Evaluation of Pharmacokinetic and Pharmacodynamic Properties of Intravenous Colistimethate Sodium

NCT02288429 | Completed

• 1 other identifier: 13-2597
• Study Type: observational
• Target: 16
• Locations: 1 country
• Sites: 1

Brief Summary

Colistin is a polymixin antibiotic used in the treatment of multidrug-resistant gram-negative infections. Given the limited use of colistin and previous challenges with laboratory assays to determine plasma concentrations, there is a lack of knowledge of the pharmacokinetic profile of colistin. The purpose of the investigators observational prospective pharmacokinetic cohort study is to examine the steady-state pharmacokinetic and pharmacodynamic properties of intravenous colistimethate sodium in cystic fibrosis and critically ill patients.

Conditions

Colistin

Keywords

pharmacokinetics; cystic fibrosis; critical illness

Outcome Measures

Primary Outcomes (1)

• Area under the plasma concentration time curve (AUC0-24)

  Steady-state plasma concentrations will be obtained after at least 2 days of therapy. Blood draws (5 ml) will be taken just before the start of the colistimethate sodium infusion and at 30, 60, 120, 240, and 360 minutes after the IV infusion.

  0, 30, 60, 120, 240, and 360 minutes after the IV infusion

Secondary Outcomes (1)

• Number of patients experiencing nephrotoxicity

  Baseline, during colistin therapy course (expected to be approximately 14 days), and until hospital discharge (participants will be followed for the duration of hospital stay, expected to be 2-4 weeks)

Other Outcomes (1)

• Number of patients experiencing neurotoxicity

  Baseline, during colistin therapy course (expected to be approximately 14 days), and until hospital discharge (participants will be followed for the duration of hospital stay, expected to be 2-4 weeks)

Study Arms (1)

Colistin

* Patients ≥ 18 years old receiving intravenous colistimethate sodium for the treatment of infection * Have cystic fibrosis and/or are critically ill (admitted to a critical care unit)

Drug: colistimethate sodium

Interventions

colistimethate sodium DRUG

Also known as: colistin, CMS

Colistin

Eligibility Criteria

• Age: 18 Years - 89 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Inpatients at the University of Colorado Hospital

You may qualify if:

• Patients ≥ 18 years old receiving intravenous colistimethate sodium for the treatment of infection
• Have cystic fibrosis and/or are critically ill (admitted to a critical care unit)

You may not qualify if:

• Pregnancy
• Breastfeeding
• Prisoners

Sponsors & Collaborators

• University of Colorado, Denver: lead

Study Sites (1)

University of Colorado Hospital

Aurora, California, 80045, United States

Location

Related Publications (7)

• Landman D, Georgescu C, Martin DA, Quale J. Polymyxins revisited. Clin Microbiol Rev. 2008 Jul;21(3):449-65. doi: 10.1128/CMR.00006-08.

  PMID: 18625681 BACKGROUND

• Karnik ND, Sridharan K, Jadhav SP, Kadam PP, Naidu RK, Namjoshi RD, Gupta V, Gore MS, Surase PV, Mehta PR, Gogtay JA, Thatte UM, Gogtay NJ. Pharmacokinetics of colistin in critically ill patients with multidrug-resistant Gram-negative bacilli infection. Eur J Clin Pharmacol. 2013 Jul;69(7):1429-36. doi: 10.1007/s00228-013-1493-9. Epub 2013 Mar 19.

  PMID: 23508665 BACKGROUND

• Plachouras D, Karvanen M, Friberg LE, Papadomichelakis E, Antoniadou A, Tsangaris I, Karaiskos I, Poulakou G, Kontopidou F, Armaganidis A, Cars O, Giamarellou H. Population pharmacokinetic analysis of colistin methanesulfonate and colistin after intravenous administration in critically ill patients with infections caused by gram-negative bacteria. Antimicrob Agents Chemother. 2009 Aug;53(8):3430-6. doi: 10.1128/AAC.01361-08. Epub 2009 May 11.

  PMID: 19433570 BACKGROUND

• Li J, Coulthard K, Milne R, Nation RL, Conway S, Peckham D, Etherington C, Turnidge J. Steady-state pharmacokinetics of intravenous colistin methanesulphonate in patients with cystic fibrosis. J Antimicrob Chemother. 2003 Dec;52(6):987-92. doi: 10.1093/jac/dkg468. Epub 2003 Oct 29.

  PMID: 14585859 BACKGROUND

• Ratjen F, Rietschel E, Kasel D, Schwiertz R, Starke K, Beier H, van Koningsbruggen S, Grasemann H. Pharmacokinetics of inhaled colistin in patients with cystic fibrosis. J Antimicrob Chemother. 2006 Feb;57(2):306-11. doi: 10.1093/jac/dki461. Epub 2006 Jan 5.

  PMID: 16396919 BACKGROUND

• Markou N, Markantonis SL, Dimitrakis E, Panidis D, Boutzouka E, Karatzas S, Rafailidis P, Apostolakos H, Baltopoulos G. Colistin serum concentrations after intravenous administration in critically ill patients with serious multidrug-resistant, gram-negative bacilli infections: a prospective, open-label, uncontrolled study. Clin Ther. 2008 Jan;30(1):143-51. doi: 10.1016/j.clinthera.2008.01.015.

  PMID: 18343250 BACKGROUND

• Imberti R, Cusato M, Villani P, Carnevale L, Iotti GA, Langer M, Regazzi M. Steady-state pharmacokinetics and BAL concentration of colistin in critically Ill patients after IV colistin methanesulfonate administration. Chest. 2010 Dec;138(6):1333-9. doi: 10.1378/chest.10-0463. Epub 2010 Jun 17.

  PMID: 20558557 BACKGROUND

Biospecimen

Retention: SAMPLES WITHOUT DNA

Plasma

MeSH Terms

Conditions

Cystic Fibrosis; Critical Illness

Interventions

colistinmethanesulfonic acid; Colistin

Condition Hierarchy (Ancestors)

Pancreatic Diseases; Digestive System Diseases; Lung Diseases; Respiratory Tract Diseases; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Infant, Newborn, Diseases; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

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

• Ty Kiser, PharmD

  University of Colorado, Denver

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: CASE ONLY
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 15, 2014
• First Posted: November 11, 2014
• Study Start: September 1, 2013
• Primary Completion: June 1, 2019
• Study Completion: June 1, 2019
• Last Updated: June 24, 2019

Record last verified: 2019-06

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)