Effects and Safety of Infusion of Low-Doses of Methylprednisolone in Early ALI and ARDS in Children

Condition(s) targeted: Acute Lung Injury; Acute Respiratory Distress Syndrome

Intervention: Methylprednisolone Arm (Drug); Sterile Saline Arm (Drug)

Phase: Phase 2

Status: Recruiting

Sponsored by: Universidade Federal do Rio de Janeiro

Official(s) and/or principal investigator(s):
Maria Clara M Barbosa, Study Chair, Affiliation: Instituto D'Or de Pesquisa
Arnaldo P Barbosa, Study Director, Affiliation: Rio de Janeiro Federal University
Antonio José LA Cunha, Study Director, Affiliation: Rio de Janeiro Federal University
Fernanda Lima, Principal Investigator, Affiliation: Instituto D'Or de Pesquisa

Overall contact:
Fernanda Lima, Phone: 55-21-87466666, Email: felimasetta@gmail.com

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.

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 design: Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Primary outcome: Effects on pulmonary organ function

Secondary outcome:

Effects on extra-pulmonary organ function

Effects on inflammatory process

Effects on hospitalization-related outcomes

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.

Minimum age: N/A. Maximum age: 17 Years. Gender(s): Both.

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).

Fernanda Lima, Phone: 55-21-87466666, Email: felimasetta@gmail.com

Universidade Federal do Rio de Janeiro, Rio de Janeiro 21.941-912, Brazil; Recruiting
Cleyde T Vanzillotta, Phone: 55-21-25453503, Email: cleydecv@yahoo.com.br
Arnaldo P Barbosa, Phone: 55-21-25453500, Email: apbarbosa@globo.com
Cleyde T Vanzillotta, Principal Investigator

Starting date: February 2014
Last updated: May 29, 2015