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

NCT ID: NCT01119963

Last Updated: 2018-06-28

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2/PHASE3
• Total Enrollment: 152 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2011-10-31
• Study Completion Date: 2014-10-31

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.

Conditions

Preterm Delivery

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: PREVENTION
• Blinding Strategy: QUADRUPLE

Study Groups

17-alpha hydroxyprogesterone caproate, Makena®

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

Group Type: ACTIVE_COMPARATOR

17-alpha-hydroxy-progesterone caproate, Makena®

Intervention Type: DRUG

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

Castor Oil (Placebo)intramuscular (IM) weekly

Group Type: PLACEBO_COMPARATOR

Castor Oil (Placebo)

Intervention Type: DRUG

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.

Interventions

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.

Intervention Type: 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.

Intervention Type: DRUG

Other Intervention Names

17 alpha hydroxyprogesterone Caproate; 17P; 17Pc; 17HP; 170HP; 170HPC; Progesterone; Makena®; Placebo; Castor Oil

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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: Yes

Sponsors

Obstetrix Medical Group

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Andrew Combs, MD

Role: PRINCIPAL_INVESTIGATOR

Obstetrix Medical Group

Locations

University of South Alabama Medical Center

Mobile, Alabama, United States

Desert Good Samaritan Hospital

Mesa, Arizona, United States

Banner Good Samaritan Hospital

Phoenix, Arizona, United States

Tucson Medical Center

Tucson, Arizona, United States

Long Beach Memorial Medical Center

Long Beach, California, United States

Good Samaritan Hospital

San Jose, California, United States

OConnor Hospital

San Jose, California, United States

Swedish Medical Center

Denver, Colorado, United States

Presbyterian/St Luke's Hospital

Denver, Colorado, United States

Norton Kosair Children's Hospital

Louisville, Kentucky, United States

Spectrum Health Hospital

Grand Rapids, Michigan, United States

Saint Luke's Hospital, Kansas City

Kansas City, Missouri, United States

Sunrise Medical Center

Las Vegas, Nevada, United States

University of Cincinnati

Cincinnati, Ohio, United States

Swedish Medical Center

Seattle, Washington, United States

Countries

United States

References

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Combs CA, McCune M, Clark R, Fishman A. Aggressive tocolysis does not prolong pregnancy or reduce neonatal morbidity after preterm premature rupture of the membranes. Am J Obstet Gynecol. 2004 Jun;190(6):1723-8; discussion 1728-31. doi: 10.1016/j.ajog.2004.02.042.

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Reference Type: DERIVED

PMID: 22206581 (View on PubMed)

Other Identifiers

OBX0012

Identifier Type: -

Identifier Source: org_study_id