Allopurinol for Renal Transplant Associated Hypertension in Children
Drug: Allopurinol and placebo
|Study Design:||Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Crossover Assignment
Masking: Double Blind (Subject, Caregiver, Investigator)
Primary Purpose: Treatment
|Official Title:||Randomized Double-blinded, Placebo-controlled, Cross-over Trial of Allopurinol for the Treatment of Post-renal-transplant Hypertension in Children|
- Systolic Blood Pressure [ Time Frame: 2 months ] [ Designated as safety issue: No ]
- Serum Creatinine [ Time Frame: 2 months ] [ Designated as safety issue: No ]
- urinary bradykinin [ Time Frame: 2 months ] [ Designated as safety issue: No ]
- urinary nitrates [ Time Frame: 2 months ] [ Designated as safety issue: No ]
|Study Start Date:||February 2006|
|Study Completion Date:||June 2008|
|Primary Completion Date:||January 2008 (Final data collection date for primary outcome measure)|
Active Comparator: A hypertension
Hypertensive renal transplant recipients with elevated uric acid will the treated with allopurinol and placebo in an randomized cross over fashion. Subjects will serve as their own controls.
placebo capsule twice daily for one monthDrug: Allopurinol and placebo
Allopurinol 200mg twice daily for one month
The study will be a double-blind, placebo-controlled, crossover trial. We will recruit 25 children between the ages of 6 and 18 years, from the pediatric renal transplant program at Texas Children's Hospital. The study consists of three phases, a screening phase, and a treatment phase, and a crossover phase.
Clinical study design: The study will be a double-blind, placebo-controlled, crossover trial. We will recruit 25 children between the ages of 6 and 18 years, from the pediatric renal transplant program at Texas Children's Hospital. The study consists of three phases, a screening phase, and a treatment phase, and a crossover phase.
Laboratory Measurements: The laboratory measurements will be performed in the CLIA approved, clinical laboratory at Texas Children's Hospital.
Definition of high blood pressure: We will use the guidelines for blood pressure measurement that have been adapted from the Update on the Task Force Report (1987) on High Blood Pressure in Children and Adolescents . Hypertension will be defined as >95th percentile blood pressure for age, height percentile (rounded to the nearest of 5th, 10th, 25th, 50th, 75th, 90th, or 95th percentile of height above the patients actual height) and gender. Each blood pressure measurement will be the mean of 3 right arm readings, taken with an mercury sphygmomanometer at least three minutes apart with the patient sitting upright and relaxed. For the purposes of the study, to be defined as hypertensive, a patient will need to have mean systolic or diastolic blood pressure >95th percentile on three consecutive occasions, on separate days over at least a 1 week period. Patients with previously confirmed hypertension will be reconfirmed during the screening period.
Screening phase: The screening phase will last between 1 and 2 weeks. Patients will be taught to use a digital blood pressure monitor with an appropriately sized cuff and be instructed to perform daily blood pressure measurements and keep a blood pressure log. Blood tests will be done to determine eligibility based on clinical laboratory parameters. Girls who are post-menarche will have a urine pregnancy test. Each child will undergo 24hr ambulatory blood pressure monitoring during the screening phase. Children will collect urine for 24-hours for the purpose of screening urinary nitrates and bradykinin.
Phase 1: The active phase will last six weeks and include a clinic visit on the first day of the phase, laboratory testing between day 4 and 7, and weekly telephone contact throughout the phase. Subjects will receive allopurinol or placebo. Laboratory tests will be performed 4 to 7 days after starting the medication to screen for hepatic or bone marrow toxicity (AST, ALT, CBC), renal function (Cr), cyclosporin or tacrolimus level and serum uric acid. Evidence for toxicity, increased creatinine or unstable cyclosporin levels will lead to immediate discontinuation of allopurinol withdrawal from the study. The families will also be instructed to continue the daily blood pressure log started in the screening phase. At the end of the phase, prior to discontinuation of the allopurinol, children will again undergo 24hr ambulatory blood pressure monitoring. Children will repeat the 24-hour urine collection for the purpose of screening urinary nitrates and bradykinin.
Washout Phase: There will be a two-week washout interval between the allopurinol and placebo phases.
Crossover Phase: The crossover phase will identical in procedures to the active phase except that the children will be receiving allopurinol or placebo, whichever was not received in Phase 1.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00288171
|United States, Texas|
|Texas Children's Hospital|
|Houston, Texas, United States, 77030|
|Principal Investigator:||Daniel I Feig, MD, PhD||Baylor College of Medicine|