Hydroxyurea for Sickle Cell Anemia

(OPTIMA Trial)

Overseen By Bianka Courcelle, Research nurse, RN

Age: < 65

Sex: Any

Trial Phase: Phase 2 & 3

Sponsor: Yves Pastore

Must be taking: Hydroxyurea

Disqualifiers: Other genotypes, Chronic transfusion, Pregnancy, 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

Compensation: Varies

Number of Visits: Unknown

Duration: 12 months

29 Participants Needed

Trial Summary

What is the purpose of this trial?

The goal of this study is to evaluate if patients with sickle cell disease can achieve a maximum tolerate dose of hydroxuyrea (HU) over a period of 12 months faster with pharmacokinetic testing than the standard of care bloodwork follow-up. Pharmacokinetic test is used to evaluate the process by which drugs are absorbed, distributed in the body, localized in the tissues, and is excreted. Patient will be a randomized (coin toss method) into 2 groups. Group A will have an increase of their HU dosage with pharmacokinetic results and Group B will have an increase of their HU dosage following the standard of care bloodwork follow-up. Group C will include patient with sickle cell disease that has been taking HU for at least 12 months and will undergo a pharmacokinetic dosage to check the level of HU only one time.

Do I need to stop my current medications to join the trial?

The trial information does not specify if you need to stop taking your current medications. However, it does require participants to take hydroxyurea for the study duration.

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

Research shows that Hydroxyurea reduces hospitalizations, pain episodes, and emergency visits in children with sickle cell anemia by significant percentages, and it also increases hemoglobin levels, which is important for carrying oxygen in the blood. Additionally, it improves quality and duration of life by reducing complications in both children and adults with sickle cell disease. ^{1 2 3 4 5}

Is hydroxyurea safe for humans?

Hydroxyurea has been studied for its safety in both adults and children with sickle cell disease. It is generally well-tolerated, with some reversible side effects like leg ulcers, and no cases of cancer were observed in a long-term study. While concerns about long-term safety exist, especially in children, the overall risk/benefit ratio is considered satisfactory. ^{6 7 8 9 10}

How does the drug hydroxyurea differ from other treatments for sickle cell anemia?

Hydroxyurea is unique because it increases fetal hemoglobin (a type of hemoglobin that reduces sickling of red blood cells) and decreases the number of certain blood cells that can cause blockages in blood vessels. This helps reduce the frequency and severity of painful sickle cell crises, making it an effective option for managing sickle cell anemia. ^{11 12 13 14 15}

Eligibility Criteria

This trial is for patients with moderate to severe sickle cell anemia. Participants must be able to undergo pharmacokinetic testing and have not reached their maximum tolerated dose of hydroxyurea. Specific inclusion and exclusion criteria details are not provided.

Inclusion Criteria

Group A and B: Have consented for participation in the study

I agree to take hydroxyurea for 12 months.

Group A and B: Have had confirmed diagnosis of SCD at CHU Sainte-Justine biochemistry lab with hemoglobin electrophoresis

Exclusion Criteria

I have received a blood transfusion within the last 4 weeks.

ALT >2x normal for age

Pregnancy

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive hydroxyurea with dosage adjustments based on pharmacokinetic testing or standard bloodwork over 12 months

12 months

Regular visits for PK sampling and bloodwork

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Hydroxyurea

Trial Overview The study tests if using pharmacokinetic testing can help patients find the best dose of hydroxyurea faster than standard bloodwork follow-up. Patients are randomly assigned to two groups: one uses pharmacokinetic results (Group A) and the other follows standard care (Group B). There's also a Group C for those already on hydroxyurea for 12 months, checked once.

Participant Groups

Group I: Group C Experimental Treatment 1 Intervention

Patient will undergo one PK sample procurement to evaluate level of HU-AUC after 12 months of taking hydroxyurea.

Group II: Group A Experimental Treatment 1 Intervention

Patient starting hydroxyurea that will have PK sample procurements at different timpoints over a period of 12 months until HU-AUC shows MTD

Group III: Group B Active Control 1 Intervention

Patient starting hydroxuyrea that will be followed as per standard of care over a period of 12 months until MTD has been reached

Who Is Running the Clinical Trial?

Yves Pastore

Lead Sponsor

Trials

1

Recruited

30+

St. Justine's Hospital

Collaborator

Trials

205

Recruited

87,300+

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. Canada pubmed.ncbi.nlm.nih.gov

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

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

Hydroxyurea use in young infants with sickle cell disease. [2019]

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. 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]

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

Impact of hydroxyurea on lymphocyte subsets in children with sickle cell anemia. [2023]

6. Switzerland pubmed.ncbi.nlm.nih.gov

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

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

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

8. England pubmed.ncbi.nlm.nih.gov

Effectiveness and Safety of Hydroxyurea in the Treatment of Sickle Cell Anaemia Children in Jos, North Central Nigeria. [2020]

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

Advances in the use of hydroxyurea. [2016]

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

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

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

Reduction of the clinical severity of sickle cell/beta-thalassemia with hydroxyurea: the experience of a single center in Greece. [2013]

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

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

13. India pubmed.ncbi.nlm.nih.gov

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

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

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

15. Nigeria pubmed.ncbi.nlm.nih.gov

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