Melatonin for Renal Protection in Patients Receiving Polymyxin B

NCT03725267 | Terminated Phase 2

• 1 other identifier: 77374017.1.0000.5327
• Study Type: interventional
• Target: 88
• Locations: 1 country
• Sites: 2

Brief 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.

Conditions

Acute Kidney Injury; Melatonin; Polymyxin B Adverse Reaction

Keywords

Melatonin; Polymixin B; RIFLE; Nephrotoxicity

Outcome Measures

Primary Outcomes (1)

• Acute Kidney Injury according to RIFLE criteria

  Acute Kidney Injury measured by Risk, Injury, Failure, Loss and End Stage Renal Disease (RIFLE) score, which takes in account variations of creatinin levels and glomerular filtration rate compared to baseline values: Risk (R) increase in 1.5 times the creatinine value or decrease \>25% glomerular filtration rate; Injury (I) increase in 2.0 times the creatinine value or decrease \>50% glomerular filtration rate, Failure (F) increase in 3.0 times the creatinine value or decrease \>75% glomerular filtration rate. Due to the study follow-up time we won´t be able to evaluate Loss (L) nor End Stage Renal Disease (E)- which would require at least 4 weeks of renal function monitoring ( we will follow patients only during polymyxin B treatment, up to 14 days).The better outcome would be not fulfilling any RIFLE criteria and the worse outcome would be Failure (F).

  14 days Renal Failure.

Secondary Outcomes (3)

• Renal Failure according to RIFLE criteria

  14 days

• Kidney Injury Molecule-1 (KIM_1)

  7 days

• 30-day mortality

  30 days

Study Arms (2)

Melatonin

EXPERIMENTAL

Patients will receive 1 pill each day with 30 mg of Melatonin during polymyxin B treatment for a maximum of 14 days.

Drug: Melatonin Pill

Placebo

PLACEBO COMPARATOR

Patients will receive 1 pill each day with Placebo during polymyxin B treatment for a maximum of 14 days.

Drug: Placebo oral capsule

Interventions

Melatonin Pill DRUG

Patients will receive 1 pill of melatonin each day during polymyxin B therapy for a maximum of 14 days.

Melatonin

Placebo oral capsule DRUG

Patients will receive 1 pill of placebo each day during polymyxin B therapy for a maximum of 14 days.

Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Agreement with the consent form

You may not qualify if:

• Suspension of polymyxin B therapy with \<48hs
• Death in \<48hs
• Dialysis or Glomerular Filtration Rate (GFR) \<10 ml/min at the beginning of treatment by the Modification in Diet in Renal Disease (MDRD) formula
• Lactose intolerance
• ICU admission at the beginning of therapy
• Previous regular use of Melatonin
• Pregnancy
• Patients deprived from liberty
• Unability to receive oral medication (i.e total parenteral nutrition)

Sponsors & Collaborators

• Hospital de Clinicas de Porto Alegre: lead
• Conselho Nacional de Desenvolvimento Científico e Tecnológico: collaborator
• Pontificia Universidade Católica do Rio Grande do Sul: collaborator

Study Sites (2)

Hospital de Clinicas de Porto Alegre

Porto Alegre, Rio Grande do Sul, 90035-903, Brazil

Location

Pontificia Universidade Católica do Rio Grande do Sul

Porto Alegre, Rio Grande do Sul, 90619-900, Brazil

Location

MeSH Terms

Conditions

Acute Kidney Injury

Interventions

Melatonin

Condition Hierarchy (Ancestors)

Renal Insufficiency; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases

Intervention Hierarchy (Ancestors)

Tryptamines; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists

Study Officials

• Maria Helena P Rigatto, Professor

  Hospital de Clínicas de Porto Alegre

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Masking Details: Melatonin and placebo pills will be manipulated in identical format. The pharmacist will provide similar packets of 7 pills each numbered from 1 to 100. Each packet will have placebo or melatonin according to a randomization list previously sent from a researcher responsible (not involved with intervention). Patients will be consecutively enrolled and receive the packet following the order of one to 100.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Randomized, double blind, placebo-controlled, 2-arm parallel trial

Study Record Dates

• First Submitted: October 11, 2018
• First Posted: October 31, 2018
• Study Start: October 1, 2018
• Primary Completion: June 15, 2021
• Study Completion: July 1, 2021
• Last Updated: August 27, 2021

Record last verified: 2021-08

Locations

BR (2)