E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
immunocompromised patients with acute respiratory failure |
patients immunodéprimés avec insuffisance respiratoire aiguë |
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E.1.1.1 | Medical condition in easily understood language |
immunocompromised patients with acute respiratory failure |
patients immunodéprimés avec insuffisance respiratoire aiguë |
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E.1.1.2 | Therapeutic area | Analytical, Diagnostic and Therapeutic Techniques and Equipment [E] - Therapeutic techniques [E02] |
MedDRA Classification |
E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
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. |
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E.2.2 | Secondary objectives of the trial |
-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 |
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E.2.3 | Trial contains a sub-study | Yes |
E.2.3.1 | Full title, date and version of each sub-study and their related objectives |
Pharmacokinetics and pharmacodynamics preplanned sub- studies from EFRAIM II |
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E.3 | Principal inclusion criteria |
1) Age >18 years and <90 years; 2) Known immunosuppression: a) immunosuppressive drug b) solid organ transplant; c) solid tumor; d) hematological malignancies; e) primary immune deficiency; 3) ICU admission for acute respiratory failure as defined by a) respiratory distress with tachypnea (respiratory rate>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 |
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E.4 | Principal 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 |
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E.5 End points |
E.5.1 | Primary end point(s) |
All-cause day-90 mortality |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
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E.5.2 | 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) |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | No |
E.6.5 | Efficacy | No |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 4 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 23 |
E.8.5 | The trial involves multiple Member States | No |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | |
E.8.9.1 | In the Member State concerned months | 36 |
E.8.9.1 | In the Member State concerned days | |