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NCT Number: NCT04093986

Hydroxyurea Exposure Limiting Pregnancy and Follow-Up Lactation

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.

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Key information

Conditions

Sickle Cell Disease Anemia Anemia, Hemolytic Anemia, Hemolytic, Congenital Anemia, Sickle Cell Congenital, Hereditary, and Neonatal Diseases and Abnormalities Genetic Diseases, Inborn Hematologic Diseases Hemic and Lymphatic Diseases Hemoglobinopathies Sickle Cell Anemia

Sex eligibility

All sexes

Study type

Observational

Primary location

About this study

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.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • Medical records or data available from previous clinical care prior to June 20, 2019 of pregnant females with SCD, including women who miscarried, had a still birth, or completed labor at any gestational stage, with any hydroxyurea exposure during either pregnancy and/or while breastfeeding.
  • 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.

Exclusion criteria

  • Unavailable medical records or lack of information about hydroxyurea exposure.

Treatment and study plan

Chart review

Other

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.

Survey

Other

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.

Primary outcomes

  1. How long pregnant women with Sickle Cell Disease (SCD) were exposed to Hydroxyurea.

    Time frame: Through completion of pregnancy, an average of 2 years

    Obtain data on length of time women with SCD were exposed to Hydroxyurea prior to pregnancy, during pregnancy, and after pregnancy.

  2. Dose of hydroxyurea taken during pregnancy.

    Time frame: Through completion of pregnancy, an average of 2 years

    Obtain data on the dose of Hydroxyurea taken prior to conception, during and after pregnancy.

  3. How long infants were exposed to Hydroxyurea.

    Time frame: Through study completion, an average of 2 years

    Obtain data on length of time infants were exposed to Hydroxyurea during gestation and while breastfeeding.

  4. Dose of hydroxyurea exposure in infants.

    Time frame: Through study completion, an average of 2 years

    Obtain data on the dose of Hydroxyurea taken by mother during gestation and while breastfeeding infant.

  5. Health outcomes of infants exposed to Hydroxyurea.

    Time frame: Through study completion, an average of 2 years

    Obtain data on the health of infant after exposure to Hydroxyurea during gestation and while breastfeeding including any complications of mother's pregnancy or delivery as well as any congenital malformations or medical conditions in infancy.

  6. Pregnancy in Sickle Cell Disease (SCD).

    Time frame: Start of pregnancy until June 2019

    Compare pregnancy and delivery complications in women with SCD exposed to Hydroxyurea to pregnancy and delivery complications in women with SCD without Hydroxyurea exposure.

  7. Comparative analysis of congenital malformations or medical conditions in infants

    Time frame: Through study completion, an average of 2 years

    Compare the rate of congenital malformations and/or medical conditions in infants exposed to hydroxyurea during gestation and breastfeeding to the rate of these events in infants without hydroxyurea exposure, with data collected descriptively by self-report or chart review as applicable.

Study contacts

Contact information is provided by the study sponsor or research team.

Teresa Latham

CONTACT

[email protected]

513-803-7922

Sponsors and collaborators

Lead sponsor

Children's Hospital Medical Center, Cincinnati

Other

Collaborators

  • Children's Hospital of Philadelphia
  • Duke University
  • Guy's and St Thomas' NHS Foundation Trust
  • University of Colorado, Denver
  • University of Connecticut

Registry information

Acronym: HELPFUL

Important dates

Study start
2019
Primary completion
2028
Study completion
2030
First posted
Sep 18, 2019
Registry last updated
Jun 18, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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