Impact of a Loading Dose of Caspofungin in Invasive Candidiasis in ICU Patients (CASPOLOAD)

April 3, 2017 updated by: Outcome Rea

Impact of a Loading Dose of Caspofungin on Pharmacokinetic and Pharmacodynamic Parameters Target Achievements for Severe Candida Infections in ICU Patients

Echinocandins are the drug of choice in severe candida infections. Efficacy of echinocandins is related to concentration and area under the curve (AUC) of the drug.

Available pharmacokinetic studies found that concentration of echinocandins mainly caspofungin is sub-optimal in severe candida infections in intensive care unit (ICU) patients.

Higher dose of caspofungin has been proven to be safe in critically ill patients but its impact on the ability to reach PK/PD target is unknown.

The aim of this study is to evaluate the impact of a loading dose of caspofungin on PK/PD parameters within the first 24-hours.

Study Overview

Status

Completed

Conditions

Detailed Description

Invasive fungal infections are associated to a high mortality rate in ICU, partly because of a delayed treatment.

PK/PD targets for caspofungin are the peak concentration over minimal inhibitory concentration (MIC) ratio which should reach 10 and the area under the inhibitory curve (AUIC) which should be over 200. High distribution volume in ICU patients and increase of MICs due to extensive use of antifungal agents make optimal concentration difficult to obtain. High doses up to 150mg of caspofungin have been reported to be safe. Thus, in our unit, a loading dose of 140mg of caspofungin is a standard practice but was never rigorously evaluated.

The aim of the present study is to measure the impact of a loading dose of 140mg of caspofungin on the pharmacokinetic parameters in the first 24 hours of treatment.

The AUIC and maximal concentration (CMax) / (MIC) according to the recovered yeasts will be measured. The investigators also planned a Monte-Carlo simulation using MICs obtained from clinically relevant candida strains isolated in Bichat and Grenoble hospitals in order to evaluate the percentage of patients appropriately treated within the first 24 hours according to Candida species and previous use of antifungals.

Recovered strains from epidemiological studies will be used for PKPD modelling and will use s. A second Monte-Carlo simulation will be done using data from the Amarcand 2 study.

All MICs will be determined using E-test ( Biomerieux® KIT's) without specifying any breakpoints as MICs and not breakpoints per se will be used.

Study Type

Observational

Enrollment (Actual)

15

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • France
      • Paris, France, 75018
        • Reanimation Medicale et Infectieuse-Hopital Bichat

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Sampling Method

Probability Sample

Study Population

All consecutive patients for whom the decision to start antifungal therapy with caspofungin loading dose was taken

Description

Inclusion Criteria:

  • Patient hospitalized in intensive care
  • Age> 18 years
  • Patient with a central catheter
  • Patient with invasive mechanical ventilation
  • Patient receiving more than 0.1 mcg / kg / min of adrenaline or noradrenaline
  • Patient treated for proven (positive blood cultures or positive specimen obtained during a surgical or percutaneous puncture) or suspected (risk factor, extra digestive colonization, absence of other uncontrolled bacterial infections, candida score> 3) invasive candidiasis.
  • Patient affiliated to medical insurance

Exclusion Criteria:

  • Expected length of stay under 48H
  • Age <18 years
  • Pregnant or breastfeeding women
  • Limited or sustained life support therapy
  • Patient unable to legally consent
  • History of Allergy, hypersensitivity or intolerance to echinocandins or Drug excipients

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Area Under the inhibitory curve (AUIC)
Time Frame: 24 hours after the loading dose
Six samples (before infusion; 2, 3, 5, 7 and 24 hours after infusion) will be obtained between inclusion and 24 hours to calculate the area under the curve. MIC will be determined with E-test technique.
24 hours after the loading dose

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Peak concentration over MIC (Cmax/MIC)
Time Frame: 2 hours avec the loading dose
One blood sample will be obtained. MIC will be determined with E-test technique.
2 hours avec the loading dose

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Outcome Rea

Collaborators

Assistance Publique - Hôpitaux de Paris

Investigators

  • Principal Investigator: Jean-Francois TIMSIT, Professor, Assistance Publique - Hôpitaux de Paris

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

May 1, 2015

Primary Completion (Actual)

January 1, 2017

Study Completion (Actual)

February 1, 2017

Study Registration Dates

First Submitted

March 9, 2015

First Submitted That Met QC Criteria

April 9, 2015

First Posted (Estimate)

April 10, 2015

Study Record Updates

Last Update Posted (Actual)

April 5, 2017

Last Update Submitted That Met QC Criteria

April 3, 2017

Last Verified

April 1, 2016

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • OCR001

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

UNDECIDED

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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