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Melatonin for Prevention of Kidney Injury

Primary Purpose

Acute Kidney Injury, Adverse Drug Event

Status
Recruiting
Phase
Phase 3
Locations
United States
Study Type
Interventional
Intervention
Melatonin
Placebo Capsule
Sponsored by
Rutgers, The State University of New Jersey
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional prevention trial for Acute Kidney Injury

Eligibility Criteria

18 Years - 65 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion criteria:

  • Aged 18 to 65 years
  • Currently prescribed vancomycin and piperacillin/tazobactam 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.

Sites / Locations

  • Robert Wood Johnson University Hospital SomersetRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

Melatonin Arm

Placebo Arm

Arm Description

Melatonin 5 mg capsule by mouth at bedtime for the duration of hospitalization or discontinuation of broad spectrum antibiotics, whichever comes first.

Placebo capsule by mouth at bedtime for the duration of hospitalization or discontinuation of broad spectrum antibiotics, whichever comes first.

Outcomes

Primary Outcome Measures

Acute kidney injury
Acute kidney injury will be defined as an increase in sCr from baseline of >/= 0.3 mg/dL or a >/= 50% increase from baseline.

Secondary Outcome Measures

Full Information

First Posted
September 13, 2021
Last Updated
August 10, 2023
Sponsor
Rutgers, The State University of New Jersey
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1. Study Identification

Unique Protocol Identification Number
NCT05084196
Brief Title
Melatonin for Prevention of Kidney Injury
Official Title
Melatonin for the Prevention of Antibiotic Associated Acute Kidney Injury
Study Type
Interventional

2. Study Status

Record Verification Date
August 2023
Overall Recruitment Status
Recruiting
Study Start Date
June 5, 2023 (Actual)
Primary Completion Date
January 1, 2025 (Anticipated)
Study Completion Date
January 1, 2026 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Rutgers, The State University of New Jersey

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Acute Kidney Injury, Adverse Drug Event

7. Study Design

Primary Purpose
Prevention
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare Provider
Allocation
Randomized
Enrollment
300 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Melatonin Arm
Arm Type
Experimental
Arm Description
Melatonin 5 mg capsule by mouth at bedtime for the duration of hospitalization or discontinuation of broad spectrum antibiotics, whichever comes first.
Arm Title
Placebo Arm
Arm Type
Placebo Comparator
Arm Description
Placebo capsule by mouth at bedtime for the duration of hospitalization or discontinuation of broad spectrum antibiotics, whichever comes first.
Intervention Type
Drug
Intervention Name(s)
Melatonin
Intervention Description
Melatonin 5 mg capsule by mouth at bedtime
Intervention Type
Other
Intervention Name(s)
Placebo Capsule
Intervention Description
Placebo capsule by mouth at bedtime
Primary Outcome Measure Information:
Title
Acute kidney injury
Description
Acute kidney injury will be defined as an increase in sCr from baseline of >/= 0.3 mg/dL or a >/= 50% increase from baseline.
Time Frame
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
Other Pre-specified Outcome Measures:
Title
Melatonin plasma trough concentration
Description
Evaluate the steady state plasma trough concentration of melatonin
Time Frame
Days 3, 5, and 7
Title
Piperacillin/tazobactam plasma trough concentration
Description
Evaluate the steady state plasma trough concentration of piperacillin/tazobactam
Time Frame
Days 3, 5, and 7
Title
Vancomycin plasma Area Under the Curve (AUC)
Description
Evaluate the steady state plasma AUC of vancomycin
Time Frame
Days 3, 5, and 7
Title
Association between Kidney Injury Molecule-1 (KIM-1) and serum creatinine
Description
Measure KIM-1 in plasma and urine and evaluate discordance between serum creatinine.
Time Frame
Days 3, 5, and 7
Title
Mitochondrial stress assessment via extracellular flux analysis to measure oxygen consumption rate of cells
Description
Evaluate mitochondrial stress in peripheral blood mononuclear cells from a subset of subjects in each group. In addition, mitochondrial stress will be evaluated on day 3 in a subset in the melatonin group.
Time Frame
Days 1 and 3
Title
Urine mitochondrial DNA copy number
Description
Measure mitochondrial DNA (mtDNA) in urine samples using polymerase chain reaction (PCR).
Time Frame
Days 1, 3, 5, and 7
Title
Fold-change in NRF-2 gene expression in peripheral blood mononuclear cells
Description
Measure gene expression level at baseline and then on day 5 (or last day of study if earlier) using polymerase chain reaction (PCR) and compare the fold-change from baseline between groups.
Time Frame
Days 1 and 5
Title
Number of subjects with NRF2 DNA single nucleotide polymorphisms
Description
Determination of the number of individuals with NRF2 DNA single nucleotide polymorphisms in the study population and compare the incidence of primary outcome in those with and without polymorphisms.
Time Frame
Day 1
Title
Number of subjects with KEAP1 DNA single nucleotide polymorphisms
Description
Determination of the number of individuals with KEAP1 DNA single nucleotide polymorphisms in the study population and compare the incidence of primary outcome in those with and without polymorphisms.
Time Frame
Day 1

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion criteria: Aged 18 to 65 years Currently prescribed vancomycin and piperacillin/tazobactam 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.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Luigi Brunetti, PhD
Phone
908-595-2645
Email
luigi.brunetti@rutgers.edu
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Luigi Brunetti, PhD
Organizational Affiliation
Rutgers, The State University of New Jersey
Official's Role
Principal Investigator
Facility Information:
Facility Name
Robert Wood Johnson University Hospital Somerset
City
Somerville
State/Province
New Jersey
ZIP/Postal Code
08876
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Luigi Brunetti, PhD
Phone
201-638-5868
Email
brunetti@pharmacy.rutgers.edu
First Name & Middle Initial & Last Name & Degree
Luigi Brunetti, PhD

12. IPD Sharing Statement

Plan to Share IPD
No

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Melatonin for Prevention of Kidney Injury

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