Acute Lung InjuryPhase 2PEDALINCT01757899

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

A Phase 2 study testing Methylprednisolone Arm and Sterile Saline Arm in people with Acute Lung Injury and Acute Respiratory Distress Syndrome, run by Universidade Federal do Rio de Janeiro at 1 site in Brazil.

Withdrawn

Withdrawn. The study stopped before anyone enrolled.

Official record

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Trial 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… Read more about this study

Who is it for?: Ages 29 days to 17 years
Conditions the study is for: Acute Lung Injury, Acute Respiratory Distress Syndrome
What is being tested?: Methylprednisolone Arm and Sterile Saline Arm
Type of treatment: Injection or infusion
Could I receive a placebo?: Yes, some participants may receive a placebo
How many people: 0 participants
Where: 1 siteBrazil
Study dates: Jan 2014to Jan 2016
Phase: Phase 2
Are there results?: None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 29 days to 17 years
All sexes
No healthy volunteers
Child

Who may be able to join

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.

Who cannot join

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

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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).

Trial locations and contacts

1 site in 1 country.

Brazil1 site

Universidade Federal do Rio de Janeiro
Rio de Janeiro, 21.941-912

Other trials in Brazil

About this study

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

Read the 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.

Conditions: Acute Lung Injury, Acute Respiratory Distress Syndrome
Being tested: Methylprednisolone Arm, Sterile Saline Arm
Keywords: ALI, Acute Lung Injury, ARDS, Acute Respiratory Distress Syndrome, Pediatric Critical Care Medicine, Inflammatory Response
Medical subject headings: Acute Lung Injury, Respiratory Distress Syndrome

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

Methylprednisolone ArmDrug
Also called Solumedrol
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
Sterile Saline ArmDrug
Also called Saline
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.

Study groups in NCT01757899
Study group	Role	What they receive
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 Receives: 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. Receives: Drug: Sterile Saline Arm

What is being measured

The primary outcome is the main question the study is designed to answer.

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
Measured: 24 months

Secondary outcomes (3)

Effects on extra-pulmonary organ function
pediatric multiple organ dysfunction score (P-MODS) by study day 7
Measured: 24 months
Effects on inflammatory process
Levels of CRP, TNFα, IL-6, IL-8, IL-10 by study day 7
Measured: 24 months
Effects on hospitalization-related outcomes
Length of PICU stay
Measured: 24 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

Jan 2014Jan 2016

First posted31 Dec 2012 (estimated)
Study startJan 2014 (estimated)
Primary completionJan 2016 (estimated)
Study completionJan 2016 (estimated)

Why it stopped: Technical problems

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Publications (1)Papers the sponsor has linked to this study.
Other trials for Acute Lung InjuryStudies of the same condition, open and under way.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 2
Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Quadruple blind
Who is masked: Participant, Care provider, Investigator, Outcomes assessor
Enrolment: 0 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT01757899
Sponsor's protocol ID: CONEP 16487
Acronym: PEDALI
Status last verified: Jul 2020
First submitted: 21 Dec 2012
Last updated: 10 Jul 2020
Results posted: No
Data monitoring committee: Yes

Publications

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.
PubMed 28422025

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

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Study at a glance

From the registry record, last updated by the sponsor on 10 Jul 2020. Recruitment status is as the sponsor reported it: confirm with the study team.

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
ClinicalTrials.gov ID: NCT01757899
Acronym / sponsor ID: PEDALI / CONEP 16487
Conditions: Acute Lung Injury, Acute Respiratory Distress Syndrome
Keywords: ALI, Acute Lung Injury, ARDS, Acute Respiratory Distress Syndrome, Pediatric Critical Care Medicine, Inflammatory Response
Phase: Phase 2
Study type: Interventional
Recruitment status: WithdrawnReason stopped: Technical problems
Enrolment: 0 participants (actual)
Lead sponsor: Universidade Federal do Rio de JaneiroUniversity, hospital or other
Collaborators: Instituto de Puericultura e Pediatria Martagão Gesteira - IPPMG/UFRJ, Instituto D'Or de Pesquisa, Rio de Janeiro State Research Supporting Foundation (FAPERJ)
Study start: Jan 2014 (estimated)
Primary completion: Jan 2016 (estimated)
Study completion: Jan 2016 (estimated)
First posted: 31 Dec 2012 (estimated)
Results: Not posted in the source record

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Detailed description

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

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Quadruple blind (participant, care provider, investigator, outcomes assessor)
Number of arms: 2

Arm	Type	Receives
Methylprednisolone Arm	Active comparator	Drug: Methylprednisolone ArmThe 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
Sterile Saline Arm	Placebo comparator	Drug: Sterile Saline ArmPatients 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.

Who may qualify

Ages: 29 days to 17 years
Sex: All
Healthy volunteers: Not accepted
Age groups: Child

Key inclusion criteria (5 listed)

Diagnosis of ALI/ARDS within the first 72 hours based on all of the following criteria:
To sign the Informed Consent to participate.

Key exclusion criteria (10 listed)

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

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
Methylprednisolone ArmAlso: SolumedrolDay 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 ArmAlso: SalinePatients 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

Primary outcome

Effects on pulmonary organ function
Time frame: 24 months
* 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

3 secondary outcomes

Effects on extra-pulmonary organ function
Time frame: 24 months
Effects on inflammatory process
Time frame: 24 months
Effects on hospitalization-related outcomes
Time frame: 24 months

Results and safety

The study was withdrawn before enrolling participants, so there are no results.

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 10 Jul 2020.
Derived from this study: PubMed 28422025Sweeney 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.

Related trials for Acute Lung Injury

Enrolling by invitation
Personalized Ventilator Settings for Patients on ECMO
Acute Respiratory Distress Syndrome (ARDS), Extracorporeal Membrane Oxygenation
Active, not recruiting
CT for Personalized Mechanical Ventilation
Ventilator-Induced Lung Injury, Sepsis Syndrome
Not yet recruitingObservational study
Development and Multicenter Validation of an Explainable System for Neonatal ARDS-Compatible Phenotyping
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RecruitingObservational study
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Recruiting
WIN Ratio Analysis to Determine a Strategy of Non- Invasive SUpport for Respiratory Failure in the EmeRgency Department
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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Maria Clara M Barbosa study chair

Instituto D'Or de Pesquisa

Arnaldo P Barbosa study director

Rio de Janeiro Federal University

Antonio José LA Cunha study director

Rio de Janeiro Federal University

1 site in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 5 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: withdrawn, as of the sponsor's last update on 10 Jul 2020. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in Brazil. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study was withdrawn before enrolling participants, so there are no results.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Effects on pulmonary organ function (time frame: 24 months). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01757899, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 10 Jul 2020.