Clinical trial NCT05084196: Melatonin for Prevention of Kidney Injury
Official title: Melatonin for the Prevention of Antibiotic Associated Acute Kidney Injury
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE3
Conditions: Acute Kidney Injury
Adverse Drug Event
Lead sponsor: Rutgers, The State University of New Jersey
Sponsor class: OTHER
First posted: 2021-10-19
Enrollment: 300
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: This study will evaluate the safety and effectiveness of melatonin for the prevention of antibiotic associated acute kidney injury in hospitalized patients.

Detailed description: Consenting subjects meeting inclusion and exclusion will be randomized to receive melatonin 5 mg daily or a matching placebo. Study subjects will be followed for the duration of hospitalization or discontinuation of broad spectrum antibiotics (vancomycin plus piperacillin/tazobactam). The primary outcome and secondary outcomes will be evaluated by the study team.

Eligibility criteria: Inclusion criteria:

* Aged 18 to 75 years
* Currently prescribed vancomycin with the presumption that therapy will be continued for at least 3 days based on a review of subject status. Because of the critical nature of starting empiric broad-spectrum antibiotics, we will allow one dose of the antibiotic combination before consent and enrollment. This strategy is necessary for the ethical conduct of the study.

Exclusion criteria:

* Estimated creatinine clearance \< 30 mL/min
* Liver impairment (liver enzymes \> 3 times upper limit)
* Any history of allergy or contraindication to melatonin
* Pregnancy or breastfeeding
* Autoimmune disease
* Requiring vasopressors
* Requiring mechanical ventilation
* History of acute kidney injury in the past 30 days
* Inability to take oral medications
* Clinical evidence of significant unstable or uncontrolled illness which, in the opinion of the research team, could confound the results of the study or put the patient at undue risk.

Primary outcomes:
measure: Acute kidney injury
timeFrame: From date of randomization until the date of first documented acute kidney injury or date of antibiotic discontinuation, whichever came first, assessed up to 28 days
Secondary outcomes:
Other outcomes:
measure: Melatonin plasma trough concentration
timeFrame: Days 3, 5, and 7
measure: Piperacillin/tazobactam plasma trough concentration
timeFrame: Days 3, 5, and 7
measure: Vancomycin plasma Area Under the Curve (AUC)
timeFrame: Days 3, 5, and 7
measure: Association between Kidney Injury Molecule-1 (KIM-1) and serum creatinine
timeFrame: Days 3, 5, and 7
measure: Mitochondrial stress assessment via extracellular flux analysis to measure oxygen consumption rate of cells
timeFrame: Days 1 and 3
measure: Urine mitochondrial DNA copy number
timeFrame: Days 1, 3, 5, and 7
measure: Fold-change in NRF-2 gene expression in peripheral blood mononuclear cells
timeFrame: Days 1 and 5
measure: Number of subjects with NRF2 DNA single nucleotide polymorphisms
timeFrame: Day 1
measure: Number of subjects with KEAP1 DNA single nucleotide polymorphisms
timeFrame: Day 1
Locations:
city: New Brunswick
country: United States
facility: Robert Wood Johnson University Hospital
state: New Jersey
city: Somerville
country: United States
facility: Robert Wood Johnson University Hospital Somerset
state: New Jersey
Study officials:
affiliation: Rutgers, The State University of New Jersey
name: Luigi Brunetti, PhD
role: PRINCIPAL_INVESTIGATOR
References: