Feasibility trial for primary stroke prevention in children with sickle cell anemia in Nigeria (SPIN trial)

Abstract

The vast majority of children with sickle cell anemia (SCA) live in Africa, where evidence-based guidelines for primary stroke prevention are lacking. In Kano, Nigeria, we conducted a feasibility trial to determine the acceptability of hydroxyurea therapy for primary stroke prevention in children with abnormal transcranial Doppler (TCD) measurements. Children with SCA and abnormal non-imaging TCD measurements (≥ 200 cm/s) received moderate fixed-dose hydroxyurea therapy (~20 mg/kg/day). A comparison group of children with TCD measurements < 200 cm/s was followed prospectively. Approximately 90% (337 of 375) of families agreed to be screened, while 92% (25 of 27) of those with abnormal TCD measurements, on two separate occasions, enrolled in the trial. No participant elected to withdraw from the trial. The average mean corpuscular volume increased from 85 fL at baseline to 101.3 fL at 24 months, demonstrating adherence to hydroxyurea. The comparison group consisted of 210 children, of which four developed abnormal TCD measurements, and were started on hydroxyurea. None of the monthly research visits were missed (n = total 603 visits). Two and ten deaths occurred in the treatment and comparison groups, with mortality rates of 2.69 and 1.81 per 100 patient-years, respectively (p = 0.67). Our results provide strong evidence, for high family recruitment, retention, and adherence rates, to undertake the first randomized controlled trial with hydroxyurea therapy for primary stroke prevention in children with SCA living in Africa.

Sickle cell disease: Reducing the global disease burden

“…(TWiTCH and SWiTCH trials), although less efficacious in the case of secondary stroke prevention. 47,48 Further, in a prospective feasibility clinical trial (SPIN) in Nigeria, hydroxyurea therapy resulted in significant decrease in transcranial Doppler (TCD) velocities >170 cm/s as well as improvement in the hematological profile of children with SCA. 49 Hence, hydroxyurea may provide an effective approach to primary stroke prevention, thus providing a feasible substitute for primary stroke prevention in low-income countries.…”

Approximately 40 000 children with sickle cell anemia require screening with TCD and treating with hydroxyurea for stroke prevention in three states in northern Nigeria

“…To decrease life-long morbidity and mortality associated with strokes in children with SCA, our team initiated a primary stroke prevention trial using hydroxyurea therapy for children with SCA, 5 to 12 years of age (NCT02560935) living in Kano Nigeria. 5 Since 2012, our stroke prevention program in children with SCA has matured to include neighboring states to Kano in northern Nigeria, Katsina and Kaduna. Two initial steps were required to establish a regional stroke prevention program in these low-resource settings; 1) assessment of children with SCA requiring TCD screening;…”

Intermittent or uneven daily administration of low‐dose hydroxyurea is effective in treating children with sickle cell anemia in Angola

“…Comparably, in studies of patients with SCA and abnormal TCD from Nigeria, children who took hydroxyurea did not experience excessive toxicity compared with those not treated with hydroxyurea. 49,52 Furthermore, studies from other resource-limited settings in India, [53][54][55] Brazil, 56 Jamaica, 48,57,58 56 and Ferster et al 6 observed mean hemoglobin increases of 0.3 and 0.6 g/dL, respectively. In contrast, studies such as the HUG-KIDS trial that gradually increased hydroxyurea to maximum tolerated dose in all subjects reported higher hydroxyurea-induced HGB and MCV than those found in our study.…”