The Adult Calfactant in Acute Respiratory Distress Syndrome Trial

Chest. 2015 Aug;148(2):356-364. doi: 10.1378/chest.14-1139.

Abstract

Background: Surfactant has been shown to be dysfunctional in ARDS, and exogenous surfactant has proven effective in many forms of neonatal and pediatric acute lung injury (ALI). In view of the positive results of our studies in children along with evidence that surfactant-associated protein B containing pharmaceutical surfactants might be more effective, we designed a multiinstitutional, randomized, controlled, and masked trial of calfactant, a calf lung surfactant, in adults and children with ALI/ARDS due to direct lung injury.

Methods: Adult subjects within 48 h of initiation of mechanical ventilation for direct ARDS were randomized to receive up to three interventions with instilled calfactant vs air placebo. The primary outcome was 90-day all-cause mortality.

Results: Three hundred seventeen subjects were enrolled, 308 of whom could be evaluated. There were no significant baseline differences between groups. Calfactant administration was not associated with improved survival, lengths of stay, or oxygenation. Calfactant instillation was frequently associated with transient hypoxia and hypotension. The study was stopped at the first interim analysis at the sponsor's request.

Conclusions: Administration of calfactant was not associated with improved oxygenation or longer-term benefits relative to placebo in this randomized, controlled, and masked trial. At present, exogenous surfactant cannot be recommended for routine clinical use in ARDS.

Trial registry: ClinicalTrials.gov; No.: NCT00682500; URL: www.clinicaltrials.gov.

Publication types

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

MeSH terms

  • Adult
  • Aged
  • Biological Products / therapeutic use*
  • Double-Blind Method
  • Early Termination of Clinical Trials
  • Female
  • Humans
  • Hypotension / chemically induced*
  • Hypoxia / chemically induced*
  • Length of Stay
  • Male
  • Middle Aged
  • Oximetry
  • Pulmonary Surfactants / therapeutic use*
  • Respiration, Artificial*
  • Respiratory Distress Syndrome / mortality
  • Respiratory Distress Syndrome / therapy*
  • Treatment Outcome

Substances

  • Biological Products
  • Pulmonary Surfactants
  • calfactant

Associated data

  • ClinicalTrials.gov/NCT00682500