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Folic Acid for Vascular Outcome Reduction In Transplantation (FAVORIT) (FAVORIT)

Primary Purpose

Chronic Kidney Disease, Cardiovascular Disease, Death

Status
Completed
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
High Dose Multivitamin
Low Dose Multivitamin
Sponsored by
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Chronic Kidney Disease focused on measuring homocysteine, multi-vitamin, cardiovascular disease, renal transplant recipients

Eligibility Criteria

35 Years - 75 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • University of Alabama at Birmingham School of Medicine
  • Banner Good Samaritan Transplant
  • Cedars-Sinai Health System/Center for Kidney Diseases and Transplantation
  • University of California at Los Angeles
  • University of California at San Francisco
  • Northwestern University
  • Southern Illinois University
  • Indiana University
  • University of Iowa Hospitals and Clinics
  • Maine Medical Center
  • University of Maryland Medical Center
  • Brigham and Women's Hospital
  • University of Michigan Medical Center
  • Hennepin County Medical Center
  • Faireview University Medical Center
  • Mayo Clinic
  • Washington University
  • Albany Medical Center
  • State University of New York Downstate Medical Center
  • Duke University Medical Center
  • East Carolina University
  • The Ohio State University Medical Center
  • Oregon Health Sciences University
  • Drexel University
  • Rhode Island Hospital
  • University of Wisconsin at Madison
  • Medical College of Wisconsin
  • Universidade Federal de Sao Paulo
  • London Health Sciences Center
  • Toronto General Hospital

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Active Comparator

Arm Label

High Dose Multivitamin

Low Dose Multivitamin

Arm Description

Multivitamin with increased folic acid, vitamin B6 and vitamin B12

Multivitamin devoid of folic acid and with estimated average requirement amounts of vitamin B6 and vitamin B12

Outcomes

Primary Outcome Measures

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

Secondary Outcome Measures

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

Full Information

First Posted
July 11, 2003
Last Updated
September 17, 2017
Sponsor
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Collaborators
Office of Dietary Supplements (ODS)
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1. Study Identification

Unique Protocol Identification Number
NCT00064753
Brief Title
Folic Acid for Vascular Outcome Reduction In Transplantation (FAVORIT)
Acronym
FAVORIT
Official Title
Folic Acid for Vascular Outcome Reduction In Transplantation (FAVORIT)
Study Type
Interventional

2. Study Status

Record Verification Date
October 2015
Overall Recruitment Status
Completed
Study Start Date
May 2002 (undefined)
Primary Completion Date
October 2011 (Actual)
Study Completion Date
October 2011 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Collaborators
Office of Dietary Supplements (ODS)

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

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

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Chronic Kidney Disease, Cardiovascular Disease, Death
Keywords
homocysteine, multi-vitamin, cardiovascular disease, renal transplant recipients

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2, Phase 3
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
4110 (Actual)

8. Arms, Groups, and Interventions

Arm Title
High Dose Multivitamin
Arm Type
Experimental
Arm Description
Multivitamin with increased folic acid, vitamin B6 and vitamin B12
Arm Title
Low Dose Multivitamin
Arm Type
Active Comparator
Arm Description
Multivitamin devoid of folic acid and with estimated average requirement amounts of vitamin B6 and vitamin B12
Intervention Type
Drug
Intervention Name(s)
High Dose Multivitamin
Other Intervention Name(s)
multivitamin
Intervention Description
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
Intervention Type
Device
Intervention Name(s)
Low Dose Multivitamin
Other Intervention Name(s)
multivitamin
Intervention Description
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
Primary Outcome Measure Information:
Title
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
Time Frame
Up to 6 years (mean 4 years)
Secondary Outcome Measure Information:
Title
Renal Graft Failure
Time Frame
Up to 6 years (mean 4 years)
Title
Mortality (All-cause)
Description
censored at 3 months after return to dialysis
Time Frame
Up to 6 years (mean 4 years)
Title
Fatal/Non-fatal Myocardial Infarction (MI)
Description
censored at 3 months after return to dialysis
Time Frame
Up to 6 years (mean 4 years)
Title
Fatal/Non-fatal Stroke
Description
censored at 3 months after return to dialysis
Time Frame
Up to 6 years (mean 4 years)
Title
Resuscitated Sudden Death (RSD)
Description
censored at 3 months after return to dialysis
Time Frame
Up to 6 years (mean 4 years)
Title
CVD Death
Description
censored at 3 months after return to dialysis
Time Frame
Up to 6 years (mean 4 years)
Title
Coronary Artery Revascularization
Description
censored at 3 months after return to dialysis
Time Frame
Up to 6 years (mean 4 years)
Title
Lower Extremity Peripheral Arterial Disease (PAD)
Description
censored at 3 months after return to dialysis
Time Frame
Up to 6 years (mean 4 years)
Title
Carotid Endarterectomy or Angioplasty
Description
censored at 3 months after return to dialysis
Time Frame
Up to 6 years (mean 4 years)
Title
Abdominal Aortic Aneurysm Repair
Description
censored at 3 months after return to dialysis
Time Frame
Up to 6 years (mean 4 years)
Title
Renal Artery Revascularization
Description
censored at 3 months after return to dialysis
Time Frame
Up to 6 years (mean 4 years)

10. Eligibility

Sex
All
Minimum Age & Unit of Time
35 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
No
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Andrew Levey, M.D.
Organizational Affiliation
Tufts Medical Center
Official's Role
Study Director
First Name & Middle Initial & Last Name & Degree
Myra A Carpenter, PhD
Organizational Affiliation
University of North Carolina, Chapel Hill
Official's Role
Principal Investigator
Facility Information:
Facility Name
University of Alabama at Birmingham School of Medicine
City
Birmingham
State/Province
Alabama
ZIP/Postal Code
35233
Country
United States
Facility Name
Banner Good Samaritan Transplant
City
Phoenix
State/Province
Arizona
ZIP/Postal Code
85004-1608
Country
United States
Facility Name
Cedars-Sinai Health System/Center for Kidney Diseases and Transplantation
City
Los Angeles
State/Province
California
ZIP/Postal Code
90048
Country
United States
Facility Name
University of California at Los Angeles
City
Los Angeles
State/Province
California
ZIP/Postal Code
90095-7306
Country
United States
Facility Name
University of California at San Francisco
City
San Francisco
State/Province
California
ZIP/Postal Code
94143-0780
Country
United States
Facility Name
Northwestern University
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60611
Country
United States
Facility Name
Southern Illinois University
City
Springfield
State/Province
Illinois
ZIP/Postal Code
62794-9638
Country
United States
Facility Name
Indiana University
City
Indianapolis
State/Province
Indiana
ZIP/Postal Code
46202
Country
United States
Facility Name
University of Iowa Hospitals and Clinics
City
Iowa City
State/Province
Iowa
ZIP/Postal Code
52242
Country
United States
Facility Name
Maine Medical Center
City
Portland
State/Province
Maine
ZIP/Postal Code
04102
Country
United States
Facility Name
University of Maryland Medical Center
City
Baltimore
State/Province
Maryland
ZIP/Postal Code
21201
Country
United States
Facility Name
Brigham and Women's Hospital
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02120
Country
United States
Facility Name
University of Michigan Medical Center
City
Ann Arbor
State/Province
Michigan
ZIP/Postal Code
48109-0364
Country
United States
Facility Name
Hennepin County Medical Center
City
Minneapolis
State/Province
Minnesota
ZIP/Postal Code
55404
Country
United States
Facility Name
Faireview University Medical Center
City
Minneapolis
State/Province
Minnesota
ZIP/Postal Code
55455
Country
United States
Facility Name
Mayo Clinic
City
Rochester
State/Province
Minnesota
ZIP/Postal Code
55905
Country
United States
Facility Name
Washington University
City
Saint Louis
State/Province
Missouri
ZIP/Postal Code
63110
Country
United States
Facility Name
Albany Medical Center
City
Albany
State/Province
New York
ZIP/Postal Code
12208
Country
United States
Facility Name
State University of New York Downstate Medical Center
City
Brooklyn
State/Province
New York
ZIP/Postal Code
11203
Country
United States
Facility Name
Duke University Medical Center
City
Durham
State/Province
North Carolina
ZIP/Postal Code
27710
Country
United States
Facility Name
East Carolina University
City
Greenville
State/Province
North Carolina
ZIP/Postal Code
27834
Country
United States
Facility Name
The Ohio State University Medical Center
City
Columbus
State/Province
Ohio
ZIP/Postal Code
43210-1228
Country
United States
Facility Name
Oregon Health Sciences University
City
Portland
State/Province
Oregon
ZIP/Postal Code
97201-2940
Country
United States
Facility Name
Drexel University
City
Philadelphia
State/Province
Pennsylvania
ZIP/Postal Code
19102-1192
Country
United States
Facility Name
Rhode Island Hospital
City
Providence
State/Province
Rhode Island
ZIP/Postal Code
02903
Country
United States
Facility Name
University of Wisconsin at Madison
City
Madison
State/Province
Wisconsin
ZIP/Postal Code
53792
Country
United States
Facility Name
Medical College of Wisconsin
City
Milwaukee
State/Province
Wisconsin
ZIP/Postal Code
53226
Country
United States
Facility Name
Universidade Federal de Sao Paulo
City
Sao Paulo
State/Province
SP
ZIP/Postal Code
04023-900
Country
Brazil
Facility Name
London Health Sciences Center
City
London
State/Province
Ontario
ZIP/Postal Code
N6A 5A5
Country
Canada
Facility Name
Toronto General Hospital
City
Toronto
State/Province
Ontario
ZIP/Postal Code
M5G 2N2
Country
Canada

12. IPD Sharing Statement

Plan to Share IPD
Yes
IPD Sharing Plan Description
Individual patient data and samples are available at the NIDDK Central repository
IPD Sharing Time Frame
December 2013
IPD Sharing URL
https://www.niddkrepository.org/studies/favorit/?query=favorit
Citations:
PubMed Identifier
22594581
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.
Results Reference
background
PubMed Identifier
22153382
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.
Results Reference
background
PubMed Identifier
22775763
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.
Results Reference
background
PubMed Identifier
16923411
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.
Results Reference
background
PubMed Identifier
25393158
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.
Results Reference
background
PubMed Identifier
24627349
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.
Results Reference
background
PubMed Identifier
19022547
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.
Results Reference
result
PubMed Identifier
21482964
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.
Results Reference
result
PubMed Identifier
30629045
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.
Results Reference
derived
PubMed Identifier
29760559
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.
Results Reference
derived
PubMed Identifier
28943384
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.
Results Reference
derived

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Folic Acid for Vascular Outcome Reduction In Transplantation (FAVORIT)

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