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 - 26/11/14

Doi : 10.1016/j.ajog.2014.10.1097

Norbert Winer, MD, PhD ^a, Florence Bretelle, MD, PhD ^b, Marie-Victoire Senat, MD, PhD ^d, Caroline Bohec, MD ^e, Philippe Deruelle, MD, PhD ^f, Frank Perrotin, MD, PhD ^g, Laure Connan, MD ^h, Christophe Vayssière, MD, PhD ⁱ, Bruno Langer, MD, PhD ^j, Marianne Capelle, MD ^c, Shohreh Azimi ^l, Raphael Porcher, PhD ^m, Patrick Rozenberg, MD ^k,^⁎
for the
Groupe de Recherche en Obstétrique et Gynécologie
^a Department of Obstetrics and Gynecology: Hôpital Mère-Enfant, Nantes, Paris, France
^b Department of Obstetrics and Gynecology: Hôpital Nord, Marseille, Paris, France
^c Department of Obstetrics and Gynecology: Hôpital de La Conception, Marseille, Paris, France
^d Department of Obstetrics and Gynecology: Assistance Publique-Hôpitaux de Paris, Hôpital Bicêtre, Hôpital Antoine Béclère, Université Paris Sud, Faculté de Médecine Paris XI, Paris, Paris, France
^e Department of Obstetrics and Gynecology: Hôpital Morvan, Brest, Paris, France
^f Department of Obstetrics and Gynecology: Hôpital Jeanne de Flandre, Lille, Paris, France
^g Department of Obstetrics and Gynecology: Hôpital Bretonneau, Tours, Paris, France
^h Department of Obstetrics and Gynecology: Hôpital Paul de Viguier, Toulouse, Paris, France
ⁱ Department of Obstetrics and Gynecology: Centre Médico-Chirurgical Obstetrical, Schiltigheim, Paris, France
^j Department of Obstetrics and Gynecology: Hôpital Hautepierre, Strasbourg, Paris, France
^k Department of Obstetrics and Gynecology: Hôpital Poissy-Saint Germain, Versailles-Saint Quentin University, Versailles, Paris, France
^l Department of Clinical Research, Ile-de-France, Hôpital Saint-Louis, Assistance Publique-Hôpitaux de Paris, Paris, France
^m Department of Biostatistics, Hôpital Saint-Louis, Paris Diderot University, and Institut National de la Santé et de la Recherche Médicale, Paris, France

^∗Corresponding author: Patrick Rozenberg, MD.

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Abstract

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).

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Key words : 17 alpha-hydroxyprogesterone caproate, cervical length, prematurity, preterm birth, preterm labor, progesterone

Plan

Materials and Methods

Subjects and screening

Randomization and follow-up

Study outcomes

Statistical analysis

Results

Patient characteristics

Primary outcome and preterm delivery

Fetal and neonatal outcome

Adverse events

Comment

Principal findings of the study

Clinical meaning of the study

The effect of progesterone on cervical ripening

Strengths and limitations of the study

Summary

	This study was supported by research grant PHRC AOM 04038 from the Département à la Recherche Clinique Ile-de-France, Assistance Publique–Hôpitaux de Paris (P.R.).
	The authors report no conflict of interest.
	Cite this article as: Winer N, Bretelle F, Senat M-V, et al. 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. Am J Obstet Gynecol 2014;212:xx-xx.