Optimization of Seasonal Malaria Chemoprevention (SMC) Delivery

Anemia Clinical Trial

— SMC  

Official title:

Optimal Delivery of Seasonal Malaria Chemoprevention and Its Effects on the Acquisition of Malaria Immunity

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT02646410
• Other study ID #: 2014-61
• Status: Recruiting
• Phase: N/A
• Start date: August 2014
• Est. completion date: December 2018

Study information

• Verified date: April 2018
• Source: University of Bamako
• Contact: Alassane Dicko, MD
• Email: adicko[@]icermali.org
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 10000
• Est. completion date: December 2018
• Est. primary completion date: December 2018
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 3 Months to 59 Months

Eligibility

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.

Related Conditions & MeSH terms

• Anemia
• Malaria

Intervention

Other:
• FPD+NDOT

• FPD+DOT

• DDD+NDOT
Door to door delivery + non directly observed treatment
• DDD+DOT
Door to door delivery + directly observed treatment

Locations

Country	Name	City	State
Mali	Malaria Research and Training Center	Bamako

Sponsors (1)

Lead Sponsor	Collaborator
University of Bamako

Country where clinical trial is conducted

Mali, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Coverage of SMC	SMC coverage will be defined as proportion of the children who have received the three treatments doses at each of the three rounds of SMC.	1-5 weeks after last round of SMC in Year1
Primary	Incidence of clinical malaria in Year 2	Clinical malaria defined as signs and symptoms suggestive of malaria with positive RDT and/or positive blood smear.	up to 4 weeks after the last round of SMC
Primary	Mortality rate	death	1, 2, 3, 4 years of the intervention
Primary	Hospital admission	Hospitalization	1, 2, 3, 4 years of the intervention
Secondary	malaria parasitemia	Parasite prevalence defined as the proportion of children with a positive malaria blood smear and parasite density	one week before the first round of SMC and 4-6 weeks after the last round of SMC
Secondary	moderate anemia	Prevalence of moderate anemia defined as hemoglobin concentration < 8 g/dL measured by hemoglobin analyzer	one week before the first round of SMC and 4-6 weeks after the last round of SMC
Secondary	immune response to malaria parasite	Cellular and humoral antimalarial immune responses to malaria parasites	one week before the first round of SMC and 4-6 weeks after the last round of SMC
Secondary	molecular markers of resistance to SP + AQ	Frequency of mutations at codons 51, 59, and 108 of the dhfr gene, 437 and 540 of the dhps gene, codon 76 in the P. falciparum chloroquine transporter gene (pfcrt), and codon 86 of the P. falciparum multidrug resistance gene one (pfmdr1).	one week before the first round of SMC and 4-6 weeks after the last round of SMC
Secondary	nutritional status	Prevalence of wasting stunting and underweight as defined by WHO Global database on Child Growth and Malnutrition	one week before the first round of SMC and 4-6 weeks after the last round of SMC
Secondary	Clinical malaria in Year 1	Clinical malaria defined as signs and symptoms suggestive of malaria with positive RDT and/or positive blood smear.	up to 4 weeks after the last round of SMC