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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests hydroxyurea to assist individuals with sickle cell disease, a condition affecting red blood cells. It aims to determine if pharmacokinetic testing, which assesses how the body processes the drug, can help patients achieve the optimal dose more quickly than standard methods. Participants will be divided into three groups: two groups will start hydroxyurea using either the new test or standard bloodwork, and one group will consist of individuals who have been on hydroxyurea for over a year to check drug levels. The trial seeks children and teens with sickle cell disease who are either beginning hydroxyurea or have been on it for at least a year. As a Phase 2 and Phase 3 trial, this research measures the treatment's effectiveness in an initial, smaller group and represents the final step before FDA approval, offering participants a chance to contribute to advancing treatment options.

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.

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

Research has shown that hydroxyurea is generally safe for people with sickle cell anemia. In one study, hydroxyurea reduced the risk of hospitalization by 85%. Another study found that people taking hydroxyurea had a lower chance of dying over nine years. This treatment also helps children by reducing their need for emergency room visits.

Hydroxyurea has been used for many years to treat sickle cell disease and is approved by the FDA for this condition, indicating that most people tolerate it well. However, like any treatment, it can have side effects, so discussing them with a doctor is important. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about hydroxyurea for sickle cell anemia because it offers a unique approach by potentially increasing fetal hemoglobin levels, which can help reduce the sickling of red blood cells. Unlike standard treatments that primarily focus on managing pain or preventing infections, hydroxyurea targets the disease at a cellular level, aiming to decrease the frequency of painful episodes and other complications. Additionally, its ability to potentially reach maximum tolerated dose (MTD) while being monitored for pharmacokinetics (PK) makes it an intriguing option for personalized treatment plans. These features offer hope for more effective management of sickle cell anemia, differentiating hydroxyurea from conventional care options.

What is the effectiveness track record for hydroxyurea in treating sickle cell anemia?

Research has shown that hydroxyurea effectively treats sickle cell anemia. Studies have found that it increases hemoglobin levels, aiding oxygen transport in the blood, and reduces white blood cell counts, which can decrease inflammation. In children with sickle cell disease, hydroxyurea has lowered emergency room visits and hospital stays over time. At doses above 20 mg/kg/day, it can prevent organ damage and increase fetal hemoglobin levels by about 18%. Overall, hydroxyurea has demonstrated lasting benefits for individuals with sickle cell disease. Participants in this trial will be assigned to different groups to evaluate the pharmacokinetics and effects of hydroxyurea over a 12-month period. ^{4 5 6 7 8}

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

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]

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]

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]

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. 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.

3. 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 ...

4. hematologyadvisor.com hematologyadvisor.com/features/hydroxyurea-for-sickle-cell-anemia-in-children/

Hydroxyurea for Sickle Cell Anemia in Children Researchers determined long-term treatment with hydroxyurea is beneficial for children with sickle cell anemia (SCA).

5. systematicreviewsjournal.biomedcentral.com systematicreviewsjournal.biomedcentral.com/articles/10.1186/s13643-024-02461-z

Role of hydroxyurea therapy in the prevention of organ ... Our study found that a hydroxyurea dose above 20 mg/kg/day with a mean rise in HbF by 18.46% post-hydroxyurea therapy had a beneficial role.

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC2879711/

The Risks and Benefits of Long-term Use of Hydroxyurea in ... A randomized, controlled clinical trial established the efficacy and safety of short-term use of hydroxyurea in adult sickle cell anemia.

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

Thirty Years of Hydroxyurea for Sickle Cell Anemia Additional follow-up research involving patients in the MSH trial found that, after 9 years, hydroxyurea was associated with reduced mortality.

8. ashpublications.org ashpublications.org/bloodadvances/article/7/16/4319/495797/Efficacy-safety-and-pharmacokinetics-of-a-new

Efficacy, safety, and pharmacokinetics of a new, ready-to-use ... The risk of hospitalization was reduced by 85% after initiation of hydroxyurea treatment (odds ratio 0.15 [95% confidence interval, 0.05-0.45]; ...