Clinical trial NCT01773876: Empirical Antifungal Treatment in ICUS
Official title: Micafungin Versus Placebo in the Nosocomial Sepsis in Patients Multi-colonized With Candida, Randomized Controlled Trial
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Invasive Candidiasis
Keywords: survival without proven invasive candidiasis
effectiveness
micafungin versus placebo
pharmacokinetic
pharmacodynamic
tolerance
Lead sponsor: University Hospital, Grenoble
Sponsor class: OTHER
First posted: 2013-01-23
Enrollment: 260
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.

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 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

Primary outcomes:
measure: survival to 28 days without proven fungal infection (a fungal infection occurring within 48 hours after inclusion will be considered available for inclusion)
timeFrame: 28 days follow-up
Secondary outcomes:
measure: pharmacokinetic parameters: estimated gross exposure indices: AUC, Cmax, Cmin
timeFrame: during 24 hours (between the two first infusions)
measure: evaluation of tolerance
timeFrame: 3 months
measure: pharmacodynamic parameters: potential serum biomarkers of treatment efficacy (PCR Candida,1,3 β-D-glucan,mannan antigenemia,anti-mannan,Procalcitonin (proCT))
timeFrame: during 28 days
measure: pharmacodynamic parameters: Early prognostic factors of response: J7 survival without proven invasive candidiasis
timeFrame: during 14 days
measure: 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)
timeFrame: during 90 days
measure: Evaluate the impact of empiric treatment with micafungin in patients with invasive candidiasis can free survival antifungal treatment at day 28
timeFrame: during 28 days
measure: Evaluate the impact of empiric treatment with micafungin in patients with invasive candidiasis possible evolution of organ failure during the study
timeFrame: during 90 days
measure: Evaluate the impact of empiric treatment with micafungin in patients with invasive candidiasis possible the use of mechanical ventilation during the study
timeFrame: during 90 days
measure: Evaluate the impact of empiric treatment with micafungin in patients with invasive candidiasis possible evolution of the colonization index during study
timeFrame: during 90 days
measure: 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
timeFrame: during 90 days
measure: Evaluate the impact of empiric treatment with micafungin in patients with invasive candidiasis possible on the incidence of pneumonia acquired bacterial mechanical ventilation (VAP).
timeFrame: during 90 days
Other outcomes:
Locations:
city: Aix en Provence
country: France
facility: Hospital Aix en Provence
city: Besançon
country: France
facility: Hospital University of Besançon
city: Bobigny
country: France
facility: University Hospital of Avicennes
city: Bordeaux
country: France
facility: Hospital University of Bordeaux
city: Clermont Ferrand
country: France
facility: Hospital University of Clermont Ferrand
city: Clichy
country: France
facility: University Hospital of Beaujon
city: Dijon
country: France
facility: University Hospital of Dijon
city: Draguignan
country: France
facility: Hospital of Draguignan
city: Grenoble
country: France
facility: Hospital University of Grenoble
city: Le Chesnay
country: France
facility: Hospital of Versailles
city: Lyon
country: France
facility: University Hospital Edouard Herriot
city: Montpellier
country: France
facility: Hospital University of Montpellier
city: Montreuil
country: France
facility: Interegional Hospital André Grégoire
city: Paris
country: France
facility: University Hospital Saint Louis
city: Paris
country: France
facility: University Hospital of La Pitié Salpetrière
city: Paris
country: France
facility: Hospital St Joseph
city: Paris
country: France
facility: Hospital University of Bichat
city: Pontoise
country: France
facility: Hospital of Pontoise
city: Reims
country: France
facility: Hospital University of Reims
city: Roche Sur Yon
country: France
facility: Departemental Hospital of Roche sur Yon
city: Saint Etienne
country: France
facility: University Hospital of Saint Etienne
city: Strasbourg
country: France
facility: University Hospital of Strasbourg
Study officials:
affiliation: University Hospital, Grenoble
name: TIMSIT JFT Jean François, PU-PH
role: PRINCIPAL_INVESTIGATOR
References:
citation: Timsit JF, Azoulay E, Schwebel C, Charles PE, Cornet M, Souweine B, Klouche K, Jaber S, Trouillet JL, Bruneel F, Argaud L, Cousson J, Meziani F, Gruson D, Paris A, Darmon M, Garrouste-Orgeas M, Navellou JC, Foucrier A, Allaouchiche B, Das V, Gangneux JP, Ruckly S, Maubon D, Jullien V, Wolff M; EMPIRICUS Trial Group. Empirical Micafungin Treatment and Survival Without Invasive Fungal Infection in Adults With ICU-Acquired Sepsis, Candida Colonization, and Multiple Organ Failure: The EMPIRICUS Randomized Clinical Trial. JAMA. 2016 Oct 18;316(15):1555-1564. doi: 10.1001/jama.2016.14655.
citation: Timsit JF, Azoulay E, Cornet M, Gangneux JP, Jullien V, Vesin A, Schir E, Wolff M. EMPIRICUS micafungin versus placebo during nosocomial sepsis in Candida multi-colonized ICU patients with multiple organ failures: study protocol for a randomized controlled trial. Trials. 2013 Nov 21;14:399. doi: 10.1186/1745-6215-14-399.