Acute Respiratory Distress Syndrome
Conditions
Interventions
Trade Name: Methylprdnisolone Mylan 120 mg poudre pour solution injectable (IM-IV)
Pharmaceutical Form: Powder for injection
Current Sponsor code: METHYLPREDNISOLONE
Other descriptive name: METHYLPRED
Sponsors
Assistance Pubique Hôpitaux de Marseille
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Age >= 18 years Continuous endotracheal ventilation Moderate – severe ARDS according to Berlin definition (see appendix) with PaO2/FiO2 = 200 with PEEP>=5 cm H2O (For patients under ECMO, arterial blood gases have to be measured with a pump blood flow of 3 L/min and a FDO2 of 0.21 and FiO2 on mechanical ventilator of 1) Date of ARDS onset : >=day 5 and = day 14 after the onset of ARDS criteria (regardless of ARDS severity) Procollagen III above 9 µg/L in a bronchoalveolar lavage performed by the attending physician between day 3 and day 13 after the onset of ARDS and realized within 5 days prior to randomization Written informed consent of patient or proxy Patients covered by or having the rights to social security 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 178 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 178
Exclusion criteria
Exclusion criteria: •Lack of informed consent •Patients deprived of freedom or under legal authority •Patients not insured under the national social security system •Known pregnancy or breast feeding •Participation to another interventional trial within 30 days with mortality or ventilator free days as the main endpoint •Clinical evidence of active untreated infection •A known, undrained abscess (e.g., Staphylococcal lung abscess or loculated empyema or intra-abdominal abscess) •Intravascular nidus of infection (e.g., bacterial or fungal endocarditis or suppurate thrombophlebitis), even if it is being treated with antibiotics. •Disseminated fungal infection (EORTC criteria), even if being treated •Active tuberculosis, even if being treated •New nosocomial infection with less than 72 hours of antibiotics •Burns requiring skin grafting •Acquired immunodeficiency syndrome •Treatment with corticosteroids (> 200 mg/day of hydrocortisone or equivalent at any moment during the month preceding inclusion) •Cytotoxic therapy within 3 weeks •Myeloproliferative syndrome •SAPS II score at the time of enrollment > 75 •Presence of an advanced directive to withhold life-sustaining treatment or decision to withhold life-sustaining treatment •Chronic respiratory disease requiring home oxygen therapy or ventilation •Chronic interstitial or fibrotic lung disease or diffuse alveolar hemorrhage from vasculitis •Acute or chronic liver disease defined as a Child-Pugh score of C. •Preexisting neurological disease with diaphragmatic components (traumatic tetraplegia, amyotrophic lateral sclerosis, diaphragm paralysis…) •Myasthenia gravis, Guillain-Barré Syndrome and others polyradiculoneuropathies •Known or suspected allergy to methylprednisolone
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To assess the efficacy of corticosteroid systemic therapy in improving the outcome of patients with persistent ARDS (5th to 14th days after the onset of ARDS) and presenting an increased alveolar level of procollagen III.;Secondary Objective: Demonstrate that methylprednisolone started in patients presenting ARDS persistent between the 5th and 14th days of ARDS onset and with alveolar level of procollagen III indicating lung fibroproliferation, could decrease: •Mortality (day 60, day 90, ICU, hospital, day 180) •Length of ICU and hospital stay Assessing if methylprednisolone could improve: • ung function evaluated by oxygenation, tidal compliance, driving pressure and other usual ventilator parameters •need for vasopressors •level of organs dysfunctions •medium-term (180 days) physical status (AM-PAC), quality of life (SF-36) and Post-Traumatic Stress Disorder (IES-R) and depression symptoms (PHQ-9) Assessing the side-effects potentially linked to methylprednisolone administration with the occurrence of: •Infections and life-threatening infections •Critical illness neuromyopathy •Delirium and pharmacological acute psychosis •Hyperglycemia •Gastro-intestinal bleeding ;Primary end point(s): Number of Ventilator Free Days to day 60 (VFD60). ;Timepoint(s) of evaluation of this end point: Day 60 | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): • Mortality to days 60, 90 and 180 • ICU and hospital mortality • Ventilator free days to day 90 • ICU-free days at day 60 and day 90 • ICU-free days to day 60 (90) are defined as the number of days alive and free of the need for intensive care, from randomization to day 60 ( 90) after randomization • Length of ICU stay • Length of hospital stay • Organ failure and change in SOFA score Organ failure is defined according to the SOFA score. Patients will be followed for the development of organ failures to days 1, 3, 7, 14, 21, 32 or to the end of study drugs administration, ICU discharge, whichever comes first • Use of vasopressors (norepinephrine, epinephrine whatever the dose) will be recorded to days 1, 3, 7, 14, 21, 32 or to the end of study drugs administration, whichever comes first • Occurrence of ICU-acquired infections ;Timepoint(s) of evaluation of this end point: Day 60 | — |
Countries
France
Contacts
Public ContactDirector
Assistance Publique-hôpitaux de Marseille
Outcome results
None listed