17OHP for Reduction of Neonatal Morbidity Due to Preterm Birth (PTB) in Twin and Triplet Pregnancies - Full Text View

Sponsored by:	Obstetrix Medical Group
Information provided by:	Obstetrix Medical Group
ClinicalTrials.gov Identifier:	NCT00163020

Purpose

Hypothesis: Among women with twin or triplet pregnancies, weekly injections of 17-alpha-hydroxyprogesterone caproate (17OHP), started before 24 weeks of gestation, will reduce neonatal morbidity by reducing the rate of preterm delivery.

This study involves two concurrent double-blinded randomized clinical trials of 17OHP versus placebo. Each trial will test the efficacy and safety of 17OHP in women with a specific risk factor for preterm birth. The two risk factors to be studied are:

Twin pregnancy
Triplet pregnancy

Condition	Intervention	Phase
Preterm Birth	Drug: 17-alpha-hydroxyprogesterone caproate injectable Drug: Placebo	Phase II Phase III

Study Type:	Interventional
Study Design:	Treatment, Randomized, Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Placebo Control, Parallel Assignment, Safety/Efficacy Study
Official Title:	17-Alpha-Hydroxyprogesterone Caproate for Reduction of Neonatal Morbidity Due to Preterm Birth in Twin and Triplet Pregnancies - A Concurrent Randomized Double-blinded Clinical Trial

Resource links provided by NLM:

MedlinePlus related topics: Nausea and Vomiting

Drug Information available for: 17-Hydroxyprogesterone Hydroxyprogesterone caproate

U.S. FDA Resources

Further study details as provided by Obstetrix Medical Group:

Primary Outcome Measures:

Respiratory distress syndrome [ Time Frame: from delivery up to 30 days post discharge from the hospital ] [ Designated as safety issue: Yes ]
Use of oxygen therapy at 28 days of newborn life [ Time Frame: with in 28 days of life ] [ Designated as safety issue: Yes ]
Neonatal sepsis [ Time Frame: during neonatal period ] [ Designated as safety issue: Yes ]
Pneumonia [ Time Frame: during neonatal period ] [ Designated as safety issue: Yes ]
Intraventricular hemorrhage grade 3 or 4 [ Time Frame: during neonatal period ] [ Designated as safety issue: Yes ]
Periventricular leukomalacia [ Time Frame: during neonatal period ] [ Designated as safety issue: Yes ]
Necrotizing enterocolitis requiring surgery [ Time Frame: during neonatal period ] [ Designated as safety issue: Yes ]
Retinopathy of prematurity [ Time Frame: during neonatal period ] [ Designated as safety issue: Yes ]
Newborn asphyxia with ischemic injury of brain, heart, kidneys, or liver [ Time Frame: during neonatal period ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:

Individual components of neonatal morbidity enumerated above [ Time Frame: any evident during neonatal period ] [ Designated as safety issue: Yes ]
Twins: Delivery prior to 28 weeks (wks), 32 wks, 37 wks [ Time Frame: noted at delivery ] [ Designated as safety issue: Yes ]
Triplets: Delivery prior to 28 wks, 32 wks, 35 wks [ Time Frame: noted at delivery ] [ Designated as safety issue: Yes ]
Gestational age at delivery [ Time Frame: noted at delivery ] [ Designated as safety issue: Yes ]
Birthweight [ Time Frame: noted at time of delivery ] [ Designated as safety issue: Yes ]
Drop-out rates [ Time Frame: any time from randomization to completion of final dose of study medication ] [ Designated as safety issue: No ]
Side effects requiring cessation of therapy [ Time Frame: anytime from initial injection to final injection at 34 weeks. ] [ Designated as safety issue: Yes ]
Specific side effects (such as: nausea, vomiting, injection site soreness, vaginal bleeding, vaginal discharge, decreased fetal movement, rash, pruritis) [ Time Frame: from first injection until one week following final injection. ] [ Designated as safety issue: Yes ]

Estimated Enrollment:	321
Study Start Date:	November 2004
Estimated Study Completion Date:	February 2010
Estimated Primary Completion Date:	January 2010 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
1 Test Group (170HP): Active Comparator Test Group will receive weekly doses of 170HP via injection as early as 19weeks until 34.0weeks gestation or delivery which ever comes first.	Drug: 17-alpha-hydroxyprogesterone caproate injectable 250mg of 17-alpha-hydroxyprogesterone caproate (+ preservatives) injectable weekly starting as early as 19wks gestation until 34.0wks gestation of delivery which ever comes first.
2 - Control (Normal Saline): Placebo Comparator Control Group will receive weekly doses of placebo (NS) via injection as early as 19weeks until 34.0weeks gestation or delivery which ever comes first.	Drug: Placebo Weekly doses of placebo (NS + preservatives) via injection as early as 19weeks until 34.0weeks gestation or delivery which ever comes first.

Detailed Description:

Prematurity is a leading cause of neonatal morbidity and mortality in the USA. Nationally, 12% of all babies deliver before term and 3% deliver before 32 wks gestational age (GA). Recent studies suggest that 17OHP and other progesterone derivatives may reduce the rate of preterm birth among women with a history of prior preterm birth. However, it has not been demonstrated that this reduction in preterm birth is accompanied by a clinically significant reduction in neonatal complications. Further, most women who deliver preterm have no history of a prior preterm birth. Little is known about whether progesterone treatment is effective in women with other risk factors for preterm birth such as multiple gestation. The proposed study will assess the role of 17OHP in women with twin or triplet pregnancies and will assess the impact on neonatal health, not merely the impact on gestational age at delivery. Prior studies were not designed to be large enough to have statistical power to assess effects on neonatal morbidity.

In the 6 trials combined in the Goldstein meta-analysis, only 279 women were treated with 17OHP and only 73 women had a preterm delivery. The NICHD study presented by Meis approximately doubles the world-wide experience, with 306 women under treatment, of whom 73 delivered prior to 35 wks. Yet, this study was not designed to have power to show a reduction in neonatal complications but only a reduction in preterm birth rates.

The present study is the first to be specifically designed to have adequate power to test whether 17OHP reduces neonatal morbidity among women with one of two specific risk factors for preterm birth.

Eligibility

Ages Eligible for Study:	18 Years to 65 Years
Genders Eligible for Study:	Female
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

Gestational age (GA) 15-23w0d gestational age at the time of recruitment
GA 16w0dk to 23w6d at the time of randomization and initiation of injections
Maternal age 18 years or older
One of these risk factors for spontaneous preterm birth:
1. Twins in current pregnancy, dichorionic placentation
2. Triplets in current pregnancy, trichorionic placentation
Intact membranes
Patient has had at least one detailed 2nd-trimester ultrasound examination documenting placentation, chorionicity, fetal number, fetal size, amniotic fluid volumes, and fetal anatomy. (This examination must comply with minimum standards such as those published by the American Institute of Ultrasound in Medicine, American College of Radiology, or American College of Obstetricians & Gynecologists It is NOT mandatory that this examination be performed at the research-study center.)
Investigator believes patient will be reliable with follow-up visits and believes that delivery data and neonatal data are likely to be available.

Exclusion Criteria:

Symptomatic uterine contractions in current pregnancy
Contraindication to interventions intended to prolong the pregnancy (including lethal fetal anomalies, amnionitis, preeclampsia, severe oligohydramnios, severe growth delay, fetal death appears imminent or inevitable)
Risk factors for major neonatal morbidity unrelated to preterm delivery (such as monochorionic placentation in multiple gestation, major malformations, certain medication exposures)
Preexisting maternal medical condition that might be worsened by progesterone therapy, including: asthma requiring medications, renal insufficiency, seizure disorder, ischemic heart disease, active cholecystitis, impaired liver function, history of thromboembolic disorder, history of breast cancer, history of major depression requiring hospitalization.
Preexisting maternal medical condition associated with a high risk of preterm delivery including:

refractory hypertension, diabetes with nephropathy or retinopathy, renal insufficiency, active systemic lupus erythematosus. Note that a history of prior preterm birth is NOT an exclusion.
Use of progesterone or progesterone-derivative medication after 15 weeks gestation in current pregnancy.
Allergy to 17OHP or oil vehicle.
Placement of emergent cerclage (defined as one placed after the occurrence of cervical change such as dilation, funneling, or effacement) with this pregnancy. Prophylactic cerclage is NOT an exclusion (defined as one placed before any cervical change, for example, because of a history of cervical incompetence, or because of a prior cervical procedure such as LEEP or cone biopsy).

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00163020

Locations

United States, Arizona
Banner Good Samaritan Hospital
Phoenix, Arizona, United States, 85006
Desert Good Samaritan Hospital
Mesa, Arizona, United States, 85202
Tucson Medical Center
Tucson, Arizona, United States, 85712
United States, California
Good Samaritan Hospital
San Jose, California, United States, 95124
Long Beach Memorial Medical Center
Long Beach, California, United States, 90801-1428
Saddleback Memorial Medical Center
Laguna Hills, California, United States, 92653
University of Southern California-Irvine Medical Center
Orange, California, United States, 92868
United States, Colorado
Presbyterian/St Luke's Hospital
Denver, Colorado, United States, 80218
Swedish Medical Center
Denver, Colorado, United States, 80110
Rose Medical Center
Denver, Colorado, United States, 80220
Skyridge Medical Center
Lonetree, Colorado, United States, 80124
United States, Iowa
Mercy Medical Center
Des Moines, Iowa, United States, 50314
United States, Missouri
Saint Luke's Hospital, Kansas City
Kansas City, Missouri, United States, 64111
United States, Tennessee
Erlanger Medical Center
Chattanooga, Tennessee, United States, 37403
United States, Texas
Harris Methodist Fort Worth Hospital
Fort Worth, Texas, United States, 76104
Baylor University Medical Center
Dallas, Texas, United States, 75246
United States, Washington
Swedish Medical Center
Seattle, Washington, United States, 98122-4307
Evergreen Hospital
Kirkland, Washington, United States, 98034

Sponsors and Collaborators

Obstetrix Medical Group

Investigators

Study Director:	Kimberly Maurel, RN, MSN, CNS	Obstetrix Medical Group, Inc.
Principal Investigator:	Andrew Combs, MD	Obstetrix Medical Group, Inc.

More Information

Additional Information:

Protocols' home page on the sponsor's Web site. Click on Protocols and then click the Progesterone for prevention of preterm birth Protocol for more information about this study. This link exits the ClinicalTrials.gov site

This link exits the ClinicalTrials.gov site

Publications:

Goldstein P, Berrier J, Rosen S, Sacks HS, Chalmers TC. A meta-analysis of randomized control trials of progestational agents in pregnancy. Br J Obstet Gynaecol. 1989 Mar;96(3):265-74.

da Fonseca EB, Bittar RE, Carvalho MH, Zugaib M. Prophylactic administration of progesterone by vaginal suppository to reduce the incidence of spontaneous preterm birth in women at increased risk: a randomized placebo-controlled double-blind study. Am J Obstet Gynecol. 2003 Feb;188(2):419-24.

Meis PJ, Klebanoff M, Thom E, Dombrowski MP, Sibai B, Moawad AH, Spong CY, Hauth JC, Miodovnik M, Varner MW, Leveno KJ, Caritis SN, Iams JD, Wapner RJ, Conway D, O'Sullivan MJ, Carpenter M, Mercer B, Ramin SM, Thorp JM, Peaceman AM, Gabbe S; National Institute of Child Health and Human Development Maternal-Fetal Medicine Units Network. Prevention of recurrent preterm delivery by 17 alpha-hydroxyprogesterone caproate. N Engl J Med. 2003 Jun 12;348(24):2379-85. Erratum in: N Engl J Med. 2003 Sep 25;349(13):1299.

American College of Obstetricians & Gynecologists. Special problems of multiple gestation. Educational Bulletin 253, 1998.

Responsible Party:	Obstetrix Medical Group, Inc. ( Kimberly Maurel )
Study ID Numbers:	OBX0003, IND # 59-536
Study First Received:	September 9, 2005
Last Updated:	August 20, 2009
ClinicalTrials.gov Identifier:	NCT00163020 History of Changes
Health Authority:	United States: Food and Drug Administration

Keywords provided by Obstetrix Medical Group:

Preterm Birth
Preterm Delivery
Multiple gestation
17-alpha-hydroxyprogesterone caproate
Progesterone

Study placed in the following topic categories:

Estrogen Antagonists
Estrogens
Pregnancy Complications
Progesterone
Obstetric Labor, Premature
Hormone Antagonists
Caproate
Estradiol valerate
Obstetric Labor Complications
Hormones, Hormone Substitutes, and Hormone Antagonists

Estradiol 17 beta-cypionate
Hormones
Estradiol
17-alpha-hydroxy-progesterone caproate
Estrogen Receptor Modulators
Progestins
Estradiol 3-benzoate
Polyestradiol phosphate
Premature Birth

Additional relevant MeSH terms:

Estrogen Antagonists
Pregnancy Complications
Hormone Antagonists
Obstetric Labor, Premature
Physiological Effects of Drugs
Obstetric Labor Complications
Hormones, Hormone Substitutes, and Hormone Antagonists

Hormones
17-alpha-hydroxy-progesterone caproate
Pharmacologic Actions
Estrogen Receptor Modulators
Progestins
Estradiol Antagonists
Premature Birth

ClinicalTrials.gov processed this record on September 11, 2009