Personalized hydroxyurea dosing using blood-level guidance for children with sickle cell anemia (ENHANCE)

Effectiveness of Nontraditional Hydroxyurea Algorithms: Novel and Clinical Evaluations (ENHANCE)

Phase 4 Interventional Children's Hospital Medical Center, Cincinnati · NCT07177300

This trial will test whether starting hydroxyurea based on how each child absorbs the drug (a PK-guided dose) helps babies and children with sickle cell anemia get higher fetal hemoglobin and better organ protection over time.

Quick facts

PhasePhase 4
Study typeInterventional
Enrollment50 (estimated)
Ages6 Months and up
SexAll
SponsorChildren's Hospital Medical Center, Cincinnati Academic / other
Locations1 site (Cincinnati, Ohio)
Trial IDNCT07177300 on ClinicalTrials.gov

What this trial studies

ENHANCE will enroll infants and children with HbSS or HbSβ0 who are starting hydroxyurea and use a pharmacokinetic (PK)-guided strategy to choose an individualized starting dose and escalate to a maximum tolerated dose (MTD) through long-term follow-up to age 15. The protocol combines clinical monitoring with novel functional organ assessments (brain, heart, kidneys, spleen, eyes), growth and pubertal hormone measurements, and state-of-the-art laboratory assays including single-cell HbF quantitation and single-cell multiome analyses in erythroblasts. Serial genomic DNA sampling will allow monitoring for clonal hematopoiesis and potential leukemic risk, while simplified PK-guided dosing aims to achieve sustained ≥30% HbF with near-pancellular distribution. All participants receive oral PK-optimized hydroxyurea at MTD with systematic long-term monitoring at Cincinnati Children’s Hospital Medical Center.

Who should consider this trial

Good fit: Ideal candidates are children aged at least 6 months with sickle cell anemia (HbSS) or sickle-β0-thalassemia (HbSβ0) whose family and provider have decided to start hydroxyurea and who are not on regular transfusion programs.

Not a fit: Patients on regular scheduled blood transfusions or those with other sickle genotypes such as HbSC or HbSβ+ would not be expected to benefit from this protocol and are excluded.

Why it matters

Potential benefit: If successful, this approach could get children to optimal hydroxyurea doses faster, increase fetal hemoglobin levels, and reduce long-term organ injury and complications.

How similar studies have performed: Hydroxyurea is a well-established therapy that improves outcomes in sickle cell disease, and smaller trials and pilot work have shown promise for individualized or PK-guided dosing, but the comprehensive long-term organ-protection and single-cell genomic approaches here are novel.

Eligibility criteria

Show full inclusion / exclusion criteria
Inclusion Criteria:

* Diagnosis of sickle cell anemia (HbSS) or sickle-β0-thalassemia (HbSβ0)
* Age 6 months at the time of enrollment
* Clinical decision by patient, family, and healthcare provider to initiate hydroxyurea therapy

Exclusion Criteria:

* Current treatment with regularly scheduled blood transfusions
* Sickle-hemoglobin C disease (HbSC), sickle-β+-thalassemia (HbSβ+)

Where this trial is running

Cincinnati, Ohio

Study contacts

How to participate

  1. Review the eligibility criteria above with your treating physician.
  2. Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
  3. Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.
Conditions Sickle Cell AnemiaSickle-β0-thalassemiasickle cell anemiaSCDsickle cellhydroxyurea
Last reviewed 2026-06-13 by the Find a Trial editorial team. Information on this page is for educational purposes and is not medical advice. Always consult qualified healthcare professionals about clinical trial participation.