Folic Acid for Vascular Outcome Reduction In Transplantation (FAVORIT)

Phase 2

Completed

• Conditions: Cardiovascular Disease; Chronic Kidney Disease; Death
• Interventions: Drug: High Dose Multivitamin; Device: Low Dose Multivitamin

• Registration Number: NCT00064753
• Lead Sponsor: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

Brief Summary

The purpose of this randomized clinical trial is to determine if lowering homocysteine levels in renal transplant recipients with a multivitamin will reduce the occurrence of cardiovascular disease outcomes.

Detailed Description

The hypothesis of the trial is as follows: Treatment with a high dose combination of folic acid, vitamin B6, and vitamin B12 will reduce the rate of pooled arteriosclerotic cardiovascular disease outcomes (i.e., pooled occurrence of non-fatal and fatal arteriosclerotic outcomes, including coronary heart, cerebrovascular, and peripheral vascular disease events) relative to treatment with an identical multivitamin containing no folic acid, and Estimated Average Requirement amounts of vitamin B6, vitamin B12, among chronic, stable renal transplant recipients

Study Timeline

• Study Start: 2002-05
• Study First Submitted: 2003-07-11
• Study First Submitted QC: 2003-07-14
• Study First Posted: 2003-07-15
• Primary Completion: 2011-10
• Study Completion: 2011-10
• Status Verified: 2015-10
• Results First Submitted: 2015-10-26
• Results First Submitted QC: 2015-10-26
• Results First Posted: 2015-11-26
• Last Update Submitted: 2017-09-17
• Last Update Posted: 2017-10-18

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 4110

Inclusion Criteria

• 35 - 75 years old
• Had kidney transplant at least 6 months
• Calculated Creatinine Clearance must be 25 mL/min or greater
• Must be willing to stop supplements (B6, B12, folic acid) for 4-6 weeks prior to visit

Exclusion Criteria

• If pregnant or lactating

• If of child bearing potential and not on birth control

• If any of the following will limit life expectancy to less than 2 yrs:

  • Cancer
  • Congestive heart failure (CHF) (end stage)
  • Liver disease (end stage)
  • Severe pulmonary disease
  • Progressive HIV
  • Any other chronic wasting illness

• If patient had myocardial infarction (MI), stroke, lower extremity amputation above ankle or percutaneous revascularization procedure (coronary, cerebrovascular, lower extremity) in past 2months

• If patient had coronary artery bypass graft (CABG) or abdominal aortic aneurysm (AAA) in past 5 months

• If patient has conditions that prevent reliable study participation e.g., depression, alcohol or drug abuse, other cardiovascular disease (CVD) studies

• If patient has had multi-organ transplant, except kidney/pancreas

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
High Dose Multivitamin	High Dose Multivitamin	Multivitamin with increased folic acid, vitamin B6 and vitamin B12
Low Dose Multivitamin	Low Dose Multivitamin	Multivitamin devoid of folic acid and with estimated average requirement amounts of vitamin B6 and vitamin B12

Primary Outcome Measures

Name	Time	Method
Recurrent or de Novo Arteriosclerotic Cardiovascular Disease (CVD) Defined as the Occurrence of Non-fatal or Fatal Arteriosclerotic Outcomes Including Coronary Heart, Cerebrovascular, and Peripheral Vascular Disease Events	Up to 6 years (mean 4 years)

Secondary Outcome Measures

Name	Time	Method
Fatal/Non-fatal Myocardial Infarction (MI)	Up to 6 years (mean 4 years)	censored at 3 months after return to dialysis
CVD Death	Up to 6 years (mean 4 years)	censored at 3 months after return to dialysis
Coronary Artery Revascularization	Up to 6 years (mean 4 years)	censored at 3 months after return to dialysis
Resuscitated Sudden Death (RSD)	Up to 6 years (mean 4 years)	censored at 3 months after return to dialysis
Mortality (All-cause)	Up to 6 years (mean 4 years)	censored at 3 months after return to dialysis
Fatal/Non-fatal Stroke	Up to 6 years (mean 4 years)	censored at 3 months after return to dialysis
Renal Graft Failure	Up to 6 years (mean 4 years)
Lower Extremity Peripheral Arterial Disease (PAD)	Up to 6 years (mean 4 years)	censored at 3 months after return to dialysis
Carotid Endarterectomy or Angioplasty	Up to 6 years (mean 4 years)	censored at 3 months after return to dialysis
Abdominal Aortic Aneurysm Repair	Up to 6 years (mean 4 years)	censored at 3 months after return to dialysis
Renal Artery Revascularization	Up to 6 years (mean 4 years)	censored at 3 months after return to dialysis

Trial Locations

Locations (30)

Medical College of Wisconsin; 🇺🇸 Milwaukee, Wisconsin, United States

Cedars-Sinai Health System/Center for Kidney Diseases and Transplantation; 🇺🇸 Los Angeles, California, United States

University of California at Los Angeles; 🇺🇸 Los Angeles, California, United States

Northwestern University; 🇺🇸 Chicago, Illinois, United States

University of Maryland Medical Center; 🇺🇸 Baltimore, Maryland, United States

Toronto General Hospital; 🇨🇦 Toronto, Ontario, Canada

Indiana University; 🇺🇸 Indianapolis, Indiana, United States

State University of New York Downstate Medical Center; 🇺🇸 Brooklyn, New York, United States

University of California at San Francisco; 🇺🇸 San Francisco, California, United States

Banner Good Samaritan Transplant; 🇺🇸 Phoenix, Arizona, United States

University of Alabama at Birmingham School of Medicine; 🇺🇸 Birmingham, Alabama, United States

Southern Illinois University; 🇺🇸 Springfield, Illinois, United States

University of Iowa Hospitals and Clinics; 🇺🇸 Iowa City, Iowa, United States

Maine Medical Center; 🇺🇸 Portland, Maine, United States

Albany Medical Center; 🇺🇸 Albany, New York, United States

Brigham and Women's Hospital; 🇺🇸 Boston, Massachusetts, United States

University of Michigan Medical Center; 🇺🇸 Ann Arbor, Michigan, United States

Faireview University Medical Center; 🇺🇸 Minneapolis, Minnesota, United States

Mayo Clinic; 🇺🇸 Rochester, Minnesota, United States

Duke University Medical Center; 🇺🇸 Durham, North Carolina, United States

University of Wisconsin at Madison; 🇺🇸 Madison, Wisconsin, United States

Universidade Federal de Sao Paulo; 🇧🇷 Sao Paulo, SP, Brazil

Hennepin County Medical Center; 🇺🇸 Minneapolis, Minnesota, United States

London Health Sciences Center; 🇨🇦 London, Ontario, Canada

The Ohio State University Medical Center; 🇺🇸 Columbus, Ohio, United States

Washington University; 🇺🇸 Saint Louis, Missouri, United States

East Carolina University; 🇺🇸 Greenville, North Carolina, United States

Drexel University; 🇺🇸 Philadelphia, Pennsylvania, United States

Oregon Health Sciences University; 🇺🇸 Portland, Oregon, United States

Rhode Island Hospital; 🇺🇸 Providence, Rhode Island, United States