Clinical trial NCT01757899: Effects and Safety of Infusion of Low-Doses of Methylprednisolone in Early ALI and ARDS in Children
Official title: Phase II, Randomized, Placebo-Controlled, Double-Blind Clinical Trial to Evaluate the Effects and Safety of Infusion of Low-Doses of Methylprednisolone in Early ALI and ARDS in Children
Study type: INTERVENTIONAL
Overall status: WITHDRAWN
Phase: PHASE2
Conditions: Acute Lung Injury
Acute Respiratory Distress Syndrome
Keywords: ALI
Acute Lung Injury
ARDS
Acute Respiratory Distress Syndrome
Pediatric Critical Care Medicine
Inflammatory Response
Lead sponsor: Universidade Federal do Rio de Janeiro
Sponsor class: OTHER
Collaborators: name: Instituto de Puericultura e Pediatria Martagão Gesteira - IPPMG/UFRJ
name: Instituto D'Or de Pesquisa
name: Rio de Janeiro State Research Supporting Foundation (FAPERJ)
First posted: 2012-12-31
Enrollment: 0
Sex: ALL
Minimum age (years): 29
Maximum age (years): 17
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to investigate the effects of prolonged low-dose methylprednisolone infusion on pulmonary function (LIS and ventilation-free days), extra pulmonary organ function (PMODS score), inflammatory markers - RCP (Reactive C Protein), IL6 (Interleukine 6), TNFα (Tumor Necrosis Factor), IL8 (Interleukine 8), IL10 (Interleukine 10) and length of Pediatric Intensive Care Unit (PICU) stay in early ALI/ARDS in children.

Detailed description: Scientific background. Dysregulated systemic inflammation - characterized by protracted elevation of inflammatory cytokines in the circulation - is a key pathogenetic mechanism for morbidity and mortality in ALI/ARDS, and is associated with tissue insensitivity and/or resistance to inappropriately elevated endogenous glucocorticoids. In one study, prolonged methylprednisolone treatment of ARDS patients resulted in rapid and sustained reduction in circulating and pulmonary levels of pro-inflammatory cytokines, chemokines, and procollagen.

Preliminary work. Two recent metanalysis evaluating the use of low doses of corticosteroids in acute lung injury/ARDS in adults reported a significant physiological improvement, a sizable reduction in duration of mechanical ventilation and ICU length of stay and reduction in mortality.

Hypothesis. We hypothesized that prolonged administration of low doses of methylprednisolone in pediatric ALI/ARDS is safe and downregulates systemic inflammation and leads to earlier resolution of pulmonary and extra pulmonary organ dysfunction and a reduction in duration of mechanical ventilation and ICU stay.

Objective. To investigate the effects of prolonged low-dose methylprednisolone infusion on pulmonary function (LIS and ventilation-free days), extra pulmonary organ function (PMODS score), inflammatory markers - RCP (Reactive C Protein), IL6 (Interleukine 6), TNFα (Tumor Necrosis Factor), IL8 (Interleukine 8), IL10 (Interleukine 10) and length of Pediatric Intensive Care Unit (PICU) stay in early ALI/ARDS in children.

Study design. Prospective randomized, placebo-controlled, double-blind clinical trial.

Eligibility criteria: Inclusion Criteria:

* Diagnosis of ALI/ARDS within the first 72 hours based on all of the following criteria:

  * Respiratory failure requiring mechanical ventilation - via endotracheal intubation or noninvasive positive pressure ventilation;
  * Acute onset of bilateral pulmonary densities on chest radiograph in the context of appropriate predisposing injury or illness with no evidence of left ventricular failure;
  * Ratio of partial pressure of arterial oxygen to fraction of inspired oxygen (PaO2:FiO2 ) ≤ 300 (criteria for ALI) or 200 (criteria for ARDS) with FiO2 ≥ 0,5 and PEEP = 5 cmH2O.
* To sign the Informed Consent to participate.

Exclusion Criteria:

* ALI/ARDS with more than 72 hours of diagnosis
* Failure to obtain written informed consent to participate in the study;
* Condition requiring \> 0.5mg/Kg/day of prednisone equivalent (i.e., acute asthma or bronchopulmonary dysplasia)
* Patients enrolled in another experimental (interventional) protocol within the past 30 days, which might adversely impact on the results of this study as determined by the investigators;
* Primary or secondary neuromuscular dysfunction
* Patients using aminoglycosides combined with neuromuscular blockers
* Cardiopulmonary arrest within 7 days or anytime during present hospitalization prior to enrollment;
* Irreversible cessation of all brain function;
* Immunosuppression, including HIV+ status, history of bone marrow or solid organ transplantation, current malignancy, neutropenia, receiving cytotoxic therapy for any reason, and acute burn injury;
* Severe chronic liver disease (Child-Pugh Class C score \> 10 points).

Primary outcomes:
measure: Effects on pulmonary organ function
timeFrame: 24 months
Secondary outcomes:
measure: Effects on extra-pulmonary organ function
timeFrame: 24 months
measure: Effects on inflammatory process
timeFrame: 24 months
measure: Effects on hospitalization-related outcomes
timeFrame: 24 months
Other outcomes:
measure: Complications
timeFrame: 12 months
measure: Complications
timeFrame: 12 months
Locations:
city: Rio de Janeiro
country: Brazil
facility: Universidade Federal do Rio de Janeiro
Study officials:
affiliation: Instituto D'Or de Pesquisa
name: Maria Clara M Barbosa
role: STUDY_CHAIR
affiliation: Rio de Janeiro Federal University
name: Arnaldo P Barbosa
role: STUDY_DIRECTOR
affiliation: Rio de Janeiro Federal University
name: Antonio José LA Cunha
role: STUDY_DIRECTOR
affiliation: Instituto D'Or de Pesquisa
name: Fernanda Lima
role: PRINCIPAL_INVESTIGATOR
References:
citation: Sweeney RM, McAuley DF. Prolonged glucocorticoid treatment in acute respiratory distress syndrome - Authors' reply. Lancet. 2017 Apr 15;389(10078):1516-1517. doi: 10.1016/S0140-6736(17)30953-4. No abstract available.