U01NS129143

Stroke Prevention in Nigeria: SPRING 2 - 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 cost-effective analysis for the Type I hybrid trial comparing low- and moderate-dose hydroxyurea.

Vanderbilt University Medical Center

(1) TO SUPPORT EXTRAMURAL RESEARCH FUNDED BY THE NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE (NINDS) INCLUDING: BASIC RESEARCH THAT EXPLORES THE FUNDAMENTAL STRUCTURE AND FUNCTION OF THE BRAIN AND THE NERVOUS SYSTEM, RESEARCH TO UNDERSTAND THE CAUSES AND ORIGINS OF PATHOLOGICAL CONDITIONS OF THE NERVOUS SYSTEM WITH THE GOAL OF PREVENTING THESE DISORDERS, RESEARCH ON THE NATURAL COURSE OF NEUROLOGICAL DISORDERS, IMPROVED METHODS OF DISEASE PREVENTION, NEW METHODS OF DIAGNOSIS AND TREATMENT, DRUG DEVELOPMENT, DEVELOPMENT OF NEURAL DEVICES, CLINICAL TRIALS, AND RESEARCH TRAINING IN BASIC, TRANSLATIONAL AND CLINICAL NEUROSCIENCE. THE INSTITUTE IS THE LARGEST FUNDER OF BASIC NEUROSCIENCE IN THE US AND SUPPORTS RESEARCH ON TOPICS INCLUDING BUT NOT LIMITED TO: DEVELOPMENT OF THE NERVOUS SYSTEM, INCLUDING NEUROGENESIS AND PROGENITOR CELL BIOLOGY, SIGNAL TRANSDUCTION IN DEVELOPMENT AND PLASTICITY, AND PROGRAMMED CELL DEATH, SYNAPSE FORMATION, FUNCTION, AND PLASTICITY, LEARNING AND MEMORY, CHANNELS, TRANSPORTERS, AND PUMPS, CIRCUIT FORMATION AND MODULATION, BEHAVIORAL AND COGNITIVE NEUROSCIENCE, SENSORIMOTOR LEARNING, INTEGRATION AND EXECUTIVE FUNCTION, NEUROENDOCRINE SYSTEMS, SLEEP AND CIRCADIAN RHYTHMS, AND SENSORY AND MOTOR SYSTEMS. IN ADDITION, THE INSTITUTE SUPPORTS BASIC, TRANSLATIONAL AND CLINICAL STUDIES ON A NUMBER OF DISORDERS OF THE NERVOUS SYSTEM INCLUDING (BUT NOT LIMITED TO): STROKE, TRAUMATIC INJURY TO THE BRAIN, SPINAL CORD AND PERIPHERAL NERVOUS SYSTEM, NEURODEGENERATIVE DISORDERS, MOVEMENT DISORDERS, BRAIN TUMORS, CONVULSIVE DISORDERS, INFECTIOUS DISORDERS OF THE BRAIN AND NERVOUS SYSTEM, IMMUNE DISORDERS OF THE BRAIN AND NERVOUS SYSTEM, INCLUDING MULTIPLE SCLEROSIS, DISORDERS RELATED TO SLEEP, AND PAIN. PROGRAMMATIC AREAS, WHICH ARE PRIMARILY SUPPORTED BY THE DIVISION OF NEUROSCIENCE, ARE ALSO SUPPORTED BY THE DIVISION OF EXTRAMURAL ACTIVITIES, THE DIVISION OF TRANSLATIONAL RESEARCH, THE DIVISION OF CLINICAL RESEARCH, THE OFFICE OF TRAINING AND WORKFORCE DEVELOPMENT, THE OFFICE OF PROGRAMS TO ENHANCE NEUROSCIENCE WORKFORCE DEVELOPMENT, AND THE OFFICE OF INTERNATIONAL ACTIVITIES. (2) TO EXPAND AND IMPROVE THE SMALL BUSINESS INNOVATION RESEARCH (SBIR) PROGRAM, TO INCREASE PRIVATE SECTOR COMMERCIALIZATION OF INNOVATIONS DERIVED FROM FEDERAL RESEARCH AND DEVELOPMENT, TO INCREASE SMALL BUSINESS PARTICIPATION IN FEDERAL RESEARCH AND DEVELOPMENT, AND TO FOSTER AND ENCOURAGE PARTICIPATION OF SOCIALLY AND ECONOMICALLY DISADVANTAGED SMALL BUSINESS CONCERNS AND WOMEN-OWNED SMALL BUSINESS CONCERNS IN TECHNOLOGICAL INNOVATION. TO UTILIZE THE SMALL BUSINESS TECHNOLOGY TRANSFER (STTR) PROGRAM, TO STIMULATE AND FOSTER SCIENTIFIC AND TECHNOLOGICAL INNOVATION THROUGH COOPERATIVE RESEARCH AND DEVELOPMENT CARRIED OUT BETWEEN SMALL BUSINESS CONCERNS AND RESEARCH INSTITUTIONS, TO FOSTER TECHNOLOGY TRANSFER BETWEEN SMALL BUSINESS CONCERNS AND RESEARCH INSTITUTIONS, TO INCREASE PRIVATE SECTOR COMMERCIALIZATION OF INNOVATIONS DERIVED FROM FEDERAL

93.989 - International Research and Research Training

National Institute of Neurological Disorders and Stroke (NNDS) [HHS - NIH]

Fogarty International Center (FIC) [HHS - NIH]

Nashville, Tennessee 37203 United States

Single Zip Code

Global Brain and Nervous System Disorders Research Across the Lifespan (R01 Clinical Trials Optional) (PAR-21-311)

Amendment Since initial award the End Date has been extended from 08/31/28 to 08/31/29 and the total obligations have increased 21% from $607,580 to $734,529.