Pharmacokinetics of Cidofovir During Continuous Venovenous Hemofiltration

Condition(s) targeted: Cytomegalovirus Retinitis; Acute Renal Failure

Intervention: Cidofovir pharmacokinetics (Other)

Phase: Phase 4

Status: Completed

Sponsored by: Medical University of Vienna

Official(s) and/or principal investigator(s):
Florian Thalhammer, Prof. MD, Principal Investigator, Affiliation: Medical University of Vienna

Cidofovir is an acyclic nucleotide analog with broad-spectrum antiviral activity against herpesviruses. Its potency in inhibiting HCMV has been shown in conventional in vitro studies. It is approved for the systemic treatment of human cytomegalovirus (HCMV) retinitis in patients with AIDS and as a second line therapy for HCMV infections not responding to ganciclovir or foscarnet. In intensive care patients continuous venovenous haemofiltration (CVVH) is a well-established extracorporal renal replacement therapy with a high clearance rate. Pharmacokinetic studies of antifungal agents in critically ill patients treated with CVVH are rare. Elimination of any given drug by renal replacement therapy is determined by several major factors which are membrane specific, due to physico-chemical properties of the drug and characteristics of the renal replacement technique used. Study objective The trial is conducted to investigate the pharmacokinetics of cidofovir during CVVH in critically ill patients. It is suspected that Hemofiltration will influence cidofovir plasma levels.

Official title: Pharmacokinetics of Cidofovir During Continuous Venovenous Hemofiltration

Study design: Endpoint Classification: Pharmacokinetics Study, Intervention Model: Single Group Assignment, Masking: Open Label

Primary outcome: AreaUnderCurve (AUC)

Secondary outcome:

half-life (t1/2) of cidofovir during hemofiltration

maximum and minimum plasma concentration (Cmax, Cmin) of cidofovir during hemofiltration

total body clearance (Cltot) of cidofovir during hemofiltration

hemofiltration clearance (ClHF) of cidofovir during hemofiltration

sieving coefficient of cidofovir during hemofiltration

elimination fraction of cidofovir during hemofiltration

Minimum age: 18 Years. Maximum age: 75 Years. Gender(s): Male.

Criteria:

Inclusion Criteria:

- Age 18 to 75 years

- Suspected of proven HCMV infection

- Suspected or proven resistancy of HCMV to the first line therapy (ganciclovir /

foscarnet).

- Continuous venovenous hemodiafiltration (CVVHDF) due to acute or chronic renal

failure. Exclusion Criteria:

- Known history of hypersensitivity to cidofovir or probenecid.

- An expected survival of less than three days.

- Known alcohol dependency, epilepsy, pregnancy or liver failure.

- Infection with a ganciclovir or foscarnet susceptible HCMV strain

Medical University of Vienna, Vienna 1190, Austria

Starting date: March 2002
Last updated: June 4, 2013