Hydroxyurea for Sickle Cell Anemia

Recruiting 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

202 Participants Needed

Trial Summary

What is the purpose of this trial?

This study will 1) Evaluate the prevalence of elevated (conditional or abnormal) transcranial Doppler (TCD) velocities in a cross-sectional analysis of children with Sickle Cell Anemia (SCA) living in Tanzania; 2) Obtain longitudinal data on TCD velocities in this population; and 3) Measure the effects of hydroxyurea therapy on TCD velocities and associated primary stroke risk.

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.

What data supports the effectiveness of the drug hydroxyurea for sickle cell anemia?

Research shows that hydroxyurea increases fetal hemoglobin levels, which helps reduce pain episodes, hospital visits, and other complications in people with sickle cell anemia. It is well-tolerated and has been shown to be effective in both children and adults, making it a valuable treatment option for managing the disease. ^{1 2 3 4 5}

Is hydroxyurea safe for humans?

Hydroxyurea is generally considered safe for humans, with studies showing it is well-tolerated in both children and adults with sickle cell disease. While some adverse events like leg ulcers can occur, they are usually reversible, and no increased risk of cancer has been observed. Long-term safety is still monitored, but current evidence supports its use as a safe treatment option. ^{4 6 7 8 9}

What makes the drug hydroxyurea unique for treating sickle cell anemia?

Hydroxyurea is unique because it increases fetal hemoglobin (HbF) levels, which helps reduce the complications and pain associated with sickle cell anemia. It is the only approved cytotoxic drug for this condition and can be effective even in low-resource settings where frequent monitoring is challenging. ^{2 10 11 12 13}

Eligibility Criteria

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

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)

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

References

1. Switzerland pubmed.ncbi.nlm.nih.gov

Pharmacological modification of hemoglobin F expression in sickle cell anemia: an update on hydroxyurea studies. [2019]

2. United States pubmed.ncbi.nlm.nih.gov

Effect of hydroxyurea on mortality and morbidity in adult sickle cell anemia: risks and benefits up to 9 years of treatment. [2022]

3. United States pubmed.ncbi.nlm.nih.gov

Hydroxyurea effectiveness in children and adolescents with sickle cell anemia: A large retrospective, population-based cohort. [2022]

4. France pubmed.ncbi.nlm.nih.gov

Hydroxycarbamide: clinical aspects. [2021]

5. Canada pubmed.ncbi.nlm.nih.gov

Hydroxyurea: Clinical and Hematological Effects in Patients With Sickle Cell Anemia. [2018]

6. United States pubmed.ncbi.nlm.nih.gov

Clinical complications in severe pediatric sickle cell disease and the impact of hydroxyurea. [2022]

7. Switzerland pubmed.ncbi.nlm.nih.gov

Clinical follow-up of hydroxyurea-treated adults with sickle cell disease. [2022]

8. Italy pubmed.ncbi.nlm.nih.gov

Hydroxycarbamine: from an Old Drug Used in Malignant Hemopathies to a Current Standard in Sickle Cell Disease. [2022]

9. United States pubmed.ncbi.nlm.nih.gov

Hydroxyurea (hydroxycarbamide) genotoxicity in pediatric patients with sickle cell disease. [2019]

10. India pubmed.ncbi.nlm.nih.gov

Perception to hydroxyurea therapy in patients with sickle cell disease: Report from 3 centers. [2021]

11. Nigeria pubmed.ncbi.nlm.nih.gov

KNOWLEDGE, ATTITUDE AND USE OF HYDROXUYREA AMONG ADULT SICKLE CELL DISEASE PATIENTS. [2022]

12. United States pubmed.ncbi.nlm.nih.gov

Hydroxyurea and erythropoietin therapy in sickle cell anemia. [2018]

13. United States pubmed.ncbi.nlm.nih.gov

Hydroxyurea for Children with Sickle Cell Anemia in Sub-Saharan Africa. [2022]