NCT04093986

Hydroxyurea Exposure Limiting Pregnancy and Follow-Up Lactation

• Status: Recruiting
• Phase: —
• Study type: Observational
• Enrollment: 200 (estimated)
• Sponsor: Children's Hospital Medical Center, Cincinnati · Academic / Other
• Sex: All
• Age: —
• Healthy volunteers: Not accepted

Summary

The purpose of this research study is to document and understand the effects of hydroxyurea exposure for women with SCD and their babies, during both gestation and lactation.

Detailed description

Hydroxyurea (hydroxycarbamide) is the primary disease-modifying therapy for individuals with sickle cell disease (SCD) and is both US FDA- and EMA-approved for SCD treatment. Decades of research have documented that hydroxyurea reduces morbidity and mortality for affected patients. Although its primary mechanism of action for SCD is the induction of fetal hemoglobin (HbF) that prevents erythrocyte sickling, hydroxyurea is also a ribonucleotide reductase inhibitor with dose-dependent cytotoxic effects. Based on laboratory data, hydroxyurea is considered to be a potential human mutagen, clastogen, teratogen, and even carcinogen. However, most of these are theoretical human risks; for example, teratogenic effects of hydroxyurea are based on in vitro cellular data and supra-pharmacological dosing of animals, with no documented abnormalities in humans. Despite the lack of in vivo human data, the package insert for hydroxyurea, sold as either Hydrea® or Droxia® (Bristol-Myers Squibb), or as Siklos® (Addmedica) lists both pregnancy and lactation as contraindications for treatment. This contraindication label is critically important, since women with SCD frequently have high-risk pregnancies throughout gestation, with increased morbidity and mortality for both the mother and baby. Acute clinical complications for the mother occur commonly during gestation, while placental insufficiency through repeated infarctions also leads to increased fetal morbidity. Protection of the mother's health during pregnancy is therefore a high priority, which historically has been aided by judicious use of transfusions and management by a multidisciplinary healthcare team. In the current era, many women with SCD of child-bearing age are taking daily oral hydroxyurea with an excellent treatment effect, so its forced discontinuation around the time of pregnancy represents cessation of effective therapy. Abrupt withdrawal of hydroxyurea is typically deleterious and may not be justified in this setting. Numerous published case reports and small series have described the safe use of hydroxyurea as anti-neoplastic therapy during pregnancy in women with cancer; moreover, anecdotal experience of \>100 pregnancies with hydroxyurea exposure did not document any teratogenicity. Based on the importance of determining the actual risks and benefits of continuing hydroxyurea as disease-modifying therapy during pregnancy to protect both mothers and babies, and the lack of documented in vivo data, the safety of hydroxyurea during gestation and subsequent lactation was recently identified as an important knowledge gap by the NHLBI evidence-based SCD guidelines. Further data collection is needed regarding the actual effects of hydroxyurea for women with SCD during both pregnancy and while breastfeeding. Accordingly, we will conduct a multinational research project to retrospectively capture known human exposures to hydroxyurea in the setting of SCD, which have occurred during gestation and/or lactation, to elucidate the outcomes for the mothers and their babies. Those outcomes will be compared to pregnancies in these same women without hydroxyurea exposure.

Conditions

• Sickle Cell Disease
• Sickle Cell Anemia

Interventions

Type	Name	Description
OTHER	Chart Review	Medical records or data available from previous clinical care prior to June 20, 2019 about pregnancy and breastfeeding outcomes, both for babies with hydroxyurea exposure and other babies by these same women.
OTHER	Survey	Women who choose to participate directly and provide information in survey format will receive a brief survey and the option to upload their medical records (if available) into Cincinnati Children's maintained REDCap database.

Timeline

• Start date: 2019-12-22
• Primary completion: 2025-12-01
• Completion: 2026-12-01
• First posted: 2019-09-18
• Last updated: 2025-07-17

Locations

1 site across 1 country: United States