17OHP for Reduction of Neonatal Morbidity Due to Preterm Birth (PTB) in Twin and Triplet Pregnancies (170HP)
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
|Preterm Birth||Drug: 17-alpha-hydroxyprogesterone caproate injectable Drug: Placebo||Phase 2 Phase 3|
|Study Design:||Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, 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|
- 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.
- 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.
|Study Start Date:||November 2004|
|Study Completion Date:||August 2009|
|Primary Completion Date:||August 2009 (Final data collection date for primary outcome measure)|
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.
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
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.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00163020
|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|
|Swedish Medical Center|
|Denver, Colorado, United States, 80110|
|Presbyterian/St Luke's Hospital|
|Denver, Colorado, United States, 80218|
|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|
|Kirkland, Washington, United States, 98034|
|Swedish Medical Center|
|Seattle, Washington, United States, 98122-4307|
|Tacoma General Hospital|
|Tacoma, Washington, United States, 98405|
|Study Director:||Kimberly Maurel, RN, MSN, CNS||Obstetrix Medical Group, Inc.|
|Principal Investigator:||Andrew Combs, MD||Obstetrix Medical Group, Inc.|