A double-blind placebo-controlled study to evaluate the safety and efficacy of L-2-oxothiazolidine-4-carboxylic acid in the treatment of patients with acute respiratory distress syndrome.
OBJECTIVE
Acute respiratory distress syndrome is an abrupt inflammatory illness that involves damage from reactive oxygen species. We examined the efficacy and safety of oxothiazolidine-4-carboxylic acid (OTZ), a free radical scavenger, in treating acute respiratory distress syndrome.


METHODS
Double-blind, placebo-controlled trial.


METHODS
Multicentered study.


METHODS
Patients with a PaO2/FiO2 < or = 200 and bilateral infiltrates on chest radiograph, and requiring mechanical ventilation.


METHODS
We randomized 215 patients to receive OTZ, 210 mg/kg per day every 8 hrs for 14 days or placebo.


RESULTS
Ventilator-free days (the number of days alive and free from ventilator requirement) during the first 30 days of study were 8.3 vs. 13.5 days for the OTZ and placebo groups, respectively (p < .001). Mortality was 30/101 (29.7%) in the OTZ group and 18/114 (15.8%) in the placebo group during the 30-day study period (p = .014). This study was terminated prematurely for safety reasons after 215 of the planned 352 patients were enrolled.


CONCLUSIONS
OTZ does not improve survival or reduce ventilator time in patients with acute respiratory distress syndrome and may worsen outcome, although mortality in the OTZ group was similar or lower than most similar trials. Alternatively, our results may be best explained by the unusually excellent outcome in the placebo group.
Morris
Peter E
PE
Department of Pulmonary/Critical Care, Wake Forest University School of Medicine, Winston-Salem, NC, USA.
Papadakos
Peter
P
Russell
James A
JA
Wunderink
Richard
R
Schuster
Daniel P
DP
Truwit
Jonathon D
JD
Vincent
Jean-Louis
JL
Bernard
Gordon R
GR
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D011761:Pyrrolidonecarboxylic Acid / Q000627:therapeutic use*; D012128:Respiratory Distress Syndrome / Q000188:drug therapy*; D053778:Thiazolidines / Q000627:therapeutic use*
D053778:Thiazolidines; D011761:Pyrrolidonecarboxylic Acid; C029536:2-oxothiazolidine-4-carboxylic acid