Pharmacokinetic Assessment of Peramivir in Hospitalized Adults Undergoing Continuous Renal Replacement Therapy

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.

Study Overview

• Status: Withdrawn
• Conditions: Renal Failure; Influenza

Detailed Description

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 No patients were enrolled as the peramivir EUA was rescinded.

• Study Type: Observational

Contacts and Locations

Study Locations

• United States
  • Illinois
    • Chicago, Illinois, United States, 60611
      • Midwestern University/Northwestern Memorial Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• 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.

Description

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.

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort

CRRT Patients receiving Peramivir; 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
The primary outcome measure will be to determine the sieving coefficient for peramivir.	upon study completion (estimated 2 yrs)

Secondary Outcome Measures

Outcome Measure	Time Frame
Determine the extracorporeal clearance for peramivir	upon study completion (estimated 2 yrs)

Collaborators and Investigators

• Sponsor: Midwestern University
• Collaborators: Northwestern University; BioCryst Pharmaceuticals
• Investigators: Principal Investigator: Marc H Scheetz, PharmD, MSc, Midwestern University and Northwestern Memorial Hospital; Principal Investigator: Michael Ison, MD, Northwestern University

Study record dates

Study Major Dates

• Study Start: February 1, 2010
• Primary Completion (ACTUAL): February 1, 2011
• Study Completion (ACTUAL): February 1, 2011

Study Registration Dates

• First Submitted: June 16, 2010
• First Submitted That Met QC Criteria: June 16, 2010
• First Posted (ESTIMATE): June 17, 2010

Study Record Updates

• Last Update Posted (ACTUAL): March 20, 2018
• Last Update Submitted That Met QC Criteria: March 17, 2018
• Last Verified: March 1, 2018

More Information

Terms related to this study

• Keywords: influenza; clearance; CRRT; CVVHD; CVVH; peramivir; sieving coefficient
• Additional Relevant MeSH Terms: RNA Virus Infections; Virus Diseases; Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Kidney Diseases; Urologic Diseases; Orthomyxoviridae Infections; Renal Insufficiency; Influenza, Human
• Other Study ID Numbers: STU00023343