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Hydroxyurea Exposure Limiting Pregnancy and Follow-Up Lactation (HELPFUL)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04093986
Recruitment Status : Recruiting
First Posted : September 18, 2019
Last Update Posted : September 18, 2019
Sponsor:
Collaborators:
University of Connecticut
University of Colorado, Denver
Guy's and St Thomas' NHS Foundation Trust
Duke University
Children's Hospital of Philadelphia
Information provided by (Responsible Party):
Children's Hospital Medical Center, Cincinnati

Brief 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.

Condition or disease Intervention/treatment
Sickle Cell Disease Sickle Cell Anemia Other: Chart Review Other: Survey

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.

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Study Type : Observational
Estimated Enrollment : 200 participants
Observational Model: Case-Only
Time Perspective: Retrospective
Official Title: Hydroxyurea Exposure Limiting Pregnancy and Follow-Up Lactation
Actual Study Start Date : July 22, 2019
Estimated Primary Completion Date : July 2021
Estimated Study Completion Date : July 2022

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Breastfeeding
Drug Information available for: Hydroxyurea

Group/Cohort Intervention/treatment
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.
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.

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.
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.




Primary Outcome Measures :
  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.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   Child, Adult, Older Adult
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Sampling Method:   Non-Probability Sample
Study Population
Clinical and laboratory data on up to 200 women with SCD with hydroxyurea exposure during either gestation or lactation.
Criteria

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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04093986


Contacts
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Contact: Teresa Latham 513-803-7922 Teresa.Latham@cchmc.org

Locations
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United States, Ohio
Cincinnati Children's Hospital Medical Center Recruiting
Cincinnati, Ohio, United States, 45229
Contact: Teresa Latham    513-803-7922    Teresa.Latham@cchmc.org   
Contact: Rebecca Geer       Rebecca.Geer@cchmc.org   
Sponsors and Collaborators
Children's Hospital Medical Center, Cincinnati
University of Connecticut
University of Colorado, Denver
Guy's and St Thomas' NHS Foundation Trust
Duke University
Children's Hospital of Philadelphia
Investigators
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Principal Investigator: Russell Ware, MD Children's Hospital Medical Center, Cincinnati

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Responsible Party: Children's Hospital Medical Center, Cincinnati
ClinicalTrials.gov Identifier: NCT04093986    
Other Study ID Numbers: HELPFUL
First Posted: September 18, 2019    Key Record Dates
Last Update Posted: September 18, 2019
Last Verified: August 2019

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Children's Hospital Medical Center, Cincinnati:
Hydroxyurea
Additional relevant MeSH terms:
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Anemia, Sickle Cell
Anemia, Hemolytic, Congenital
Anemia, Hemolytic
Anemia
Hematologic Diseases
Hemoglobinopathies
Genetic Diseases, Inborn
Hydroxyurea
Antineoplastic Agents
Antisickling Agents
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Nucleic Acid Synthesis Inhibitors