Empirical Antifungal Treatment in ICUS (EMPIRICUS)

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
University Hospital, Grenoble
ClinicalTrials.gov Identifier:
NCT01773876
First received: January 14, 2013
Last updated: March 23, 2015
Last verified: March 2015
  Purpose

Invasive Candida infections are burdened with a high mortality rate and is very common in intensive care units. This study aims to evaluate the efficacy of empirical treatment with micafungin in adult patients with suspected invasive candidiasis.


Condition Intervention Phase
Invasive Candidiasis
Drug: Micafungin
Drug: PLACEBO
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator)
Primary Purpose: Treatment
Official Title: Micafungin Versus Placebo in the Nosocomial Sepsis in Patients Multi-colonized With Candida, Randomized Controlled Trial

Resource links provided by NLM:


Further study details as provided by University Hospital, Grenoble:

Primary Outcome Measures:
  • survival to 28 days without proven fungal infection (a fungal infection occurring within 48 hours after inclusion will be considered available for inclusion) [ Time Frame: 28 days follow-up ] [ Designated as safety issue: No ]
    breakthrough infection defined as a proven infection occurs at least 48 hours after initiation of treatment Proven infection is considered purchased after enrollment if the first significant positive levy occurs after the 48 th hour after enrollment.


Secondary Outcome Measures:
  • pharmacokinetic parameters: estimated gross exposure indices: AUC, Cmax, Cmin [ Time Frame: during 24 hours (between the two first infusions) ] [ Designated as safety issue: No ]
    Reports AUC / MIC and Cmax / MIC will be calculated

  • evaluation of tolerance [ Time Frame: 3 months ] [ Designated as safety issue: No ]

    For all patients who received at least one dose of treatment:

    • number of adverse events reported after randomization up to 28 days, only death will count up to 3 months post-randomization (information on the long-term survival collected by telephone),
    • changes in the clinical examination, vital signs and laboratory results,
    • overall survival defined as the time from randomization to date of death from any cause.
    • Changes in liver function tests (bilirubin, ALT, AST, rate prothrombin, alkaline phosphatase) at the end of treatment and at the end study

  • pharmacodynamic parameters: potential serum biomarkers of treatment efficacy (PCR Candida,1,3 β-D-glucan,mannan antigenemia,anti-mannan,Procalcitonin (proCT)) [ Time Frame: during 28 days ] [ Designated as safety issue: No ]
  • pharmacodynamic parameters: Early prognostic factors of response: J7 survival without proven invasive candidiasis [ Time Frame: during 14 days ] [ Designated as safety issue: No ]
  • Evaluate the impact of empiric treatment with micafungin in patients with invasive candidiasis possible on all-cause mortality at day 28 (end of study) and J90 (3 months post-randomization) [ Time Frame: during 90 days ] [ Designated as safety issue: No ]
  • Evaluate the impact of empiric treatment with micafungin in patients with invasive candidiasis can free survival antifungal treatment at day 28 [ Time Frame: during 28 days ] [ Designated as safety issue: No ]
  • Evaluate the impact of empiric treatment with micafungin in patients with invasive candidiasis possible evolution of organ failure during the study [ Time Frame: during 90 days ] [ Designated as safety issue: No ]
  • Evaluate the impact of empiric treatment with micafungin in patients with invasive candidiasis possible the use of mechanical ventilation during the study [ Time Frame: during 90 days ] [ Designated as safety issue: No ]
  • Evaluate the impact of empiric treatment with micafungin in patients with invasive candidiasis possible evolution of the colonization index during study [ Time Frame: during 90 days ] [ Designated as safety issue: No ]
  • Evaluate the impact of empiric treatment with micafungin in patients with invasive candidiasis possible changes in serum biomarkers (1-3 β-D-glucan, mannan antigenemia, anti-mannan Candida PCR) during the study [ Time Frame: during 90 days ] [ Designated as safety issue: No ]
  • Evaluate the impact of empiric treatment with micafungin in patients with invasive candidiasis possible on the incidence of pneumonia acquired bacterial mechanical ventilation (VAP). [ Time Frame: during 90 days ] [ Designated as safety issue: No ]

Enrollment: 260
Study Start Date: July 2012
Study Completion Date: February 2015
Primary Completion Date: February 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Micafungin
MYCAMINE 100 mg intravenous an injection of 24 hours
Drug: Micafungin

MYCAMINE 100 mg intravenous 100 mg of powder reconstituted in a 100 ml infusion bag of sodium chloride 0.9%

infusion over 24 hours for 14 days discontinuation of treatment if proven invasive candidiasis

Placebo Comparator: PLACEBO
0.9% sodium chlorides 100ml infusion
Drug: PLACEBO
solution of sodium chloride 0.9% 100 ml for intravenous infusion infusion over 24 hours for 14 days discontinuation of placebo if proven invasive candidiasis

Detailed Description:

Multicenter, randomized, double-blind parallel groups comparing adult patients with suspected invasive candidiasis input from a 14-day empirical treatment with micafungin (MYCAMINE 100 mg) with placebo on survival without invasive candidiasis in 28 days after initiation of study treatment.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Age ≥ 18 years
  • Persistent sepsis without documented invasive candidiasis:

systemic inflammatory response syndrome (SIRS) presence of two signs on the 4 [temperature <36 ° C or> 38 ° C, heart rate> 90/min, respiratory rate> 20/min or PaCO2 <32 mmHg, leukocytosis> 12,000 / mm3, <4.000/mm3 or presence of circulating immature forms (> 10% of cells)] mechanical ventilation (intubation or tracheostomy) for over 4 days (96 hours) central line use of broad-spectrum antibacterial for more than 4 calendar days (96 hours) in the previous week presence of at least one extra-digestive site colonized by Candida sp. (Urine, mouth, throat, upper and lower respiratory tract, skin folds, and suction drains after surgery ...), not lower digestive tract, are not taken into account the positive samples of rectal swabs and / or stool cultures, absence of proven bacterial infections untreated no evidence of invasive fungal infections (positive blood culture, positive culture of a surgical site, deep biopsy with fungal) infection or mold according to the criteria of the group "fungal infection of the EORTC" organ failure

  • Hospitalization in intensive care for over 5 days (120 hours)
  • Giving a free, informed and in writing. In the absence of the person of trust or a family member (if present)consent to emergency possible.
  • Receiving a social security system,
  • Negative pregnancy test for patients of childbearing age

Exclusion Criteria:

  • Proven invasive fungal infection (positive blood culture, positive culture of a surgical site, deep biopsy with fungal infection), including aspergillosis requiring antifungal therapy at the time of randomization
  • Prognosis of less than 48 hours (for which the patient outcome will be fatal whatever treatment),
  • Echinocandin antifungal treatment by more than one day or another antifungal for over 72 hours in the week before the inclusion visit,
  • Allergy, hypersensitivity or known intolerance to echinocandins antifungal or any of the excipients of the drug
  • Neutropenia (ANC <500/mm3)
  • History of organ and bone marrow,
  • Recent chemotherapy (less than 6 months)
  • Systemic immunosuppressive therapy in progress, other than with corticosteroids at doses below 2 mg / kg / day of prednisolone or equivalent
  • Participation in another interventional study in the same ICU stay or making treatment being evaluated within 28 days prior to randomization
  • Any clinical investigator deems incompatible with the conduct of the study in acceptable security conditions
  • Pregnant and lactating women,
  • Adults subject to a legal protection measure
  • Persons deprived of their liberty by a judicial or administrative decision, those hospitalized without consent, persons admitted to a health facility or social purposes other than research
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01773876

Locations
France
Hospital Aix en Provence
Aix en Provence, France, 13616
Hospital University of Besançon
Besançon, France, 67091
University Hospital of Avicennes
Bobigny, France, 93009
Hospital University of Bordeaux
Bordeaux, France, 33000
Hospital University of Clermont Ferrand
Clermont Ferrand, France, 63003
University Hospital of Beaujon
Clichy, France, 92110
University Hospital of Dijon
Dijon, France, 21000
Hospital of Draguignan
Draguignan, France, 83300
Hospital University of Grenoble
Grenoble, France, 38043
Hospital of Versailles
Le Chesnay, France, 78150
University Hospital Edouard Herriot
Lyon, France, 96433
Hospital University of Montpellier
Montpellier, France, 34295
Interegional Hospital André Grégoire
Montreuil, France, 93105
Hospital St Joseph
Paris, France, 75014
Hospital University of Bichat
Paris, France, 75877
University Hospital of La Pitié Salpetrière
Paris, France, 75013
University Hospital Saint Louis
Paris, France, 75010
Hospital of Pontoise
Pontoise, France, 95303
Hospital University of Reims
Reims, France, 51092
Departemental Hospital of Roche sur Yon
Roche Sur Yon, France, 85925
University Hospital of Saint Etienne
Saint Etienne, France, 42055
University Hospital of Strasbourg
Strasbourg, France, 67091
Sponsors and Collaborators
University Hospital, Grenoble
Investigators
Principal Investigator: TIMSIT JFT Jean François, PU-PH University Hospital, Grenoble
  More Information

No publications provided by University Hospital, Grenoble

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: University Hospital, Grenoble
ClinicalTrials.gov Identifier: NCT01773876     History of Changes
Other Study ID Numbers: 1126, 2011-005451-14
Study First Received: January 14, 2013
Last Updated: March 23, 2015
Health Authority: France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)

Keywords provided by University Hospital, Grenoble:
survival without proven invasive candidiasis
effectiveness
micafungin versus placebo
pharmacokinetic
pharmacodynamic
tolerance

Additional relevant MeSH terms:
Candidiasis
Candidiasis, Invasive
Mycoses
Micafungin
Anti-Infective Agents
Antifungal Agents
Pharmacologic Actions
Therapeutic Uses

ClinicalTrials.gov processed this record on April 26, 2015