Folic Acid for Vascular Outcome Reduction In Transplantation (FAVORIT)

Cardiovascular Disease Clinical Trial

— FAVORIT  

Official title:

Folic Acid for Vascular Outcome Reduction In Transplantation (FAVORIT)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00064753
• Other study ID #: FAVORIT dk61700 IND
• Secondary ID: U01DK061700
• Status: Completed
• Phase: Phase 2/Phase 3
• First received: July 11, 2003
• Last updated: September 17, 2017
• Start date: May 2002
• Est. completion date: October 2011

Study information

• Verified date: October 2015
• Source: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 4110
• Est. completion date: October 2011
• Est. primary completion date: October 2011
• Accepts healthy volunteers: No
• Gender: All
• Age group: 35 Years to 75 Years

Eligibility

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

Related Conditions & MeSH terms

• Cardiovascular Disease
• Cardiovascular Diseases
• Chronic Kidney Disease
• Death
• Kidney Diseases
• Renal Insufficiency, Chronic

Intervention

Drug:
• High Dose Multivitamin
Vitamin B6 (Pyridoxine HCl): 50 mg Folic acid: 5.0 mg Vitamin B12: 1.0 mg Vitamin B1 (Thiamine HNO3): 1.5 mg Vitamin B2 (Riboflavin): 1.5 mg Vitamin C (Ascorbic Acid): 60 mg d-Biotin: 300 mcg Niacinamide: 20 mg Pantothenic Acid Calcium Pantothenate): 10 mg

Device:
• Low Dose Multivitamin
Vitamin B6 (Pyridoxine HCl): 1.4 mg Folic acid: 0.0 mg Vitamin B12: 2.0 mcg Vitamin B1 (Thiamine HNO3): 1.5 mg Vitamin B2 (Riboflavin): 1.5 mg Vitamin C (Ascorbic Acid): 60 mg d-Biotin: 300 mcg Niacinamide: 20 mg Pantothenic Acid Calcium Pantothenate): 10 mg

Locations

Country	Name	City	State
Brazil	Universidade Federal de Sao Paulo	Sao Paulo	SP
Canada	London Health Sciences Center	London	Ontario
Canada	Toronto General Hospital	Toronto	Ontario
United States	Albany Medical Center	Albany	New York
United States	University of Michigan Medical Center	Ann Arbor	Michigan
United States	University of Maryland Medical Center	Baltimore	Maryland
United States	University of Alabama at Birmingham School of Medicine	Birmingham	Alabama
United States	Brigham and Women's Hospital	Boston	Massachusetts
United States	State University of New York Downstate Medical Center	Brooklyn	New York
United States	Northwestern University	Chicago	Illinois
United States	The Ohio State University Medical Center	Columbus	Ohio
United States	Duke University Medical Center	Durham	North Carolina
United States	East Carolina University	Greenville	North Carolina
United States	Indiana University	Indianapolis	Indiana
United States	University of Iowa Hospitals and Clinics	Iowa City	Iowa
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	University of Wisconsin at Madison	Madison	Wisconsin
United States	Medical College of Wisconsin	Milwaukee	Wisconsin
United States	Faireview University Medical Center	Minneapolis	Minnesota
United States	Hennepin County Medical Center	Minneapolis	Minnesota
United States	Drexel University	Philadelphia	Pennsylvania
United States	Banner Good Samaritan Transplant	Phoenix	Arizona
United States	Maine Medical Center	Portland	Maine
United States	Oregon Health Sciences University	Portland	Oregon
United States	Rhode Island Hospital	Providence	Rhode Island
United States	Mayo Clinic	Rochester	Minnesota
United States	Washington University	Saint Louis	Missouri
United States	University of California at San Francisco	San Francisco	California
United States	Southern Illinois University	Springfield	Illinois

Sponsors (2)

Lead Sponsor	Collaborator
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)	Office of Dietary Supplements (ODS)

Countries where clinical trial is conducted

United States,  Brazil,  Canada, 

References & Publications (8)

Bostom AG, Carpenter MA, Hunsicker L, Jacques PF, Kusek JW, Levey AS, McKenney JL, Mercier RY, Pfeffer MA, Selhub J; FAVORIT Study Investigators. Baseline characteristics of participants in the Folic Acid for Vascular Outcome Reduction in Transplantation — View Citation

Bostom AG, Carpenter MA, Kusek JW, Hunsicker LG, Pfeffer MA, Levey AS, Jacques PF, McKenney J; FAVORIT Investigators. Rationale and design of the Folic Acid for Vascular Outcome Reduction In Transplantation (FAVORIT) trial. Am Heart J. 2006 Sep;152(3):448.e1-7. — View Citation

Bostom AG, Carpenter MA, Kusek JW, Levey AS, Hunsicker L, Pfeffer MA, Selhub J, Jacques PF, Cole E, Gravens-Mueller L, House AA, Kew C, McKenney JL, Pacheco-Silva A, Pesavento T, Pirsch J, Smith S, Solomon S, Weir M. Homocysteine-lowering and cardiovascul — View Citation

Carpenter MA, John A, Weir MR, Smith SR, Hunsicker L, Kasiske BL, Kusek JW, Bostom A, Ivanova A, Levey AS, Solomon S, Pesavento T, Weiner DE. BP, cardiovascular disease, and death in the Folic Acid for Vascular Outcome Reduction in Transplantation trial. J Am Soc Nephrol. 2014 Jul;25(7):1554-62. doi: 10.1681/ASN.2013040435. Epub 2014 Mar 13. — View Citation

Carpenter MA, Weir MR, Adey DB, House AA, Bostom AG, Kusek JW. Inadequacy of cardiovascular risk factor management in chronic kidney transplantation - evidence from the FAVORIT study. Clin Transplant. 2012 Jul-Aug;26(4):E438-46. doi: 10.1111/j.1399-0012.2012.01676.x. Epub 2012 Jul 9. — View Citation

Troen AM, Scott TM, D'Anci KE, Moorthy D, Dobson B, Rogers G, Weiner DE, Levey AS, Dallal GE, Jacques PF, Selhub J, Rosenberg IH; FACT Study Investigators. Cognitive dysfunction and depression in adult kidney transplant recipients: baseline findings from the FAVORIT Ancillary Cognitive Trial (FACT). J Ren Nutr. 2012 Mar;22(2):268-76.e1-3. doi: 10.1053/j.jrn.2011.07.009. Epub 2011 Dec 6. — View Citation

Weiner DE, Carpenter MA, Levey AS, Ivanova A, Cole EH, Hunsicker L, Kasiske BL, Kim SJ, Kusek JW, Bostom AG. Kidney function and risk of cardiovascular disease and mortality in kidney transplant recipients: the FAVORIT trial. Am J Transplant. 2012 Sep;12(9):2437-45. doi: 10.1111/j.1600-6143.2012.04101.x. Epub 2012 May 17. — View Citation

Weir MR, Gravens-Muller L, Costa N, Ivanova A, Manitpisitkul W, Bostom AG, Diamantidis CJ; FAVORIT Study Investigators. Safety events in kidney transplant recipients: results from the folic Acid for vascular outcome reduction in transplant trial. Transplantation. 2015 May;99(5):1003-8. doi: 10.1097/TP.0000000000000454. — View Citation

Outcome

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

External Links

•   FAVORIT website