Steroids in Patients With Early ARDS
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|ClinicalTrials.gov 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
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|
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||400 participants|
|Intervention Model:||Parallel Assignment|
|Masking:||Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)|
|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|
Active Comparator: 1
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
- 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 ]
- 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 ]
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 ClinicalTrials.gov identifier (NCT number): NCT00562835
|Contact: Massimo Antonelli, MD||0039 06 30151 ext firstname.lastname@example.org|
|UCSC, Policlinico Universitario A. Gemelli, ICU|
|Rome, Italy, 00168|
|Contact: Massimo Antonelli, MD +39 06 30 15 32 26 email@example.com|
|Contact: Mariano A Pennisi, MD + 39 06 30 15 43 86 firstname.lastname@example.org|
|Principal Investigator: Massimo Antonelli, MD|
|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|