17 alpha-hydroxyprogesterone caproate does not prolong pregnancy or reduce the rate of preterm birth in women at high risk for preterm delivery and a short cervix: a randomized controlled trial

• Published in: American journal of obstetrics and gynecology Vol. 212; no. 4; pp. 485.e1 - 485.e10
• Main Authors: Winer, Norbert, MD, PhD, Bretelle, Florence, MD, PhD, Senat, Marie-Victoire, MD, PhD, Bohec, Caroline, MD, Deruelle, Philippe, MD, PhD, Perrotin, Frank, MD, PhD, Connan, Laure, MD, Vayssière, Christophe, MD, PhD, Langer, Bruno, MD, PhD, Capelle, Marianne, MD, Azimi, Shohreh, Porcher, Raphael, PhD, Rozenberg, Patrick, MD
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.04.2015; Elsevier
• Subjects: 17 alpha-hydroxyprogesterone caproate; Adult; cervical length; Drug Administration Schedule; Female; Follow-Up Studies; Food and Nutrition; Human health and pathology; Humans; Hydroxyprogesterones - therapeutic use; Injections, Intramuscular; Intention to Treat Analysis; Life Sciences; Obstetrics and Gynecology; Pregnancy; Premature Birth - etiology; Premature Birth - prevention & control; prematurity; Prenatal Care - methods; preterm birth; preterm labor; progesterone; Progestins - therapeutic use; Proportional Hazards Models; Risk Factors; Santé publique et épidémiologie; Treatment Outcome; Urogenital Abnormalities - complications; Uterine Cervical Incompetence; Uterus - abnormalities; preterm birth; preterm labor; prematurity; 17 alpha-hydroxyprogesterone caproate; cervical length; progesterone
• ISSN: 0002-9378; 1097-6868
• DOI: 10.1016/j.ajog.2014.10.1097

Objective The objective of the study was to evaluate the efficacy of 17 alpha-hydroxyprogesterone caproate (17OHP-C) in prolonging gestation in patients with a short cervix and other risk factors for preterm delivery, such as previous preterm birth, cervical surgery, uterine anomalies, or prenatal diethylstilbestrol (DES) exposure. Study Design This open-label, multicenter, randomized controlled trial included asymptomatic singleton pregnancies from 20+0 through 31+6 weeks of gestation with a cervical length less than 25 mm and a history of preterm delivery or cervical surgery or uterine malformation or prenatal DES exposure. Randomization assigned them to receive (or not) 500 mg of intramuscular 17OHP-C weekly until 36 weeks. The primary outcome was time from randomization to delivery. Results After enrolling 105 patients, an interim analysis demonstrated the lack of efficacy of 17OHP-C in prolonging pregnancy. The study was discontinued because of futility. The groups were similar for maternal age, body mass index, parity, gestational age at inclusion, history of uterine anomalies, DES syndrome, previous preterm delivery or midtrimester abortion, and cervical length at randomization. The enrollment-to-delivery interval did not differ between patients allocated to 17OHP-C (n = 51) and those allocated to the control group (n = 54) (median [interquartile range] time to delivery: 77 [54–103] and 74 [52–99] days, respectively). The rate of preterm delivery less than 37 (45% vs 44%, P > .99), less than 34 (24% vs 30%, P  = .51), or less than 32 (14% vs 20%, P  = .44) weeks was similar in patients allocated to 17OHP-C and those in the control group. Conclusion 17OHP-C did not prolong pregnancy in women with singleton gestations, a sonographic short cervix, and other risk factors of preterm delivery (prior history, uterine malformations, cervical surgery, or prenatal DES exposure).