Randomized Trial of Maternal Progesterone Therapy
Condition: Congenital Heart Disease; Periventricular Leucomalacia; Brain Development; Cardiac Surgery; Neurodevelopmental Disability; Fetal Neuroprotection
MeSH terms: Leukomalacia, Periventricular; Heart Diseases; Heart Defects, Congenital
Intervention: Progesterone; Vaginal lubricant
Intervention description: Crinone is supplied in a single use, disposable, white polypropylene vaginal applicator with a teal twist-off cap. Each applicator delivers 1.125 grams of Crinone gel containing 90 mg (8% gel) of progesterone in a base containing glycerin, mineral oil, polycarbophil, carbomer 934P, hydrogenated palm oil glyceride, sorbic acid, purified water and may contain sodium hydroxide. Crinone 8% is administered vaginally at a dose of 90 mg twice daily. The rounded tip of the applicator is inserted into the vagina. After insertion, the plunger is pushed to release the gel into the vagina. The applicator is removed.; Replens Long-Lasting Moisturizer is supplied in pre-filled, sealed and individually wrapped applicators.Replens Long-Lasting Moisturizer will also be dosed at one applicator intravaginally twice daily.
Intervention MeSH terms: Progesterone
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 102.0
Sex: All
Healthy volunteers: No
Keywords: progesterone; congenital heart disease; periventricular leucomalacia; brain development; cardiac surgery; neurodevelopmental disability; fetus; fetal neuroprotection

Summary:

      Neurodevelopmental disability is now recognized as the most common long-term complication
      after cardiac surgery in neonates. Research studies have shown that progesterone is critical
      to the development of the brain and in a variety of clinical situations including brain
      injury can protect the brain.

      The purpose of this research study is to determine whether progesterone administered during
      the 3rd trimester of pregnancy (24-39 weeks) to pregnant women protects the brain of unborn
      babies with CHD and improves their neurodevelopmental outcomes after heart surgery.
    

Eligibility criteria:

        Inclusion Criteria: Mother carrying a fetus with CHD (maternal-fetal dyad) requiring
        surgery with cardiopulmonary bypass (CPB) prior to 44 weeks corrected gestational age (GA)
        identified prior to 28 weeks GA.

        Exclusion Criteria:

          1. Major genetic or extra-cardiac anomaly other than 22q11 deletion

          2. Language other than English spoken in the home

          3. Known sensitivity or listed contraindication to progesterone (known allergy or
             hypersensitivity to progesterone, severe hepatic dysfunction, undiagnosed vaginal
             bleeding, mammary or genital tract carcinoma, thrombophlebitis, thromboembolic
             disorders, cerebral hemorrhage, porphyria)

          4. Prescription or ingestion of medications known to interact with progesterone (e.g.
             Bromocriptine, Rifamycin, Ketoconazole or Cyclosporin)

          5. Maternal use of progesterone within 30 days of enrollment

          6. History of preterm birth or short cervix (defined as cervical length ≤ 25 mm at 18-24
             weeks GA necessitating progesterone therapy

          7. Multiple gestation

          8. Maternal contraindication for magnetic resonance imaging (MRI)

          9. Subjects with a known history of non-compliance with medical therapy