Table 1 Characteristics of trials to date
From: Pharmacological treatments in ARDS; a state-of-the-art update
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) |