# Stroke Prevention in Nigeria: SPRING 2

> **NIH NIH U01** · VANDERBILT UNIVERSITY MEDICAL CENTER · 2024 · $116,949

## Abstract

SUMMARY:
We propose a multicenter open-label, single-arm type I hybrid trial to assess the effectiveness of hydroxyurea
therapy for primary stroke prevention in children with sickle cell anemia (SCA) living in Nigeria. Our team just
completed a double-blind, parallel-group phase III randomized controlled trial (SPRING), where we compared
low-dose to moderate-dose hydroxyurea for primary stroke prevention in children with SCA and abnormal
transcranial Doppler (TCD) velocities (>200 cm/sec). Children with abnormal TCD velocities have a high stroke
risk of approximately 10.7 events per 100 person-years (observation arm in the STOP trial). In the low- (n=109)
and moderate-dose (n=111) hydroxyurea groups, the stroke incidence rates were 1.2 and 1.9 per 100 person-
years, respectively, p=0.77 (combined incidence rate 1.5 per 100 person-year). Despite equal efficacy for
stroke prevention in both treatment groups, moderate- when compared to low-dose hydroxyurea, was more
effective in preventing severe acute pain and all-cause hospitalizations. Our findings supported the American
Society of Hematology's evidence-based guidelines for hydroxyurea therapy for primary stroke prevention in
low-income settings. Our hypothesis to be tested: in a multicenter single-arm type I hybrid trial, for children with
abnormal TCD velocities treated with hydroxyurea, the stroke incidence rate will be non-inferior to the SPRING
trial results, with an upper non-inferiority margin of 4 strokes per 100-person-years. The point estimate method
was used to determine the non-inferiority margin based on the Nigerian pediatrician's judgment of what
maximum stroke rate would be clinically meaningful to demonstrate the effectiveness and justify treatment for
the high-risk stroke group. A non-inferiority test with an overall sample size of 220 participants will achieve 91%
power at a 0.050 significance level to detect non-inferiority when the expected proportion of strokes is 0.035, a
minimum follow-up period of 2.5 years and a loss to follow-up of 10% per year. Participants will be followed as
per standard care, including clinic visits every 3 months and complete blood cell counts every 6 months. We
will conduct the following aims:1) Determine the incidence of the first stroke and TIA in children with abnormal
TCD velocities treated with hydroxyurea for 2.5 years in the type 1 hybrid trial; 2) Evaluate the implementation
and sustainability of the intervention within the extended RE-AIM framework; 3) Evaluate the cost-effectiveness
of low- compared to a higher dose of hydroxyurea for primary stroke prevention in children with abnormal TCD
velocities. Capacity building for the three Nigerian Multiple Principal Investigators, the statisticians, and nurses
will be focused on three areas- a) developing a Nigerian data coordinating center and the required skills to
support a clinical trial; b) developing a regional TCD course for nurses, enhancing task shifting and reach, and
c) performing c...

## Key facts

- **NIH application ID:** 10994102
- **Project number:** 3U01NS129143-01A1S1
- **Recipient organization:** VANDERBILT UNIVERSITY MEDICAL CENTER
- **Principal Investigator:** SHEHU UMAR ABDULLAHI
- **Activity code:** U01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $116,949
- **Award type:** 3
- **Project period:** 2023-09-01 → 2029-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10994102

## Citation

> US National Institutes of Health, RePORTER application 10994102, Stroke Prevention in Nigeria: SPRING 2 (3U01NS129143-01A1S1). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10994102. Licensed CC0.

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