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

NCT01757899 | Withdrawn Phase 2 DMC

• 1 other identifier: CONEP 16487
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

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.

Conditions

Acute Lung Injury; Acute Respiratory Distress Syndrome

Keywords

ALI; Acute Lung Injury; ARDS; Acute Respiratory Distress Syndrome; Pediatric Critical Care Medicine; Inflammatory Response

Outcome Measures

Primary Outcomes (1)

• Effects on pulmonary organ function

  * a ≥ 1-point reduction in LIS by study day 7 or successful extubation by day 7 * For patients remaining intubated on study day 7, improvement in lung function is defined as a 7-day LIS ≤ 2 (if initial LIS ≤ 2,9) or a 7-day LIS ≥ 2,5 (if initial LIS ≥ 3) Duration of mechanical ventilation defined as: * ventilator free days at 28 days of entry study * days of mechanical ventilation on day 28

  24 months

Secondary Outcomes (3)

• Effects on extra-pulmonary organ function

  24 months

• Effects on inflammatory process

  24 months

• Effects on hospitalization-related outcomes

  24 months

Other Outcomes (2)

• Complications

  12 months

• Complications

  12 months

Study Arms (2)

Methylprednisolone Arm

ACTIVE COMPARATOR

The patients in this arm will receive methylprednisolone, which is available in vials containing 125 mg/2mL after dilution, as it follows: Day 0 Loading dose 1 mg/kg IV bolus mixed in 5 mL NS (30 min) followed by continuous infusion Days 0 to 07 - 1 mg/kg/day mixed in 24cc NS and infused at 1 cc/hr Days 08 to 10 - 0.5 mg/kg/day mixed in 24cc NS and infused at 1 cc/hr Days 11 to 12 - 0.25 mg/kg/day Days 13 to 14 - 0.125 mg/kg/day

Drug: Methylprednisolone Arm

Sterile Saline Arm

PLACEBO COMPARATOR

Patients randomized to the control arm will receive sterile normal saline in an amount that would equal the total diluted dose of study drug (ie. if initial loading dose equals a total of 24 cc \[methylprednisolone + diluting fluid\], then the patient will receive 24 cc of sterile normal saline). Tapering doses will be equivalent to that of the study arm, so that investigators will remain blinded to therapy. The unblinded party will be composed of the research ARDS pharmacist. Five days after the patient is able to ingest medications, placebo is administered per os (PO) in one single daily equivalent dose. The placebo will be manipulated by the pharmacist as to resemble identical to the active drug.

Drug: Sterile Saline Arm

Interventions

Methylprednisolone Arm DRUG

Day 0 - Loading dose 1 mg/kg IV bolus mixed in 5 mL NS (30 min) followed by continuous infusion Days 0 to 07 - 1 mg/kg/day mixed in 24cc NS and infused at 1 cc/hr Days 08 to 10 - 0.5 mg/kg/day mixed in 24cc NS and infused at 1 cc/hr Days 11 to 12 - 0.25 mg/kg/day Days 13 to 14 - 0.125 mg/kg/day

Also known as: Solumedrol

Methylprednisolone Arm

Sterile Saline Arm DRUG

Patients randomized to the control arm will receive sterile normal saline in an amount that would equal the total diluted dose of study drug (ie. if initial loading dose equals a total of 24 cc \[methylprednisolone + diluting fluid\], then the patient will receive 24 cc of sterile normal saline). Tapering doses will be equivalent to that of the study arm, so that investigators will remain blinded to therapy. The unblinded party will be composed of the research ARDS pharmacist. Five days after the patient is able to ingest medications, placebo is administered per os (PO) in one single daily equivalent dose. The placebo will be manipulated by the pharmacist as to resemble identical to the active drug.

Also known as: Saline

Sterile Saline Arm

Eligibility Criteria

• Age: 29 Days - 17 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• 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.

You may not qualify if:

• 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).

Sponsors & Collaborators

• Universidade Federal do Rio de Janeiro: lead
• Instituto de Puericultura e Pediatria Martagão Gesteira - IPPMG/UFRJ: collaborator
• Instituto D'Or de Pesquisa: collaborator
• Rio de Janeiro State Research Supporting Foundation (FAPERJ): collaborator

Study Sites (1)

Universidade Federal do Rio de Janeiro

Rio de Janeiro, 21.941-912, Brazil

Location

Related Publications (1)

• 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.

  PMID: 28422025 DERIVED

MeSH Terms

Conditions

Acute Lung Injury; Respiratory Distress Syndrome

Interventions

Methylprednisolone Hemisuccinate; Sodium Chloride

Condition Hierarchy (Ancestors)

Lung Injury; Lung Diseases; Respiratory Tract Diseases; Respiration Disorders

Intervention Hierarchy (Ancestors)

Methylprednisolone; Prednisolone; Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Chlorides; Hydrochloric Acid; Chlorine Compounds; Inorganic Chemicals; Sodium Compounds

Study Officials

• Maria Clara M Barbosa

  Instituto D'Or de Pesquisa

  STUDY CHAIR

• Arnaldo P Barbosa

  Rio de Janeiro Federal University

  STUDY DIRECTOR

• Antonio José LA Cunha

  Rio de Janeiro Federal University

  STUDY DIRECTOR

• Fernanda Lima

  Instituto D'Or de Pesquisa

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: MD Msc

Study Record Dates

• First Submitted: December 21, 2012
• First Posted: December 31, 2012
• Study Start: January 1, 2014
• Primary Completion: January 1, 2016
• Study Completion: January 1, 2016
• Last Updated: July 10, 2020

Record last verified: 2020-07

Locations

BR (1)