17-OHPC to Prevent Recurrent Preterm Birth in Singleton Gestations (PROLONG Study): A Multicenter, International, Randomized Double-Blind Trial

Sean C. Blackwell, Suneet P. Chauhan, Cynthia Gyamfi-Bannerman, Joseph R. Biggio, Brenna L. Hughes, Judette M. Louis, Tracy A. Manuck, Hugh S. Miller, Anita F. Das, George R. Saade, Peter Nielsen, Jeff Baker, Oleksandr M. Yuzko, Galyna I. Reznichenko, Nataliya Y. Reznichenko, Oleg Pekarev, Nina Tatarova, Jennifer Gudeman, Monique Duncan, Laura WilliamsJulie Krop, Robert Birch, Michael J. Jozwiakowski

Research output: Contribution to journalArticle

7 Scopus citations

Abstract

Background âwomen with a history of spontaneous preterm birth (SPTB) are at a significantly increased risk for recurrent preterm birth (PTB). To date, only one large U.S. clinical trial comparing 17-OHPC (17-α-hydroxyprogesterone caproate or 17P) to placebo has been published, and this trial was stopped early due to a large treatment benefit. Objective âThis study aimed to assess whether 17-OHPC decreases recurrent PTB and neonatal morbidity in women with a prior SPTB in a singleton gestation. Study Design âThis was a double-blind, placebo-controlled international trial involving women with a previous singleton SPTB (clinicaltrials.gov: NCT 01004029). Women were enrolled at 93 clinical centers (41 in the United States and 52 outside the United States) between 16 0/7 to 20 6/7 weeks in a 2:1 ratio, to receive either weekly intramuscular (IM) injections of 250 mg of 17-OHPC or an inert oil placebo; treatment was continued until delivery or 36 weeks. Co-primary outcomes were PTB < 35 weeks and a neonatal morbidity composite index. The composite included any of the following: Neonatal death, grade 3 or 4 intraventricular hemorrhage, respiratory distress syndrome, bronchopulmonary dysplasia, necrotizing enterocolitis, or proven sepsis. A planned sample size of 1,707 patients was estimated to provide 98% power to detect a 30% reduction in PTB < 35 weeks (30% to 21%) and 90% power to detect a 35% reduction in neonatal composite index (17%-11%) using a two-sided type-I error of 5%. Finally, this sample size would also provide 82.8% power to rule out a doubling in the risk of fetal/early infant death assuming a 4% fetal/early infant death rate. Analysis was performed according to the intention-to-treat principle. Results âaseline characteristics between the 1,130 women who received 17-OHPC and 578 women who received placebo were similar. Overall, 87% of enrolled women were Caucasian, 12% had >1 prior SPTB, 7% smoked cigarettes, and 89% were married/lived with partner. Prior to receiving study drug, 73% women had a transvaginal cervical length measurement performed and <2% had cervical shortening <25 mm. There were no significant differences in the frequency of PTB < 35 weeks (17-OHPC 11.0% vs. placebo 11.5%; relative risk = 0.95 [95% confidence interval (CI): 0.71-1.26]) or neonatal morbidity index (17-OHPC 5.6% vs. placebo 5.0%; relative risk = 1.12 [95% CI: 0.68-1.61]). There were also no differences in frequency of fetal/early infant death (17-OHPC 1.7% vs. placebo 1.9%; relative risk = 0.87 [95% CI: 0.4-1.81]. Maternal outcomes were also similar. In the subgroup of women enrolled in the United States (n = 391; 23% of all patients), although the rate of PTB < 35 weeks was higher than the overall study population, there were no statistically significant differences between groups (15.6% vs. 17.6%; relative risk = 0.88 [95% CI: 0.55, 1.40]. Conclusion âin this study population, 17-OHPC did not decrease recurrent PTB and was not associated with increased fetal/early infant death.

Original languageEnglish (US)
Pages (from-to)127-136
Number of pages10
JournalAmerican Journal of Perinatology
Volume37
Issue number2
DOIs
StatePublished - 2020

Keywords

  • 17-HPC
  • 17-OHPC
  • 17-P
  • 17-hydroxyprogesterone caproate
  • preterm birth
  • progestogens
  • recurrent preterm birth
  • spontaneous preterm birth

ASJC Scopus subject areas

  • Pediatrics, Perinatology, and Child Health
  • Obstetrics and Gynecology

Fingerprint Dive into the research topics of '17-OHPC to Prevent Recurrent Preterm Birth in Singleton Gestations (PROLONG Study): A Multicenter, International, Randomized Double-Blind Trial'. Together they form a unique fingerprint.

  • Cite this

    Blackwell, S. C., Chauhan, S. P., Gyamfi-Bannerman, C., Biggio, J. R., Hughes, B. L., Louis, J. M., Manuck, T. A., Miller, H. S., Das, A. F., Saade, G. R., Nielsen, P., Baker, J., Yuzko, O. M., Reznichenko, G. I., Reznichenko, N. Y., Pekarev, O., Tatarova, N., Gudeman, J., Duncan, M., ... Jozwiakowski, M. J. (2020). 17-OHPC to Prevent Recurrent Preterm Birth in Singleton Gestations (PROLONG Study): A Multicenter, International, Randomized Double-Blind Trial. American Journal of Perinatology, 37(2), 127-136. https://doi.org/10.1055/s-0039-3400227