Clinical trial NCT01119963
Conditions: Preterm Delivery
Keywords: Preterm delivery
Sponsor: Obstetrix Medical Group
Start date: 2011-10-01; Completion date: 2014-10-01
Enrollment: 152 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
The objective of the study is to determine if a weekly dose of 17 hydroxyprogesterone caproate (17P, Makena®) given to women with preterm rupture of the membranes will:

1. increase the probability of continuing the pregnancy until a favorable gestational age.
2. increase the interval between randomization and delivery.
3. decrease neonatal morbidity.

Detailed description:
Preterm rupture of the membranes (PROM) is the leading identifiable cause of prematurity and accounts for about one-third of all preterm deliveries and 18-20% of perinatal deaths in the USA. When PROM occurs at very early gestational ages, the clinician must make a decision whether to attempt to prolong the pregnancy or whether to recommend prompt delivery. Both approaches carry substantial risk. The strategy of continuing the pregnancy is commonly called "expectant management." During expectant management, gestational age steadily increases, and the balance naturally shifts toward favoring delivery. Once the gestational age reaches 34 weeks, the risk of lethal or permanent sequelae of prematurity or minimal, so most clinicians agree that delivery is warranted. Despite an attempt at expectant management, the majority of patients with PROM will be delivered within the first week or so. Unfortunately, no intervention other than antibiotic prophylaxis or corticosteroids have been shown to prolong latency or reduce neonatal morbidity after PROM. Recent evidence suggests that prophylactic administration of progesterone medications may reduce the risk of preterm delivery in women with certain risk factors, notably those with a history of a prior preterm delivery and those with a shortened cervix discovered by ultrasound examination. Clearly, women with PROM are at very high risk of preterm delivery, so there is a pressing need to study whether 17 hydroxyprogesterone caproate (17P) is effective after PROM. Progesterone might be beneficial after PROM both because it tends to promote uterine quiescence by suppressing the formation of myometrial gap junctions and because it has anti-inflammatory properties, suppressing the production of inflammatory cytokines and thereby inhibiting cervical ripening. Inflammation is a major pathway leading to preterm labor, cervical dilation \& preterm delivery. 17P would seem to be like an ideal candidate for prolongation of pregnancy after PROM.

This is a double-blinded, placebo-controlled, multicenter, randomized clinical trial of 17P versus placebo. The primary outcome measure will be the percentage of each group reaching either a gestational age of 34w0d or documentation of fetal lung maturity at 32w0d to 33w6d. Secondary outcomes will include the latency period for each group and the percentage of newborns in each group who have major neonatal morbidity or death.

Arms: arm 1: 250 mg of 17P, Makena® intramuscular (IM) weekly. arm 2: Castor Oil (Placebo)intramuscular (IM) weekly
Interventions: intervention 1: 17-alpha-hydroxy-progesterone caproate, Makena® intervention 2: Castor Oil (Placebo)
Intervention descriptions: intervention 1: Intramuscular (IM) injection of 17P,Makena® (250mg) beginning as early as 23w0d administered weekly until 34w0d, documented fetal lung maturity at 32w0d - 33w6d, or delivery which ever comes first. intervention 2: IM injections of Placebo (castor oil) beginning as early as 23w0d administered weekly until 34w0d, documented fetal lung maturity at 32w0d - 33w6d, or delivery which ever comes first.

Protocol documents: