Table 1.

Characteristics of trials to date

Study title and abbreviation	Design (all placebo-controlled)	Population of ALI/ARDS A) Timing from ALI onset B) P/F ratio	Number recruited	Intervention	Primary outcome	Result (intervention vs control)	Mortality (intervention vs control)
Neuromuscular Blockade in Early ARDS [5]	Phase 2 RCT	A) 48 hours B) <150	340	Cisatracuriumbesylate: 15 mg initially, then 37.5 mg per hour for 48 hours	90-day survival	31.6% vs 40.7% (P= 0.08)	28-day: 23.7% vs 33.3% (P= 0.05)
The β-Agonist Lung Injury Trial (BALTI) [6]	Phase 1 RCT	A) 48 hours B) <300	40	Intravenous (IV) salbutamol for seven days (15 μg kg-1 h-1)	Extravascular lung water (EVLW) at Day 7	9.2 ± 6 vs 13.2 ±3 ml kg-1 (P= 0.04)	28-day: 58% vs 66% (P= 0.4)
Randomized, Placebo-Controlled Clinical Trial of an Aerosolized β2-Agonist for Treatment of Acute Lung Injury (ALTA) [7]	Phase 2 RCT	A) 48 hours B) < 300	282	Inhaled salbutamol (5 mg) every 4 hours for 10 days/24 hours after extubation	Ventilator-free days (VFD)	Stopped early 14.4 ± 0.9 vs 16.6 ± 0.9 (P= 0.087)	Death before discharge: 24.3 ± 3.5 vs 18.5 ± 3.4 (P= 0.261)
Effect of Intravenous β-2 Agonist Treatment on Clinical Outcomes in Acute Respiratory Distress Syndrome (BALTI-2) [8]	Phase 2 RCT	A) 72 hours B) <200	326	IV salbutamol for seven days (15 μg kg-1 (ideal body weight) h-1)	28-day mortality	Stopped early 34% vs 23% (P= 0.03)
Neutrophil Elastase Inhibition in Acute Lung Injury (STRIVE) [9]	Phase 3 RCT	A) 48 hours B) <300	492	Sivelestat infusion	1. 28-day mortality2. VFD	Stopped early 1 26.6% vs 26% (P= 0.847)2. 11.4 ±10.27 vs 11.9 ± 10.1 (P= 0.536)
Efficacy and Safety of Corticosteroids for Persistent ARDS (LaSRS) [14]	Phase 2 RCT	A) 7 to 28 days B) P/F <200	180	Moderate-dose IV methylprednisolone, for up to 25 days	60-day mortality	29.2% vs 28.6% (P= 1.0)
Methylprednisolone Infusion in Early Severe ARDS [15]	Phase 1 RCT	A) 72 hours B) <300	91	Low-dose IV methylprednisolone, for up to 28 days	Improvement in Lung Injury Score by Day 7	69.8% vs 35.7% (P= 0.002)	Hospital survival 76.2% vs 57.1% (P= 0.07)
A Randomized Clinical Trial of Hydroxymethylglutaryl–Coenzyme A Reductase Inhibition for Acute Lung Injury (HARP) [19]	Phase 2 RCT	A) 48 hours B) <300	60	Simvastatin 80 mg daily, up to 14 days	Reduction in EVLW indexed to actual body weight	13.7 vs 13.4 (P= 0.90) Improvements in secondary outcomes	Hospital survival: 19 vs 19 (P= 1.0)
Nebulized Heparin is Associated with Fewer Days of Mechanical Ventilation in Critically Ill Patients: a Randomized Controlled Trial [21]	Phase 2 RCT	Patients expected to require ventilation for >48 hours, and within 24 hours of ventilation	50	Heparin 25,000 units every 4 to 6 hours, for up to 14 days	Average daily P/F ratio	194.2 ± 62.8 vs 187 ± 38.6 mmHg (P= 0.6) Improvements in secondary outcomes	28-day: 20% vs 16% (P= 0.7)