Different Dosing Strategies of Colistin in Multidrug-Resistant Gram-Negative Bacilli Infections
Trial statusRecruiting
Trial phasePhase 2, Phase 3
Trial typeInterventional
Biological sexAll
Age18+
SponsorMansoura University
About this trial
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.
Eligibility criteria
This trial does not accept healthy volunteersQualifiers
Patients age ≥ 18 years old.
Patients who will be treated with CMS for MR GNB infections.
Patients who are admitted to the ICUs.
Disqualifiers
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 design
Design model
Parallel
Treatments tested in this trial
EMA colistin dosing strategy
DrugThe 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 strategy
DrugThe 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.
Treatment groups
120 Participants
are divided into 2 treatment groupsGroup A: The EMA (fixed dose) colistin groupExperimental treatment 1 intervention
Group B: US FDA (weight-based dose) colistin groupActive comparator 1 intervention
Trial outcomes
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.
Time frame
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%.
Time frame
14 daysSponsors and contacts
Click on the lead sponsor to view all of their trials.
Source ClinicalTrials.gov