Multidrug-Resistant Gram-Negative Bacterial InfectionsPhase 3NCT07503600
The Effect of Adjunctive Melatonin With Colistin in Patients With Multidrug-Resistant Gram-Negative Bacterial Infections
A Phase 3 study testing Melatonin in people with Multidrug-Resistant Gram-Negative Bacterial Infections and Antimicrobial Resistance, run by Ain Shams University.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 70 years
- Conditions the study is for
- Multidrug-Resistant Gram-Negative Bacterial Infections, Antimicrobial Resistance
- What is being tested?
- Melatonin
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 70 participants
- Where
- No sites listed yet
- Study dates
- 26 Mar 2026to 26 Aug 2026
- Phase
- Phase 3
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 70 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- • 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
Who cannot join
- • 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
Trial locations and contacts
No sites are listed yet. Contact the study team or a site near you to ask about taking part.
About this study
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.
Read the detailed description
Antimicrobial resistance is a major global health challenge, particularly among Gram-negative bacteria, which have developed resistance to multiple antibiotic classes, including last-line agents such as colistin. These infections are especially prevalent in intensive care units and are associated with poor clinical outcomes.
Given the limited development of new antibiotics, alternative strategies such as the use of adjunctive therapies are being explored. Melatonin (N-acetyl-5-methoxytryptamine) is an endogenous hormone known for its role in circadian rhythm regulation, but it also exhibits antioxidant, anti-inflammatory, and immunomodulatory effects. Emerging experimental evidence suggests that melatonin may enhance antibiotic activity and help overcome resistance mechanisms, including those affecting colistin.
This study is a prospective, randomized, double-blind, placebo-controlled clinical trial conducted in adult patients with confirmed MDR Gram-negative bacterial infections requiring intravenous colistin therapy in the intensive care setting.
Participants will be randomly assigned in a 1:1 ratio to receive either oral melatonin (60 mg once daily) or a matching placebo, initiated concurrently with colistin therapy. All patients will receive standard antimicrobial treatment and supportive care according to institutional protocols.
The primary objective is to evaluate the effect of adjunctive melatonin on oxidative stress, measured by changes in serum malondialdehyde (MDA) levels. Secondary objectives include assessment of microbiological eradication, clinical response, inflammatory markers, renal safety (including the incidence of acute kidney injury), and overall clinical outcomes such as length of stay.
This study aims to determine whether melatonin can serve as a safe and effective adjunctive therapy to improve outcomes and potentially restore the efficacy of colistin in the treatment of multidrug-resistant Gram-negative infections.
- Being tested
- Melatonin, Placebo
- Keywords
- Gram-Negative Infections, multidrug resistance, colistin, gram negative infections
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
MelatoninDrug
Patients will receive oral melatonin 60 mg once daily, initiated concurrently with the administration of the colistin loading dose
PlaceboOther
Patients will receive matching placebo capsules following the same dosing schedule.
| Study group | Role | What they receive |
|---|---|---|
| melatonin | Experimental | Patients will receive oral melatonin 60 mg once daily, initiated concurrently with the administration of the colistin loading dose Receives: Drug: Melatonin |
| Placebo | Placebo comparator | Patients will receive matching placebo capsules following the same dosing schedule. Receives: Other: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Oxidative stress marker
serum malondialdehyde (MDA) levels
Measured: day 7
Secondary outcomes (2)
microbiological eradication
Clearance of the baseline MDR Gram-negative pathogen, confirmed by negative follow-up culture
Measured: Day 7
inflammatory response
C reactive protein will be measured
Measured: Day 7
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted31 Mar 2026
- Study start26 Mar 2026 (estimated)
- Primary completion26 Aug 2026 (estimated)
- Study completion26 Aug 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Multidrug-Resistant Gram-Negative Bacterial InfectionsStudies of the same condition, open and under way.
- More trials run by Ain Shams UniversityThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Supportive care
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 70 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Ain Shams University
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Eman Mohamed El Mokadem, Ain Shams University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07503600
- Sponsor's protocol ID
- REC-FPFUE-NO 5/2026
- Status last verified
- Mar 2026
- First submitted
- 26 Mar 2026
- Last updated
- 31 Mar 2026
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
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.
PubMed 36428216
Study at a glance
From the registry record, last updated by the sponsor on 31 Mar 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Effect of Adjunctive Melatonin With Colistin in Patients With Multidrug-Resistant Gram-Negative Bacterial Infections
- ClinicalTrials.gov ID
- NCT07503600
- Acronym / sponsor ID
- REC-FPFUE-NO 5/2026
- Keywords
- Gram-Negative Infections, multidrug resistance, colistin, gram negative infections
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Not yet recruiting
- Enrolment
- 70 participants (estimated)
- Lead sponsor
- Ain Shams UniversityUniversity, hospital or other
- Study start
- 26 Mar 2026 (estimated)
- Primary completion
- 26 Aug 2026 (estimated)
- Study completion
- 26 Aug 2026 (estimated)
- First posted
- 31 Mar 2026 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
Antimicrobial resistance is a major global health challenge, particularly among Gram-negative bacteria, which have developed resistance to multiple antibiotic classes, including last-line agents such as colistin. These infections are especially prevalent in intensive care units and are associated with poor clinical outcomes.
Given the limited development of new antibiotics, alternative strategies such as the use of adjunctive therapies are being explored. Melatonin (N-acetyl-5-methoxytryptamine) is an endogenous hormone known for its role in circadian rhythm regulation, but it also exhibits antioxidant, anti-inflammatory, and immunomodulatory effects. Emerging experimental evidence suggests that melatonin may enhance antibiotic activity and help overcome resistance mechanisms, including those affecting colistin.
This study is a prospective, randomized, double-blind, placebo-controlled clinical trial conducted in adult patients with confirmed MDR Gram-negative bacterial infections requiring intravenous colistin therapy in the intensive care setting.
Participants will be randomly assigned in a 1:1 ratio to receive either oral melatonin (60 mg once daily) or a matching placebo, initiated concurrently with colistin therapy. All patients will receive standard antimicrobial treatment and supportive care according to institutional protocols.
The primary objective is to evaluate the effect of adjunctive melatonin on oxidative stress, measured by changes in serum malondialdehyde (MDA) levels. Secondary objectives include assessment of microbiological eradication, clinical response, inflammatory markers, renal safety (including the incidence of acute kidney injury), and overall clinical outcomes such as length of stay.
This study aims to determine whether melatonin can serve as a safe and effective adjunctive therapy to improve outcomes and potentially restore the efficacy of colistin in the treatment of multidrug-resistant Gram-negative infections.
Study design
- Primary purpose
- Supportive care
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| melatonin | Experimental | Drug: MelatoninPatients will receive oral melatonin 60 mg once daily, initiated concurrently with the administration of the colistin loading dose |
| Placebo | Placebo comparator | Other: PlaceboPatients will receive matching placebo capsules following the same dosing schedule. |
Who may qualify
- Ages
- 18 to 70 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- • Confirmed diagnosis of infection caused by multidrug-resistant Gram-negative bacteria based on microbiological culture and sensitivity testing
Key exclusion criteria (6 listed)
- • Pregnancy or lactation
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| MelatoninPatients will receive oral melatonin 60 mg once daily, initiated concurrently with the administration of the colistin loading dose | Drug | melatonin |
| PlaceboPatients will receive matching placebo capsules following the same dosing schedule. | Other | Placebo |
Primary outcome
Oxidative stress marker
Time frame: day 7
serum malondialdehyde (MDA) levels
2 secondary outcomes
microbiological eradication
Time frame: Day 7
inflammatory response
Time frame: Day 7
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 31 Mar 2026.
- Background: PubMed 36428216Mansilla-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.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Melatonin in people with Multidrug-Resistant Gram-Negative Bacterial Infections and Antimicrobial Resistance, run by Ain Shams University.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: opening soon, as of the sponsor's last update on 31 Mar 2026. Status can change between updates, so confirm with the study contact before making plans.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Aalaa Kamal Shata, MD (+201129214940, aalaashata@yahoo.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Oxidative stress marker (time frame: day 7). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT07503600, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 31 Mar 2026.