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Candida InfectionsCASPOLOADNCT02413892

Impact of a Loading Dose of Caspofungin in Invasive Candidiasis in ICU Patients

An observational study of Candida Infections, run by Outcome Rea at 1 site in France.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

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… Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Candida Infections
How many people
15 participants
Where
1 siteFrance
Study dates
May 2015to Feb 2017
Phase
Observational
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

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

Who may be able to join

  • 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

Who cannot join

  • 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

Trial locations and contacts

1 site in 1 country.

France1 site

  • Reanimation Medicale et Infectieuse-Hopital Bichat

    Paris, 75018

Other trials in France

About this study

Official title: 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.

Read the 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.

Medical subject headings
Candidiasis

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Area Under the inhibitory curve (AUIC)

    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.

    Measured: 24 hours after the loading dose

Secondary outcomes (1)

  1. Peak concentration over MIC (Cmax/MIC)

    One blood sample will be obtained. MIC will be determined with E-test technique.

    Measured: 2 hours avec the loading dose

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted10 Apr 2015 (estimated)
  2. Study startMay 2015
  3. Primary completionJan 2017
  4. Study completionFeb 2017

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Observational
Observational model
Cohort
Time perspective
Prospective
Enrolment
15 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02413892
Sponsor's protocol ID
OCR001
Acronym
CASPOLOAD
Status last verified
Apr 2016
First submitted
9 Mar 2015
Last updated
5 Apr 2017
Results posted
No
Data monitoring committee
No
Individual data sharing
Undecided

Publications

  • Shields RK, Nguyen MH, Press EG, Updike CL, Clancy CJ. Caspofungin MICs correlate with treatment outcomes among patients with Candida glabrata invasive candidiasis and prior echinocandin exposure. Antimicrob Agents Chemother. 2013 Aug;57(8):3528-35. doi: 10.1128/AAC.00136-13. Epub 2013 May 13.

    PubMed 23669387

  • Safdar A, Rodriguez G, Rolston KV, O'Brien S, Khouri IF, Shpall EJ, Keating MJ, Kantarjian HM, Champlin RE, Raad II, Kontoyiannis DP. High-dose caspofungin combination antifungal therapy in patients with hematologic malignancies and hematopoietic stem cell transplantation. Bone Marrow Transplant. 2007 Feb;39(3):157-64. doi: 10.1038/sj.bmt.1705559.

    PubMed 17245424

  • Betts RF, Nucci M, Talwar D, Gareca M, Queiroz-Telles F, Bedimo RJ, Herbrecht R, Ruiz-Palacios G, Young JA, Baddley JW, Strohmaier KM, Tucker KA, Taylor AF, Kartsonis NA; Caspofungin High-Dose Study Group. A Multicenter, double-blind trial of a high-dose caspofungin treatment regimen versus a standard caspofungin treatment regimen for adult patients with invasive candidiasis. Clin Infect Dis. 2009 Jun 15;48(12):1676-84. doi: 10.1086/598933.

    PubMed 19419331

  • Louie A, Deziel M, Liu W, Drusano MF, Gumbo T, Drusano GL. Pharmacodynamics of caspofungin in a murine model of systemic candidiasis: importance of persistence of caspofungin in tissues to understanding drug activity. Antimicrob Agents Chemother. 2005 Dec;49(12):5058-68. doi: 10.1128/AAC.49.12.5058-5068.2005.

    PubMed 16304173

  • Sinnollareddy M, Peake SL, Roberts MS, Lipman J, Roberts JA. Using pharmacokinetics and pharmacodynamics to optimise dosing of antifungal agents in critically ill patients: a systematic review. Int J Antimicrob Agents. 2012 Jan;39(1):1-10. doi: 10.1016/j.ijantimicag.2011.07.013. Epub 2011 Sep 16.

    PubMed 21925845

  • Nguyen TH, Hoppe-Tichy T, Geiss HK, Rastall AC, Swoboda S, Schmidt J, Weigand MA. Factors influencing caspofungin plasma concentrations in patients of a surgical intensive care unit. J Antimicrob Chemother. 2007 Jul;60(1):100-6. doi: 10.1093/jac/dkm125. Epub 2007 May 24.

    PubMed 17525052

  • Bailly S, Gautier-Veyret E, Le MP, Bouadma L, Andremont O, Neuville M, Mourvillier B, Sonneville R, Magalhaes E, Lebut J, Radjou A, Smonig R, Wolff M, Massias L, Dupuis C, Timsit JF. Impact of Loading Dose of Caspofungin in Pharmacokinetic-Pharmacodynamic Target Attainment for Severe Candidiasis Infections in Patients in Intensive Care Units: the CASPOLOAD Study. Antimicrob Agents Chemother. 2020 Nov 17;64(12):e01545-20. doi: 10.1128/AAC.01545-20. Print 2020 Nov 17.

    PubMed 32958709

Questions about this trial

What is this clinical trial studying?

An observational study of Candida Infections, run by Outcome Rea at 1 site in France.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 7 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 5 Apr 2017. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in France. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Area Under the inhibitory curve (AUIC) (time frame: 24 hours after the loading dose). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02413892, which also lists 7 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 5 Apr 2017.

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