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

NCT02413892 | Completed

• 1 other identifier: OCR001
• Study Type: observational
• Target: 15
• Locations: 1 country
• Sites: 1

Brief 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 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.

Conditions

Candida Infections

Outcome Measures

Primary Outcomes (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.

  24 hours after the loading dose

Secondary Outcomes (1)

• Peak concentration over MIC (Cmax/MIC)

  2 hours avec the loading dose

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Probability Sample

Study Population

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

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Outcome Rea: lead
• Assistance Publique - Hôpitaux de Paris: collaborator

Study Sites (1)

Reanimation Medicale et Infectieuse-Hopital Bichat

Paris, 75018, France

Location

Related Publications (7)

• 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.

  PMID: 23669387 BACKGROUND

• 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.

  PMID: 17245424 BACKGROUND

• 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.

  PMID: 19419331 BACKGROUND

• 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.

  PMID: 16304173 BACKGROUND

• 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.

  PMID: 21925845 BACKGROUND

• 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.

  PMID: 17525052 BACKGROUND

• 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.

  PMID: 32958709 DERIVED

Biospecimen

Retention: SAMPLES WITHOUT DNA

The samples were collected as part of patient care in medical monitoring and resuscitation infectious Bichat Hospital. They will be used to search within the site. In these severe patients, arterial catheter is systematically implemented. The investigators plan to collect thru this catheter five blood 4ml tubes on 24hours to measure the pharmacodynamic parameters of caspofungin.

MeSH Terms

Conditions

Candidiasis

Condition Hierarchy (Ancestors)

Mycoses; Bacterial Infections and Mycoses; Infections

Study Officials

• Jean-Francois TIMSIT, Professor

  Assistance Publique - Hôpitaux de Paris

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 9, 2015
• First Posted: April 10, 2015
• Study Start: May 1, 2015
• Primary Completion: January 1, 2017
• Study Completion: February 1, 2017
• Last Updated: April 5, 2017

Record last verified: 2016-04

Locations

FR (1)