Progesterone (17P, Makena®) for Prolongation of Pregnancy in Women With Preterm Rupture of the Membranes (PROM)

17-alpha-Hydroxyprogesterone Caproate (17P, Makena®) for Prolongation of Pregnancy in Women With Preterm Rupture of the Membranes (PROM), Double-blinded Randomized Clinical Trial

Sponsors

Lead Sponsor: Obstetrix Medical Group

Source Mednax Center for Research, Education, Quality and Safety
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.

Overall Status Completed
Start Date 2011-10-01
Completion Date 2014-10-01
Primary Completion Date 2014-04-01
Phase Phase 2/Phase 3
Study Type Interventional
Primary Outcome
Measure Time Frame
Gestational Age at Delivery Measured from day of last menstrual cycle to day of birth and measured in weeks.
Secondary Outcome
Measure Time Frame
Duration of Latency Period average number of days measured from day of study entry until day of delivery
Enrollment 152
Condition
Intervention

Intervention Type: Drug

Intervention Name: 17-alpha-hydroxy-progesterone caproate, Makena®

Description: 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.

Arm Group Label: 17-alpha hydroxyprogesterone caproate, Makena®

Intervention Type: Drug

Intervention Name: Castor Oil (Placebo)

Description: 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.

Arm Group Label: Placebo

Eligibility

Criteria:

Inclusion Criteria: 1. Participant is 18 years old or older 2. Gestational Age (GA) 23w0d and 30w6d @ time of enrollment 3. Singleton pregnancy 4. PROM defined as either (a) or (b) or (c) below (a) Documentation of vaginal leakage of indigo carmine dye instilled via amniocentesis (b) Positive Amnisure® test (c) Two or more of (i) through (iv): i. Nitrazine test with pH of 7 or more ii. Positive fern test iii. Gross pooling of clear fluid iv. US exam showing oligohydramnios Exclusion Criteria: 1. Any contraindication to expectant management 2. Any fetal condition likely to cause serious neonatal morbidity independent of gestational age 3. History of allergy to 17P 4. Any contraindications to 17P use (e.g. Thrombosis, Breast CA, abnormal vaginal bleeding unrelated to pregnancy, jaundice, liver disease, uncontrolled HTN) 5. Any medical condition currently treated with systemic steroid medications 6. Cervical cerclage present at the time of PROM 7. Informed consent not obtained.

Gender:

Female

Minimum Age:

18 Years

Maximum Age:

N/A

Healthy Volunteers:

Accepts Healthy Volunteers

Overall Official
Last Name Role Affiliation
Andrew Combs, MD Principal Investigator Obstetrix Medical Group
Location
Facility:
University of South Alabama Medical Center | Mobile, Alabama, 36617, United States
Desert Good Samaritan Hospital | Mesa, Arizona, 85202, United States
Banner Good Samaritan Hospital | Phoenix, Arizona, 85006, United States
Tucson Medical Center | Tucson, Arizona, 85712, United States
Long Beach Memorial Medical Center | Long Beach, California, 90801-1428, United States
Good Samaritan Hospital | San Jose, California, 95124, United States
OConnor Hospital | San Jose, California, 95128, United States
Swedish Medical Center | Denver, Colorado, 80110, United States
Presbyterian/St Luke's Hospital | Denver, Colorado, 80218, United States
Norton Kosair Children's Hospital | Louisville, Kentucky, 40202, United States
Spectrum Health Hospital | Grand Rapids, Michigan, 49503, United States
Saint Luke's Hospital, Kansas City | Kansas City, Missouri, 64111, United States
Sunrise Medical Center | Las Vegas, Nevada, 89109, United States
University of Cincinnati | Cincinnati, Ohio, 45267-0526, United States
Swedish Medical Center | Seattle, Washington, 98122-4307, United States
Location Countries

United States

Verification Date

2018-05-01

Responsible Party

Type: Sponsor

Keywords
Has Expanded Access No
Condition Browse
Number Of Arms 2
Arm Group

Label: 17-alpha hydroxyprogesterone caproate, Makena®

Type: Active Comparator

Description: 250 mg of 17P, Makena® intramuscular (IM) weekly.

Label: Placebo

Type: Placebo Comparator

Description: Castor Oil (Placebo)intramuscular (IM) weekly

Acronym 17PinPROM
Study Design Info

Allocation: Randomized

Intervention Model: Parallel Assignment

Primary Purpose: Prevention

Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

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