Clinical trial NCT00064753: Folic Acid for Vascular Outcome Reduction In Transplantation (FAVORIT)
Official title: Folic Acid for Vascular Outcome Reduction In Transplantation (FAVORIT)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
PHASE3
Conditions: Chronic Kidney Disease
Cardiovascular Disease
Death
Keywords: homocysteine
multi-vitamin
cardiovascular disease
renal transplant recipients
Lead sponsor: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Sponsor class: NIH
Collaborators: name: Office of Dietary Supplements (ODS)
First posted: 2003-07-15
Enrollment: 4110
Sex: ALL
Minimum age (years): 35
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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

Eligibility criteria: 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

Primary outcomes:
measure: 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
timeFrame: Up to 6 years (mean 4 years)
Secondary outcomes:
measure: Renal Graft Failure
timeFrame: Up to 6 years (mean 4 years)
measure: Mortality (All-cause)
timeFrame: Up to 6 years (mean 4 years)
measure: Fatal/Non-fatal Myocardial Infarction (MI)
timeFrame: Up to 6 years (mean 4 years)
measure: Fatal/Non-fatal Stroke
timeFrame: Up to 6 years (mean 4 years)
measure: Resuscitated Sudden Death (RSD)
timeFrame: Up to 6 years (mean 4 years)
measure: CVD Death
timeFrame: Up to 6 years (mean 4 years)
measure: Coronary Artery Revascularization
timeFrame: Up to 6 years (mean 4 years)
measure: Lower Extremity Peripheral Arterial Disease (PAD)
timeFrame: Up to 6 years (mean 4 years)
measure: Carotid Endarterectomy or Angioplasty
timeFrame: Up to 6 years (mean 4 years)
measure: Abdominal Aortic Aneurysm Repair
timeFrame: Up to 6 years (mean 4 years)
measure: Renal Artery Revascularization
timeFrame: Up to 6 years (mean 4 years)
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: University of Alabama at Birmingham School of Medicine
state: Alabama
city: Phoenix
country: United States
facility: Banner Good Samaritan Transplant
state: Arizona
city: Los Angeles
country: United States
facility: Cedars-Sinai Health System/Center for Kidney Diseases and Transplantation
state: California
city: Los Angeles
country: United States
facility: University of California at Los Angeles
state: California
city: San Francisco
country: United States
facility: University of California at San Francisco
state: California
city: Chicago
country: United States
facility: Northwestern University
state: Illinois
city: Springfield
country: United States
facility: Southern Illinois University
state: Illinois
city: Indianapolis
country: United States
facility: Indiana University
state: Indiana
city: Iowa City
country: United States
facility: University of Iowa Hospitals and Clinics
state: Iowa
city: Portland
country: United States
facility: Maine Medical Center
state: Maine
city: Baltimore
country: United States
facility: University of Maryland Medical Center
state: Maryland
city: Boston
country: United States
facility: Brigham and Women's Hospital
state: Massachusetts
city: Ann Arbor
country: United States
facility: University of Michigan Medical Center
state: Michigan
city: Minneapolis
country: United States
facility: Hennepin County Medical Center
state: Minnesota
city: Minneapolis
country: United States
facility: Faireview University Medical Center
state: Minnesota
city: Rochester
country: United States
facility: Mayo Clinic
state: Minnesota
city: Saint Louis
country: United States
facility: Washington University
state: Missouri
city: Albany
country: United States
facility: Albany Medical Center
state: New York
city: Brooklyn
country: United States
facility: State University of New York Downstate Medical Center
state: New York
city: Durham
country: United States
facility: Duke University Medical Center
state: North Carolina
city: Greenville
country: United States
facility: East Carolina University
state: North Carolina
city: Columbus
country: United States
facility: The Ohio State University Medical Center
state: Ohio
city: Portland
country: United States
facility: Oregon Health Sciences University
state: Oregon
city: Philadelphia
country: United States
facility: Drexel University
state: Pennsylvania
city: Providence
country: United States
facility: Rhode Island Hospital
state: Rhode Island
city: Madison
country: United States
facility: University of Wisconsin at Madison
state: Wisconsin
city: Milwaukee
country: United States
facility: Medical College of Wisconsin
state: Wisconsin
city: Sao Paulo
country: Brazil
facility: Universidade Federal de Sao Paulo
state: SP
city: London
country: Canada
facility: London Health Sciences Center
state: Ontario
city: Toronto
country: Canada
facility: Toronto General Hospital
state: Ontario
Study officials:
affiliation: Tufts Medical Center
name: Andrew Levey, M.D.
role: STUDY_DIRECTOR
affiliation: University of North Carolina, Chapel Hill
name: Myra A Carpenter, PhD
role: PRINCIPAL_INVESTIGATOR
References:
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.
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):268-276.e3. doi: 10.1053/j.jrn.2011.07.009. Epub 2011 Dec 6.
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.
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. doi: 10.1016/j.ahj.2006.03.004.
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.
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.
citation: 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 (FAVORIT) Trial. Am J Kidney Dis. 2009 Jan;53(1):121-8. doi: 10.1053/j.ajkd.2008.08.010. Epub 2008 Nov 20.
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 cardiovascular disease outcomes in kidney transplant recipients: primary results from the Folic Acid for Vascular Outcome Reduction in Transplantation trial. Circulation. 2011 Apr 26;123(16):1763-70. doi: 10.1161/CIRCULATIONAHA.110.000588. Epub 2011 Apr 11.
citation: Kang AW, Garber CE, Eaton CB, Risica PM, Bostom AG. Physical Activity and Cardiovascular Risk among Kidney Transplant Patients. Med Sci Sports Exerc. 2019 Jun;51(6):1154-1161. doi: 10.1249/MSS.0000000000001886.
citation: Weinrauch LA, Claggett B, Liu J, Finn PV, Weir MR, Weiner DE, D'Elia JA. Smoking and outcomes in kidney transplant recipients: a post hoc survival analysis of the FAVORIT trial. Int J Nephrol Renovasc Dis. 2018 Apr 27;11:155-164. doi: 10.2147/IJNRD.S161001. eCollection 2018.
citation: Weinrauch LA, D'Elia JA, Weir MR, Bunnapradist S, Finn PV, Liu J, Claggett B, Monaco AP. Infection and Malignancy Outweigh Cardiovascular Mortality in Kidney Transplant Recipients: Post Hoc Analysis of the FAVORIT Trial. Am J Med. 2018 Feb;131(2):165-172. doi: 10.1016/j.amjmed.2017.08.038. Epub 2017 Sep 21.