Table 1.

Summary of Clinical Studies of Surfactant in Acute Lung Injury (ALI)/Acute Respiratory Distress Syndrome (ARDS)

Intervention	Author & Year	Study Design	Study Population & Number of Patients	Results
Exosurf with DPPC 40.5 mg/mL or 81 mg/mL or placebo Continuously aerosolized for up to 5 d.	Reines et al 1992 [54]	Prospective, randomized, controlled trial	Patients with sepsis-induced ARDS, N = 49	14-d mortality (all surfactant doses vs control): RR 0.61 (95% CI 0.3–1.24)
Porcine surfactant; single dose; 4 g in 50 mL Delivered via bronchoscope to each lobar bronchi	Spragg et al 1994 [55]	Case series	Patients with ARDS, N = 6	Modest, transient improvement in gas exchange; no change in lung compliance
Exosurf with DPPC 13.5 mg/mL Continuously aerosolized, 175 mL every 4 h × 12 h/d or 175 mL × 24 h/d or placebo for up to 5 d	Weg et al 1994 [56]	Multiple-center, prospective, randomized, double-blind, placebo- controlled trial phase II study	Patients with ALI and sepsis <18 h, N = 51	No difference in mortality at 30 d (RR 0.81; 95% CI 0.42–1.57) Dose-dependent trend in reduction of mortality (47% in placebo, 41% in 12 h/d group and 35% in 24 h/d group)
Exosurf with DPPC 13.5 mg/mL or placebo Continuously aerosolized 240 mL daily for up to 5 d	Anzueto et al 1996 [57]	Multiple-center, prospective, randomized, double-blind, placebo- controlled trial, phase III study	Patients with sepsis-induced ARDS, N = 725	Mortality at 30 d in both groups was 40% (RR 1.01; 95% CI 0.84–1.20) No difference in length of mechanical ventilation, did not improve oxygenation
Survanta 50 mg/kg × 8 doses or 100 mg/kg × 4 doses or 100 mg/kg × 8 doses or standard therapy Delivered intratracheally	Gregory et al 1997 [62]	Multiple-center, prospective, randomized trial, not blinded, phase II study	Patients with ARDS <48 h, N = 51	Mortality in the Survanta 100 mg/kg × 4 doses 18.8% vs control group 43.8% (P = .075)
Surfaxin: 3 dosing regimens Administered via bronchoscope to each of the 19 segments	Wiswell et al 1999 [60]	Case series, phase I study	Patients with ARDS, N = 12	Decrease FiO2 (0.8–052) and PEEP (10.3-7.6) at 96 h
Alveofact 300 mg/kg × 1 treatment; delivered via bronchoscope into segmental bronchi within 45 min	Walmrath et al 1996 [58], 2002 [59]	Case series	Patients with severe ARDS and septic shock APAPCHE II 33.2 ± 1.3, N = 10, N = 12	Improved PaO2/FiO2 (109–210) within 12 h Overall mortality rate 44.4% lower than calculated risk of death given the APACHE II (74 ± 3.5%)
Venticute 1 mL/kg up to 4 doses/24 h or 0.5 mL/kg up to 4 doses/24 h or standard therapy	Spragg et al 2003 [61]	Multiple-center, randomized, controlled trial, phase I/II study	Patients with ARDS <48 h, N = 40	No significant difference in 28-d mortality rate or ventilator-free days
Venticute 1 mL/kg up to 4 doses/24 h or standard therapy; intratracheal instillation	Spragg et al 2004 [63]	Multiple-center, randomized, double-blind controlled trial, phase III	Patients with ARDS, N = 448	Mortality rate at 28 d 36% in surfactant group vs 32% in placebo (P = .54); no difference
(a) North American study	2 independent trials, published as pooled data	ARDS <48 h, N = 221	Improvement of gas exchange during the 24-h period in surfactant group
(b) European/African study		ARDS <72 h, N = 227

DPPC – dipalmitoylphosphatidylcholine; RR – relative risk; CI – confidence interval; PEEP – positive end-expiratory pressure; APACHE –Acute Physiology and Chronic Health Evaluation.

Surfactant preparations used in the clinical trials:

Exosurf: artificial surfactant (lipid complex only, no protein)

Survanta: modified natural bovine surfactant (lipid-protein complex, contains apoprotein)

Alveofact: natural bovine surfactant (lipid-protein complex)

Surfaxin: KL4-surfactant; artificial preparation containing a synthetic 21-amino-acid peptide (KL4-peptide)

Venticute: recombinant surfactant protein C-based surfactant; containing 1 mg recombinant surfactant protein C and 50 mg phospholipid per milliliter