Ignite Creation Date:
2024-10-26 @ 3:36 PM
Last Modification Date:
2024-10-26 @ 3:36 PM
Study NCT ID:
NCT06526117
Status:
RECRUITING
Last Update Posted:
None
First Post:
2024-07-23
Brief Title:
Stroke Prevention in Nigeria 2 Trial
Sponsor:
None
Organization:
None
Study Overview
Official Title:
Primary Prevention of Stroke in Children With SCD in Sub-Saharan Africa II A Multicenter Open-label Single-arm Type I Hybrid Clinical Trial
Status:
RECRUITING
Status Verified Date:
2024-08
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
No
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
SPRING-2
Brief Summary:
The primary goal of this study is to complete a multicenter single-arm type I hybrid trial to assess the effectiveness of hydroxyurea therapy for primary stroke prevention in high-risk children with sickle cell anemia SCA living in Nigeria in routine care settings
Detailed Description:
Strokes in sickle cell anemia SCA particularly in children living in Africa are associated with significant morbidity and an increased risk of premature death In the US primary stroke prevention in children with SCA involves screening for elevated Transcranial Doppler ultrasound TCD velocity coupled with regular blood transfusion therapy for persons with elevated velocities However regular blood transfusion therapy is not a viable option for children with SCA in Nigeria for several reasons including 1 inadequate supply of blood still donor exchange system 2 availability and cost of monthly blood transfusions for preventive therapy as opposed to emergency therapy 3 unsafe blood supplies with a high probability of blood-borne infections and alloimmunization and 4 children that receive regular blood transfusion will ultimately require daily iron chelation an unaffordable undertaking in low-income countries
This multicenter open-label single-arm type I hybrid trial will assess the effectiveness of Hydroxyurea therapy for primary stroke prevention in children with sickle cell anemia SCA living in Nigeria A recently completed double-blind parallel-group phase III randomized controlled trial SPRING involved comparing low-dose to moderate-dose hydroxyurea for primary stroke prevention in children with SCA and abnormal transcranial Doppler TCD velocities 200 cmsec Children with abnormal TCD velocities have a high stroke risk of approximately 107 events per 100 person-years observation arm in the STOP trial In the low- n109 and moderate-dose n111 hydroxyurea groups the stroke incidence rates were 12 and 19 per 100 person-years respectively p077 combined incidence rate 15 per 100 person-years 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 Hematologys evidence-based guidelines for hydroxyurea therapy for primary stroke prevention in low-income settings The hypothesis to be tested in the SPRING-2 study is 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 pediatricians 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 will achieve 91 power at a 0050 significance level to detect non-inferiority when the expected proportion of strokes is 0035 a minimum follow-up period of 25 years and a loss to follow-up of 10 per year The study will follow standard of care procedures including clinic visits every 3 months and complete blood cell counts every 6 months The following aims will be conducted as part of the trial 1 Determine the incidence of the first stroke in children with abnormal TCD velocities treated with hydroxyurea for 25 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 three Nigerian Multiple Principal Investigators statisticians and nurses will be focused on three areas- 1 developing a Nigerian data coordinating center and the required skills to support a clinical trial 2 developing a regional TCD course for nurses enhancing task shifting and reach and 3 performing cost-effective analysis for the type I hybrid trial comparing low-and moderate dose hydroxyurea
This multicenter open-label single-arm type I hybrid trial will assess the effectiveness of Hydroxyurea therapy for primary stroke prevention in children with sickle cell anemia SCA living in Nigeria A recently completed double-blind parallel-group phase III randomized controlled trial SPRING involved comparing low-dose to moderate-dose hydroxyurea for primary stroke prevention in children with SCA and abnormal transcranial Doppler TCD velocities 200 cmsec Children with abnormal TCD velocities have a high stroke risk of approximately 107 events per 100 person-years observation arm in the STOP trial In the low- n109 and moderate-dose n111 hydroxyurea groups the stroke incidence rates were 12 and 19 per 100 person-years respectively p077 combined incidence rate 15 per 100 person-years 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 Hematologys evidence-based guidelines for hydroxyurea therapy for primary stroke prevention in low-income settings The hypothesis to be tested in the SPRING-2 study is 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 pediatricians 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 will achieve 91 power at a 0050 significance level to detect non-inferiority when the expected proportion of strokes is 0035 a minimum follow-up period of 25 years and a loss to follow-up of 10 per year The study will follow standard of care procedures including clinic visits every 3 months and complete blood cell counts every 6 months The following aims will be conducted as part of the trial 1 Determine the incidence of the first stroke in children with abnormal TCD velocities treated with hydroxyurea for 25 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 three Nigerian Multiple Principal Investigators statisticians and nurses will be focused on three areas- 1 developing a Nigerian data coordinating center and the required skills to support a clinical trial 2 developing a regional TCD course for nurses enhancing task shifting and reach and 3 performing cost-effective analysis for the type I hybrid trial comparing low-and moderate dose hydroxyurea
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None