17OHP for Reduction of Neonatal Morbidity Due to Preterm Birth (PTB) in Twin and Triplet Pregnancies (170HP)

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Obstetrix Medical Group
ClinicalTrials.gov Identifier:
NCT00163020
First received: September 9, 2005
Last updated: October 9, 2012
Last verified: October 2012
  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:

  1. Twin pregnancy
  2. Triplet pregnancy

Condition Intervention Phase
Preterm Birth
Drug: 17-alpha-hydroxyprogesterone caproate injectable
Drug: 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: Treatment
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:


Further study details as provided by Obstetrix Medical Group:

Primary Outcome Measures:
  • Newborn Respiratory Distress Syndrome (RDS) [ Time Frame: Measured from delivery until 30 days after baby was discharged from the hospital ] [ Designated as safety issue: Yes ]

    Newborn RDS in the twin arm is defined as compatible symptoms with radiographically confirmed hyaline membrane disease or with respiratory insufficiency of prematurity requiring ventilator support.

    Data expressed as mean n(%),Odds ratio, CI, and P-value were determined using repeated measures model wherein each twin/triplet within a given pregnancy is considered a repeated measure. Exceptions are comparison with 0 outcomes in one or both groups, so Fisher's Exact Test was used.

    Morbidity measures were based on live births with data available for the outcomes.


  • Use of Oxygen Therapy at 28 Days of Newborn Life [ Time Frame: Measured at 28 days after birth. ] [ Designated as safety issue: Yes ]
    Supplemental oxygen use by the baby measured at the point that the baby reaches 28 days old (after birth)within the twin group.

  • Newborn Sepsis [ Time Frame: measured during the first week following birth ] [ Designated as safety issue: Yes ]
    Newborn Sepsis in the twin group was defined as the presence of positive blood culture obtained in the first week of life in association with clinical findings suggesting illness for which the neonate received antibiotics.

  • Newborn Pneumonia [ Time Frame: measure during the first 28 days after birth. ] [ Designated as safety issue: Yes ]
    Newborn Pneumonia in the twin group is described as compatible symptoms with diagnostic radiograph findings and positive results on blood cultures, persistent leukopenia

  • Newborn Intraventricular Hemorrhage Grade 3 or 4 [ Time Frame: measured during the first 28 days after birth ] [ Designated as safety issue: Yes ]

    Newborn Intraventricular hemorrhage (IVH) Stage III in the twin group is described as - IVH with ventricular dilatation.

    Neonatal Intraventricular hemorrhage (IVH)Stage IV in the twin group is described as - IVH with parenchymal extension.


  • Newborn Periventricular Leukomalacia (PVL) [ Time Frame: measured in the first 28 days after birth. ] [ Designated as safety issue: Yes ]
    Newborn Periventricular leukomalacia (PVL) in the twin group is described as the presence of more than 1 obvious hypo echoic cyst in the periventricular white matter.

  • Newborn Necrotizing Enterocolitis (NEC)Requiring Surgery [ Time Frame: measured in the first 28 days after birth ] [ Designated as safety issue: Yes ]
    Newborn NEC in the twin group is described as the presence of any of the following: (1)unequivocal intramural air in abdominal radiograph; (2) perforation abdominal radiograph; (3) clinical evidence of perforation (erythema and induration of the abdominal wall or intrabdominal abscess formation); (4) characteristic findings observed at surgery or autopsy; (5) Stricture formation after an episode of suspected necrotizing enterocolitis.

  • Newborn Retinopathy of Prematurity (ROP) [ Time Frame: measured during the first 28 day after birth ] [ Designated as safety issue: Yes ]
    Newborn ROP within the twin group is described as retinopathy confirmed on fundoscopic examination, felt to be due to prematurity and subsequent oxygen therapy.

  • Newborn Asphyxia With Ischemic Injury of Brain, Heart, Kidneys, or Liver [ Time Frame: measured during the first 28 days after delivery ] [ Designated as safety issue: Yes ]
    Newborn Asphyxia or Hypoxic-ischemic encephalopathy (HEI) within the twin group is characterized by clinical and laboratory evidence of acute or subacute brain injury due to asphyxia (ie, hypoxia, acidosis).

  • Perinatal Death [ Time Frame: measured from randomization to 28 days after birth. ] [ Designated as safety issue: Yes ]
    Perinatal death within the twin group is described as a stillbirth, neonatal death, or miscarriage after randomization.


Secondary Outcome Measures:
  • Individual Components of Neonatal Morbidity (RDS, IVH-III/IV, BPD, PVL, Sepsis, NEC, ROP-Stage 3/4, Perinatal Death) [ Time Frame: measured as any event noted in the first 28 day following birth. ] [ Designated as safety issue: Yes ]
    Composite Neonatal Morbidity within the twin group is described as the presence of any one or more of the following neonatal morbidities (RDS, IVH-III/IV, BPD, PVL, sepsis, NEC, ROP-Stage 3/4, Perinatal Death).

  • Twins: Delivery Prior to 28 Weeks (Wks), 32 Wks, 34wks, and 37 Wks [ Time Frame: Gestational age noted at time of birth ] [ Designated as safety issue: Yes ]
    Gestational age was noted at time of delivery and stratified into three categories (Twins: Delivery prior to 28 weeks (wks), 32 wks, 34 wks, and 37 wks)

  • Triplets: Delivery Prior to 28 Wks, 32 Wks, 35 Wks [ Time Frame: noted at delivery ] [ Designated as safety issue: Yes ]
    Gestational age was noted at time of delivery and stratified into three categories (Triplets: Delivery prior to 28 wks, 32 wks, 35 wks)

  • Newborn Gestational Age (GA) at Delivery [ Time Frame: determined at the time of birth ] [ Designated as safety issue: Yes ]
    Newborn Gestational age at delivery within the twin group is described as the gestational age of the baby on the day of birth.

  • Newborn Birthweight [ Time Frame: measure following delivery ] [ Designated as safety issue: Yes ]
    Newborn Birthweight within the twins group was measure following delivery and noted in grams.

  • Participant Drop-out Rates [ Time Frame: any time from randomization to completion of final dose of study medication ] [ Designated as safety issue: No ]
    Drop-out rates in the twin group are described as any randomized participant who is withdrawn from the trial between randomization (as early at 16 weeks of pregnancy) and completion of the final dose of study medication (as late as 34 weeks of pregnancy).

  • Participant Side Effects Requiring Cessation of Therapy [ Time Frame: anytime from initial injection to final injection at 34 weeks. ] [ Designated as safety issue: Yes ]
    Describe as the cessation of study related therapy for the participant within the twin group at anytime from initial study related injection until the final injection at 34 weeks of pregnancy.


Enrollment: 321
Study Start Date: November 2004
Study Completion Date: August 2009
Primary Completion Date: August 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: 1 Test Group (170HP)
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.
Other Name: 170HP
Placebo Comparator: 2 - Control (Normal Saline)
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.
Other Name: Normal Saline

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:

  1. Gestational age (GA) 15-23w0d gestational age at the time of recruitment
  2. GA 16w0dk to 23w6d at the time of randomization and initiation of injections
  3. Maternal age 18 years or older
  4. One of these risk factors for spontaneous preterm birth:

    1. Twins in current pregnancy, dichorionic placentation
    2. Triplets in current pregnancy, trichorionic placentation
  5. Intact membranes
  6. 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.)
  7. 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:

  1. Symptomatic uterine contractions in current pregnancy
  2. 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)
  3. Risk factors for major neonatal morbidity unrelated to preterm delivery (such as monochorionic placentation in multiple gestation, major malformations, certain medication exposures)
  4. 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.
  5. 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.
  6. Use of progesterone or progesterone-derivative medication after 15 weeks gestation in current pregnancy.
  7. Allergy to 17OHP or oil vehicle.
  8. 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
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: NCT00163020

Locations
United States, Arizona
Banner Good Samaritan Hospital
Phoenix, Arizona, United States, 85006
Tucson Medical Center
Tucson, Arizona, United States, 85712
United States, California
Saddleback Memorial Medical Center
Laguna Hills, California, United States, 92653
Long Beach Memorial Medical Center
Long Beach, California, United States, 90801-1428
University of Southern California-Irvine Medical Center
Orange, California, United States, 92868
Good Samaritan Hospital
San Jose, California, United States, 95124
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
Baylor University Medical Center
Dallas, Texas, United States, 75246
Harris Methodist Fort Worth Hospital
Fort Worth, Texas, United States, 76104
United States, Washington
Evergreen Hospital
Kirkland, Washington, United States, 98034
Swedish Medical Center
Seattle, Washington, United States, 98122-4307
Tacoma General Hospital
Tacoma, Washington, United States, 98405
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:
Publications:
Responsible Party: Obstetrix Medical Group
ClinicalTrials.gov Identifier: NCT00163020     History of Changes
Other Study ID Numbers: OBX0003, OBX 0012
Study First Received: September 9, 2005
Results First Received: June 5, 2012
Last Updated: October 9, 2012
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

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

ClinicalTrials.gov processed this record on October 21, 2014