Folic Acid for Vascular Outcome Reduction In Transplantation (FAVORIT)

Study Overview
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Brief Summary
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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
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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

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

Conditions
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Chronic Kidney Disease, Cardiovascular Disease, Death

Intervention / Treatment
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* Drug: High Dose Multivitamin
* Device: Low Dose Multivitamin


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 35 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: High Dose Multivitamin<br>Multivitamin with increased folic acid, vitamin B6 and vitamin B12 | Drug: High Dose Multivitamin<br>* 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<br>* Other names: multivitamin;|
| Active Comparator: Low Dose Multivitamin<br>Multivitamin devoid of folic acid and with estimated average requirement amounts of vitamin B6 and vitamin B12 | Device: Low Dose Multivitamin<br>* 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<br>* Other names: multivitamin;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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

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

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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homocysteine, multi-vitamin, cardiovascular disease, renal transplant recipients