Empirical Antifungal Treatment in ICUS

Invasive Candidiasis Clinical Trial

— EMPIRICUS  

Official title:

Micafungin Versus Placebo in the Nosocomial Sepsis in Patients Multi-colonized With Candida, Randomized Controlled Trial

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01773876
• Other study ID #: 1126
• Secondary ID: 2011-005451-14
• Status: Completed
• Phase: Phase 3
• First received: January 14, 2013
• Last updated: March 23, 2015
• Start date: July 2012
• Est. completion date: February 2015

Study information

• Verified date: March 2015
• Source: University Hospital, Grenoble
• Contact: n/a
• Is FDA regulated: No
• Health authority: France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 260
• Est. completion date: February 2015
• Est. primary completion date: February 2015
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Candidiasis
• Candidiasis, Invasive
• Invasive Candidiasis

Intervention

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
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

Locations

Country	Name	City	State
France	Hospital Aix en Provence	Aix en Provence
France	Hospital University of Besançon	Besançon
France	University Hospital of Avicennes	Bobigny
France	Hospital University of Bordeaux	Bordeaux
France	Hospital University of Clermont Ferrand	Clermont Ferrand
France	University Hospital of Beaujon	Clichy
France	University Hospital of Dijon	Dijon
France	Hospital of Draguignan	Draguignan
France	Hospital University of Grenoble	Grenoble
France	Hospital of Versailles	Le Chesnay
France	University Hospital Edouard Herriot	Lyon
France	Hospital University of Montpellier	Montpellier
France	Interegional Hospital André Grégoire	Montreuil
France	Hospital St Joseph	Paris
France	Hospital University of Bichat	Paris
France	University Hospital of La Pitié Salpetrière	Paris
France	University Hospital Saint Louis	Paris
France	Hospital of Pontoise	Pontoise
France	Hospital University of Reims	Reims
France	Departemental Hospital of Roche sur Yon	Roche Sur Yon
France	University Hospital of Saint Etienne	Saint Etienne
France	University Hospital of Strasbourg	Strasbourg

Sponsors (1)

Lead Sponsor	Collaborator
University Hospital, Grenoble

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	survival to 28 days without proven fungal infection (a fungal infection occurring within 48 hours after inclusion will be considered available for inclusion)	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.	28 days follow-up	No
Secondary	pharmacokinetic parameters: estimated gross exposure indices: AUC, Cmax, Cmin	Reports AUC / MIC and Cmax / MIC will be calculated	during 24 hours (between the two first infusions)	No
Secondary	evaluation of tolerance	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	3 months	No
Secondary	pharmacodynamic parameters: potential serum biomarkers of treatment efficacy (PCR Candida,1,3 ß-D-glucan,mannan antigenemia,anti-mannan,Procalcitonin (proCT))		during 28 days	No
Secondary	pharmacodynamic parameters: Early prognostic factors of response: J7 survival without proven invasive candidiasis		during 14 days	No
Secondary	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)		during 90 days	No
Secondary	Evaluate the impact of empiric treatment with micafungin in patients with invasive candidiasis can free survival antifungal treatment at day 28		during 28 days	No
Secondary	Evaluate the impact of empiric treatment with micafungin in patients with invasive candidiasis possible evolution of organ failure during the study		during 90 days	No
Secondary	Evaluate the impact of empiric treatment with micafungin in patients with invasive candidiasis possible the use of mechanical ventilation during the study		during 90 days	No
Secondary	Evaluate the impact of empiric treatment with micafungin in patients with invasive candidiasis possible evolution of the colonization index during study		during 90 days	No
Secondary	Evaluate the impact of empiric treatment with micafungin in patients with invasive candidiasis possible changes in serum biomarkers (1-3 ß-D-glucan, mannan antigenemia, anti-mannan Candida PCR) during the study		during 90 days	No
Secondary	Evaluate the impact of empiric treatment with micafungin in patients with invasive candidiasis possible on the incidence of pneumonia acquired bacterial mechanical ventilation (VAP).		during 90 days	No