immunocompromised patients with acute respiratory failure
Conditions
Interventions
Trade Name: CRESEMBA
Product Name: ISAVUCONAZOLE
Pharmaceutical Form: Powder for infusion
Pharmaceutical form of the placebo: Solution for infusion
Route of administration of the placebo: Intravenous
Sponsors
Assistance Publique Hôpitaux de Paris
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1) Age >18 years and 30/min); b) cyanosis; c) laboured breathing; d) Need for more than 6l of standard oxygen to maintain SpO2>95%, or for high flow oxygen, non-invasive or invasive mechanical ventilation; 4) No established ARF etiology at day 3; 6) Informed consent signed: - by the patient, - Or informed consent signed by a family members/trustworthy person if his condition does not allow him to express his consent by written as per L. 1111-6, -Or in an situation urgently and in the absence of family members/trustworthy person, the patient can be enrolled. The consent to participate to the research will be requested as soon as the condition of the patient will allow him to consent. Obs: Patient with Pneumocistis pneumonia can be included given that their treatment does not require the use of neither antifungal drugs nor corticosteroids Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 300 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 120
Exclusion criteria
Exclusion criteria: 1) Patient who improved enough to be discharged from the ICU at day 3; 2) Documented invasive fungal infection requiring antifungal therapy; 3) Patient needing or receiving prophylactic or empirical antifungal treatment for clinical care 4) Patient receiving corticoid therapy; 5) Palliative care with comfort measures only (Do Not Intubate (DNI) and Do Not Resuscitate (DNR) patients can be included); 6) Pregnant or breastfeeding; 7) No social security coverage; 8) Known hypersensitivity to isavuconazole or to any of excipients of CRESEMBA® specialty; 9) Treatment with ketoconazole, ritonavir, or any CYP3A4/5 inductor; 10) Short QT syndrome and/or patient with a family history of short QT syndrome; 11) Liver insufficiency (any stage); 12) moribund patients; 13) Participation in another interventional research. 14) Person deprived of liberty. 15) Person subject of psychiatric care. 16) Patient under enforced hospitalization. 17) Adults under legal protection or unable to give their consent
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: to reduce 90-day mortality in immunocompromised patients with ARF from undetermined etiology at day-3. The intervention would evaluate the impact of steroids ± isavuconazole for 14 days or until ICU discharge. ;Secondary Objective: -Evaluate how early empirical therapy can affect ICU, hospital and day-28 mortality. -Evaluate whether steroids increase the proportion of patients with ICU acquired microbiologically documented bacterial infections within 3 months following randomization. -Evaluate the proportion of patients with invasive fungal infection within 3 months following randomization. -Evaluate the proportion of patients with HSV, VZV or CMV reactivation within 3 months following randomization. -Evaluate whether steroids are complicated by severe hypokaliemia (<2,5 meq/l), newly acquired or decompensated diabetes, or severe or newly acquired hypertension -Evaluate whether isavuconazole will favor the emergence of Aspergillus or mucorale infections with decreased sensitivity to isavuconazole -occurence of Candida infection -Evaluate how steroids affect psychiatric symptoms (Post traumatic Stress Disorder, anxiety and depression) -Evaluate how early intervention can improve quality of life;Primary end point(s): All-cause day-90 mortality;Timepoint(s) of evaluation of this end point: LVLS | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): - ICU mortality - hospital mortality - day 28 mortality - proportion of patients with ICU acquired microbiologically documented bacterial infections - proportion of patients with invasive fungal infection within 3 months following randomization - proportion of patients with HSV, VZV or CMV reactivation within 3 months following randomization -occurrence of severe hypokalemia (<2,5 meq/l), decompensated diabetes or severe or newly acquired hypertension -emergence of Aspergillus species with decreased sensitivity to isavuconazole -incidence of Candida infection -incidence of post-traumatic Stress Disorder (IES-R), anxiety and depression at 6 months (HADS) - quality of life at 6 months (SF36);Timepoint(s) of evaluation of this end point: LVLS | — |
Countries
France
Contacts
Public ContactProject manager
Assistance Publique Hôpitaux de Paris
Outcome results
None listed