Clinical trial NCT02329301: Mass Drug Administration With Dihydroartemisinin + Piperaquine for Reducing Malaria in Southern Zambia
Official title: Assessing the Effectiveness of Mass Drug Administration (MDA) With Dihydroartemisinin + Piperaquine for Reducing Malaria Parasite Infection Prevalence and Incidence in Southern Province Zambia
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Malaria
Malaria, Falciparum
Keywords: malaria
malaria, falciparum
antimalarials
Lead sponsor: PATH
Sponsor class: OTHER
Collaborators: name: Ministry of Health, Zambia
name: Minister of Community Development, Mother and Child Health, Zambia
name: Tulane University
First posted: 2014-12-31
Enrollment: 2430
Sex: ALL
Minimum age (years): 3
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: To quantify the relative effectiveness, cost, and cost-effectiveness of fMDA and MDA with DHAp against no mass treatment for reducing P. falciparum parasite prevalence, confirmed OPD malaria case incidence and cohort infection incidence in areas of high and low malaria transmission and in a program-relevant manner that will permit adoption and adaptation for wider-scale deployment.

Detailed description: To quantify the relative effectiveness, cost, and cost-effectiveness of fMDA and MDA with DHAp against no mass treatment for reducing P. falciparum parasite prevalence, confirmed OPD malaria case incidence and cohort infection incidence in areas of high and low malaria transmission and in a program-relevant manner that will permit adoption and adaptation for wider-scale deployment.

In areas stratified by high and low malaria transmission, are 2 rounds of fMDA and MDA with DHAp more effective than no mass treatment (current standard of care) at reducing malaria parasite prevalence, health facility confirmed case incidence and community infection incidence over a 12 month period

* Null hypothesis (H0): There is no benefit of 2 rounds of fMDA or MDA with DHAp over current standard of care (national policy of case management) at reducing malaria parasite prevalence, health facility confirmed case incidence and community infection incidence over a 12 month period.
* Research hypothesis (HR): 2 rounds of fMDA and MDA with DHAp during the low transmission season will be significantly more effective than no mass treatment (standard of care) at reducing malaria parasite prevalence, health facility confirmed case incidence and community infection incidence over a 12 month period.

The research objectives are:

1. In areas stratified by high and low malaria transmission, evaluate the relative effectiveness of 2 rounds of fMDA with DHAp (fMDA arm), 2 rounds of community-wide MDA with DHAp (MDA arm) and no mass treatment (current standard of care - control arm) on the outcomes of reducing malaria parasite prevalence, confirmed case incidence and infection incidence over a 12 month period;
2. In areas stratified by high and low malaria transmission, assess the percent of health facility catchment areas (HFCA) with fMDA and MDA interventions that are able to reduce annual confirmed malaria case incidence to below 25 cases per 1,000 catchment population, which would permit the transition to a passive case investigation approach for malaria elimination;
3. Quantify the population coverage of the fMDA and MDA interventions in the study areas, including the identification of systematic barriers to achieving high coverage, under best programmatic efforts using directly observed treatment (DOT) to assure full treatment;
4. Assess and compare the cost and cost-effectiveness of fMDA and MDA with DHAp to no mass treatment in areas of high and low transmission;
5. Assess the adherence of taking a full course of DHAp by the fMDA and MDA interventions in areas of high and low transmission, under best programmatic efforts using DOT to assure full treatment;
6. Assess the clearance of asexual stage parasites at day 7 following the administration of DHAp under the best programmatic efforts using DOT to assure full treatment; and
7. Assess the acceptability of participating in the fMDA and MDA interventions among community members and health care leaders in areas of high and low transmission.

The study population includes:

Population of \~560,000 people in \~112,000 households in 60 health facility catchment areas near Lake Kariba in Southern Province.

Cluster randomized controlled trial in high and low transmission areas will be used to evaluate the fMDA and MDA interventions against current standard of care for the effect on population-wide parasite prevalence (RDT and more sensitive assay), community cohort infection incidence and routinely collected confirmed malaria case incidence.

The primary outcomes are:

1. Parasite prevalence during the high transmission season among children \<6 years old (excluding neonates \<1 month)
2. Pf infection incidence rate among individuals ≥3 months
3. Total and confirmed outpatient (OPD) malaria case incidence and inpatient (IPD) malaria case incidence among all ages
4. RDT test positivity rate from fMDA and MDA interventions (plus control group)
5. Population coverage of the fMDA and MDA interventions at each round

The entire population will be included in the study; interventions will be grouped/assigned randomly according to health facility catchment area (n= 60 health facilities), matched on potential confounding factors. Household surveys in the high transmission season before and after the interventions will be used for ascertaining malaria parasite prevalence. A longitudinal cohort will be used for ascertaining the infection incidence rate. The health system rapid reporting system will be used for ascertaining confirmed malaria case incidence.

Eligibility criteria: Inclusion Criteria:

* anyone not excluded and consenting

Exclusion Criteria:

* contraindications from manufacturer for medications including currently taking haloperidol, artane, Phenergan (Promethazine), chlorpromazine, erythromycin, Azithromycin, clarithromycin, Ketoconazole, fluconazole, mefloquine (as prophylaxis), lumefantrine (in Coartem), quinine, Septrin
* anyone seriously ill
* currently taking antimalarial medicines
* allergy to artemisinin drugs
* pregnant women in first trimester
* children under 3 months of age
* reported heart condition

Primary outcomes:
measure: Parasite prevalence during the high transmission season among children <6 years old (excluding neonates <1 month)
timeFrame: For up to 12 months
measure: P.falciparum infection incidence rate among individuals ≥3 months
timeFrame: For up to 12 months
Secondary outcomes:
measure: Total and confirmed outpatient (OPD) malaria case incidence and inpatient (IPD) malaria case incidence among all ages
timeFrame: For up to 48 months (including retrospectively)
measure: Malaria rapid diagnostic test test positivity rate from focal mass drug administration (fMDA) and mass drug administration (MDA) interventions (plus control group)
timeFrame: For up to 10 months
Other outcomes:
measure: Population coverage of the fMDA and MDA interventions at each round
timeFrame: For up to 4 months
Locations:
city: Choma
country: Zambia
facility: Southern province medical office
state: Southern
Study officials:
affiliation: PATH
name: John M Miller, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Eisele TP, Silumbe K, Finn T, Chalwe V, Kamuliwo M, Hamainza B, Moonga H, Bennett A, Yukich J, Keating J, Steketee RW, Miller JM. Assessing the effectiveness of household-level focal mass drug administration and community-wide mass drug administration for reducing malaria parasite infection prevalence and incidence in Southern Province, Zambia: study protocol for a community randomized controlled trial. Trials. 2015 Aug 13;16:347. doi: 10.1186/s13063-015-0862-3.
citation: Eisele TP, Bennett A, Silumbe K, Finn TP, Chalwe V, Kamuliwo M, Hamainza B, Moonga H, Kooma E, Chizema Kawesha E, Yukich J, Keating J, Porter T, Conner RO, Earle D, Steketee RW, Miller JM. Short-term Impact of Mass Drug Administration With Dihydroartemisinin Plus Piperaquine on Malaria in Southern Province Zambia: A Cluster-Randomized Controlled Trial. J Infect Dis. 2016 Dec 15;214(12):1831-1839. doi: 10.1093/infdis/jiw416.
citation: Alonso PL. The Role of Mass Drug Administration of Antimalarials. Am J Trop Med Hyg. 2020 Aug;103(2_Suppl):1-2. doi: 10.4269/ajtmh.20-0729. No abstract available.
citation: Eisele TP, Bennett A, Silumbe K, Finn TP, Porter TR, Chalwe V, Hamainza B, Moonga H, Kooma E, Chizema Kawesha E, Kamuliwo M, Yukich JO, Keating J, Schneider K, Conner RO, Earle D, Slutsker L, Steketee RW, Miller JM. Impact of Four Rounds of Mass Drug Administration with Dihydroartemisinin-Piperaquine Implemented in Southern Province, Zambia. Am J Trop Med Hyg. 2020 Aug;103(2_Suppl):7-18. doi: 10.4269/ajtmh.19-0659.
citation: Yukich JO, Scott C, Silumbe K, Larson BA, Bennett A, Finn TP, Hamainza B, Conner RO, Porter TR, Keating J, Steketee RW, Eisele TP, Miller JM. Cost-Effectiveness of Focal Mass Drug Administration and Mass Drug Administration with Dihydroartemisinin-Piperaquine for Malaria Prevention in Southern Province, Zambia: Results of a Community-Randomized Controlled Trial. Am J Trop Med Hyg. 2020 Aug;103(2_Suppl):46-53. doi: 10.4269/ajtmh.19-0661.
citation: Finn TP, Porter TR, Moonga H, Silumbe K, Daniels RF, Volkman SK, Yukich JO, Keating J, Bennett A, Steketee RW, Miller JM, Eisele TP. Adherence to Mass Drug Administration with Dihydroartemisinin-Piperaquine and Plasmodium falciparum Clearance in Southern Province, Zambia. Am J Trop Med Hyg. 2020 Aug;103(2_Suppl):37-45. doi: 10.4269/ajtmh.19-0667.
citation: Finn TP, Yukich JO, Bennett A, Porter TR, Lungu C, Hamainza B, Chizema Kawesha E, Conner RO, Silumbe K, Steketee RW, Miller JM, Keating J, Eisele TP. Treatment Coverage Estimation for Mass Drug Administration for Malaria with Dihydroartemisinin-Piperaquine in Southern Province, Zambia. Am J Trop Med Hyg. 2020 Aug;103(2_Suppl):19-27. doi: 10.4269/ajtmh.19-0665.
citation: Silumbe K, Finn TP, Jennings T, Sikombe C, Chiyende E, Hamainza B, Chizema Kawesha E, Eisele TP, Earle D, Steketee RW, Miller JM. Assessment of the Acceptability of Testing and Treatment during a Mass Drug Administration Trial for Malaria in Zambia Using Mixed Methods. Am J Trop Med Hyg. 2020 Aug;103(2_Suppl):28-36. doi: 10.4269/ajtmh.19-0663.
citation: Miller JM, Eisele TP, Fraser MS, Lewis MT, Slutsker L, Chizema Kawesha E. Moving from Malaria Burden Reduction toward Elimination: An Evaluation of Mass Drug Administration in Southern Province, Zambia. Am J Trop Med Hyg. 2020 Aug;103(2_Suppl):3-6. doi: 10.4269/ajtmh.19-0669.
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citation: Shah MP, Hwang J, Choi L, Lindblade KA, Kachur SP, Desai M. Mass drug administration for malaria. Cochrane Database Syst Rev. 2021 Sep 29;9(9):CD008846. doi: 10.1002/14651858.CD008846.pub3.