A placebo-controlled randomized trial of antithrombin therapy in neonatal respiratory distress syndrome

Neonatal respiratory distress syndrome (RDS) is associated with decreased plasma activity of antithrombin (AT) and increased formation of thrombin. We tested whether AT reduces thrombin formation, improves gas exchange, and decreases the duration of mechanical ventilation and supplemental oxygen. One hundred twenty-two infants were randomized to pasteurized AT concentrate or to placebo. Two ml/kg (equivalent to 100 IU AT/kg) were followed by 1 ml/kg (50 IU/kg) every 6 h for 48 h. Outcome measures included plasma AT activity, thrombin-AT (TAT) complex, prothrombin fragment (F1+2), the ratio of arterial to alveolar oxygen pressure [(a/A)PO2], and the ventilator efficiency index (VEI). In the AT group (n = 61), mean (SD) birth weight was 1,198 (301) g, mean (SD) gestational age (GA) was 28.3 (2.0) wk, 54% were male. In the placebo group (n = 61), mean (SD) birth weight was 1,201 (315) g, mean (SD) GA was 28.8 (2. 3) wk, 51% were male. In treated infants, AT activity was raised to means of 1.69 and 2.25 U/ml at 24 and 48 h, respectively. Corresponding means in control infants were 0.37 and 0.44 U/ml (p < 0.0001). F1+2, but not TAT, was significantly reduced by AT (p = 0. 004). VEI and (a/A)PO2 were similar in both groups throughout the first week of life. Median days receiving mechanical ventilation were 7.1 (AT) versus 4.8 (placebo), p = 0.0014. Median days receiving supplemental oxygen were 7.9 (AT) versus 5.5 (placebo), p < 0.0001. There were seven (11.5%) deaths in the AT group and three (4.9%) deaths in the placebo group. We conclude that treatment with AT cannot be recommended in premature infants with RDS.