Propranolol for Induction of Labor in Nulliparas (The PIN Trial): A double blind, randomized, placebo-controlled trial.

Abstract

BACKGROUND\nPropranolol hydrochloride is a non-selective beta-adrenergic antagonist that has known activity in myometrium. In small trials, it has been shown to decrease duration of induced labor, though these studies are limited by methodological variability.\n\n\nOBJECTIVE\nOur objective was to determine if the addition of a single dose of propranolol to nulliparous induction of labor would decrease total time to vaginal delivery.\n\n\nSTUDY DESIGN\nThis was a double blind, randomized, placebo-controlled trial of nulliparous patients undergoing term induction with a singleton, non-anomalous gestation. Subjects were randomized to 2 mg of intravenous propranolol hydrochloride or an identical-appearing saline placebo, administered 30 minutes after starting the induction. Investigators, labor floor staff, and patients were blinded to study drug allocation. The primary outcome was time to vaginal delivery. Secondary outcomes included mode of delivery, duration of the phases of labor, time to full dilation, composite maternal morbidity, and composite neonatal morbidity. Data were analyzed by intention-to-treat with a p-value of ≤0.05 considered significant.\n\n\nRESULTS\nThere were 240 patients enrolled from December 2017 to December 2018, with 121 patients randomized to propranolol and 119 to placebo. The two groups had similar baseline characteristics. Of the patients randomized, 154 (64.2%) delivered vaginally. There was no significant difference in time from the start of induction to vaginal delivery (propranolol 13.8±5.4 hours vs. placebo 14.3±5.3 hours, p=0.58). There were also no differences in rate of cesarean section (38% vs. 33.6%, p=0.48), time to active labor (11.0±5.0 vs. 11.2±4.5 hours, p=0.77), or time to full dilation (12.4±5.1 vs. 12.8±5.2 hours, p=0.60) in patients receiving propranolol compared to placebo. Subjects randomized to propranolol had a significantly lower rate of composite maternal morbidity (28.9% vs. 41.2%, RR 0.70 [95% CI 0.49, 1.00], p=0.047). Rates of postpartum hemorrhage (12.4% vs. 21.8%, p=0.05) and transfusion (0% vs. 4.2%, p=0.03) were also lower in the treated group. There were no significant differences in neonatal outcomes or composite morbidity (RR 0.74, 95% CI 0.44, 1.22).\n\n\nCONCLUSIONS\nIn this study, there is no evidence that the addition of a one-time dose of propranolol to nulliparous induction decreases time to delivery or the rate of cesarean section. However, propranolol significantly reduced composite maternal morbidity without adverse neonatal effects.