Ignite Creation Date:
2024-05-06 @ 7:15 PM
Last Modification Date:
2024-10-26 @ 3:03 PM
Study NCT ID:
NCT05946642
Status:
RECRUITING
Last Update Posted:
2023-11-22
First Post:
2023-06-27
Brief Title:
Innovative Intermittent Preventive Treatment Approaches to Reduce Malaria Burden in School-age Children in Burkina Faso
Sponsor:
Malaria Consortium
Organization:
Malaria Consortium
Study Overview
Official Title:
Clinical Trial to Evaluate Efficacy and Safety of SulfadoxinePyrimethamine-Amodiaquine and Dihydroartemsinin-Piperaquine Plus Ivermectin Administered Monthly as Intermittent Preventive Treatment in School-aged Children in Burkina Faso
Status:
RECRUITING
Status Verified Date:
2023-07
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:
BF-IPTsc
Brief Summary:
This will be an open label cluster randomized study with two active intervention and one control arm A cluster will be defined as a selected village One district implementing seasonal malaria chemoprevention SMC will be selected and six villages will be randomly selected in this district These six villages will be randomly allocated to each of the three study arms 1 Arm 1 will receive IPTsc with sulphadoxine-pyrimethamine plus amodiaquine SPAQ and 2 Arm 2 will receive dihydroartemisinin-piperaquine DP plus Ivermectin IVM all given monthly during the transmission season and 3 Control Arm which will have standard malaria control measures including case management and vector control measures as applicable
Detailed Description:
The overall objective of this study is to evaluate the efficacy safety implementation feasibility and cost-effectiveness of IPTsc with sulphadoxine-pyrimethamine plus amodiaquine SPAQ and dihydroartemisinin-piperaquine DP plus Ivermectin IVM for malaria prevention in this population
Specific Objectives include the following
1 To evaluate the impact of IPTsc with SPAQ and DP plus IVM administered monthly during the transmission season on malaria burden 3 To understand the feasibility of and identify the most socially acceptable and sustainable way of achieving and maintaining high coverage of IPTsc with SPAQ and DP plus IVM 4 To determine the immunological and molecular epidemiological changes that occur in a nested population following IPTsc 5 To determine the cost and cost-effectiveness of these IPTsc approaches compared to existing standard malaria control interventions
This will be an open label cluster randomized study with two active intervention and one control arm A cluster will be defined as a selected village One SMC implementing district will be selected 6 villages will be randomly selected and allocated to each of the three study arms 1 Arm 1 to receive IPTsc with SPAQ and 2 Arm 2 to receive DP and IVM all given monthly during the transmission season and 3 Control Arm standard malaria control measures including case management and vector control measures as applicable This will result in a total of 18 clusters villages with 6 randomized to either of the three study arms All children meeting eligibility criteria will be eligible to participate and to receive the IPTsc interventions These criteria will include residence in the selected villages willingness of parentguardian to provide written informed consent and written assent by children no known allergy to or contraindication to study medication no history of cardiac conditions or long QT syndrome and no current use of medications known to prolong QT interval Participants will receive the study drugs over one transmission season monthly for five months DP will be available as tablets of 32040mg and 16020mg piperaquinedihydroartemisinin per tablet Administration of a full course of DP will be done as per manufacturers guidelines once daily for 3 days and according to body weight DP will be taken orally with water and without food IVM will be available as tablets of 3mg or 6mg strength It will be given at 300-400μgkgday over 3 days to the nearest whole tablet IVM will also be taken on an empty stomach with water The three-day SPAQ treatment course will consist of a co-blistered pack of dispersible tablets of sulfadoxine-pyrimethamine SP given on day 1 plus dispersible tablets of amodiaquine AQ which will be given once a day for 3 days SPAQ will be dosed based on the childs age The full 3-day course of all IPTsc medications will be administered each month under directly observed therapy DOT The controlstandard of care arm will continue with the standard malaria control interventions provided by the malaria programme including case management and long-lasting insecticidal nets LLINs
Study follow-up evaluations will be done using a system of passive case detection PCD established in the selected villages with the existing health facilities and community health workers and one cross sectional survey during the peak of the transmission season to determine prevalence of clinical malaria and malaria parasite prevalence Sample size for this cross-sectional survey will be determined assuming study power of 80 an alpha of 005 and an intra-cluster correlation coefficient of 001 A total of 50 children aged 5 to 15 years in each villagecluster 300 per study arms - total 900 children will be required to detect a difference of at least a 10-point reduction by either of the two IPTsc approaches in malaria prevalence from the 17 national estimate Children will also be evaluated retrospectively for any illness and prospectively for adverse events In addition a convenience sample of 20 participants in the 5 years age group and 20 participants in the 15years age group will be randomly selected from each villagecluster 240 per study arm total 720 participants for enrollment into the cross sectional study to assess malaria prevalence in these age groups not receiving IPTsc as a measure of the potential impact of IPTsc on the general population malaria burden These participants will be household contacts of children in the 5 - 15-year age group The investigators will also conduct a process evaluation alongside the main clinical trial to track the standard malaria control interventions including quality of case management practices including availability of diagnostics and antimalarial drug stock levels and LLINIRS coverage and utilization rates throughout the study period in all study arms The mosquitocidal effect of IVM will be assessed by determining mosquito densities in households of selected participants Mosquitoes will be collected using CDC light traps in 4 randomly selected households in each arm 12 in total using a list randomly generated from the cluster database monthly for 4 nights each month for the duration of transmission season Sporozoïte rates and mosquito densities will be compared across the different study arms As IVM also has a broad range of activity against numerous species of endo- and ectoparasites the investigators will measure its impact on common ectoparasitic infections including head lice and scabies Reducing these infections would be an important auxiliary benefit of IVM Dry blood spots will also be collected and stored for future immunological and molecular studies The investigators will conduct a qualitative study to run alongside the main trial to investigate acceptability of IPTsc and the potential feasibility of integrating this intervention into routine health services and school or community systems This will be done through key informant interviews in-depth interviews focus group discussions and ethnographic observations in a randomly selected number of children school administrators and relevant government departments Although high acceptability of intermittent preventive treatment for other target groups has been previously reported theres limited literature on acceptability in older children and adolescents The investigators aim to identify best practices and challenges for integrating health programmes into existing programmes in Burkina Faso and other similar low resource settings and to identify potential intervention methods and content to support future IPTsc scale-up Post-intervention follow up will be done to assess for any rebound phenomenon using standard methodologies
Laboratory Analysis The following Lab evaluations will be done Rapid Diagnostic Test RDTs will be performed according to the directions provided for the specific tests using the blood transfer device and reagent provided by the manufacturer Microcopy - thick blood smears will be stained with 2 Giemsa for 30 minutes and will be evaluated for the presence of parasitaemia asexual forms only and gametocytes Parasite and gametocyte densities will be calculated from thick blood smears by counting the number of asexual parasites and gametocytes respectively per 200 leukocytes or per 500 if the count is less than 10 parasites or gametocytes per 200 leukocytes assuming a leukocyte count of 8000µl A thick blood smear will be considered negative when the examination of 100 high power fields does not reveal asexual parasites or gametocytes For quality control all slides will be read by a second microscopist and a third reviewer will settle any discrepant Molecular studies samples will be analyzed with varATS qPCR using 5μL of extracted DNA per assay The sensitivity of the assay will be approximately 002 parasitesμL of blood Hemoglobin measurement will be done using a battery-operated portable HemoCue analyzer HemoCue Anglom Sweden Entomological monitoring - mosquitoes will be collected using CDC light traps in 3 randomly selected households in each arm 12 in total using a list randomly generated from the cluster database monthly for the duration of one transmission season Mosquito densities will be determined and Sporozoïtes will be identified using an enzyme linked immunosorbent assay ELISA
Markers of drug resistance - the investigators will determine the baseline prevalences of SP AQ Dihydroartemisinin and Piperaquine resistance and any increase in resistance prevalence after one annual round of IPTsc as assessed via molecular markers in the population Prevalence of the following mutations will be determined over time dhfr dhps pfcrt pfmdr1 K13 and pfplm2 Serological Assays immunological studies will be done at baseline and post intervention
Malaria prevalence will be determined by technicians blinded to the treatment arms Mosquitoes will be sampled using light-traps indoors a sampling method that is not affected by operator bias Mosquito analysis will be done in the laboratory by individuals blinded to the origin of samples Data on potential confounding factors eg LLIN coverage will be collected and used for adjustments in the analysis
Qualitative research methods will assess potential sources of social desirability bias and potential factors for residual confounding
Adverse Event Monitoring adverse event monitoring will focus on severe adverse events SAEs and suspected unexpected adverse events SUSARs The prevalence and incidence of SAEs in children enrolled in the different intervention arms will be determined
Specific Objectives include the following
1 To evaluate the impact of IPTsc with SPAQ and DP plus IVM administered monthly during the transmission season on malaria burden 3 To understand the feasibility of and identify the most socially acceptable and sustainable way of achieving and maintaining high coverage of IPTsc with SPAQ and DP plus IVM 4 To determine the immunological and molecular epidemiological changes that occur in a nested population following IPTsc 5 To determine the cost and cost-effectiveness of these IPTsc approaches compared to existing standard malaria control interventions
This will be an open label cluster randomized study with two active intervention and one control arm A cluster will be defined as a selected village One SMC implementing district will be selected 6 villages will be randomly selected and allocated to each of the three study arms 1 Arm 1 to receive IPTsc with SPAQ and 2 Arm 2 to receive DP and IVM all given monthly during the transmission season and 3 Control Arm standard malaria control measures including case management and vector control measures as applicable This will result in a total of 18 clusters villages with 6 randomized to either of the three study arms All children meeting eligibility criteria will be eligible to participate and to receive the IPTsc interventions These criteria will include residence in the selected villages willingness of parentguardian to provide written informed consent and written assent by children no known allergy to or contraindication to study medication no history of cardiac conditions or long QT syndrome and no current use of medications known to prolong QT interval Participants will receive the study drugs over one transmission season monthly for five months DP will be available as tablets of 32040mg and 16020mg piperaquinedihydroartemisinin per tablet Administration of a full course of DP will be done as per manufacturers guidelines once daily for 3 days and according to body weight DP will be taken orally with water and without food IVM will be available as tablets of 3mg or 6mg strength It will be given at 300-400μgkgday over 3 days to the nearest whole tablet IVM will also be taken on an empty stomach with water The three-day SPAQ treatment course will consist of a co-blistered pack of dispersible tablets of sulfadoxine-pyrimethamine SP given on day 1 plus dispersible tablets of amodiaquine AQ which will be given once a day for 3 days SPAQ will be dosed based on the childs age The full 3-day course of all IPTsc medications will be administered each month under directly observed therapy DOT The controlstandard of care arm will continue with the standard malaria control interventions provided by the malaria programme including case management and long-lasting insecticidal nets LLINs
Study follow-up evaluations will be done using a system of passive case detection PCD established in the selected villages with the existing health facilities and community health workers and one cross sectional survey during the peak of the transmission season to determine prevalence of clinical malaria and malaria parasite prevalence Sample size for this cross-sectional survey will be determined assuming study power of 80 an alpha of 005 and an intra-cluster correlation coefficient of 001 A total of 50 children aged 5 to 15 years in each villagecluster 300 per study arms - total 900 children will be required to detect a difference of at least a 10-point reduction by either of the two IPTsc approaches in malaria prevalence from the 17 national estimate Children will also be evaluated retrospectively for any illness and prospectively for adverse events In addition a convenience sample of 20 participants in the 5 years age group and 20 participants in the 15years age group will be randomly selected from each villagecluster 240 per study arm total 720 participants for enrollment into the cross sectional study to assess malaria prevalence in these age groups not receiving IPTsc as a measure of the potential impact of IPTsc on the general population malaria burden These participants will be household contacts of children in the 5 - 15-year age group The investigators will also conduct a process evaluation alongside the main clinical trial to track the standard malaria control interventions including quality of case management practices including availability of diagnostics and antimalarial drug stock levels and LLINIRS coverage and utilization rates throughout the study period in all study arms The mosquitocidal effect of IVM will be assessed by determining mosquito densities in households of selected participants Mosquitoes will be collected using CDC light traps in 4 randomly selected households in each arm 12 in total using a list randomly generated from the cluster database monthly for 4 nights each month for the duration of transmission season Sporozoïte rates and mosquito densities will be compared across the different study arms As IVM also has a broad range of activity against numerous species of endo- and ectoparasites the investigators will measure its impact on common ectoparasitic infections including head lice and scabies Reducing these infections would be an important auxiliary benefit of IVM Dry blood spots will also be collected and stored for future immunological and molecular studies The investigators will conduct a qualitative study to run alongside the main trial to investigate acceptability of IPTsc and the potential feasibility of integrating this intervention into routine health services and school or community systems This will be done through key informant interviews in-depth interviews focus group discussions and ethnographic observations in a randomly selected number of children school administrators and relevant government departments Although high acceptability of intermittent preventive treatment for other target groups has been previously reported theres limited literature on acceptability in older children and adolescents The investigators aim to identify best practices and challenges for integrating health programmes into existing programmes in Burkina Faso and other similar low resource settings and to identify potential intervention methods and content to support future IPTsc scale-up Post-intervention follow up will be done to assess for any rebound phenomenon using standard methodologies
Laboratory Analysis The following Lab evaluations will be done Rapid Diagnostic Test RDTs will be performed according to the directions provided for the specific tests using the blood transfer device and reagent provided by the manufacturer Microcopy - thick blood smears will be stained with 2 Giemsa for 30 minutes and will be evaluated for the presence of parasitaemia asexual forms only and gametocytes Parasite and gametocyte densities will be calculated from thick blood smears by counting the number of asexual parasites and gametocytes respectively per 200 leukocytes or per 500 if the count is less than 10 parasites or gametocytes per 200 leukocytes assuming a leukocyte count of 8000µl A thick blood smear will be considered negative when the examination of 100 high power fields does not reveal asexual parasites or gametocytes For quality control all slides will be read by a second microscopist and a third reviewer will settle any discrepant Molecular studies samples will be analyzed with varATS qPCR using 5μL of extracted DNA per assay The sensitivity of the assay will be approximately 002 parasitesμL of blood Hemoglobin measurement will be done using a battery-operated portable HemoCue analyzer HemoCue Anglom Sweden Entomological monitoring - mosquitoes will be collected using CDC light traps in 3 randomly selected households in each arm 12 in total using a list randomly generated from the cluster database monthly for the duration of one transmission season Mosquito densities will be determined and Sporozoïtes will be identified using an enzyme linked immunosorbent assay ELISA
Markers of drug resistance - the investigators will determine the baseline prevalences of SP AQ Dihydroartemisinin and Piperaquine resistance and any increase in resistance prevalence after one annual round of IPTsc as assessed via molecular markers in the population Prevalence of the following mutations will be determined over time dhfr dhps pfcrt pfmdr1 K13 and pfplm2 Serological Assays immunological studies will be done at baseline and post intervention
Malaria prevalence will be determined by technicians blinded to the treatment arms Mosquitoes will be sampled using light-traps indoors a sampling method that is not affected by operator bias Mosquito analysis will be done in the laboratory by individuals blinded to the origin of samples Data on potential confounding factors eg LLIN coverage will be collected and used for adjustments in the analysis
Qualitative research methods will assess potential sources of social desirability bias and potential factors for residual confounding
Adverse Event Monitoring adverse event monitoring will focus on severe adverse events SAEs and suspected unexpected adverse events SUSARs The prevalence and incidence of SAEs in children enrolled in the different intervention arms will be determined
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?:
None
Is an FDA AA801 Violation?:
None