Clinical trial NCT04864444: Mass Drug Administration of Dihydroartemisinin-piperaquine + Single Low-dose Primaquine to Accelerate Toward Elimination Activities
Official title: Mass Drug Administration With Dihydroartemisinin-piperaquine and Primaquine to Reduce Malaria in a Moderate-low Transmission Setting in Senegal: A Cluster Randomized Controlled Trial
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Malaria,Falciparum
Malaria
Keywords: Antimalarials
Mass drug administration
Dihydroartemsinin
Piperaquine
Primaquine
Parasitic Diseases
Lead sponsor: University of California, San Francisco
Sponsor class: OTHER
Collaborators: name: L'université de Thiès
name: Programme National de Lutte contre le Paludisme (PNLP), Senegal
name: Population Services International
name: Centers for Disease Control and Prevention
name: US President's Malaria Initiative
First posted: 2021-04-28
Enrollment: 10715
Sex: ALL
Minimum age (years): 3
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: This is a two-arm cluster randomized controlled trial. A total of 60 villages will be randomized to receive the intervention (three rounds of MDA with DHA-PPQ + SLD-PQ) or control (standard malaria control measures, including SMC) at a ratio of 1:1
Primary purpose: PREVENTION

Brief summary: This community-based cluster randomized controlled trial aims to evaluate the effectiveness of time-limited, community-wide mass drug administration (MDA) with dihydroartemisinin-piperaquine (DHA-PPQ) and single low-dose primaquine (SLD-PQ) on Plasmodium falciparum transmission compared to standard-of-care seasonal malaria chemoprevention (SMC). The study will be conducted in a moderate-to-low malaria transmission setting of Senegal with optimized malaria control measures (e.g., proactive community case management and piperonyl butoxide pyrethroid long-lasting insecticidal nets (PBO LLINS)).

Detailed description: Over the past two decades in Senegal, the scale-up of malaria control measures \[e.g., access to prompt testing and case management, LLINs, and SMC\] has led to a 78% reduction in malaria incidence. However, gains have not been uniform, with lower transmission areas in the north implementing pre-elimination activities and higher transmission areas in the south implementing control interventions (including SMC). The purpose of this study is determine whether MDA will be able to rapidly reduce malaria incidence in areas of moderate-to-low malaria transmission of southern Senegal (where control activities are ongoing) so that the program can reorient their malaria strategy to implement elimination interventions in these settings.

The study aims to deliver three rounds of community-wide MDA with DHA-PPQ + SLD-PQ. MDA drugs will be administered over the course of three days. All three doses of DHA-PPQ will be given via supervised DOT (as per administration of SMC by national malaria guidelines) through a door-to-door approach.

The research objectives are:

1. To evaluate the impact of three rounds of MDA with DHA-PPQ and SLD-PQ on village-level confirmed malaria case incidence, malaria prevalence, and on reaching a target malaria incidence of \<5 cases per 1000 person-years compared to standard-of-care SMC when provided in the context of optimized control (proactive community case management + PBO LLINs).
2. To determine the cost, coverage, operational feasibility, and acceptability of three rounds of MDA with DHA-PPQ and SLD-PQ compared to standard-of-care SMC.
3. To determine the impact of three rounds of MDA with DHA-PPQ and SLD-PQ compared to standard-of-care SMC on parasite population dynamics and drug resistance.

Eligibility criteria: Inclusion Criteria:

* Age ≥3 months
* Willingness to comply with trial procedures and written informed consent to be obtained at the beginning of the study

Exclusion Criteria:

* Severe illness or self-reported chronic illness (e.g., HIV, tuberculosis, heart/liver/kidney disease, and severe malnutrition)
* Known hypersensitivity to study drug

Additional exclusion criteria for DHA-PPQ:

* First trimester pregnancy assessed by history and/or urine pregnancy testing
* Concurrent artemisinin-based combination therapy (ACT) use
* Taking drugs that influence cardiac function or prolong QTc interval

Additional exclusion criteria for PQ:

* Pregnancy (any trimester) or currently breastfeeding an infant \<6 months of age assessed by history and/or urine pregnancy testing
* \<2 years of age

Primary outcomes:
measure: Difference in village-level confirmed incidence of malaria
timeFrame: one year post-MDA
Secondary outcomes:
measure: Difference in parasite prevalence by microscopy during high malaria transmission season
timeFrame: 3 months after last round of MDA
measure: Difference in parasite prevalence by polymerase chain reaction (PCR) during high malaria transmission season
timeFrame: 3 months after last round of MDA
measure: Difference in serological markers of recent infection
timeFrame: 3 months after last round of MDA
measure: Difference in the change in prevalence of drug resistance markers
timeFrame: Change from baseline to endline; 1 year period
measure: Difference in the change in prevalence of parasite population dynamics
timeFrame: Change from baseline to endline; 1 year period
Other outcomes:
measure: Population coverage of MDA
timeFrame: Up to 18 weeks
measure: Difference in the cost-effectiveness of MDA versus SMC
timeFrame: Up to 24 months
Locations:
city: Tambacounda
country: Senegal
facility: Tambacounda Health District
Study officials:
affiliation: Université de Thiès
name: Jean Louis Ndiaye, MD PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: University of California, San Francisco
name: Michelle Hsiang, MD MSc
role: PRINCIPAL_INVESTIGATOR
affiliation: Senegal Programme National de Lutte contre le Paludisme (PNLP)
name: Doudou Séne, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: US President's Malaria Initiative/CDC
name: Katharine Sturm-Ramirez, PhD
role: PRINCIPAL_INVESTIGATOR
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