NCT06843668

Different Dosing Strategies of Colistin in Multidrug-Resistant Gram-Negative Bacilli Infections

Recruiting now Phase 2, PHASE3 Last updated 4 July 2025

What this trial tests

Phase 2, PHASE3 trial testing EMA colistin dosing strategy in Critical Ill Patients in 120 participants. Currently enrolling.

Timeline

25 December 2023

Primary endpoint
25 September 2025

25 October 2025

Quick facts

Lead sponsor	Mansoura University
Phase	Phase 2, PHASE3
Status	Recruiting now
Study type	INTERVENTIONAL
Allocation	randomized
Design	parallel
Masking	single
Primary purpose	treatment
Enrollment	120
Start date	25 December 2023
Primary completion	25 September 2025
Estimated completion	25 October 2025
Sites	1 location across Saudi Arabia

Drugs / interventions tested

• EMA colistin dosing strategy — full drug profile →
• US FDA colistin dosing strategy — full drug profile →

Conditions studied

• Critical Ill Patients — all drugs for Critical Ill Patients →
• Multi Drug Resistant — all drugs for Multi Drug Resistant →

Sponsor

Mansoura University

Who can join

18 and older, any sex, with Critical Ill Patients or Multi Drug Resistant. Patients with the condition only — healthy volunteers not accepted.

Sponsor's own description

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.

Publications & conference data

No peer-reviewed publications indexed yet for this trial.