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

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 vs. Placebo	Phase II Phase III

Further Study Details: 

Primary Outcomes: 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
Secondary Outcomes: 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)
Expected Total Enrollment:  321

Prematurity is a leading cause of neonatal morbidity & mortality in the USA. Nationally, 12% of all babies deliver before term & 3% deliver before 32 wks gestational age (GA). Recent studies suggest that 17OHP & 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 & 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.

Ages Eligible for Study:  18 Years   -   65 Years,  Genders Eligible for Study:  Female

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 & 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, & 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 & believes that delivery data & 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).

Please refer to this study by ClinicalTrials.gov identifier  NCT00163020

Diana Abril, RN, BSN      480-659-8644    diana_abril@pediatrix.com
Kimberly Maurel, RN, MSN      714-593-9171    Kimberly_phair@pediatrix.com

Arizona
      Banner Good Sammaritan Hospital, Phoenix,  Arizona,  85006,  United States; Recruiting
      Desert Good Samaritan Hospital, Mesa,  Arizona,  85202,  United States; Recruiting
      Tucson Medical Center, Tucson,  Arizona,  85712,  United States; Not yet recruiting
California
      Good Samaritan Hospital, San Jose,  California,  95124,  United States; Recruiting
      Long Beach Memorial Medical Center, Long Beach,  California,  90801-1428,  United States; Recruiting
      Saddleback Memorial Medical Center, Laguna Hills,  California,  92653,  United States; Recruiting
      University of Sourthern California-Irvine Medical Center, Orange,  California,  92868,  United States; Not yet recruiting
Colorado
      Presbyterian/St Luke’s Hospital, Denver,  Colorado,  80218,  United States; Recruiting
      Swedish Medical Center, Denver,  Colorado,  80110,  United States; Recruiting
      Rose Medical Center, Denver,  Colorado,  80220,  United States; Recruiting
      Skyridge Medical Center, Lonetree,  Colorado,  80124,  United States; Recruiting
Iowa
      Mercy Medical Center, Des Moines,  Iowa,  50314,  United States; Recruiting
Missouri
      Saint Luke''''s Hospital, Kansas City, Kansas City,  Missouri,  64111,  United States; Recruiting
Tennessee
      Erlanger Medical Center, Chattanooga,  Tennessee,  37403,  United States; Recruiting
Texas
      Harris Methodist Fort Worth Hospital, Fort Worth,  Texas,  76104,  United States; Recruiting
      Baylor University Medical Center, Dallas,  Texas,  75246,  United States; Recruiting
Washington
      Swedish Medical Center, Seattle,  Washington,  98122-4307,  United States; Recruiting
      Tacoma General Hospital, Tacoma,  Washington,  98405,  United States; Not yet recruiting
      Evergreen Hospital, Kirkland,  Washington,  98034,  United States; Not yet recruiting

Study chairs or principal investigators

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

Study ID Numbers:  OBX0003; IND # 59-536
Last Updated:  September 12, 2005
Record first received:  September 9, 2005
ClinicalTrials.gov Identifier:  NCT00163020
Health Authority: United States: Food and Drug Administration
ClinicalTrials.gov processed this record on 2005-09-13