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Steroids in Patients With Early ARDS

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00562835
Recruitment Status : Unknown
Verified November 2007 by Catholic University of the Sacred Heart.
Recruitment status was:  Not yet recruiting
First Posted : November 22, 2007
Last Update Posted : November 22, 2007
Information provided by:
Catholic University of the Sacred Heart

Brief Summary:

Scientific background. Dysregulated systemic inflammation 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. Five randomized trials (N = 518) investigating prolonged glucocorticoid treatment in acute lung injury/ARDS reported a significant physiological improvement and a sizable reduction in duration of mechanical ventilation and ICU length of stay. Insufficient data is available on the effects of low dose prolonged methylprednisolone treatment initiated in early ALI/ARDS on mortality.

Hypothesis. We hypothesized that the anti-inflammatory activity associated with prolonged methylprednisolone administration improves pulmonary and extra-pulmonary organ dysfunction in early ALI/ARDS and reduces mortality.

Objective. To investigate the effects of prolonged low-dose methylprednisolone infusion on mortality and morbidity in early ALI/ARDS.

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

Entry criteria. Patients with ALI/ARDS of less than 72 hours duration.

Stratification. Patients are prospectively stratified prior to randomization as (1) intubated versus NPPV treated, and (2) ARDS versus severe ARDS. The purpose of stratification is to distribute equally in both arms intubated versus NPPV treated, and ARDS versus severe ARDS.

End-points. The primary end-point of trial is 28 days all cause mortality; the secondary end-points are (a) ventilator-free days at 28 days following study entry, (b) organ failure-free days at 28 days following study entry, and (c) duration of ICU stay.

Condition or disease Intervention/treatment Phase
Acute Lung Injury ARDS, Human Drug: Methylprednisolone Other: Normal saline intravenously and vitamin B1 per os Phase 2 Phase 3

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 400 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Randomized, Placebo-Controlled, Double-Blind Clinical Trial to Evaluate the Safety and Efficacy of Low-Dose Glucocorticoid Infusion in Acute Respiratory Distress Syndrome (ARDS)
Study Start Date : February 2008
Estimated Study Completion Date : February 2009

Arm Intervention/treatment
Active Comparator: 1
Drug: Methylprednisolone

Drug: Methylprednisolone Day 0 Loading dose 1 mg/kg IV bolus (30 min) followed by continuous infusion; Days 0 to 14*† ‡ 1 mg/kg/day mixed in 240cc Normal saline (NS) and infused at 10 cc/hr; Days 15 to 21*‡ 0.5 mg/kg/day mixed in 240cc NS and infused at 10 cc/hr; Days 22 to 25*‡ 0.25 mg/kg/day; Days 26 to 28*‡ 0.125 mg/kg/day

*Five days after the patient is able to ingest medications, methylprednisolone is given per os in one single daily equivalent dose.

†If between days 1 to 14 the patient is extubated, he is advanced to day 15 of drug therapy and tapered according to schedule.

‡ When leaving ICU, if the patient is still not tolerating p.o. intake for at least five days, he should receive the specified dosage as IV push every 6 hours until tolerating oral ingestion

Placebo Comparator: 2 Other: Normal saline intravenously and vitamin B1 per os
Patients in this group 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 25 cc [prednisolone + diluting fluid], then the patient will receive 25 cc of sterile normal saline). Tapering doses will be equivalent to that of the study arm. Five days after the patient is able to ingest medications, placebo is administered per os in one single daily equivalent dose. The placebo will be a Vitamin B1 (thiamine) 50-mg tablet. We will now designate each placebo tab as a 16-mg equivalent to each tablet of active drug. These tablets are scored and half tabs can be given if needed. Therefore if a patient is receiving 40 mg of study drug: 40/16 = 2.5 tabs x 50 mg = 125 mg actual dose of thiamine.
Other Name: Thiamine

Primary Outcome Measures :
  1. The primary aim is to determine if low-dose methylprednisolone infusion, compared to placebo, will reduce all cause 28-day mortality, defined as the proportion of patients alive in each group on study day 28 at midnight. [ Time Frame: one year ]

Secondary Outcome Measures :
  1. The secondary aims are the effects of treatment on: a. Systemic inflammation b. Duration of mechanical ventilation c. Multiple organ dysfunction syndrome d. Duration of ICU and hospital stay e. Cardiovascular morbidity-mortality f. Complications [ Time Frame: one year ]

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • Age. Patients age 18 years or older admitted to the intensive care unit.
  • ALI/ARDS criteria. The diagnosis of ALI/ARDS requires 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 contest of appropriate predisposing injury or illness with no evidence of left ventricular failure,
    • Static pulmonary compliance < 50 cm H2O
    • Ratio of partial pressure of arterial oxygen to partial pressure of alveolar oxygen (PaO2:FiO2 ) equal or less than 300 (criteria for ALI) or 200 (criteria for ARDS) with FiO2 1.0.
  • Severe ARDS. PaO2:FiO2 equal or less than 200 after 30 minutes of standardized ventilatory management on PEEP of 10 cm H2O with FiO2 1.0.

Exclusion Criteria:

  • Failure to obtain written informed consent from the patient or a next of kin.
  • Trauma-induced ARDS.
  • Major gastrointestinal bleeding requiring transfusion of 5 units or more of packed red blood cells (PRBC) within 3 months current hospitalization
  • Condition requiring > 0.5mg/Kg/day of prednisone equivalent (i.e., acute asthma or chronic obstructive pulmonary disease [COPD])
  • 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
  • Pregnancy confirmed by urine or serum test
  • Weight is > 200% of ideal body weight
  • Non-ambulatory resident of long-term care facility
  • Primary care physician not committed to full, aggressive support of the patient at the time of randomization
  • Moribund patient (i.e., not expected to live more than 24 hr) or with recent (within 7 days or anytime during present hospitalization) cardiopulmonary arrest
  • Known or suspected irreversible cessation of all brain function
  • Presence of preexisting medical condition which is irreversible and expected to be fatal within 3 months
  • 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)

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00562835

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Contact: Massimo Antonelli, MD 0039 06 30151 ext 4507

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UCSC, Policlinico Universitario A. Gemelli, ICU
Rome, Italy, 00168
Contact: Massimo Antonelli, MD    +39 06 30 15 32 26   
Contact: Mariano A Pennisi, MD    + 39 06 30 15 43 86   
Principal Investigator: Massimo Antonelli, MD         
Sponsors and Collaborators
Catholic University of the Sacred Heart
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Principal Investigator: Massimo Antonelli, MD Catholic University of Sacred Heart, Rome
Study Director: Umberto Meduri, MD University of Tennessee Health Science Center Memphis, TN, USA
Publications of Results:
Other Publications:

Layout table for additonal information Identifier: NCT00562835    
Other Study ID Numbers:
First Posted: November 22, 2007    Key Record Dates
Last Update Posted: November 22, 2007
Last Verified: November 2007
Keywords provided by Catholic University of the Sacred Heart:
Additional relevant MeSH terms:
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Lung Injury
Acute Lung Injury
Respiratory Distress Syndrome, Adult
Lung Diseases
Respiratory Tract Diseases
Thoracic Injuries
Wounds and Injuries
Respiration Disorders
Growth Substances
Physiological Effects of Drugs
Anti-Inflammatory Agents
Autonomic Agents
Peripheral Nervous System Agents
Gastrointestinal Agents
Hormones, Hormone Substitutes, and Hormone Antagonists
Neuroprotective Agents
Protective Agents
Vitamin B Complex