Preterm birth remains a major problem throughout the world. Treatment efficacy in women with a documented previous spontaneous preterm birth has recently been demonstrated in one randomized trial using a 17 α-hydroxyprogesterone caproate (17P) and a second using a vaginal progesterone. Presently, 17P as prophylaxis for preterm delivery has not been demonstrated to be effective in any other group of women and its indicated use remains limited to women with a prior preterm delivery. One risk factor for preterm delivery that has been consistently demonstrated is short cervical length, especially in nulliparous women.
Progesterone administration has been hypothesized in various studies to reduce preterm birth since at least the early 1960s. However, these studies were limited in scope since they had low power due to a small number of women enrolled. The MFMU progesterone trial, which enrolled women who were at high risk by virtue of a prior preterm birth in a two to one allocation of subjects to study drug and placebo, demonstrated that 17P substantially reduced the risk of preterm birth at < 37 weeks, < 35 weeks, and < 32 weeks.7 Other clinical trials and meta-analyses have been conducted with results indicating a decrease in preterm birth rates.8,16, 17,18 These studies are describe in more detail in Section 2.2.2 of the full protocol.
This randomized trial will address the primary research question: does treatment with 17 α-hydroxyprogesterone caproate (17P) initiated prior to 23 weeks of gestation prevent delivery prior to 37 weeks in nulliparous women with singleton pregnancies who have a short cervix?
This study is a randomized double-masked placebo-controlled multicenter clinical trial. Participants will be nulliparous women with a short cervix measured between 16 weeks 0 days and 22 weeks 3 days who will be randomized between 16 weeks 0 days and 22 weeks and 6 days to one of two treatments:
• 17 α-hydroxyprogesterone caproate (17P): weekly injections containing 250 mg of 17P until 37 weeks gestation or delivery
• Placebo: weekly injections until 37 weeks gestation or delivery
Principle Investigator: Michael Varner
Principle Department: Maternal-Fetal Medicine