Clinical Trial Details
— Status: Terminated
Administrative data
NCT number |
NCT03725267 |
Other study ID # |
77374017.1.0000.5327 |
Secondary ID |
|
Status |
Terminated |
Phase |
Phase 2
|
First received |
|
Last updated |
|
Start date |
October 1, 2018 |
Est. completion date |
July 1, 2021 |
Study information
Verified date |
August 2021 |
Source |
Hospital de Clinicas de Porto Alegre |
Contact |
n/a |
Is FDA regulated |
No |
Health authority |
|
Study type |
Interventional
|
Clinical Trial Summary
This study has the objective to evaluate the effect in renal function of 30mg of Melatonin
versus placebo in patients ≥18 years old treated with polymyxin B. The development of
nephrotoxicity will be evaluated by RIFLE(Risk, Injury, Failure, Loss, End stage renal
disease) score and KIM-1 urinary biomarker for the first 14 days of polymyxin B therapy.
Description:
This will be a randomized, double-blind, placebo controlled, phase 2 superiority trial.
Patients ≥18 years old admitted in two tertiary care hospitals from Porto Alegre-Brazil
receiving intravenous polymyxin B (PMB) will be included after agreeing with the informed
consent. Exclusion criteria will be use of PMB for less than 48 hours, chronic dialysis or
glomerular filtration rate <10ml/min or Intensive Care Unit (ICU) admission at baseline,
previous regular use of melatonin, pregnancy, unability to receive oral medications or
deprived from liberty individuals. All eligible patients will be consecutively recruited.
Primary outcome will be nephrotoxicity evaluated by RIFLE criteria. Secondary outcomes will
be development of Renal Failure (by RIFLE criteria), Kidney Injury Molecule-1 (KIM-1) urinary
biomarker evaluated at days 2,4 and 7 after the start of PMB and 30 day mortality. Potential
confounding factors will be evaluated, such as: demographic variables, comorbidities, PMB
dose, concomitant use of other antimicrobials, though concentration of PMB after the 4th dose
of the antibiotic.
Patients will be randomized in a 1:1 ratio by a computer system in blocks of 4 for melatonin
30mg or placebo. Analysis will be stratified by center. Patients, attending physicians and
researchers responsible for the intervention and data collection will be blinded.
Univariate analysis of variables that could potentially impact on nephrotoxicity will be done
by T-test or Wilcoxon rank-sum and Fisher test according to the variables characteristics. A
Cox regression model for time to nephrotoxicity during PMB therapy will be done, censoring
patients if death, end of therapy or completion of 14 days of PMB therapy. The main analysis
will be for intention- to-treat and a secondary per-protocol analysis will be done for
patients that received at least 80% of the planned doses. All tests will be two-sided and
P≤0.05 will be considered statistically significant.
A subgroup analysis is planned for patients with baseline glomerular filtration rate
≥60ml/min and ≥60years old.
The calculated sample size for this study is of 100 patients, 50 in each arm. An interim
analysis is planned when half of the sample is recruited (25 in each arm). If the number of
patients that achieve nephrotoxicity criteria is at least 30% less in one of the arms
compared to the other, with a P≤0,01, the study will be interrupted.