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

Publication ,  Journal Article
Blackwell, SC; Gyamfi-Bannerman, C; Biggio, JR; Chauhan, SP; Hughes, BL; Louis, JM; Manuck, TA; Miller, HS; Das, AF; Saade, GR; Nielsen, P ...
Published in: Am J Perinatol
January 2020

BACKGROUND: Women 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: This 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: This was a double-blind, placebo-controlled international trial involving women with a previous singleton SPTB (clinicaltrials.gov: NCT01004029). Women were enrolled at 93 clinical centers (41 in the United States and 52 outside the United States) between 160/7 to 206/7 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: Baseline 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: In this study population, 17-OHPC did not decrease recurrent PTB and was not associated with increased fetal/early infant death.

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Published In

Am J Perinatol

DOI

EISSN

1098-8785

Publication Date

January 2020

Volume

37

Issue

2

Start / End Page

127 / 136

Location

United States

Related Subject Headings

  • Treatment Failure
  • Secondary Prevention
  • Progestins
  • Premature Birth
  • Pregnancy Outcome
  • Pregnancy Complications
  • Pregnancy
  • Perinatal Death
  • Obstetrics & Reproductive Medicine
  • Injections, Intramuscular
 

Citation

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Blackwell, S. C., Gyamfi-Bannerman, C., Biggio, J. R., Chauhan, S. P., Hughes, B. L., Louis, J. M., … Krop, J. (2020). 17-OHPC to Prevent Recurrent Preterm Birth in Singleton Gestations (PROLONG Study): A Multicenter, International, Randomized Double-Blind Trial. Am J Perinatol, 37(2), 127–136. https://doi.org/10.1055/s-0039-3400227
Blackwell, Sean C., Cynthia Gyamfi-Bannerman, Joseph R. Biggio, Suneet P. Chauhan, Brenna L. Hughes, Judette M. Louis, Tracy A. Manuck, et al. “17-OHPC to Prevent Recurrent Preterm Birth in Singleton Gestations (PROLONG Study): A Multicenter, International, Randomized Double-Blind Trial.Am J Perinatol 37, no. 2 (January 2020): 127–36. https://doi.org/10.1055/s-0039-3400227.
Blackwell SC, Gyamfi-Bannerman C, Biggio JR, Chauhan SP, Hughes BL, Louis JM, et al. 17-OHPC to Prevent Recurrent Preterm Birth in Singleton Gestations (PROLONG Study): A Multicenter, International, Randomized Double-Blind Trial. Am J Perinatol. 2020 Jan;37(2):127–36.
Blackwell, Sean C., et al. “17-OHPC to Prevent Recurrent Preterm Birth in Singleton Gestations (PROLONG Study): A Multicenter, International, Randomized Double-Blind Trial.Am J Perinatol, vol. 37, no. 2, Jan. 2020, pp. 127–36. Pubmed, doi:10.1055/s-0039-3400227.
Blackwell SC, Gyamfi-Bannerman C, Biggio JR, Chauhan SP, Hughes BL, Louis JM, Manuck TA, Miller HS, Das AF, Saade GR, Nielsen P, Baker J, Yuzko OM, Reznichenko GI, Reznichenko NY, Pekarev O, Tatarova N, Gudeman J, Birch R, Jozwiakowski MJ, Duncan M, Williams L, Krop J. 17-OHPC to Prevent Recurrent Preterm Birth in Singleton Gestations (PROLONG Study): A Multicenter, International, Randomized Double-Blind Trial. Am J Perinatol. 2020 Jan;37(2):127–136.
Journal cover image

Published In

Am J Perinatol

DOI

EISSN

1098-8785

Publication Date

January 2020

Volume

37

Issue

2

Start / End Page

127 / 136

Location

United States

Related Subject Headings

  • Treatment Failure
  • Secondary Prevention
  • Progestins
  • Premature Birth
  • Pregnancy Outcome
  • Pregnancy Complications
  • Pregnancy
  • Perinatal Death
  • Obstetrics & Reproductive Medicine
  • Injections, Intramuscular