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Omega-3 Fatty Acid Supplementation to Prevent Preterm Birth in High Risk Pregnancies

Phase 3
Completed
Conditions
Preterm Birth
Interventions
Drug: 17 alpha-Hydroxyprogesterone Caproate and Omega-3 supplement
Drug: 17 alpha-hydroxy progesterone caproate and Placebo supplement
Registration Number
NCT00135902
Lead Sponsor
The George Washington University Biostatistics Center
Brief Summary

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."

Detailed Description

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.

Recruitment & Eligibility

Status
COMPLETED
Sex
Female
Target Recruitment
800
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

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
17P plus Omega-3 Supplement17 alpha-Hydroxyprogesterone Caproate and Omega-3 supplementWeekly 17 alpa hydroxyprogesterone caproate (17p) injections plus Omega 3 supplements, 4 capsules per day for up to 5 weeks. Each capsule contained 200 mg of docosahexaenoic acid (DHA) and 300 mg of eicosapentaenoic acid (EPA).
17P plus Placebo Supplement17 alpha-hydroxy progesterone caproate and Placebo supplementWeekly 17 alpa hydroxyprogesterone caproate (17p) injections plus placebo capsules, 4 capsules per day for up to 5 weeks
Primary Outcome Measures
NameTimeMethod
Delivery before than 37 weeks gestationUp to 37 weeks gestation

Delivery before 37 weeks including any miscarriages occurring after randomization

Secondary Outcome Measures
NameTimeMethod
Birth weight less than 2,500 gramsBirth
Birth weight less than 1,500 gramsBirth
Delivery before 35 weeks gestationUp to 35 weeks gestation
Delivery before 32 weeks gestationUp to 32 weeks gestation
Delivery after 40 weeks gestation40 weeks gestation or greater
Pregnancy loss or neonatal deathRandomization to hospital discharge (up to 25 weeks)
Gestational age at deliveryDelivery
Neonatal surfactant useDelivery through neonatal discharge (up to 2 weeks)
Neonatal bronchopulmonary dysplasiaDelivery through neonatal discharge (up to 2 weeks)
Neonatal transient tacypneaDelivery through neonatal discharge (up to 2 weeks)
Neonatal supplemental oxygen supportDelivery through neonatal discharge (up to 2 weeks)
Neonatal ventilator supportDelivery through neonatal discharge (up to 2 weeks)
Birth size small for gestational age at less than 10th percentileBirth
Birth size large for gestational age at more than 90th percentileBirth
Admission to neonatal intensive care or intermediate care nurseryDelivery through neonatal discharge (up to 2 weeks)
Neonatal retinopathy of prematurityDelivery through neonatal discharge (up to 2 weeks)
Intraventricular Hemorrhage at any gradeDelivery through neonatal discharge (up to 2 weeks)
Intraventricular Hemorrhage Grade 3 or 4Delivery through neonatal discharge (up to 2 weeks)
Neonatal patent ductus arteriosusDelivery through neonatal discharge (up to 2 weeks)
Neonatal necrotizing enterocolitisDelivery through neonatal discharge (up to 2 weeks)
Neonatal sepsisDelivery through neonatal discharge (up to 2 weeks)
Neonatal respiratory distress syndromeDelivery through neonatal discharge (up to 2 weeks)

Trial Locations

Locations (12)

Ohio State University

🇺🇸

Columbus, Ohio, United States

University of Pittsburgh Magee Womens Hospital

🇺🇸

Pittsburgh, Pennsylvania, United States

Northwestern University

🇺🇸

Chicago, Illinois, United States

Drexel University

🇺🇸

Philadelphia, Pennsylvania, United States

University of Utah Medical Center

🇺🇸

Salt Lake City, Utah, United States

University of Alabama - Birmingham

🇺🇸

Birmingham, Alabama, United States

Wayne State University

🇺🇸

Detroit, Michigan, United States

Columbia University

🇺🇸

New York, New York, United States

University of North Carolina - Chapel Hill

🇺🇸

Chapel Hill, North Carolina, United States

Wake Forest University School of Medicine

🇺🇸

Winston-Salem, North Carolina, United States

Case Western University

🇺🇸

Cleveland, Ohio, United States

Brown University

🇺🇸

Providence, Rhode Island, United States

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