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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Obstetrix Medical Group
ClinicalTrials.gov Identifier:
NCT01119963
First received: February 16, 2010
Last updated: October 16, 2014
Last verified: October 2014
  Purpose

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.

Condition Intervention Phase
Preterm Delivery
Drug: 17-alpha-hydroxy-progesterone caproate, Makena®
Drug: Castor Oil (Placebo)
Phase 2
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, 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

Resource links provided by NLM:


Further study details as provided by Obstetrix Medical Group:

Primary Outcome Measures:
  • Interval from PROM until delivery of 34w0d which ever comes first. [ Time Frame: measured from PROM until 34w0d or delivery if that comes first. ] [ Designated as safety issue: Yes ]
    Measures in average time in hours from PROM until 34w0d of gestation or delivery is that comes first.


Secondary Outcome Measures:
  • Duration of latency period [ Time Frame: average number of hours measured from randomization until birth ] [ Designated as safety issue: Yes ]

    Secondary Outcomes:

    - Duration of latency period (time from randomization to birth)



Enrollment: 152
Study Start Date: October 2011
Study Completion Date: October 2014
Primary Completion Date: April 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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.
Other Names:
  • 17 alpha hydroxyprogesterone Caproate
  • 17P
  • 17Pc
  • 17HP
  • 170HP
  • 170HPC
  • Progesterone
  • Makena®
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.
Other Names:
  • Placebo
  • Castor Oil

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   Yes
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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01119963

Locations
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
OConnor Hospital
San Jose, California, United States, 95128
Good Samaritan Hospital
San Jose, California, United States, 95124
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
Sponsors and Collaborators
Obstetrix Medical Group
Investigators
Principal Investigator: Andrew Combs, MD Obstetrix Medical Group
  More Information

Publications:
Armstrong J, Nageotte M for the Society for Maternal-Fetal Medicine. Can progesterone prevent preterm birth? Contemp Obstet Gynecol 2005 (Oct);30-43

Responsible Party: Obstetrix Medical Group
ClinicalTrials.gov Identifier: NCT01119963     History of Changes
Other Study ID Numbers: OBX0012
Study First Received: February 16, 2010
Last Updated: October 16, 2014
Health Authority: United States: Institutional Review Board

Keywords provided by Obstetrix Medical Group:
Preterm delivery

Additional relevant MeSH terms:
Premature Birth
Obstetric Labor Complications
Obstetric Labor, Premature
Pregnancy Complications
11-hydroxyprogesterone
17-alpha-hydroxy-progesterone caproate
Castor Oil
Progesterone
Cathartics
Estradiol Antagonists
Estrogen Antagonists
Estrogen Receptor Modulators
Gastrointestinal Agents
Hormone Antagonists
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Pharmacologic Actions
Physiological Effects of Drugs
Progestins
Therapeutic Uses

ClinicalTrials.gov processed this record on October 20, 2014