Clinical trial NCT01146353: Pharmacokinetic Assessment of Peramivir in Hospitalized Adults Undergoing Continuous Renal Replacement Therapy
Official title: Pharmacokinetic Assessment of Peramivir in Hospitalized Adults Undergoing Continuous Renal Replacement Therapy
Study type: OBSERVATIONAL
Overall status: WITHDRAWN
Conditions: Influenza
Renal Failure
Keywords: peramivir
CVVH
CRRT
CVVHD
influenza
sieving coefficient
clearance
Lead sponsor: Midwestern University
Sponsor class: OTHER
Collaborators: name: Northwestern University
name: BioCryst Pharmaceuticals
First posted: 2010-06-17
Enrollment: 0
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Eligible patients are male or female patients ≥18 years of age who are hospitalized, undergoing CVVH or CVVHD, and receiving peramivir.

Eligible patients will additionally have the following: blood flow rate will be required to be ≥100 mL/ min with an ultrafiltrate +/- dialysis flow rate greater than or equal to 3000mL/hr, and the continuous renal replacement therapy must be scheduled to run for the full duration of the dosing interval (full 24 hours).

Written informed consent in a form approved by the Northwestern University and the Midwestern University Institutional Review Boards will be granted by the patient.

Brief summary: Pharmacokinetics for peramivir have not been well characterized in patients undergoing continuous renal replacement therapy CRRT - either Continuous veno-venous hemofiltration (CVVH) +/- dialysis (CVVHD). CRRT is commonly utilized in the hospital setting for patients with acute kidney injury for metabolic correction, slow continuous fluid removal, and to maintain hemodynamic stability. CRRT commonly alters drug disposition and clearance, and dosing regimens often need alteration in patients receiving CRRT. Doses required to generate predictable serum concentrations can be calculated from known patient parameters such as replacement fluid and dialysate flow rate, sieving coefficients, and desired serum concentrations. However, pharmacokinetic studies must be performed in CRRT patients to generate drug removal constants or sieving coefficients. Of note, the clearance of drugs by conventional hemodialysis cannot be used to extrapolate clearances with CRRT secondary to differences in ultrafiltration rates and dialysis membranes. The investigators propose an open label study to obtain peramivir pharmacokinetics in patients undergoing CRRT.

Detailed description: This study has been closed. No patients were enrolled as the peramivir EUA was rescinded.

Eligibility criteria: Inclusion Criteria

* Patient is hospitalized and undergoing continuous renal replacement therapy (CRRT) as a result of the clinical management of the patient (i.e. CRRT is not initiated for the purpose of this study).
* Patient is receiving peramivir for a positive rapid antigen test for influenza or on the basis of clinical suspicion with a high local epidemiological prevalence of H1N1 disease.
* Patient has a CRRT blood flow rate greater than or equal to 100 mL/min with an ultrafiltrate +/- dialysis flow rate greater than or equal to 3000mL/hr,
* The patient is anticipated to require CRRT and peramivir treatment for a full 24 hours (i.e. life expectancy is not less than 24 hours).

Exclusion Criteria

* The patient has received greater than 5 doses of peramivir.
* The subject has a pre-existing illness that, in the opinion of the investigator, would place the subject at an unreasonably increased risk through participation in this study.
* The patient is receiving CRRT utilizing a pre-membrane dilution method.

Primary outcomes:
measure: The primary outcome measure will be to determine the sieving coefficient for peramivir.
timeFrame: upon study completion (estimated 2 yrs)
Secondary outcomes:
measure: Determine the extracorporeal clearance for peramivir
timeFrame: upon study completion (estimated 2 yrs)
Other outcomes:
Locations:
city: Chicago
country: United States
facility: Midwestern University/Northwestern Memorial Hospital
state: Illinois
Study officials:
affiliation: Midwestern University and Northwestern Memorial Hospital
name: Marc H Scheetz, PharmD, MSc
role: PRINCIPAL_INVESTIGATOR
affiliation: Northwestern University
name: Michael Ison, MD
role: PRINCIPAL_INVESTIGATOR
References: