Clinical trial NCT02646410: Optimization of Seasonal Malaria Chemoprevention (SMC) Delivery
Official title: Optimal Delivery of Seasonal Malaria Chemoprevention and Its Effects on the Acquisition of Malaria Immunity
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
Conditions: Malaria
Anemia
Keywords: malaria
seasonal malaria chemoprevention
immunity
resistance
sulfadoxine-pyrimethamine
amodiaquine
delivery method
Lead sponsor: University of Bamako
Sponsor class: OTHER
First posted: 2016-01-05
Enrollment: 10000
Sex: ALL
Minimum age (years): 3
Maximum age (years): 59
Standard ages: CHILD
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: FACTORIAL
Primary purpose: PREVENTION

Brief summary: Based in part on the pivotal studies conducted in Mali, SMC was approved by WHO as a policy for malaria control in countries with seasonal malaria transmission such as Mali in March 2012. The goals are to identify the most effective method to deliver SMC, and to obtain more information on the long term impact of SMC on malaria immunity. Our specific aims are 1) to determine the optimal mode (fixed-point (FPD) vs door-to-door delivery (DDD); directly observed treatment (DOT) vs non-DOT (NDOT)) and frequency (3 vs 4 doses per season) of SMC delivery; 2) to compare quantitative measures of immunity in children who do and do not receive SMC. A cluster-randomized design will be sued. The target population will be children aged 3-59 months old in Ouelessebougou district, Mali. In Year 1, villages in four sub-districts will be randomized into four groups (FPD+DOT; FPD+NDOT; DDD+DOT; DDD+NDOT). The optimal mode of delivery will be selected based on the SMC coverage during the first year, and will then be implemented in villages of two additional sub-districts. Villages in these two newly selected sub-districts will be randomized in two groups. Children in the first group will received three rounds of SMC and those in the second group will receive four rounds of SMC to determine the optimal frequency of SMC based on the incidence rate of clinical malaria as measured by passive surveillance. In Year 3, children in the selected sub-districts will received SMC by the optimal delivery system determined in Years 1 -2. A survey will be conducted collect data on mortality and hospital admission and compare these outcomes in areas where SMC was implemented and areas where SMC was not implemented.

Detailed description: Based in part on the pivotal studies conducted in Mali, SMC was approved by WHO as a policy for malaria control in countries with seasonal malaria transmission such as Mali in March 2012. The strategy is a highly cost-effective approach to reduce childhood mortality in these areas. Despite the huge benefit of the SMC on malaria infection and disease, the optimal approach to deliver SMC remains to be determined and there is no data on the long term effect of this strategy on the development of immunity to malaria. While fixed-point delivery (FPD) combined with non directly observed treatment (NDOT) by community health workers is attractive for the SMC implementation, it is need to be evaluated and compared to other mode of delivery. The objectives are to identify the most effective method to deliver SMC, and to obtain information on the long term impact of SMC on malaria immunity. Specifically, i) to determine the optimal mode (fixed-point (FPD) vs door-to-door delivery (DDD); directly observed treatment (DOT) vs. non-DOT (NDOT)) and frequency (3 vs. 4 doses per season) of SMC delivery; ii) to compare quantitative measures of immunity in children who do and do not receive SMC over a three year period.

The design is a cluster-randomized trial over three years. The target population is children aged 3-59 months old living in Ouelessebougou district, Mali. In Year 1, villages in four sub-districts will be randomized into four groups (FPD+DOT; FPD+NDOT; DDD+DOT; DDD+NDOT). The optimal mode of delivery will be selected based on the SMC coverage during the first year, and will then be implemented in villages of two additional sub-districts. Villages in these two newly selected sub-districts will be randomized in two groups. Children in the first group will received three rounds of SMC and those in the second group will receive four rounds of SMC to determine the optimal frequency of SMC based on the incidence rate of clinical malaria as measured by passive surveillance. Children in the four sub-districts selected in Year 1 will continue to receive three rounds of SMC in Year 2 using the optimal mode of delivery. In Year 3, children in the randomly selected sub-districts will received SMC by the optimal delivery system determined in Years 1 -2. Immune responses will be measured and compared between the children receiving SMC to a cohort of children not receiving SMC, to assess the impact of SMC on key antimalarial antibody responses over the three year period using cross-sectional surveys at the beginning and the end of the transmission season.

In Year 3, 4 and 5 surveys will be conducted to collect data on mortality and hospital admissions and compare these outcomes in areas where SMC was implemented and areas where SMC was not implemented.

Eligibility criteria: Inclusion Criteria:

Age \>= 3 months \& \< 60 months

Exclusion Criteria:

* severe, chronic illness
* known allergy to one of the study drugs (SP or AQ)
* known HIV positive subjects using Cotrimoxazole.

Primary outcomes:
measure: Coverage of SMC
timeFrame: 1-5 weeks after last round of SMC in Year1
measure: Incidence of clinical malaria in Year 2
timeFrame: up to 4 weeks after the last round of SMC
measure: Mortality rate
timeFrame: 1, 2, 3, 4 years of the intervention
measure: Hospital admission
timeFrame: 1, 2, 3, 4 years of the intervention
Secondary outcomes:
measure: malaria parasitemia
timeFrame: one week before the first round of SMC and 4-6 weeks after the last round of SMC
measure: moderate anemia
timeFrame: one week before the first round of SMC and 4-6 weeks after the last round of SMC
measure: immune response to malaria parasite
timeFrame: one week before the first round of SMC and 4-6 weeks after the last round of SMC
measure: molecular markers of resistance to SP + AQ
timeFrame: one week before the first round of SMC and 4-6 weeks after the last round of SMC
measure: nutritional status
timeFrame: one week before the first round of SMC and 4-6 weeks after the last round of SMC
measure: Clinical malaria in Year 1
timeFrame: up to 4 weeks after the last round of SMC
Other outcomes:
Locations:
city: Bamako
country: Mali
facility: Malaria Research and Training Center
Study officials:
References:
citation: Issiaka D, Barry A, Traore T, Diarra B, Cook D, Keita M, Sagara I, Duffy P, Fried M, Dicko A. Impact of seasonal malaria chemoprevention on hospital admissions and mortality in children under 5 years of age in Ouelessebougou, Mali. Malar J. 2020 Mar 3;19(1):103. doi: 10.1186/s12936-020-03175-y.
citation: Barry A, Issiaka D, Traore T, Mahamar A, Diarra B, Sagara I, Kone D, Doumbo OK, Duffy P, Fried M, Dicko A. Optimal mode for delivery of seasonal malaria chemoprevention in Ouelessebougou, Mali: A cluster randomized trial. PLoS One. 2018 Mar 5;13(3):e0193296. doi: 10.1371/journal.pone.0193296. eCollection 2018.