Pharmacokinetics of Colistin in Critically-ill Patients With AKI Who Receive SLED

NCT05586438 | Completed Phase 4 DMC

• 1 other identifier: 223-2564-EC3
• Study Type: interventional
• Target: 13
• Locations: 1 country
• Sites: 1

Brief Summary

Colistin was developed in the 1960s and preliminary pharmacokinetic studies were performed at that time. Dosing recommendations, on the basis of these pharmacokinetic studies, are listed in the drug's product information. However, there are no optimal dosing recommendations for patients with acute kidney injury who receive sustained low-efficiency dialysis. Furthermore, the science of antibiotic dosing ("pharmacodynamics") has changed significantly since the 1960s and it is quite possible that the dosing recommendations listed in the product information are not optimal. Furthermore, even though physicians refer to "colistin" administration, the only intravenous form of the drug is colistin methanesulfonate (CMS). CMS is converted in the body to colistin. Both CMS and colistin have different pharmacokinetic and antimicrobial activities. For this reason, we, the investigators at the Mahidol university, are performing a pharmacokinetic study of the intravenous CMS/colistin in patients requiring sustained low-efficiency dialysis. Plasma concentrations will be determined around a CMS/colistin dose once the drug has reached steady state. Microbiologic and clinical endpoints will be determined and will be correlated with these concentrations. The measurement of CMS and colistin levels will be determined by a laboratory in Australia.

Conditions

Bacterial Infections

Keywords

colistin

Outcome Measures

Primary Outcomes (2)

• Area under the concentration-time curve [AUC]

  The area under the plasma drug concentration-time curve (AUC) reflects the actual body exposure to colistin after administration of a dose of colistin and is expressed in mg\*h/L. Predose, and 1, 2, 5, 8, 12 hours after administration

  24 hours

• Maximum Plasma Concentration [Cmax]

  Cmax is the maximum (or peak) serum concentration that colistin achieves in a specified compartment or test area of the body after colistin has been administered and before the administration of a second dose. Predose, and 1, 2, 5, 8, 12 hours after administration.

  24 hours

Secondary Outcomes (1)

• Treatment-Related Adverse Events CTCAE v4.0

  14 days

Study Arms (1)

blood draws

EXPERIMENTAL

All patients enrolled will have PK blood samples obtained around a colistin dosing

Drug: Colistin Sulfomethate

Interventions

Colistin Sulfomethate DRUG

The patients receive colistin 150 mg intravenous once daily on non-dialysis day and receive colistin 150 mg intravenous every 12 hours on dialysis day

Also known as: Colistin

blood draws

Eligibility Criteria

• Age: 18 Years - 95 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Males or females greater than 18 years of age.
• All patients will remain in the hospital for pharmacokinetic sampling.
• All subjects must be on the medication colistin as part of their standard of care.
• All subjects must be on sustained low-efficiency dialysis

You may not qualify if:

• Pregnancy and lactation
• The patients receiving colistin inhalation

Sponsors & Collaborators

• Mahidol University: lead
• Monash University: collaborator

Study Sites (1)

Faculty of Medicine Siriraj Hospital, Mahidol University

Bangkok, 10700, Thailand

Location

Related Publications (2)

• Nation RL, Garonzik SM, Thamlikitkul V, Giamarellos-Bourboulis EJ, Forrest A, Paterson DL, Li J, Silveira FP. Dosing guidance for intravenous colistin in critically-ill patients. Clin Infect Dis. 2017 Mar 1;64(5):565-571. doi: 10.1093/cid/ciw839. Epub 2016 Dec 23.

  PMID: 28011614 BACKGROUND

• Jitmuang A, Nation RL, Koomanachai P, Chen G, Lee HJ, Wasuwattakul S, Sritippayawan S, Li J, Thamlikitkul V, Landersdorfer CB. Extracorporeal clearance of colistin methanesulphonate and formed colistin in end-stage renal disease patients receiving intermittent haemodialysis: implications for dosing. J Antimicrob Chemother. 2015;70(6):1804-11. doi: 10.1093/jac/dkv031. Epub 2015 Feb 18.

  PMID: 25698772 BACKGROUND

MeSH Terms

Conditions

Bacterial Infections

Interventions

colistinmethanesulfonic acid; Colistin

Condition Hierarchy (Ancestors)

Bacterial Infections and Mycoses; Infections

Intervention Hierarchy (Ancestors)

Polymyxins; Peptides, Cyclic; Macrocyclic Compounds; Polycyclic Compounds; Lipopeptides; Lipids; Antimicrobial Cationic Peptides; Peptides; Amino Acids, Peptides, and Proteins; Antimicrobial Peptides; Pore Forming Cytotoxic Proteins; Membrane Proteins; Proteins

Study Officials

• Adhiratha Boonyasiri, MD

  Mahidol University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NA
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 10, 2022
• First Posted: October 19, 2022
• Study Start: October 18, 2021
• Primary Completion: October 31, 2022
• Study Completion: October 31, 2022
• Last Updated: November 28, 2022

Record last verified: 2022-11

Data Sharing

• IPD Sharing: Will not share

Locations

TH (1)