Critical Ill PatientsPhase 2/3NCT06843668
Different Dosing Strategies of Colistin in Multidrug-Resistant Gram-Negative Bacilli Infections
A Phase 2/3 study testing EMA colistin dosing strategy and US FDA colistin dosing strategy in people with Critical Ill Patients and Multi Drug Resistant, run by Mansoura University at 1 site in Saudi Arabia.
Trial summary
Nosocomial infections caused by multi-drug-resistant (MDR) and extensively drug-resistant (XDR) Gram-negative pathogens represent a major threat worldwide. The increasing trend of multi-drug resistance in Gram-negative bacteria (MDR-GNB) poses a particularly acute challenge to health systems especially in critically… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Critical Ill Patients, Multi Drug Resistant
- What is being tested?
- EMA colistin dosing strategy and US FDA colistin dosing strategy
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 120 participants
- Where
- 1 siteSaudi Arabia
- Study dates
- 25 Dec 2023to 25 Oct 2025
- Phase
- Phase 2/3
- 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 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Patients age ≥ 18 years old.
- Patients who will be treated with CMS for MR GNB infections.
- Patients who are admitted to the ICUs.
Who cannot join
- Known hypersensitivity to colistin.
- Pregnant and lactating women.
- Patients who are treated with colistin for < 24 hours.
- Patients with myasthenia gravis or concomitant anesthetics or neuromuscular blocking drugs.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Saudi Arabia1 site, 1 recruiting
- Recruiting
King Fahad Specialist Hospital
Buraidah
Ayman A Alharbi, phd, 00966540865609, Dr.aymn.a.h@gmail.com
About this study
Official title: Efficacy and Safety of Different Dosing Strategies of Colistin in Multidrug-Resistant Gram-Negative Bacilli Infections in Critically Ill Patients
Nosocomial infections caused by multi-drug-resistant (MDR) and extensively drug-resistant (XDR) Gram-negative pathogens represent a major threat worldwide. The increasing trend of multi-drug resistance in Gram-negative bacteria (MDR-GNB) poses a particularly acute challenge to health systems especially in critically ill patients.
Patients in intensive care units (ICUs) have encountered an increasing emergence and spread of antibiotic-resistant pathogens. In Saudi Arabia mainly MDR-GNB such as Acinetobacter Baumannii, Pseudomonas Aeruginosa, Klebsiella Pnemoniae and Enterobacter are observed in ICUs.
Read more
Polymyxins are the last line therapy in the treatment of infection caused by these MDR-GNB. Colistin is the most widely used polymyxin antibiotic, it is administered as inactive prodrug colistimethate sodium (CMS) that is hydrolyzed to an active moiety of colistin base activity (CBA). It acts as cationic detergent and damages bacterial cytoplasmic membrane causing leaking of intracellular substances and then cell death.
During the first years of their use, polymyxin-associated neurotoxicity occurred in patients with an incidence as high as 27% following parenteral administration. However, other retrospective clinical trials have not exposed neurotoxicity to be a major concern. On the other hand, nephrotoxicity is by far the most common and dose-limiting side effect associated with parenteral polymyxins, with incidence rates in patients as high as 60%. Despite the high incidence of colistin induced nephrotoxicity, in 2012, the World Health Organization (WHO) reclassified polymyxins as critically important for the management of MDR-GNB infection, renewing the interest in these antibiotics.
To the best of our knowledge no study compared the efficacy and safety of both dosing strategies in critically ill patients. Moreover, there is still a lack of evidence on the efficacy and safety of both dosing strategies in obese patients. Therefore, this study aims at comparing the efficacy and toxicity of both strategies in colistin dosing (the fixed dose and the weight-based dosing) in obese patients and non- obese patients.
- Conditions
- Critical Ill Patients, Multi Drug Resistant
- Being tested
- EMA colistin dosing strategy, US FDA colistin dosing strategy
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
EMA colistin dosing strategyDrug
The EMA colistin group will receive I.V colistin based on creatinine clearance (mL/min) level , with fixed loading dose 9 MIU equivalent to 300 mg of colistin-based activity (CBA). The maintenance dose will be administered after 12 h following the loading dose over 1 h every 12h (twice daily).
US FDA colistin dosing strategyDrug
The weight-based colistin group will receive I.V. colistin based on the lower (ideal body weight or actual body weight) with a loading dose of (4) X (patient weight in kg). Loading dose might exceed 300 mg.
| Study group | Role | What they receive |
|---|---|---|
| The EMA (fixed dose) colistin group | Experimental | The EMA colistin group will receive I.V colistin using fixed dose strategy. Receives: Drug: EMA colistin dosing strategy |
| US FDA (weight-based dose) colistin group | Active comparator | The weight-based colistin group will receive I.V. colistin using weight based dosing strategy. Receives: Drug: US FDA colistin dosing strategy |
What is being measured
The primary outcome is the main question the study is designed to answer.
Clinical and microbiological success in eradication of infection reported as the number and percentage of patients with successful clinical improvement and microbiological clearance (Efficacy).
having a white blood cell count (WBC) of less than 12,000 cells/mm3 or a ≥ 25% reduction in WBC, being afebrile for ≥ 48 h,.
- Microbiological clearance will be defined as eradication of the original causative organism from subsequent blood cultures by day 14 of therapy.
Measured: 14 days post colistin initiation.
Secondary outcomes (1)
Nephrotoxicity (Safety)
nephrotoxicity was defined as doubling of baseline serum creatinine level or drop-in baseline creatinine clearance rate by ≥50%.
Measured: 14 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted25 Feb 2025
- Study start25 Dec 2023
- Primary completion25 Sep 2025 (estimated)
- Study completion25 Oct 2025 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Critical Ill PatientsStudies of the same condition, open and under way.
- More trials run by Mansoura 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 2/3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- This is a prospective, single blind, randomized, comparative intervention study .
- Masking
- Single blind
- Who is masked
- Participant
- Enrolment
- 120 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Mansoura University
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Mona Mohammed El-Tamalawy, Mansoura University
- Investigators
- Mohamed E Shams, Professor, Principal investigator, Mansoura University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06843668
- Sponsor's protocol ID
- H-04-Q001
- Status last verified
- Feb 2025
- First submitted
- 13 Feb 2025
- Last updated
- 4 Jul 2025
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Li J, Nation RL, Turnidge JD, Milne RW, Coulthard K, Rayner CR, Paterson DL. Colistin: the re-emerging antibiotic for multidrug-resistant Gram-negative bacterial infections. Lancet Infect Dis. 2006 Sep;6(9):589-601. doi: 10.1016/S1473-3099(06)70580-1.
PubMed 16931410Maraki S, Mantadakis E, Nioti E, Samonis G. Susceptibility of 2,252 Pseudomonas aeruginosa Clinical Isolates Over 4 Years to 9 Antimicrobials in a Tertiary Greek Hospital. Chemotherapy. 2014;60(5-6):334-41. doi: 10.1159/000437252. Epub 2015 Aug 18.
PubMed 26302835
Study at a glance
From the registry record, last updated by the sponsor on 4 Jul 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Efficacy and Safety of Different Dosing Strategies of Colistin in Multidrug-Resistant Gram-Negative Bacilli Infections in Critically Ill Patients
- ClinicalTrials.gov ID
- NCT06843668
- Acronym / sponsor ID
- H-04-Q001
- Conditions
- Critical Ill Patients, Multi Drug Resistant
- Phase
- Phase 2/3
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 120 participants (estimated)
- Lead sponsor
- Mansoura UniversityUniversity, hospital or other
- Study start
- 25 Dec 2023 (actual)
- Primary completion
- 25 Sep 2025 (estimated)
- Study completion
- 25 Oct 2025 (estimated)
- First posted
- 25 Feb 2025 (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.
Nosocomial infections caused by multi-drug-resistant (MDR) and extensively drug-resistant (XDR) Gram-negative pathogens represent a major threat worldwide. The increasing trend of multi-drug resistance in Gram-negative bacteria (MDR-GNB) poses a particularly acute challenge to health systems especially in critically ill patients.
Patients in intensive care units (ICUs) have encountered an increasing emergence and spread of antibiotic-resistant pathogens. In Saudi Arabia mainly MDR-GNB such as Acinetobacter Baumannii, Pseudomonas Aeruginosa, Klebsiella Pnemoniae and Enterobacter are observed in ICUs.
Polymyxins are the last line therapy in the treatment of infection caused by these MDR-GNB. Colistin is the most widely used polymyxin antibiotic, it is administered as inactive prodrug colistimethate sodium (CMS) that is hydrolyzed to an active moiety of colistin base activity (CBA). It acts as cationic detergent and damages bacterial cytoplasmic membrane causing leaking of intracellular substances and then cell death.
During the first years of their use, polymyxin-associated neurotoxicity occurred in patients with an incidence as high as 27% following parenteral administration. However, other retrospective clinical trials have not exposed neurotoxicity to be a major concern. On the other hand, nephrotoxicity is by far the most common and dose-limiting side effect associated with parenteral polymyxins, with incidence rates in patients as high as 60%. Despite the high incidence of colistin induced nephrotoxicity, in 2012, the World Health Organization (WHO) reclassified polymyxins as critically important for the management of MDR-GNB infection, renewing the interest in these antibiotics.
To the best of our knowledge no study compared the efficacy and safety of both dosing strategies in critically ill patients. Moreover, there is still a lack of evidence on the efficacy and safety of both dosing strategies in obese patients. Therefore, this study aims at comparing the efficacy and toxicity of both strategies in colistin dosing (the fixed dose and the weight-based dosing) in obese patients and non- obese patients.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (participant)
- Number of arms
- 2
- Model description
- This is a prospective, single blind, randomized, comparative intervention study .
| Arm | Type | Receives |
|---|---|---|
| The EMA (fixed dose) colistin group | Experimental | Drug: EMA colistin dosing strategyThe EMA colistin group will receive I.V colistin using fixed dose strategy. |
| US FDA (weight-based dose) colistin group | Active comparator | Drug: US FDA colistin dosing strategyThe weight-based colistin group will receive I.V. colistin using weight based dosing strategy. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- Patients age ≥ 18 years old.
- Patients who will be treated with CMS for MR GNB infections.
- Patients who are admitted to the ICUs.
Key exclusion criteria (4 listed)
- Known hypersensitivity to colistin.
- Pregnant and lactating women.
- Patients who are treated with colistin for < 24 hours.
- Patients with myasthenia gravis or concomitant anesthetics or neuromuscular blocking drugs.
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 |
|---|---|---|
| EMA colistin dosing strategyThe EMA colistin group will receive I.V colistin based on creatinine clearance (mL/min) level , with fixed loading dose 9 MIU equivalent to 300 mg of colistin-based activity (CBA). The maintenance dose will be administered after 12 h following the loading dose over 1 h every 12h (twice daily). | Drug | The EMA (fixed dose) colistin group |
| US FDA colistin dosing strategyThe weight-based colistin group will receive I.V. colistin based on the lower (ideal body weight or actual body weight) with a loading dose of (4) X (patient weight in kg). Loading dose might exceed 300 mg. | Drug | US FDA (weight-based dose) colistin group |
Primary outcome
Clinical and microbiological success in eradication of infection reported as the number and percentage of patients with successful clinical improvement and microbiological clearance (Efficacy).
Time frame: 14 days post colistin initiation.
having a white blood cell count (WBC) of less than 12,000 cells/mm3 or a ≥ 25% reduction in WBC, being afebrile for ≥ 48 h,. • Microbiological clearance will be defined as eradication of the original causative organism from subsequent blood cultures by day 14 of therapy.
1 secondary outcome
Nephrotoxicity (Safety)
Time frame: 14 days
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 4 Jul 2025.
- Background: PubMed 16931410Li J, Nation RL, Turnidge JD, Milne RW, Coulthard K, Rayner CR, Paterson DL. Colistin: the re-emerging antibiotic for multidrug-resistant Gram-negative bacterial infections. Lancet Infect Dis. 2006 Sep;6(9):589-601. doi: 10.1016/S1473-3099(06)70580-1.
- Background: PubMed 26302835Maraki S, Mantadakis E, Nioti E, Samonis G. Susceptibility of 2,252 Pseudomonas aeruginosa Clinical Isolates Over 4 Years to 9 Antimicrobials in a Tertiary Greek Hospital. Chemotherapy. 2014;60(5-6):334-41. doi: 10.1159/000437252. Epub 2015 Aug 18.
- 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.
Mohamed E Shams, Professor principal investigator
Mansoura University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2/3 study testing EMA colistin dosing strategy and US FDA colistin dosing strategy in people with Critical Ill Patients and Multi Drug Resistant, run by Mansoura University at 1 site in Saudi Arabia.
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 4 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: looking for participants now, as of the sponsor's last update on 4 Jul 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Saudi Arabia. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
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 Abdulmajeed S Alharbi, Master (00966503984099, majeed4440@hotmail.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Clinical and microbiological success in eradication of infection reported as the number and percentage of patients with successful clinical improvement and microbiological clearance (Efficacy). (time frame: 14 days post colistin initiation.). 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 NCT06843668, which also lists 2 linked publications.
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 4 Jul 2025.