Progesterone (17P, Makena®) for Prolongation of Pregnancy in Women With Preterm Rupture of the Membranes (PROM) (17PinPROM)
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:
- increase the probability of continuing the pregnancy until a favorable gestational age.
- increase the interval between randomization and delivery.
- decrease neonatal morbidity.
|Preterm Delivery||Drug: 17-alpha-hydroxy-progesterone caproate, Makena® Drug: Castor Oil (Placebo)||Phase 2 Phase 3|
|Study Design:||Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double Blind (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Prevention
|Official Title:||17-alpha-Hydroxyprogesterone Caproate (17P, Makena®) for Prolongation of Pregnancy in Women With Preterm Rupture of the Membranes (PROM), Double-blinded Randomized Clinical Trial|
- Interval from PROM until delivery of 34w0d which ever comes first. [ Time Frame: measured from PROM until 34w0d or delivery if that comes first. ]Measures in average time in hours from PROM until 34w0d of gestation or delivery is that comes first.
- Duration of latency period [ Time Frame: average number of hours measured from randomization until birth ]
- Duration of latency period (time from randomization to birth)
|Study Start Date:||October 2011|
|Study Completion Date:||October 2014|
|Primary Completion Date:||April 2014 (Final data collection date for primary outcome measure)|
Active Comparator: 17-alpha hydroxyprogesterone caproate, Makena®
250 mg of 17P, Makena® intramuscular (IM) weekly.
Drug: 17-alpha-hydroxy-progesterone caproate, Makena®
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.
Placebo Comparator: Placebo
Castor Oil (Placebo)intramuscular (IM) weekly
Drug: Castor Oil (Placebo)
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.
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.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01119963
|United States, Alabama|
|University of South Alabama Medical Center|
|Mobile, Alabama, United States, 36617|
|United States, Arizona|
|Desert Good Samaritan Hospital|
|Mesa, Arizona, United States, 85202|
|Banner Good Samaritan Hospital|
|Phoenix, Arizona, United States, 85006|
|Tucson Medical Center|
|Tucson, Arizona, United States, 85712|
|United States, California|
|Long Beach Memorial Medical Center|
|Long Beach, California, United States, 90801-1428|
|Good Samaritan Hospital|
|San Jose, California, United States, 95124|
|San Jose, California, United States, 95128|
|United States, Colorado|
|Swedish Medical Center|
|Denver, Colorado, United States, 80110|
|Presbyterian/St Luke's Hospital|
|Denver, Colorado, United States, 80218|
|United States, Kentucky|
|Norton Kosair Children's Hospital|
|Louisville, Kentucky, United States, 40202|
|United States, Michigan|
|Spectrum Health Hospital|
|Grand Rapids, Michigan, United States, 49503|
|United States, Missouri|
|Saint Luke's Hospital, Kansas City|
|Kansas City, Missouri, United States, 64111|
|United States, Nevada|
|Sunrise Medical Center|
|Las Vegas, Nevada, United States, 89109|
|United States, Ohio|
|University of Cincinnati|
|Cincinnati, Ohio, United States, 45267-0526|
|United States, Washington|
|Swedish Medical Center|
|Seattle, Washington, United States, 98122-4307|
|Principal Investigator:||Andrew Combs, MD||Obstetrix Medical Group|