Sickle Cell DiseaseHELPFULNCT04093986
Hydroxyurea Exposure Limiting Pregnancy and Follow-Up Lactation
An observational study of Sickle Cell Disease and Sickle Cell Anemia, run by Children's Hospital Medical Center, Cincinnati at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Any age
- Conditions the study is for
- Sickle Cell Disease, Sickle Cell Anemia
- What is being tested?
- Chart Review and Survey
- How many people
- 200 participants
- Where
- 1 siteUnited States
- Study dates
- 22 Dec 2019to 31 Dec 2030
- Phase
- Observational
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages Any age
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Study population: Clinical and laboratory data on up to 200 women with SCD with hydroxyurea exposure during either gestation or lactation.
Who may be able to join
- 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.
Who cannot join
- Unavailable medical records or lack of information about hydroxyurea exposure.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
United States1 site, 1 recruiting
- Recruiting
Cincinnati Children's Hospital Medical Center
Cincinnati, Ohio, 45229
Teresa Latham, 513-803-7922, Teresa.Latham@cchmc.org
Rebecca Geer, Rebecca.Geer@cchmc.org
About this study
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.
Read the 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
- Being tested
- Chart Review, Survey
- Keywords
- Hydroxyurea
- Medical subject headings
- Anemia, Sickle Cell
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Chart ReviewOther
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.
SurveyOther
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.
| Study group | Role | What they receive |
|---|---|---|
| Retrospective Chart Review | Medical record chart review of women seen previously for clinical care prior to June 20, 2019 at participating institutions with SCD and hydroxyurea exposure during gestation or lactation will be identified by healthcare providers. Receives: Other: Chart Review | |
| Participant Survey and Retrospective Chart Review | Participants providing their medical records without the assistance of a health care provider will be asked to complete a questionnaire through REDCap and will have the option to upload their deidentified medical records if they are available. Receives: Other: Chart Review; Other: Survey |
What is being measured
The primary outcome is the main question the study is designed to answer.
How long pregnant women with Sickle Cell Disease (SCD) were exposed to Hydroxyurea.
Obtain data on length of time women with SCD were exposed to Hydroxyurea prior to pregnancy, during pregnancy, and after pregnancy.
Measured: Through completion of pregnancy, an average of 2 years
Dose of hydroxyurea taken during pregnancy.
Obtain data on the dose of Hydroxyurea taken prior to conception, during and after pregnancy.
Measured: Through completion of pregnancy, an average of 2 years
How long infants were exposed to Hydroxyurea.
Obtain data on length of time infants were exposed to Hydroxyurea during gestation and while breastfeeding.
Measured: Through study completion, an average of 2 years
Dose of hydroxyurea exposure in infants.
Obtain data on the dose of Hydroxyurea taken by mother during gestation and while breastfeeding infant.
Measured: Through study completion, an average of 2 years
Health outcomes of infants exposed to Hydroxyurea.
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.
Measured: Through study completion, an average of 2 years
Pregnancy in Sickle Cell Disease (SCD).
Compare pregnancy and delivery complications in women with SCD exposed to Hydroxyurea to pregnancy and delivery complications in women with SCD without Hydroxyurea exposure.
Measured: Start of pregnancy until June 2019
Comparative analysis of congenital malformations or medical conditions in infants
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.
Measured: Through study completion, an average of 2 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 Sep 2019
- Study start22 Dec 2019
- Primary completion31 Dec 2028 (estimated)
- Study completion31 Dec 2030 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Sickle Cell DiseaseStudies of the same condition, open and under way.
- More trials run by Children's Hospital Medical Center, CincinnatiThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Case only
- Time perspective
- Retrospective
- Enrolment
- 200 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Children's Hospital Medical Center, Cincinnati
- Sponsor type
- University, hospital or other
- Collaborators
- University of Connecticut, University of Colorado, Denver, Guy's and St Thomas' NHS Foundation Trust, Duke University, Children's Hospital of Philadelphia
- Responsible party
- Sponsor
- Investigators
- Russell Ware, MD, Principal investigator, Children's Hospital Medical Center, Cincinnati
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04093986
- Sponsor's protocol ID
- HELPFUL
- Acronym
- HELPFUL
- Status last verified
- Jun 2026
- First submitted
- 22 Aug 2019
- Last updated
- 18 Jun 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 18 Jun 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Hydroxyurea Exposure Limiting Pregnancy and Follow-Up Lactation
- ClinicalTrials.gov ID
- NCT04093986
- Acronym / sponsor ID
- HELPFUL / HELPFUL
- Conditions
- Sickle Cell Disease, Sickle Cell Anemia
- Keywords
- Hydroxyurea
- Study type
- Observational
- Recruitment status
- Recruiting
- Enrolment
- 200 participants (estimated)
- Lead sponsor
- Children's Hospital Medical Center, CincinnatiUniversity, hospital or other
- Collaborators
- University of Connecticut, University of Colorado, Denver, Guy's and St Thomas' NHS Foundation Trust, Duke University, Children's Hospital of Philadelphia
- Study start
- 22 Dec 2019 (actual)
- Primary completion
- 31 Dec 2028 (estimated)
- Study completion
- 31 Dec 2030 (estimated)
- First posted
- 18 Sep 2019 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Observational model
- Case only
- Time perspective
- Retrospective
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Retrospective Chart Review | – | Other: Chart ReviewMedical record chart review of women seen previously for clinical care prior to June 20, 2019 at participating institutions with SCD and hydroxyurea exposure during gestation or lactation will be identified by healthcare providers. |
| Participant Survey and Retrospective Chart Review | – | Other: Chart Review, Other: SurveyParticipants providing their medical records without the assistance of a health care provider will be asked to complete a questionnaire through REDCap and will have the option to upload their deidentified medical records if they are available. |
Who may qualify
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
- Study population
- Clinical and laboratory data on up to 200 women with SCD with hydroxyurea exposure during either gestation or lactation.
Key inclusion criteria (2 listed)
- 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.
Key exclusion criteria (1 listed)
- Unavailable medical records or lack of information about hydroxyurea exposure.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Chart ReviewMedical 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 | Participant Survey and Retrospective Chart Review, Retrospective Chart Review |
| SurveyWomen 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. | Other | Participant Survey and Retrospective Chart Review |
Primary outcome
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.
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.
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.
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.
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.
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.
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.
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 18 Jun 2026.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Russell Ware, MD principal investigator
Children's Hospital Medical Center, Cincinnati
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Sickle Cell Disease and Sickle Cell Anemia, run by Children's Hospital Medical Center, Cincinnati at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 2 inclusion and 1 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 18 Jun 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Teresa Latham (513-803-7922, Teresa.Latham@cchmc.org), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
How long pregnant women with Sickle Cell Disease (SCD) were exposed to Hydroxyurea. (time frame: Through completion of pregnancy, an average of 2 years). The study lists 7 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 18 Jun 2026.