Randomized Trial of Maternal Progesterone Therapy

NCT02133573 | Completed Phase 2 Results DMC

• 1 other identifier: 13-010710
• Study Type: interventional
• Target: 102
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Congenital Heart Disease; Periventricular Leucomalacia; Brain Development; Cardiac Surgery; Neurodevelopmental Disability; Fetal Neuroprotection

Keywords

progesterone; congenital heart disease; periventricular leucomalacia; brain development; cardiac surgery; neurodevelopmental disability; fetus; fetal neuroprotection

Outcome Measures

Primary Outcomes (1)

• Motor Scale of the Bayley Scales of Infant and Toddler Development-III

  The composite motor score is normed and has a mean of 100 (SD 15) and a range of 40-160. Scores between 71 and 85 indicate mild impairment and scores lower than 70 indicate moderate or severe impairment.

  When baby is 18 months of age

Secondary Outcomes (5)

• Cognitive and Language Scales of the Bayley Scale of Infant and Toddler Development-III

  When baby is 18 months of age

• Fetal Brain Growth and Maturation by MRI

  fTMS score change from 24-28 weeks gestational age to 34-36 weeks gestational age

• Myelination During Fetal Brain Development by MRI

  Change from 24-28 weeks gestational age to 34-36 weeks gestational age

• Prevalence of PVL/WMI in the Pre Operative Study Participants

  Preoperative on day of surgery

• Prevalence of PVL/WMI in the Post Operative Study Participants

  Postoperative within 10 days of surgery

Study Arms (2)

Progesterone

EXPERIMENTAL

Vaginal gel, 90mg twice a day (BID)

Drug: Progesterone

Vaginal Lubricant

PLACEBO COMPARATOR

Vaginal twice a day (BID)

Drug: Vaginal lubricant

Interventions

Progesterone DRUG

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.

Also known as: Crinone 8%

Progesterone

Vaginal lubricant DRUG

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.

Also known as: Replens

Vaginal Lubricant

Eligibility Criteria

• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may not qualify if:

• Major genetic or extra-cardiac anomaly other than 22q11 deletion
• Language other than English spoken in the home
• 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)
• Prescription or ingestion of medications known to interact with progesterone (e.g. Bromocriptine, Rifamycin, Ketoconazole or Cyclosporin)
• Maternal use of progesterone within 30 days of enrollment
• History of preterm birth or short cervix (defined as cervical length ≤ 25 mm at 18-24 weeks GA necessitating progesterone therapy
• Multiple gestation
• Maternal contraindication for magnetic resonance imaging (MRI)
• Subjects with a known history of non-compliance with medical therapy

Sponsors & Collaborators

• Children's Hospital of Philadelphia: lead

Study Sites (1)

The Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, 19104, United States

Location

Related Publications (1)

• Gaynor JW, Moldenhauer JS, Zullo EE, Burnham NB, Gerdes M, Bernbaum JC, D'Agostino JA, Linn RL, Klepczynski B, Randazzo I, Gionet G, Choi GH, Karaj A, Russell WW, Zackai EH, Johnson MP, Gebb JS, Soni S, DeBari SE, Szwast AL, Ahrens-Nicklas RC, Drivas TG, Jacobwitz M, Licht DJ, Vossough A, Nicolson SC, Spray TL, Rychik J, Putt ME. Progesterone for Neurodevelopment in Fetuses With Congenital Heart Defects: A Randomized Clinical Trial. JAMA Netw Open. 2024 May 1;7(5):e2412291. doi: 10.1001/jamanetworkopen.2024.12291.

  PMID: 38805228 DERIVED

Related Links

• The Children's Hospital of Philadelphia Fetal Neuroprotection and Neuroplasticity Program

MeSH Terms

Conditions

Heart Defects, Congenital; Leukomalacia, Periventricular

Interventions

Progesterone; Replens

Condition Hierarchy (Ancestors)

Cardiovascular Abnormalities; Cardiovascular Diseases; Heart Diseases; Congenital Abnormalities; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Encephalomalacia; Vascular Diseases; Infant, Premature, Diseases; Infant, Newborn, Diseases

Intervention Hierarchy (Ancestors)

Pregnenediones; Pregnenes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Corpus Luteum Hormones; Gonadal Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Progesterone Congeners; Gonadal Steroid Hormones

Results Point of Contact

• Title: Dr. J. William Gaynor
• Organization: Children's Hospital of Philadelphia

gaynor@chop.edu

215-590-5806

Study Officials

• J. William Gaynor, MD

  Children's Hospital of Philadelphia

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 7, 2014
• First Posted: May 8, 2014
• Study Start: July 1, 2014
• Primary Completion: November 1, 2021
• Study Completion: November 1, 2021
• Last Updated: August 9, 2023
• Results First Posted: February 28, 2023

Record last verified: 2023-08

Locations

US (1)