Clinical Trial Details
— Status: Completed
Administrative data
| NCT number |
NCT02752633 |
| Other study ID # |
RDCRN Protocol #6412 |
| Secondary ID |
2013-000975-33U5 |
| Status |
Completed |
| Phase |
Phase 4
|
| First received |
|
| Last updated |
|
| Start date |
May 2013 |
| Est. completion date |
May 2015 |
Study information
| Verified date |
December 2017 |
| Source |
Landspitali University Hospital |
| Contact |
n/a |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Interventional
|
Clinical Trial Summary
This exploratory pilot study was an open-label, crossover, single-center and non-randomized
clinical trial designed to compare the effect of the standardly employed doses of allopurinol
(400 mg/day) and febuxostat (80 mg/day) on the urinary 2,8-dihydroxyadenine (DHA) excretion
in patients with adenine phosphoribosyltransferase (APRT) deficiency.
Description:
This exploratory pilot study was an open-label, crossover, single-center and non-randomized
clinical trial designed to compare the effect of the standardly employed doses of allopurinol
(400 mg/day) and febuxostat (80 mg/day) on the urinary DHA excretion in patients with APRT
deficiency. The study was conducted between May 2013 and May 2015 as participants were
enrolled at different times. The only study site was Landspitali - The National University
Hospital of Iceland in Reykjavik, Iceland. The Data (Observational) Safety Monitoring Board
(D/OSMB) constituted by the National Institutes of Health had oversight responsibility of the
Data Safety Monitoring Plan for this clinical trial. The monitoring board reviewed accrual,
patterns and frequencies of all adverse events, and protocol compliance every 6-12 months.
All study subjects gave a written informed consent for their participation.
Study participants were recruited from a group of patients with confirmed APRT deficiency
enrolled in the National Institutes of Health supported APRT Deficiency Registry of the Rare
Kidney Stone Consortium (RKSC, http://www.rarekidneystones.org/). Confirmation of APRT
deficiency was based upon the determination of known biallelic pathogenic APRT mutations or
absent APRT enzyme activity. Participants were eligible for inclusion if they a) were
currently receiving allopurinol therapy (the currently recommended treatment for patients
with APRT deficiency); b) were willing to interrupt their allopurinol treatment for a total
of 3 weeks as outlined below and c) were at least 18 years of age. There were no other
exclusion criteria if the above inclusions criteria were met.
Study interventions After a 7-day washout period, all consenting subjects were prescribed 400
mg of allopurinol in a single daily dose for 14 days. After a second 7-day washout period,
all subjects were prescribed 80 mg febuxostat in a single daily dose for another 14 days.
Twenty-four hour and first morning urine samples were collected at the end of the first
washout period, and at the end of allopurinol and febuxostat treatment periods, respectively
(days 7, 21 and 42). To minimize the potential adverse effect of dietary purine intake on the
results, participants were asked to keep a food record while they collected the first 24 hr
urine sample and adhere to the same diet when they collected the other two 24 hr urine
samples. No further measures were taken to control dietary purine intake during the study
period. At the end of the study, all patients were advised to return to their regular
allopurinol dosing regimens.
Measurements Urinary DHA was measured using a rapid and robust ultra high power liquid
chromatography - electrospray tandem mass spectrometry (UPLC-MS/MS)), recently developed by
our group. The 24-hour urinary DHA excretion (mg/24-hours) was measured and the urinary
DHA-to-creatinine ratio (mg/mmol) in first morning urine samples was calculated. Urine and
serum creatinine concentrations were measured with an isotope dilution mass spectrometry
(IDMS) standardized laboratory method.
Outcome measures The primary trial endpoint is the 24 hr urinary DHA excretion and in
patients taking the two study drugs, allopurinol (daily dose 400 mg) and febuxostat (daily
dose 80 mg), evaluated at the conclusion of each 14 day drug treatment period.
Statistical Analysis Data are presented as urinary DHA excretion (mg/day) for timed
collections and urinary DHA-to-creatinine ratio in first morning urine samples. Data for the
whole group are presented as a median (range). Differences in the median urinary DHA
excretion and the urinary DHA-to-creatinine ratio, off pharmacotherapy and on the two study
drugs, febuxostat and allopurinol, were compared with a paired t-test.
