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

Study Overview
=================
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.

Official Title
-----------------
A Randomized Trial of Omega-3 Fatty Acid Supplementation to Prevent Preterm Birth in Pregnancies at High Risk

Conditions
-----------------
Preterm Birth

Intervention / Treatment
-----------------
* Drug: 17 alpha-Hydroxyprogesterone Caproate and Omega-3 supplement
* Drug: 17 alpha-hydroxy progesterone caproate and Placebo supplement


Participation Criteria
=================
Eligibility 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
Sexes Eligible for Study
-----------------
Female

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: 17P plus Omega-3 Supplement<br>Weekly 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). | Drug: 17 alpha-Hydroxyprogesterone Caproate and Omega-3 supplement<br>* Participants receive a weekly progesterone injection (17 alpha hydroxyprogesterone caproate) up to 37 weeks gestation and take daily Omega-3 supplements.<br>|
| Placebo Comparator: 17P plus Placebo Supplement<br>Weekly 17 alpa hydroxyprogesterone caproate (17p) injections plus placebo capsules, 4 capsules per day for up to 5 weeks | Drug: 17 alpha-hydroxy progesterone caproate and Placebo supplement<br>* Participants receive a weekly progesterone injection (17P) up to 37 weeks gestation and take daily placebo supplements<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Delivery before than 37 weeks gestation | Delivery before 37 weeks including any miscarriages occurring after randomization | Up to 37 weeks gestation | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Delivery before 35 weeks gestation |  | Up to 35 weeks gestation | 
| Delivery before 32 weeks gestation |  | Up to 32 weeks gestation | 
| Delivery after 40 weeks gestation |  | 40 weeks gestation or greater | 
| Pregnancy loss or neonatal death |  | Randomization to hospital discharge (up to 25 weeks) | 
| Gestational age at delivery |  | Delivery | 
| Birth weight less than 2,500 grams |  | Birth | 
| Birth weight less than 1,500 grams |  | Birth | 
| Birth size small for gestational age at less than 10th percentile |  | Birth | 
| Birth size large for gestational age at more than 90th percentile |  | Birth | 
| Admission to neonatal intensive care or intermediate care nursery |  | Delivery through neonatal discharge (up to 2 weeks) | 
| Neonatal retinopathy of prematurity |  | Delivery through neonatal discharge (up to 2 weeks) | 
| Intraventricular Hemorrhage at any grade |  | Delivery through neonatal discharge (up to 2 weeks) | 
| Intraventricular Hemorrhage Grade 3 or 4 |  | Delivery through neonatal discharge (up to 2 weeks) | 
| Neonatal patent ductus arteriosus |  | Delivery through neonatal discharge (up to 2 weeks) | 
| Neonatal necrotizing enterocolitis |  | Delivery through neonatal discharge (up to 2 weeks) | 
| Neonatal sepsis |  | Delivery through neonatal discharge (up to 2 weeks) | 
| Neonatal respiratory distress syndrome |  | Delivery through neonatal discharge (up to 2 weeks) | 
| Neonatal surfactant use |  | Delivery through neonatal discharge (up to 2 weeks) | 
| Neonatal bronchopulmonary dysplasia |  | Delivery through neonatal discharge (up to 2 weeks) | 
| Neonatal transient tacypnea |  | Delivery through neonatal discharge (up to 2 weeks) | 
| Neonatal supplemental oxygen support |  | Delivery through neonatal discharge (up to 2 weeks) | 
| Neonatal ventilator support |  | Delivery through neonatal discharge (up to 2 weeks) | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Preterm birth, Progesterone, Omega-3 fatty acid, Pregnancy