Pharmacokinetics of Cidofovir During Continuous Venovenous Hemofiltration

Study Overview
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Brief Summary
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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
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Pharmacokinetics of Cidofovir During Continuous Venovenous Hemofiltration

Conditions
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Cytomegalovirus Retinitis, Acute Renal Failure

Intervention / Treatment
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* Other: Cidofovir pharmacokinetics


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cidofovir pharmacokinetics<br>Patient received cidofovir due to clinical necessity (therapy resistant HCMV retinitis) while being on continuous hemofiltration. Pre- and postfilter plasma samples were taken at multiple timepoints during 24 hours. | Other: Cidofovir pharmacokinetics<br>* Blood samples were drawn before and 15, 30, 60, 120, 240, 360, 720 and 1440 minutes after the start of the cidofovir infusion. Plasma and ultrafiltration samples were collected from the outlet of the ultrafiltrate compartment of the hemofilter.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| AreaUnderCurve (AUC) | AUC (plasma concentration) of cidofovir during 24 hours of hemofiltration | 24 hours | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| half-life (t1/2) of cidofovir during hemofiltration |  | 24 hours | 
| maximum and minimum plasma concentration (Cmax, Cmin) of cidofovir during hemofiltration |  | 24 hours | 
| total body clearance (Cltot) of cidofovir during hemofiltration |  | 24 hours | 
| hemofiltration clearance (ClHF) of cidofovir during hemofiltration |  | 24 hours | 
| sieving coefficient of cidofovir during hemofiltration |  | 24 hours | 
| elimination fraction of cidofovir during hemofiltration |  | 24 hours | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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cidofovir, cvvh, renal replacement therapy, HCMV, Pharmacokinetics of cidofovir during CVVH, continuous venovenous hemofiltration