NCT00235690

Pharmacokinetics and Pharmacodynamics of Intravenous Colistin- Pilot Study

Completed NA Last updated 16 December 2015

What this trial tests

NA trial testing Blood draws in Bacteremia in 10 participants. Completed in 1 August 2015.

Timeline

1 June 2008

Primary endpoint
1 August 2015

1 August 2015

Quick facts

Lead sponsor	University of Pittsburgh
Phase	NA
Status	Completed
Study type	INTERVENTIONAL
Allocation	na
Design	single group
Masking	none
Primary purpose	prevention
Enrollment	10
Start date	1 June 2008
Primary completion	1 August 2015
Estimated completion	1 August 2015
Sites	1 location across United States

Drugs / interventions tested

• Blood draws — full drug profile →
• Blood draw — full drug profile →

Conditions studied

• Bacteremia — all drugs for Bacteremia →
• Pseudomonas Infections — all drugs for Pseudomonas Infections →

Sponsor

University of Pittsburgh

Who can join

18 and older, any sex, with Bacteremia or Pseudomonas Infections. Patients with the condition only — healthy volunteers not accepted.

What's being measured

Primary outcomes are the specific endpoints the trial is designed to prove or disprove.

• To provide pharmacokinetic data on intravenous (IV) CMS/colistin
  Time frame: 5 years

Sponsor's own description

More than 80 patients at the University of Pittsburgh Medical Center have been infected with Pseudomonas aeruginosa, lacking susceptibility to all commercially available antibiotics except "colistin". This antibiotic 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 dosing recommendations for patients requiring renal replacement therapy (either intermittent hemodialysis or continuous venovenous hemofiltration). 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 University of Pittsburgh, are performing a pilot study of the pharmacokinetics of intravenous CMS/colistin in patients requiring this antibiotic for clinical purposes. Plasma concentrations will be determined around a CMS/colistin dose once the drug has reached steady state. Concentrations in pulmonary epithelial lining fluid will also be determined in patients with pneumonia. 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 which developed these assays. A submission is being made to the National Institutes of Health (NIH) for funding of a multicenter study which will address this research question with a greater sample size. The study proposed here is a pilot study in order to prove the feasibility of the research approach and to provide preliminary data for the NIH proposal.

Publications & conference data

2 peer-reviewed publications reference this trial (live from Europe PMC):

1. Dosing guidance for intravenous colistin in critically-ill patients.
   Nation RL, Garonzik SM, Thamlikitkul V, Giamarellos-Bourboulis EJ, et al · · 2017 · cited 185× · PMID 28011614 · DOI 10.1093/cid/ciw839
2. Updated US and European Dose Recommendations for Intravenous Colistin: How Do They Perform?
   Nation RL, Garonzik SM, Li J, Thamlikitkul V, et al · · 2016 · cited 123× · PMID 26607424 · DOI 10.1093/cid/civ964