 2005 due to lack of compliance of
the participants caused by media reports from the NORVIT study (NCT00266487) on potential
increased cancer risk associated by B vitamin supplementation. The patients had then been
followed for 1.5 - 5 years.
STUDY END POINTS Primary clinical endpoints during follow-up are all cause death, non-fatal
acute myocardial infarction, acute hospitalization for unstable angina and non-fatal
thromboembolic stroke (infarction). Secondary endpoints are fatal and non-fatal acute
myocardial infarction (including procedure related myocardial infarction), acute
hospitalization for angina, stable angina with angiographic verified progression, myocardial
revascularization, fatal and non-fatal thromboembolic stroke.
Phase:
Phase 3
Details
Lead Sponsor:
Haukeland University Hospital
Collaborators:
Alpharma Pharmaceuticals LLC, a subsidiary of Pfizer Inc. Foundation to Promote Research into Functional Vitamin B12 Deficiency, Bergen, Norway Locus for Cardiac Research, University of Bergen, Norway Locus for Homocysteine and Related Vitamins, University of Bergen, Norway Norwegian Foundation for Health and Rehabilitation Norwegian Heart and Lung Patient Organisation The Research Council of Norway The Royal Norwegian Ministry of Health
Treatments:
Folic Acid Hydroxocobalamin Pyridoxal Pyridoxine Vitamin B 12 Vitamin B 6 Vitamin B Complex Vitamins