Hydroxyurea for Sickle Cell Anemia

Enrolling by invitation at 1 trial location

Age: < 18

Sex: Any

Trial Phase: Phase 2

Sponsor: Children's Hospital Medical Center, Cincinnati

Must be taking: Hydroxyurea

Disqualifiers: Febrile illness, Hospitalization, Transfusion, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 3 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 3

Duration: 12 months

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests hydroxyurea, a medication, to determine if it can reduce stroke risk in children with sickle cell anemia by examining blood flow in the brain. Researchers will study children in Tanzania to assess the prevalence of abnormal blood flow and its changes over time. Children with sickle cell anemia who exhibit abnormal blood flow patterns in their brains may qualify for this trial. As a Phase 2 trial, this research measures hydroxyurea's effectiveness in an initial, smaller group of children, providing an opportunity to contribute to important findings.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the study team or your doctor.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Studies have shown that hydroxyurea is generally safe for people with sickle cell anemia. Research indicates it does not cause immediate serious health problems, and no known long-term issues arise from its use.

In children with sickle cell anemia, hydroxyurea has proven effective and safe for long-term use. It reduces hospital visits and stays, demonstrating its safety and effectiveness. However, hydroxyurea is not recommended for pregnant or breastfeeding women with sickle cell anemia.

Overall, for those considering joining a trial, hydroxyurea appears to be a safe option based on existing research. Discuss any concerns with a doctor. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about hydroxyurea for sickle cell anemia because it offers a unique approach by increasing fetal hemoglobin levels, which can reduce the sickling of red blood cells. Unlike standard treatments that mainly focus on managing pain or preventing infections, like blood transfusions and pain medications, hydroxyurea targets the root cause by modifying the blood itself. This can potentially lead to fewer complications and hospital visits for patients, making it an appealing option for long-term management of the disease.

What evidence suggests that hydroxyurea might be an effective treatment for sickle cell anemia?

Research has shown that hydroxyurea effectively treats sickle cell anemia. One study found that it reduces painful episodes, known as vaso-occlusive crises, common in this condition. Another study showed that hydroxyurea decreases emergency room visits and hospital stays for children with sickle cell disease. Long-term use of hydroxyurea in children has been linked to fewer days spent in the hospital and fewer emergency visits. The treatment also helps increase levels of fetal hemoglobin, which can further reduce complications. In this trial, participants with an elevated initial screening TCD will receive hydroxyurea therapy. Overall, strong evidence supports the benefits of hydroxyurea in managing sickle cell anemia. ^{5 6 7 8 9}

Are You a Good Fit for This Trial?

The SPHERE trial is for children in Tanzania with Sickle Cell Anemia who can attend study visits, stay near the study center, and take oral medication. They must have a confirmed diagnosis of SCA and be willing to follow the treatment schedule. Exclusions include recent illness, hospitalization or transfusion, certain abnormal lab values, pregnancy or lactation, known allergies to hydroxyurea components, or previous stroke.

Inclusion Criteria

Willingness to sign informed consent

I can take pills and follow a treatment plan.

Available for study visits for the duration of the study and no plans to move away from study center

Exclusion Criteria

Currently pregnant or lactating.

Hospitalized within the past two weeks. (Temporary Exclusion)

I have not had a blood transfusion in the last two weeks.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

Baseline

1 visit (in-person)

Treatment

Participants with elevated initial screening TCD receive open-label hydroxyurea therapy

12 months

Monthly visits (in-person)

Observation/Control

Participants with normal initial screening TCD undergo repeat TCD every 12 months

24 months

Annual visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

12 months

2 visits (in-person)

What Are the Treatments Tested in This Trial?

Interventions

• Elevated Arm TCD Examination
• Hydroxyurea
• Normal Arm TCD Examination

Trial Overview This trial aims to find out how common elevated TCD velocities are among Tanzanian children with SCA and see if hydroxyurea therapy can reduce these velocities and lower primary stroke risk. It involves initial TCD screening followed by longitudinal data collection on TCD velocities after starting hydroxyurea treatment.

How Is the Trial Designed?

Group I: Normal Initial Screening TCD Experimental Treatment 1 Intervention

Those who are found to have a normal TCD at enrolment are a part of the observation/control cohort and will undergo repeat TCD every 12 months after enrolment. If the TCD at 12 months has changed to an elevated velocity (conditional or abnormal), the study participant will be reassigned to the elevated initial screening TCD arm and can begin study treatment (hydroxyurea), but will not be included in the primary endpoint analysis.

Group II: Elevated Initial Screening TCD Experimental Treatment 2 Interventions

Those who have an elevated initial screening TCD (either conditional or abnormal TAMV) and will be a treatment cohort that receives open-label hydroxyurea therapy as per the dosing and administration schedule.

Hydroxyurea is already approved in United States, European Union, Canada for the following indications:

Approved in United States as Hydroxyurea for:

• Sickle cell disease
• Chronic myeloid leukemia
• Solid tumors
• Thrombocythemia

Approved in European Union as Hydroxycarbamide for:

• Sickle cell syndrome
• Chronic myeloid leukaemia
• Essential thrombocythaemia
• Polycythaemia vera

Approved in Canada as Hydroxyurea for:

• Sickle cell disease
• Chronic myeloid leukemia
• Thrombocythemia

Who Is Running the Clinical Trial?

Children's Hospital Medical Center, Cincinnati

Lead Sponsor

Trials

844

Recruited

6,566,000+

The American Society of Hematology

Collaborator

Trials

1

Recruited

200+

Bugando Medical Centre

Collaborator

Trials

2

Recruited

1,000+

Published Research Related to This Trial

In a study of 523 pediatric patients with sickle cell disease, those treated with hydroxyurea (HU) were more likely to experience organ-specific complications, such as cardiovascular, hepatic, renal, and pulmonary issues, compared to those not treated with HU.

Despite the increased likelihood of complications in the HU-treated group, the study concluded that HU is not associated with the development of serious adverse events, suggesting it can be safely administered to severely ill children with sickle cell disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical complications in severe pediatric sickle cell disease and the impact of hydroxyurea. Tripathi, A., Jerrell, JM., Stallworth, JR.[2022]

Hydroxyurea (HU) treatment in children with sickle cell disease (SCD) at doses ≤30 mg/kg/day does not increase DNA damage compared to untreated SCD patients, suggesting its long-term safety in this regard.

Good responders to HU treatment show significantly less DNA damage than poor responders, indicating that the effectiveness of the treatment may correlate with lower genotoxic effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Hydroxyurea (hydroxycarbamide) genotoxicity in pediatric patients with sickle cell disease. Rodriguez, A., Duez, P., Dedeken, L., et al.[2019]

In a study of 134 children with sickle cell anemia who started hydroxyurea treatment, there was a significant reduction in hospitalizations (47%), pain encounters (36%), and emergency department visits (43%) after two years of treatment.

Additionally, the average hemoglobin levels in these children increased by 0.7 g/dl, indicating that hydroxyurea not only reduces complications but also improves blood health in pediatric patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Hydroxyurea effectiveness in children and adolescents with sickle cell anemia: A large retrospective, population-based cohort. Quarmyne, MO., Dong, W., Theodore, R., et al.[2022]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11546997/

The Current Role of Hydroxyurea in the Treatment of Sickle ... This study showed that the MTD achieved greater increases in HbF and total hemoglobin levels, as well as a more significant reduction in white ...

2. nejm.org nejm.org/doi/full/10.1056/NEJMp2511272

Thirty Years of Hydroxyurea for Sickle Cell Anemia A study published in 1995 provided evidence that hydroxyurea reduces vaso-occlusive crises in people with sickle cell anemia.

3. ashpublications.org ashpublications.org/bloodadvances/article/9/14/3585/536727/Evaluating-the-long-term-benefits-of-hydroxyurea

Evaluating the long-term benefits of hydroxyurea in pediatric ... This study demonstrates that hydroxyurea has sustained clinical benefits in reducing ED visits and hospital days across years of use in children with SCA.

4. hematology.org hematology.org/newsroom/press-releases/2025/hydroxyurea-effective-long-term-in-children-living-with-scd

Hydroxyurea Effective Long Term in Children Living With ... Hydroxyurea remains effective long-term in reducing emergency department visits and hospital days for children living with sickle cell disease (SCD), according ...

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC3374046/

Hydroxyurea for the Treatment of Sickle Cell Disease: Efficacy ... We have compelling evidence that hydroxyurea can reduce painful events and hospitalizations in children of all ages with HbSS.

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC4022916/

Hydroxyurea in Sickle Cell Disease: Drug Review - PMC Safety: no major short-term toxicities, plus no known long-term sequelae or complications of therapy. Based on currently available data, hydroxyurea ...

7. haematologica.org haematologica.org/article/view/11891

The modern use of hydroxyurea for children with sickle cell ... Safety of hydroxyurea in children with sickle cell anemia: results of the HUG-KIDS study, a phase I/II trial. Blood. 1999; 94(5):1550-1554. Google Scholar ...

8. accpjournals.onlinelibrary.wiley.com accpjournals.onlinelibrary.wiley.com/doi/10.1002/phar.2793

Hydroxyurea treatment for sickle cell anemia during ... Hydroxyurea is currently contraindicated for pregnant and lactating women with SCA. Clinical experience of hydroxyurea use during pregnancy is increasingly ...

9. ashpublications.org ashpublications.org/blood/article/124/21/560/100823/Long-Term-Safety-of-Hydroxyurea-in-Sickle-Cell

Long-Term Safety of Hydroxyurea in Sickle Cell Anemia and ... The use of HU in treating patients with hemoglobinopathies does not appear to be associated with increase risk of secondary malignancies nor MDS.