Preventing strokes in children with sickle cell disease in Nigeria using hydroxyurea

Primary Prevention of Stroke in Children With SCD in Sub-Saharan Africa II: A Multicenter, Open-label, Single-arm Type I Hybrid Clinical Trial

This study is testing if hydroxyurea can help prevent strokes in children with sickle cell disease in Nigeria who are at high risk.

Quick facts

• Phase: Phase 4
• Study type: Interventional
• Enrollment: 220 (estimated)
• Ages: 5 Years to 12 Years
• Sex: All
• Sponsor: Vanderbilt University Medical Center (Academic / other)
• Locations: 2 sites (Kano and 1 other locations)
• Trial ID: NCT06526117 on ClinicalTrials.gov

What this trial studies

This trial aims to evaluate the effectiveness of hydroxyurea therapy for preventing strokes in high-risk children with sickle cell anemia living in Nigeria. It is a multicenter, open-label, single-arm trial that will assess children aged 5 to 12 years who have elevated Transcranial Doppler (TCD) velocities. The study addresses the challenges of traditional stroke prevention methods, such as blood transfusions, which are not feasible in low-resource settings. By utilizing hydroxyurea, the trial seeks to provide a safer and more accessible option for stroke prevention in this vulnerable population.

Who should consider this trial

Good fit: Ideal candidates for this study are children aged 5 to 12 years diagnosed with sickle cell anemia who have specific elevated TCD flow velocities.

Not a fit: Patients who have previously experienced a stroke or have significant neurological deficits may not benefit from this study.

Why it matters

Potential benefit: If successful, this study could significantly reduce the incidence of strokes in children with sickle cell anemia in Nigeria, improving their quality of life and survival rates.

How similar studies have performed: Previous studies have shown promising results with hydroxyurea for stroke prevention in sickle cell disease, indicating potential for success in this approach.

Eligibility criteria

Inclusion Criteria:

The inclusion criteria for the SPRING-2 Trial will consist of:

* Diagnosis of HbSS or HbSB0 confirmed by high-performance liquid chromatography (HPLC);
* Informed consent from the parent/legal guardian and assent from the patient at least 7 years of age;
* Two TCD flow velocity readings of \>or equal to180 cm/sec and \< 220 cm/sec or one TCD velocity reading \> or equal to 220 cm/sec; typically the repeat TCD is performed on the same day so treatment can start immediately;
* Age between 5 and 12 years (assessment can take place up until the 13th birthday), which includes the peak age of onset of strokes in SCA, \~ 6 yo; and
* Ability to swallow the hydroxyurea capsule.

Exclusion Criteria:

The exclusion criteria will be the following:

* Prior stroke or TIA by history, or concern for moderate or severe neurological deficit based on a positive validated "10 questions" screening;
* Other significant organ system dysfunction or other contraindication to hydroxyurea;
* Children who are already on therapy with either blood transfusion or hydroxyurea therapy;
* Significant cytopenias (absolute neutrophil count (ANC) \<1500, platelets \<150,000/ul, reticulocytes \<80,000/ul, unless Hb is \> 9 g/dl\], renal insufficiency (creatinine \> 0.8 mg/dl); and
* History of seizures or diagnosis of epilepsy, and 6) metal in the body that would make MRI unsafe. The rationale for excluding children under 5 years old: Despite being a vulnerable age group for strokes, children younger than 5 years were excluded because a significant proportion of this population is unable to swallow a capsule, the only stable form of hydroxyurea available in Nigeria.

Where this trial is running

Kano and 1 other locations

• Aminu Kano Teaching Hospital — Kano, Nigeria (Recruiting)
• Murtala Muhammad Specialist Hospital — Kano, Nigeria (Recruiting)

Study contacts

• Principal investigator: Michael R DeBaun, MD, MPH — Vanderbilt University Medical Center
• Study coordinator: Michael R DeBaun, MD, MPH

Conditions Sickle Cell Disease; Stroke; primary stroke prevention; hydroxyurea; low income country; sub-Saharan Africa