Effect of recombinant surfactant protein C-based surfactant on the acute respiratory distress syndrome

N Engl J Med. 2004 Aug 26;351(9):884-92. doi: 10.1056/NEJMoa033181.

Abstract

Background: Preclinical studies suggest that exogenous surfactant may be of value in the treatment of the acute respiratory distress syndrome (ARDS), and two phase 2 clinical trials have shown a trend toward benefit. We conducted two phase 3 studies of a protein-containing surfactant in adults with ARDS.

Methods: In two multicenter, randomized, double-blind trials involving 448 patients with ARDS from various causes, we compared standard therapy alone with standard therapy plus up to four intratracheal doses of a recombinant surfactant protein C-based surfactant given within a period of 24 hours.

Results: The overall survival rate was 66 percent 28 days after treatment, and the median number of ventilator-free days was 0 (68 percent range, 0 to 26); there was no significant difference between the groups in terms of mortality or the need for mechanical ventilation. Patients receiving surfactant had a significantly greater improvement in blood oxygenation during the initial 24 hours of treatment than patients receiving standard therapy, according to both univariate and multivariate analyses.

Conclusions: The use of exogenous surfactant in a heterogeneous population of patients with ARDS did not improve survival. Patients who received surfactant had a greater improvement in gas exchange during the 24-hour treatment period than patients who received standard therapy alone, suggesting the potential benefit of a longer treatment course.

Publication types

  • Clinical Trial
  • Clinical Trial, Phase III
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • APACHE
  • Analysis of Variance
  • Causality
  • Double-Blind Method
  • Female
  • Humans
  • Logistic Models
  • Male
  • Middle Aged
  • Oxygen / blood
  • Pulmonary Surfactant-Associated Protein C / adverse effects
  • Pulmonary Surfactant-Associated Protein C / therapeutic use*
  • Pulmonary Surfactants / adverse effects
  • Pulmonary Surfactants / therapeutic use*
  • Recombinant Proteins / adverse effects
  • Recombinant Proteins / therapeutic use
  • Respiration, Artificial
  • Respiratory Distress Syndrome / drug therapy*
  • Respiratory Distress Syndrome / etiology
  • Respiratory Distress Syndrome / mortality
  • Respiratory Distress Syndrome / therapy
  • Survival Rate
  • Treatment Failure

Substances

  • Pulmonary Surfactant-Associated Protein C
  • Pulmonary Surfactants
  • Recombinant Proteins
  • Oxygen