Ignite Creation Date:
2024-06-16 @ 11:47 AM
Last Modification Date:
2024-10-26 @ 3:30 PM
Study NCT ID:
NCT06429475
Status:
NOT_YET_RECRUITING
Last Update Posted:
2024-05-28
First Post:
2024-04-08
Brief Title:
Anti-Inflammatory Reliever South Africa
Sponsor:
University of KwaZulu
Organization:
University of KwaZulu
Study Overview
Official Title:
Anti-Inflammatory Reliever Therapy for Asthma Using Inhaled BudesonideFormoterol As-needed With or Without Maintenance in South African Children A Pragmatic Open Label Phase 3 Randomised Controlled Trial
Status:
NOT_YET_RECRUITING
Status Verified Date:
2024-03
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
AIRSA001
Brief Summary:
This is a Phase 3 single-centre open label randomised controlled trial with two equal sized groups to assess the efficacy of budesonideformoterol 8045 6-11 years and 16045 12-18 years compared to the standard of care in reducing asthma exacerbations over 52 weeks
Children and adolescents with a diagnosis of asthma or newly diagnosed with asthma will be screened for eligibility for enrolment Those who had an asthma exacerbation in the previous year will be randomised 11 to either receive budesonideformoterol inhaler for both symptom relief and for chronic anti- inflammatory maintenance therapy or the standard of care which is separate inhalers for symptom relief short acting bronchodilator salbutamol and chronic maintenance therapy with inhaled corticosteroids beclomethasone or budesonide andor long-acting beta agonists or montelukast as determined by treating physicians All asthma exacerbations and clinichospital admissions will be recorded for the duration of the 52-week follow-up Participants will be followed up at 13 26 39 and 52 weeks The 13- and 39-week visit will be telephonic visits to capture the primary end-point ie asthma exacerbations Adverse events and medication changes data will also be collected
An independent Data and Safety Monitoring Board DSMB will be convened for this study with expertise in asthma and asthma clinical trials The purpose of the DSMB will be to monitor the study for safety and operational futility with pre-defined stopping criteria In addition a Trial Steering Committee TSC will also provide overall supervision of the trial and ensure the trial is delivered in accordance with ICH-GCP The TSC has been established with an independent Chair and include additional independent members including an observer early career researcher Representatives of the Trial Funder NIHR and Sponsor AHRI will be invited to all TSC meetings
Children and adolescents with a diagnosis of asthma or newly diagnosed with asthma will be screened for eligibility for enrolment Those who had an asthma exacerbation in the previous year will be randomised 11 to either receive budesonideformoterol inhaler for both symptom relief and for chronic anti- inflammatory maintenance therapy or the standard of care which is separate inhalers for symptom relief short acting bronchodilator salbutamol and chronic maintenance therapy with inhaled corticosteroids beclomethasone or budesonide andor long-acting beta agonists or montelukast as determined by treating physicians All asthma exacerbations and clinichospital admissions will be recorded for the duration of the 52-week follow-up Participants will be followed up at 13 26 39 and 52 weeks The 13- and 39-week visit will be telephonic visits to capture the primary end-point ie asthma exacerbations Adverse events and medication changes data will also be collected
An independent Data and Safety Monitoring Board DSMB will be convened for this study with expertise in asthma and asthma clinical trials The purpose of the DSMB will be to monitor the study for safety and operational futility with pre-defined stopping criteria In addition a Trial Steering Committee TSC will also provide overall supervision of the trial and ensure the trial is delivered in accordance with ICH-GCP The TSC has been established with an independent Chair and include additional independent members including an observer early career researcher Representatives of the Trial Funder NIHR and Sponsor AHRI will be invited to all TSC meetings
Detailed Description:
Over the last two decades non-communicable diseases NCDs have been rising in sub-Saharan Africa and NCDs are set to overtake communicable maternal neonatal and nutritional diseases combined as the leading cause of mortality in sub-Saharan Africa by 2030 Many NCDs have their roots in childhood with lifestyle changes in combination with an increasing median population age in Africa making a further dramatic rise in NCDs in Africas near future highly likely The World Health Organization WHO now considers the prevention and control of NCDs as an urgent development issue and essential to the achievement of the Sustainable Development Goals SDG and this can only be achieved with childhood interventions The 2018 WHO report on NCDs reported 38 million deaths annually from non-communicable respiratory diseases asthma and chronic obstructive pulmonary disease with 78 of deaths in low-income and middle-income countries LMICs Asthma morbidity and mortality are preventable with inhaled therapies-however there is lack of evidence on how to deliver these in an affordable and effective way
The WHO highlights asthma as an under-appreciated cause of poverty in LMICs that retards economic and social development erodes the health and well-being of those affected and has a negative impact on families and societies Asthma aggravates poverty and poverty aggravates asthma Children miss out on education adults lose days at work and the costs of drugs emergency visits and hospitalization are major financial burdens not only for individualsfamilies but also for struggling health systems
In South Africa asthma is the most common NCD in childhood affecting 1 in 5 children with a prevalence of asthma symptoms at 21 in adolescence Despite the availability of asthma medicines in the Essential Medicines List asthmatic children report having severe asthma symptoms in over 50 of those with asthma South Africa still reports the fourth highest mortality rate globally The core to asthma management includes use of chronic use of anti-inflammatory inhaled corticosteroids to address the inflammatory process in the airways maintenance and bronchodilators relievers for relief of the bronchospasm Many studies have shown that asthma mortality is linked to poor use of anti-inflammatory inhaler treatment and over-reliance on short- acting β2 bronchodilator reliever therapy to treat asthma exacerbations In many LMICs including South Africa the use of controller treatment use of anti-inflammatory inhalers is limited with only 40 of people with severe asthma symptoms using regular ICS for chronic asthma treatment but with over 89 using their short-acting β2 agonists There is a large body of evidence showing that overuse of SABAs is linked with asthma mortality and poorer outcomes
The combination treatment with budesonideformoterol for the management of asthma has transformed asthma treatment in high-income countries HIC where it is recommended in the very first step of asthma treatment as both an anti-inflammatory and reliever therapy With the as needed use of budesonideformoterol asthmatics benefit from the additional dose of a maintenance anti-inflammatory dose which improves symptom control and reduces exacerbations This approach has not been adopted in many LMICs related to access to budesonideformoterol and its cost and therefore people in LMICs are relegated to use of Track 2 of Global Initiative of Asthma GINA treatment which still suggests the use of separate anti-inflammatory and reliever inhalers
To address this gap a large body of randomized controlled clinical trial evidence SYGMA Novel START PRACTICAL and several trials of SMART have shown that use of budesonideformoterol as needed for exacerbations and for long-term controller treatment compared to separate inhaled corticosteroid and short-acting bronchodilators reduces the number of asthma exacerbations and improves quality of life The trials have though been limited in that there is no data on the cost-effectiveness of this approach in lower resourced settings and limited data from small studies participant numbers 100 of this approach in children 6-11 years of age Based on this the approach of using budesonideformoterol has not been recommended by the Global Initiative of Asthma GINA strategy for global asthma management in Step 1 and 2 of treatment in children 6-11 years of age both in HIC and LMICs but rather on the higher steps of asthma treatment where symptoms are more severe
The investigators therefore propose in a randomized controlled trial to assess the efficacy of budesonideformoterol compared to the standard of care separate inhaled corticosteroid and bronchodilator inhaler approach to prevent asthma exacerbations improve asthma control and quality of life and to also assess the cost-effectiveness of budesonideformoterol compared to standard of care in children and adolescents in South Africa The data will be novel as the investigators will for the first time include a large number of children in a clinical trial comparing the two approaches to provide definitive evidence of the efficacy and cost-effectiveness of this approach in children and adolescents
The WHO highlights asthma as an under-appreciated cause of poverty in LMICs that retards economic and social development erodes the health and well-being of those affected and has a negative impact on families and societies Asthma aggravates poverty and poverty aggravates asthma Children miss out on education adults lose days at work and the costs of drugs emergency visits and hospitalization are major financial burdens not only for individualsfamilies but also for struggling health systems
In South Africa asthma is the most common NCD in childhood affecting 1 in 5 children with a prevalence of asthma symptoms at 21 in adolescence Despite the availability of asthma medicines in the Essential Medicines List asthmatic children report having severe asthma symptoms in over 50 of those with asthma South Africa still reports the fourth highest mortality rate globally The core to asthma management includes use of chronic use of anti-inflammatory inhaled corticosteroids to address the inflammatory process in the airways maintenance and bronchodilators relievers for relief of the bronchospasm Many studies have shown that asthma mortality is linked to poor use of anti-inflammatory inhaler treatment and over-reliance on short- acting β2 bronchodilator reliever therapy to treat asthma exacerbations In many LMICs including South Africa the use of controller treatment use of anti-inflammatory inhalers is limited with only 40 of people with severe asthma symptoms using regular ICS for chronic asthma treatment but with over 89 using their short-acting β2 agonists There is a large body of evidence showing that overuse of SABAs is linked with asthma mortality and poorer outcomes
The combination treatment with budesonideformoterol for the management of asthma has transformed asthma treatment in high-income countries HIC where it is recommended in the very first step of asthma treatment as both an anti-inflammatory and reliever therapy With the as needed use of budesonideformoterol asthmatics benefit from the additional dose of a maintenance anti-inflammatory dose which improves symptom control and reduces exacerbations This approach has not been adopted in many LMICs related to access to budesonideformoterol and its cost and therefore people in LMICs are relegated to use of Track 2 of Global Initiative of Asthma GINA treatment which still suggests the use of separate anti-inflammatory and reliever inhalers
To address this gap a large body of randomized controlled clinical trial evidence SYGMA Novel START PRACTICAL and several trials of SMART have shown that use of budesonideformoterol as needed for exacerbations and for long-term controller treatment compared to separate inhaled corticosteroid and short-acting bronchodilators reduces the number of asthma exacerbations and improves quality of life The trials have though been limited in that there is no data on the cost-effectiveness of this approach in lower resourced settings and limited data from small studies participant numbers 100 of this approach in children 6-11 years of age Based on this the approach of using budesonideformoterol has not been recommended by the Global Initiative of Asthma GINA strategy for global asthma management in Step 1 and 2 of treatment in children 6-11 years of age both in HIC and LMICs but rather on the higher steps of asthma treatment where symptoms are more severe
The investigators therefore propose in a randomized controlled trial to assess the efficacy of budesonideformoterol compared to the standard of care separate inhaled corticosteroid and bronchodilator inhaler approach to prevent asthma exacerbations improve asthma control and quality of life and to also assess the cost-effectiveness of budesonideformoterol compared to standard of care in children and adolescents in South Africa The data will be novel as the investigators will for the first time include a large number of children in a clinical trial comparing the two approaches to provide definitive evidence of the efficacy and cost-effectiveness of this approach in children and adolescents
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
False
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
False
Is an FDA AA801 Violation?:
None