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
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
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
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.
Weekly doses of placebo (NS + preservatives) via injection as early as 19weeks until 34.0weeks gestation or delivery which ever comes first.
Banner Good Samaritan Hospital
Phoenix, Arizona, United States
Tucson Medical Center
Tucson, Arizona, United States
Newborn Respiratory Distress Syndrome (RDS)
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.
Time frame: Measured from delivery until 30 days after baby was discharged from the hospital
Use of Oxygen Therapy at 28 Days of Newborn Life
Supplemental oxygen use by the baby measured at the point that the baby reaches 28 days old (after birth)within the twin group.
Time frame: Measured at 28 days after birth.
Newborn Sepsis
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.
Time frame: measured during the first week following birth
Newborn Pneumonia
Newborn Pneumonia in the twin group is described as compatible symptoms with diagnostic radiograph findings and positive results on blood cultures, persistent leukopenia
Time frame: measure during the first 28 days after birth.
Newborn Intraventricular Hemorrhage Grade 3 or 4
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.
Time frame: measured during the first 28 days after birth
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Masking
QUADRUPLE
Enrollment
321
Saddleback Memorial Medical Center
Laguna Hills, California, United States
Long Beach Memorial Medical Center
Long Beach, California, United States
University of Southern California-Irvine Medical Center
Orange, California, United States
Good Samaritan Hospital
San Jose, California, United States
Swedish Medical Center
Denver, Colorado, United States
Presbyterian/St Luke's Hospital
Denver, Colorado, United States
Rose Medical Center
Denver, Colorado, United States
Skyridge Medical Center
Lonetree, Colorado, United States
...and 8 more locations
Newborn Periventricular Leukomalacia (PVL)
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.
Time frame: measured in the first 28 days after birth.
Newborn Necrotizing Enterocolitis (NEC)Requiring Surgery
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.
Time frame: measured in the first 28 days after birth
Newborn Retinopathy of Prematurity (ROP)
Newborn ROP within the twin group is described as retinopathy confirmed on fundoscopic examination, felt to be due to prematurity and subsequent oxygen therapy.
Time frame: measured during the first 28 day after birth
Newborn Asphyxia With Ischemic Injury of Brain, Heart, Kidneys, or Liver
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).
Time frame: measured during the first 28 days after delivery
Perinatal Death
Perinatal death within the twin group is described as a stillbirth, neonatal death, or miscarriage after randomization.
Time frame: measured from randomization to 28 days after birth.
Individual Components of Neonatal Morbidity (RDS, IVH-III/IV, Bronchopulmonary Dysplasia(BPD), PVL, Sepsis, NEC, ROP-Stage 3/4, Perinatal Death)
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).
Time frame: measured as any event noted in the first 28 day following birth.
Twins: Delivery Prior to 28 Weeks (Wks), 32 Wks, 34wks, and 37 Wks
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)
Time frame: Gestational age noted at time of birth
Triplets: Delivery Prior to 28 Wks, 32 Wks, 35 Wks
Gestational age was noted at time of delivery and stratified into three categories (Triplets: Delivery prior to 28 wks, 32 wks, 35 wks)
Time frame: noted at delivery
Newborn Gestational Age (GA) at Delivery
Newborn Gestational age at delivery within the twin group is described as the gestational age of the baby on the day of birth.
Time frame: determined at the time of birth
Newborn Birthweight
Newborn Birthweight within the twins group was measure following delivery and noted in grams.
Time frame: measure following delivery
Participant Drop-out Rates
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).
Time frame: any time from randomization to completion of final dose of study medication
Participant Side Effects Requiring Cessation of Therapy
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.
Time frame: anytime from initial injection to final injection at 34 weeks.