The Effect of Adjunctive Melatonin With Colistin in Patients With Multidrug-Resistant Gram-Negative Bacterial Infections

NCT07503600 | Not Yet Recruiting Phase 3

• 1 other identifier: REC-FPFUE-NO 5/2026
• Study Type: interventional
• Target: 70
• Locations: 0 countries
• Sites: N/A

Brief Summary

This study evaluates whether adding melatonin to standard colistin therapy improves outcomes in patients with multidrug-resistant (MDR) Gram-negative bacterial infections. These infections are difficult to treat and are associated with high morbidity and mortality, particularly in critically ill patients. Colistin is often used as a last-line antibiotic for these infections; however, its effectiveness may be limited, and it is associated with side effects such as kidney injury. Melatonin, a naturally occurring hormone, has antioxidant, anti-inflammatory, and immune-modulating properties that may enhance the effectiveness of antibiotics and reduce treatment-related complications. In this randomized, double-blind, placebo-controlled study, adult patients receiving colistin will be assigned to receive either melatonin or a placebo in addition to standard care. The study will assess whether melatonin improves oxidative stress, infection control, and clinical outcomes while maintaining safety.

Conditions

Multidrug-Resistant Gram-Negative Bacterial Infections; Antimicrobial Resistance

Keywords

Gram-Negative Infections; multidrug resistance; colistin; gram negative infections

Outcome Measures

Primary Outcomes (1)

• Oxidative stress marker

  serum malondialdehyde (MDA) levels

  day 7

Secondary Outcomes (2)

• microbiological eradication

  Day 7

• inflammatory response

  Day 7

Study Arms (2)

melatonin

EXPERIMENTAL

Patients will receive oral melatonin 60 mg once daily, initiated concurrently with the administration of the colistin loading dose

Drug: Melatonin

Placebo

PLACEBO COMPARATOR

Patients will receive matching placebo capsules following the same dosing schedule.

Other: Placebo

Interventions

Melatonin DRUG

Patients will receive oral melatonin 60 mg once daily, initiated concurrently with the administration of the colistin loading dose

melatonin

Placebo OTHER

Patients will receive matching placebo capsules following the same dosing schedule.

Placebo

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Confirmed diagnosis of infection caused by multidrug-resistant Gram-negative bacteria based on microbiological culture and sensitivity testing
• Patients receiving intravenous colistin therapy according to institutional protocols
• Clinical diagnosis of sepsis or severe infection in accordance with established critical care criteria

You may not qualify if:

• Pregnancy or lactation
• Terminal medical or surgical illness (e.g., advanced malignancy)
• Severe chronic liver disease or end-stage renal failure
• Impaired cognitive function or active psychiatric illness under treatment
• Known hypersensitivity to melatonin
• Use of melatonin within 48 hours prior to enrollment

Sponsors & Collaborators

• Ain Shams University: lead

Related Publications (1)

• Mansilla-Rosello A, Hernandez-Magdalena J, Dominguez-Bastante M, Olmedo-Martin C, Comino-Pardo A, Escames G, Acuna-Castroviejo D. A phase II, single-center, double-blind, randomized placebo-controlled trial to explore the efficacy and safety of intravenous melatonin in surgical patients with severe sepsis admitted to the intensive care unit. J Pineal Res. 2023 Mar;74(2):e12845. doi: 10.1111/jpi.12845. Epub 2022 Dec 2.

  PMID: 36428216 BACKGROUND

MeSH Terms

Interventions

Melatonin

Intervention Hierarchy (Ancestors)

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

Central Study Contacts

Aalaa Kamal Shata, MD

CONTACT

+201129214940; aalaashata@yahoo.com

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: SUPPORTIVE CARE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Lecturer of Pharmacy Practice and Clinical Pharmacy

Study Record Dates

• First Submitted: March 26, 2026
• First Posted: March 31, 2026
• Study Start: March 26, 2026
• Primary Completion (Estimated): August 26, 2026
• Study Completion (Estimated): August 26, 2026
• Last Updated: March 31, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will not share