Study | Design | Cohort | Number of patients | Surfactant type | Delivery mode and dose | Outcome | Comments |
---|---|---|---|---|---|---|---|
Spragg and colleagues [46] | Multicentre RCT, phase III | Direct lung injury with PaO2/FiO2 ≤170 mmHg (aspiration+ pneumonia) | 843 | rSP-C based (synthetic), 1 ml = 1 mg rSP-C and 50 mg PLs | Intratracheal, 1 ml/kg LBW for maximum of eight doses until 96 hours | 1. No difference in 28-day mortality, oxygenation or ventilator-free days | 1. Differ from other rSP-C studies by no improvement in oxygenation |
 |  |  |  |  |  | 2. Similar adverse events | 2. Shearing step used to improve dispersion may have altered the property |
 |  |  |  |  |  |  | 3. Prematurely stopped due to futility |
Kesecioglu and colleagues [42] | Multicentre RCT, phase III ALI/ARDS | ALI/ARDS | 418 | HL10 - freeze dried natural porcine surfactant (90-95% phospholipids and 1-2% of SP-B and SP-C) | Intratracheal, up to three doses - cumulative doses of 600 mg/kg at 0, 12, 36 hours | 1. Increased trend towards mortality in surfactant group with no improvements in secondary outcomes such as oxygenation and SOFA scores | 1. Prematurely terminated due to futility |
 |  |  |  |  |  | 2. More adverse events in the surfactant group |  |
Markart and colleagues [45] | Multicentre RCT, phase I/II | ARDS | 31 | rSP-C based (synthetic), 1 ml = 1 mg rSP-C and 50 mg PLs | Intratracheal, 1 ml/ kg LBW up to four doses in the first 24 hours | 1. Improved gas exchange in surfactant group | 1. Not designed to assess mortality |
 |  |  |  |  |  | 2. Normalisation of surfactant PLs and proteins | 2. Treatment period was 24 hours |
Spragg and colleagues [44] | Multicentre RCT, phase III | ARDS | 221 and 227 | rSP-C based (synthetic), 1 ml = 1 mg rSP-C and 50 mg PLs | Intratracheal, 1 ml/kg LBW up to four doses at 4-hour intervals in the first 24 hours | 1. No difference in survival or ventilator free days but improved oxygenation in the surfactant group | 1. Post hoc analysis for intrinsic ARDS showed trend towards improved mortality. |
 |  |  |  |  |  | 2. More adverse events in the surfactant group in the first 24 hours after treatment | 2. Treatment period was 24 hours |
Spragg and colleagues [43] | Multicentre RCT, phase I/II | ARDS | 40 | rSP-C based (synthetic), 1 ml = 1 mg rSP-C and 50 mg PLs | Intratracheal, two groups: group 1, 1 ml/kg LBW; group 2, 0.5 mg/kg LBW, up to four times in the first 24 hours | 1. Safety was comparable with no differences in oxygenation and ventilator free days | 1. Treatment period was 24 hours |
 |  |  |  |  |  | 2. Decreased plasma IL-6 in group 1 |  |
Gregory and colleagues [41] | Multicentre RCT, phase II/III | ARDS | 59 | Natural bovine lung extract (Survanta; contains phospholipids, neutral lipids, fatty acids, and surfactant proteins with additional DPPC, palmitic acid and tripalmitin) | Intratracheal, three groups: group 1, 8×50 mg/ kg LBW; group 2, 4×100 mg/kg LBW; group 3, 8×100 mg/kg LBW | 1. Oxygenation was better with surfactant group 2 | 1. Small number of patients in each group |
 |  |  |  |  |  | 2. Trend towards improved mortality in groups 2 and 3 |  |
Anzueto and colleagues [40] | Multicentre RCT, phase III | Sepsis-induced ARDS | 725 | Exosurf (synthetic), 13.5 mg DPPC/ml | Aerosol, 112 mg DPPC/kg/day for 5 days | 1. No difference in 30 day mortality, oxygenation or mean number of ventilation days | 1. Only sepsis cohort was studied |
 |  |  |  |  |  |  | 2. Aerosolised preparation with poor alveolar deposition |
 |  |  |  |  |  |  | 3. No surfactant proteins in the preparation |
Weg and colleagues [39] | Multicentre RCT, phase II | Sepsis-induced ARDS | 51 | Exosurf (synthetic), 13.5 mg DPPC/ml | Aerosol, two groups: group 1, 21.9 mg DPPC/ kg/day; group 2, 43.5 mg DPPC/kg/ day. Aerosolised for either 12 or 24 hours for 5 days | 1. Safety was comparable between three groups | 1. Aerosolised preparation with poor alveolar deposition |
 |  |  |  |  |  |  | 2. No surfactant proteins in the preparation |