A recently completed trial of weekly injections of 17 alpha hydroxyprogesterone caproate (17P) found significant effectiveness for 17P in preventing recurrent preterm birth. However, the group who received 17P in this trial still had a high rate of preterm birth. Several reports have shown that dietary supplementation of fish oil, which is rich in Omega-3 fatty acids, reduces the risk of preterm birth. This trial tests whether adding the Omega-3 supplement to 17P therapy has the potential for further reducing the risk of preterm birth in women who have previously had a spontaneous preterm delivery. The trial will compare Omega-3 fatty acid with placebo in women receiving 17P therapy. The hypothesis being tested is: "Among women at high risk for preterm birth receiving weekly injections of 17P, the addition of Omega-3 nutritional supplement will further reduce the rate of preterm birth."

Condition	Intervention	Phase
Preterm Birth Pregnancy	Drug: 17 P Hydroxyprogesterone Caproate and Omega-3 fish oils	Phase III

Further Study Details: 

Primary Outcomes: Primary Outcome:; Delivery less than 37 completed weeks gestation including any miscarriages occurring after randomization
Secondary Outcomes: Secondary Outcomes:; MATERNAL; * Delivery less than 35 weeks; * Delivery less than 32 weeks; * Spontaneous preterm delivery; * Indicated preterm delivery; * Tocolytic therapy; * Time from randomization to delivery; * Delivery on or after 41 weeks of gestation; * Occurrence of gestational hypertension or preeclampsia; * Maternal hospital days; * Fatty acid constituents in maternal plasma samples, before and after supplementation; * Postpartum hemorrhage; FETAL AND NEONATAL; * Fetal and neonatal death; * Gestational age at delivery; * Small for gestational age; * Birth weight; * Apgar score at 1 and 5 minutes; * Number of days of neonatal respiratory therapy; * Admission to NICU and total number of days in hospital; * Intraventricular hemorrhage; * Retinopathy of prematurity; * Necrotizing enterocolitis; * Deep infection; * Periventricular leukomalacia; * Bronchopulmonary dysplasia; * Respiratory distress syndrome; * Composite neonatal outcome
Expected Total Enrollment:  800

Preterm birth is the leading cause of perinatal mortality and morbidity. In a recently completed trial of weekly injections of 17 alpha hydroxyprogesterone caproate (17P), the National Institute of Child Health and Human Development (NICHD) Maternal Fetal Medicine Units (MFMU) Network found the treatments significantly beneficial in the prevention of recurrent preterm birth. Other studies have shown that fish oil supplementation can reduce the risk for preterm birth. The purpose of this study is to determine whether Omega-3, a polyunsaturated fatty acid nutritional supplement, in addition to injections of 17P, further decreases the rate of preterm birth in women at risk.

This study is a randomized, double-masked clinical trial with two study arms: a daily supplement of Omega-3 capsules containing 800 mg of DHA and 1200 mg of EPA or a daily supplement of a matching placebo. All patients will also receive weekly injections of 17P. Eight hundred pregnant women with a history of previous preterm delivery will be recruited for this study. After successfully completing a compliance run-in, which can begin as early as 15 weeks gestation, patients will be randomized and begin treatment between 16 and 22 weeks gestation. They will remain on study drug until 36 week and 6 days or delivery, whichever occurs first. Blood will be drawn at randomization and at a monthly visit falling between 25-29 weeks of gestation to test for compliance, to analyze genetic polymorphisms and to determine whether Omega-3 affects the production of inflammatory cytokines.

Genders Eligible for Study:  Female

Accepts Healthy Volunteers

Criteria

Inclusion Criteria:

• Documented history of previous singleton spontaneous birth
• Singleton pregnancy
• Gestational age at randomization between 16 and 22 weeks

Exclusion Criteria:

• Major fetal anomaly or demise
• Regular intake of fish oil supplements
• Daily use of nonsteroidal anti-inflammatory agents
• Allergy to fish or fish products
• Gluten intolerant
• Heparin use or known thrombophilia
• Hemophilia
• Planned termination
• Current hypertension or current use of antihypertensive medications
• Type D, F or R diabetes
• Maternal medical complications
• Current or planned cerclage
• Illicit drug or alcohol abuse during current pregnancy
• Delivery at a non-Network hospital
• Participation in another pregnancy intervention study
• Participation in this trial in a previous pregnancy

Please refer to this study by ClinicalTrials.gov identifier  NCT00135902

Alabama
      University of Alabama - Birmingham, Birmingham,  Alabama,  United States; Recruiting
Illinois
      Northwestern University, Chicago,  Illinois,  United States; Recruiting
Michigan
      Wayne State University, Detroit,  Michigan,  United States; Recruiting
New York
      Columbia University, New York,  New York,  United States; Recruiting
North Carolina
      Wake Forest University School of Medicine, Winston Salem,  North Carolina,  United States; Recruiting
      University of North Carolina - Chapel Hill, Chapel Hill,  North Carolina,  United States; Recruiting
Ohio
      Ohio State University, Columbus,  Ohio,  United States; Recruiting
      Case Western University, Cleveland,  Ohio,  United States; Recruiting
Pennsylvania
      University of Pittsburgh Magee Womens Hospital, Pittsburgh,  Pennsylvania,  United States; Recruiting
      Drexel University, Philadelphia,  Pennsylvania,  United States; Recruiting
Rhode Island
      Brown University, Providence,  Rhode Island,  United States; Recruiting
Texas
      University of Texas - Southwest, Dallas,  Texas,  United States; Recruiting
Utah
      University of Utah Medical Center, Salt Lake City,  Utah,  United States; Recruiting

Study chairs or principal investigators

Catherine Y Spong, MD,  Principal Investigator,  National Institute of Child Health and Human Development (NICHD)   
Elizabeth A Thom, PhD,  Principal Investigator,  George Washington University Biostatistics Center   
Margaret Harper, MD,  Principal Investigator,  Wake Forest University   

Study ID Numbers:  HD36801-Omega-3; HD21410; HD27869; HD27917; HD27860; HD27915; HD34116; HD34208; HD34136; HD40500; HD40485; HD40544; HD40545; HD40560; HD40512
Last Updated:  August 25, 2005
Record first received:  August 25, 2005
ClinicalTrials.gov Identifier:  NCT00135902
Health Authority: United States: Food and Drug Administration
ClinicalTrials.gov processed this record on 2005-08-30