BACKGROUND AND PURPOSE:

• 17-alpha-hydroxyprogesterone caproate (17-OHPC) has been used to prevent recurrent preterm birth since 2003, when the Meis trial was published showing its efficacy
  • A recently completed confirmatory trial, PROLONG, did not demonstrate similar efficacy
• Sibai et al. (Journal of Perinatology, 2020) analyzed the 17-alpha-hydroxyprogesterone caproate (17-OHPC) safety data from both the Meis and PROLONG RCT datasets separately and also as an integrated dataset

METHODS:

• Both Meis and PROLONG were multi-center, randomized, double-blind, placebo-controlled trials
• Participants
  • Individuals with a history of spontaneous preterm birth (SPTB)
• Interventions
  • 17-OHPC group: 250 mg weekly IM | Beginning at 16 to 20 weeks and continuing until 37 weeks of gestation or delivery
  • Placebo group

Study Design Related to Side Effects and Adverse Outcome Reporting

• Meis:
  • Side effects not mentioned by the participant but recorded by study coordinator were documented as adverse events
  • Participants were asked open ended questions about symptoms as well as focused questions for specific adverse events
  • Serious events, including unexpected events, were recorded
• PROLONG
  • Adverse events collected using standardized Good Clinical Practice guidelines
  • Participants were asked about change in well-being
  • Adverse events included if reported by the participants or the investigator | Investigator assessed causality

RESULTS:

• Meis: 310 in 17-OHPC group | 153 in placebo group
• PROLONG: 1130 in 17-OHPC | 578 in placebo group

Adverse Events

• Adverse event profiles were similar between 17-OHPC and placebo groups in both studies
  • Meis: 57.7% vs 56.2%
  • PROLONG: 57.3% vs 57.8%
• Serious adverse events were infrequent
• Integrated maternal adverse events
  • GDM rate: No differences between groups
    • 17-OHPC group: 3.6%
    • Placebo: 3.8%
  • Similar findings for other adverse events, including hypertension and preeclampsia
• Integrated perinatal adverse events: No statistical differences between groups
  • Miscarriage: 0.66 (95% CI, 0.25 to 1.78)
  • Stillbirth: 1.83 (95% CI, 0.68 to 4.91)
  • All fetal and neonatal death: 0.86 (95% CI, 0.53 to 1.41)

CONCLUSION:

• 17-OHPC had a favorable safety profile in the integrated dataset, comparable to that of placebo
• The authors also note that post-marketing safety data are consistent with the findings of this study

Learn More – Primary Sources:

Safety review of hydroxyprogesterone caproate in women with a history of spontaneous preterm birth

Related ObG Topics:

FDA, SMFM and ACOG Respond to PROLONG Study Results: Does IM 17-OHPC Impact Preterm Delivery?

17-OHPC Treatment and Prevention of Preterm Birth: Does Timing Matter?

Do Progestogens for Preterm Birth Prevention Increase Risk of Gestational Diabetes?

Progesterone, Cerclage or Pessary for Prevention of Preterm Birth: A Comparison