EMPIRICUS: Empirical Antifungal Treatment in ICUS

Sponsor

University Hospital, Grenoble (Other)

Overall Status

Completed

CT.gov ID

NCT01773876

Collaborator

(none)

260

Enrollment

Locations

Arms

Duration (Months)

11.8

Patients Per Site

0.4

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Invasive Candidiasis	Drug: Micafungin Drug: PLACEBO	Phase 3

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.

Study Design

Study Type:

Interventional

Actual Enrollment :

260 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Triple (Participant, Care Provider, Investigator)

Primary Purpose:

Treatment

Official Title:

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

Study Start Date :

Jul 1, 2012

Actual Primary Completion Date :

Feb 1, 2015

Actual Study Completion Date :

Feb 1, 2015

Arms and Interventions

Arm	Intervention/Treatment
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

Arm

Intervention/Treatment

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

Outcome Measures

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) [28 days follow-up]
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 [during 24 hours (between the two first infusions)]
Reports AUC / MIC and Cmax / MIC will be calculated
evaluation of tolerance [3 months]
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)) [during 28 days]
pharmacodynamic parameters: Early prognostic factors of response: J7 survival without proven invasive candidiasis [during 14 days]
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]
Evaluate the impact of empiric treatment with micafungin in patients with invasive candidiasis can free survival antifungal treatment at day 28 [during 28 days]
Evaluate the impact of empiric treatment with micafungin in patients with invasive candidiasis possible evolution of organ failure during the study [during 90 days]
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]
Evaluate the impact of empiric treatment with micafungin in patients with invasive candidiasis possible evolution of the colonization index during study [during 90 days]
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 [during 90 days]
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]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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

Locations

	Site	City	Country	Postal Code
1	Hospital Aix en Provence	Aix en Provence	France	13616
2	Hospital University of Besançon	Besançon	France	67091
3	University Hospital of Avicennes	Bobigny	France	93009
4	Hospital University of Bordeaux	Bordeaux	France	33000
5	Hospital University of Clermont Ferrand	Clermont Ferrand	France	63003
6	University Hospital of Beaujon	Clichy	France	92110
7	University Hospital of Dijon	Dijon	France	21000
8	Hospital of Draguignan	Draguignan	France	83300
9	Hospital University of Grenoble	Grenoble	France	38043
10	Hospital of Versailles	Le Chesnay	France	78150
11	University Hospital Edouard Herriot	Lyon	France	96433
12	Hospital University of Montpellier	Montpellier	France	34295
13	Interegional Hospital André Grégoire	Montreuil	France	93105
14	University Hospital Saint Louis	Paris	France	75010
15	University Hospital of La Pitié Salpetrière	Paris	France	75013
16	Hospital St Joseph	Paris	France	75014
17	Hospital University of Bichat	Paris	France	75877
18	Hospital of Pontoise	Pontoise	France	95303
19	Hospital University of Reims	Reims	France	51092
20	Departemental Hospital of Roche sur Yon	Roche Sur Yon	France	85925
21	University Hospital of Saint Etienne	Saint Etienne	France	42055
22	University Hospital of Strasbourg	Strasbourg	France	67091