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

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ClinicalTrials.gov Identifier: NCT00163020
Recruitment Status : Completed
First Posted : September 13, 2005
Results First Posted : November 7, 2012
Last Update Posted : April 11, 2016
Sponsor:
Information provided by (Responsible Party):
Mednax Center for Research, Education, Quality and Safety ( Obstetrix Medical Group )

Tracking Information
First Submitted Date  ICMJE September 9, 2005
First Posted Date  ICMJE September 13, 2005
Results First Submitted Date  ICMJE June 5, 2012
Results First Posted Date  ICMJE November 7, 2012
Last Update Posted Date April 11, 2016
Study Start Date  ICMJE November 2004
Actual Primary Completion Date August 2009   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: October 9, 2012)
  • Newborn Respiratory Distress Syndrome (RDS) [ Time Frame: Measured from delivery until 30 days after baby was discharged from the hospital ]
    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. ]
    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 ]
    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. ]
    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 ]
    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. ]
    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 ]
    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 ]
    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 ]
    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. ]
    Perinatal death within the twin group is described as a stillbirth, neonatal death, or miscarriage after randomization.
Original Primary Outcome Measures  ICMJE
 (submitted: September 9, 2005)
  • Major neonatal morbidity, defined as one or more of:
  • 1. Perinatal death
  • 2. Respiratory distress syndrome
  • 3. Use of oxygen therapy at 28 days of newborn life
  • 4. Neonatal sepsis
  • 5. Pneumonia
  • 6. Intraventricular hemorrhage grade 3 or 4
  • 7. Periventricular leukomalacia
  • 8. Necrotizing enterocolitis requiring surgery
  • 9. Retinopathy of prematurity
  • 10. Newborn asphyxia with ischemic injury of brain, heart, kidneys, or liver
Change History Complete list of historical versions of study NCT00163020 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: November 4, 2015)
  • Individual Components of Neonatal Morbidity (RDS, IVH-III/IV, Bronchopulmonary Dysplasia(BPD), PVL, Sepsis, NEC, ROP-Stage 3/4, Perinatal Death) [ Time Frame: measured as any event noted in the first 28 day following birth. ]
    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 ]
    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 ]
    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 ]
    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 ]
    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 ]
    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. ]
    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.
Original Secondary Outcome Measures  ICMJE
 (submitted: September 9, 2005)
  • Secondary Outcome Measures:
  • 1. Individual components of neonatal morbidity enumerated above
  • 2. Twins: Delivery prior to 28 wks, 32 wks, 37 wks
  • Triplets: Delivery prior to 28 wks, 32 wks, 35 wks
  • 3. Gestational age at delivery
  • 4. Birthweight
  • 5. Drop-out rates
  • 6. Side effects requiring cessation of therapy
  • a. Specific side effects ( such as: nausea, vomiting, injection site soreness, vaginal bleeding, vaginal discharge, decreased fetal movement, rash, pruritis)
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE 17OHP for Reduction of Neonatal Morbidity Due to Preterm Birth (PTB) in Twin and Triplet Pregnancies
Official Title  ICMJE 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
Brief Summary

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
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.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Condition  ICMJE Preterm Birth
Intervention  ICMJE
  • 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
  • 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
Study Arms  ICMJE
  • 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.
    Intervention: Drug: 17-alpha-hydroxyprogesterone caproate injectable
  • 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.
    Intervention: Drug: Placebo
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: September 9, 2005)
321
Original Enrollment  ICMJE Same as current
Actual Study Completion Date  ICMJE August 2009
Actual Primary Completion Date August 2009   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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).
Sex/Gender  ICMJE
Sexes Eligible for Study: Female
Ages  ICMJE 18 Years to 65 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT00163020
Other Study ID Numbers  ICMJE OBX0003
OBX 0012 ( Other Identifier: Obstetrix CREQ Protocol Number )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE
Plan to Share IPD: Undecided
Responsible Party Mednax Center for Research, Education, Quality and Safety ( Obstetrix Medical Group )
Study Sponsor  ICMJE Obstetrix Medical Group
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Kimberly Maurel, RN, MSN, CNS Obstetrix Medical Group, Inc.
Principal Investigator: Andrew Combs, MD Obstetrix Medical Group, Inc.
PRS Account Mednax Center for Research, Education, Quality and Safety
Verification Date March 2016

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP