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

NCT01119963 | Completed Phase 2 Results DMC

• 1 other identifier: OBX0012
• Study Type: interventional
• Target: 152
• Locations: 1 country
• Sites: 15

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

Conditions

Preterm Delivery

Keywords

Preterm delivery

Outcome Measures

Primary Outcomes (1)

• Gestational Age at Delivery

  Gestational age is measured in weeks, from the first day of the woman's last menstrual cycle to the date the baby was born.

  Measured from day of last menstrual cycle to day of birth and measured in weeks.

Secondary Outcomes (1)

• Duration of Latency Period

  average number of days measured from day of study entry until day of delivery

Study Arms (2)

17-alpha hydroxyprogesterone caproate, Makena®

ACTIVE COMPARATOR

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

Drug: 17-alpha-hydroxy-progesterone caproate, Makena®

Placebo

PLACEBO COMPARATOR

Castor Oil (Placebo)intramuscular (IM) weekly

Drug: Castor Oil (Placebo)

Interventions

17-alpha-hydroxy-progesterone caproate, Makena® 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.

Also known as: 17 alpha hydroxyprogesterone Caproate, 17P, 17Pc, 17HP, 170HP, 170HPC, Progesterone, Makena®

17-alpha hydroxyprogesterone caproate, Makena®

Castor Oil (Placebo) 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.

Also known as: Placebo, Castor Oil

Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: female
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Participant is 18 years old or older
• Gestational Age (GA) 23w0d and 30w6d @ time of enrollment
• Singleton pregnancy
• 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

You may not qualify if:

• Any contraindication to expectant management
• Any fetal condition likely to cause serious neonatal morbidity independent of gestational age
• History of allergy to 17P
• Any contraindications to 17P use (e.g. Thrombosis, Breast CA, abnormal vaginal bleeding unrelated to pregnancy, jaundice, liver disease, uncontrolled HTN)
• Any medical condition currently treated with systemic steroid medications
• Cervical cerclage present at the time of PROM
• Informed consent not obtained.

Sponsors & Collaborators

• Obstetrix Medical Group: lead

Study Sites (15)

University of South Alabama Medical Center

Mobile, Alabama, 36617, United States

Location

Desert Good Samaritan Hospital

Mesa, Arizona, 85202, United States

Location

Banner Good Samaritan Hospital

Phoenix, Arizona, 85006, United States

Location

Tucson Medical Center

Tucson, Arizona, 85712, United States

Location

Long Beach Memorial Medical Center

Long Beach, California, 90801-1428, United States

Location

Good Samaritan Hospital

San Jose, California, 95124, United States

Location

OConnor Hospital

San Jose, California, 95128, United States

Location

Swedish Medical Center

Denver, Colorado, 80110, United States

Location

Presbyterian/St Luke's Hospital

Denver, Colorado, 80218, United States

Location

Norton Kosair Children's Hospital

Louisville, Kentucky, 40202, United States

Location

Spectrum Health Hospital

Grand Rapids, Michigan, 49503, United States

Location

Saint Luke's Hospital, Kansas City

Kansas City, Missouri, 64111, United States

Location

Sunrise Medical Center

Las Vegas, Nevada, 89109, United States

Location

University of Cincinnati

Cincinnati, Ohio, 45267-0526, United States

Location

Swedish Medical Center

Seattle, Washington, 98122-4307, United States

Location

Related Publications (12)

• Amon E, Lewis SV, Sibai BM, Villar MA, Arheart KL. Ampicillin prophylaxis in preterm premature rupture of the membranes: a prospective randomized study. Am J Obstet Gynecol. 1988 Sep;159(3):539-43. doi: 10.1016/s0002-9378(88)80002-4.

  PMID: 3421250 BACKGROUND

• Committee on Obstetric Practice.. ACOG committee opinion. Antenatal corticosteroid therapy for fetal maturation. American College of Obstetricians and Gynecologists. Int J Gynaecol Obstet. 2002 Jul;78(1):95-7.

  PMID: 12197491 BACKGROUND

• ACOG Committee on Obstetric Practice. Use of progesterone to reduce preterm birth. ACOG Committee Opinion 291: 1-2, American College of Obstetricians and Gynecologists, 2003

  BACKGROUND

• ACOG Committee on Practice Bulletins. Premature rupture of membranes. ACOG Practice Bulletin 80: 1-13, American College of Obstetricians and Gynecologists, 2007

  BACKGROUND

• Ananth CV, Savitz DA, Williams MA. Placental abruption and its association with hypertension and prolonged rupture of membranes: a methodologic review and meta-analysis. Obstet Gynecol. 1996 Aug;88(2):309-18. doi: 10.1016/0029-7844(96)00088-9.

  PMID: 8692522 BACKGROUND

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

  BACKGROUND

• Bengtson JM, VanMarter LJ, Barss VA, Greene MF, Tuomala RE, Epstein MF. Pregnancy outcome after premature rupture of the membranes at or before 26 weeks' gestation. Obstet Gynecol. 1989 Jun;73(6):921-7. doi: 10.1097/00006250-198906000-00002.

  PMID: 2726113 BACKGROUND

• Beydoun SN, Yasin SY. Premature rupture of the membranes before 28 weeks: conservative management. Am J Obstet Gynecol. 1986 Sep;155(3):471-9. doi: 10.1016/0002-9378(86)90257-7.

  PMID: 3752169 BACKGROUND

• Caritis SN, Rouse DJ, Peaceman AM, Sciscione A, Momirova V, Spong CY, Iams JD, Wapner RJ, Varner M, Carpenter M, Lo J, Thorp J, Mercer BM, Sorokin Y, Harper M, Ramin S, Anderson G; Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), Maternal-Fetal Medicine Units Network (MFMU). Prevention of preterm birth in triplets using 17 alpha-hydroxyprogesterone caproate: a randomized controlled trial. Obstet Gynecol. 2009 Feb;113(2 Pt 1):285-92. doi: 10.1097/AOG.0b013e318193c677.

  PMID: 19155896 BACKGROUND

• Caughey AB, Robinson JN, Norwitz ER. Contemporary diagnosis and management of preterm premature rupture of membranes. Rev Obstet Gynecol. 2008 Winter;1(1):11-22.

  PMID: 18701929 BACKGROUND

• 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.

  PMID: 15284781 BACKGROUND

• Combs CA, Garite TJ, Maurel K, Mallory K, Edwards RK, Lu G, Porreco R, Das A; Obstetrix Collaborative Research Network. 17-Hydroxyprogesterone caproate to prolong pregnancy after preterm rupture of the membranes: early termination of a double-blind, randomized clinical trial. BMC Res Notes. 2011 Dec 29;4:568. doi: 10.1186/1756-0500-4-568.

  PMID: 22206581 DERIVED

MeSH Terms

Conditions

Premature Birth

Interventions

17 alpha-Hydroxyprogesterone Caproate; Progesterone; Castor Oil

Condition Hierarchy (Ancestors)

Obstetric Labor, Premature; Obstetric Labor Complications; Pregnancy Complications; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases

Intervention Hierarchy (Ancestors)

17-alpha-Hydroxyprogesterone; Hydroxyprogesterones; Pregnenediones; Pregnenes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Progesterone Congeners; Gonadal Steroid Hormones; Gonadal Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Corpus Luteum Hormones; Fats, Unsaturated; Fats; Lipids; Plant Oils; Oils; Plant Preparations; Biological Products; Complex Mixtures

Limitations and Caveats

One limitation is that we only studied one dose of 17OHPc (250mg) and only one frequency (once a week) however we did this to coincide with the study that showed benefits of 17OHPc in women with intact membranes with a history of preterm birth.

Results Point of Contact

• Title: Kimberly Maurel
• Organization: Mednax. Inc

kimberly_maurel@mednax.com

714-593-9171

Study Officials

• Andrew Combs, MD

  Obstetrix Medical Group

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 16, 2010
• First Posted: May 10, 2010
• Study Start: October 1, 2011
• Primary Completion: April 1, 2014
• Study Completion: October 1, 2014
• Last Updated: June 28, 2018
• Results First Posted: May 30, 2018

Record last verified: 2018-05

Locations

US (15)