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

NCT06843668 | Recruiting Phase 2

• 1 other identifier: H-04-Q001
• Study Type: interventional
• Target: 120
• Locations: 1 country
• Sites: 1

Brief 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 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.

Conditions

Critical Ill Patients; Multi Drug Resistant

Outcome Measures

Primary Outcomes (1)

• 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.

  14 days post colistin initiation.

Secondary Outcomes (1)

• Nephrotoxicity (Safety)

  14 days

Study Arms (2)

The EMA (fixed dose) colistin group

EXPERIMENTAL

The EMA colistin group will receive I.V colistin using fixed dose strategy.

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.

Drug: US FDA colistin dosing strategy

Interventions

EMA colistin dosing strategy DRUG

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).

The EMA (fixed dose) colistin group

US FDA colistin dosing strategy DRUG

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.

US FDA (weight-based dose) colistin group

Eligibility Criteria

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

You may qualify if:

• Patients age ≥ 18 years old.
• Patients who will be treated with CMS for MR GNB infections.
• Patients who are admitted to the ICUs.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Mansoura University: lead

Study Sites (1)

King Fahad Specialist Hospital

Buraidah, Saudi Arabia

RECRUITING

Related Publications (2)

• 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.

  PMID: 16931410 BACKGROUND

• Maraki 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.

  PMID: 26302835 BACKGROUND

Study Officials

• Mohamed E Shams, Professor

  Mansoura University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Abdulmajeed S Alharbi, Master

CONTACT

00966503984099; majeed4440@hotmail.com

Mona M El-Tamalawy, Master

CONTACT

01220650700; mona.m.eltamalawy@gmail.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Masking Details: Masking Description
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Lecturer of Clinical Pharmacy

Model Details: This is a prospective, single blind, randomized, comparative intervention study .

Study Record Dates

• First Submitted: February 13, 2025
• First Posted: February 25, 2025
• Study Start: December 25, 2023
• Primary Completion: September 25, 2025
• Study Completion: October 25, 2025
• Last Updated: July 4, 2025

Record last verified: 2025-02

Data Sharing

• IPD Sharing: Will not share

Locations

SA (1)