Mass Drug Administration of Dihydroartemisinin-piperaquine + Single Low-dose Primaquine to Accelerate Toward Elimination Activities

Mass Drug Administration With Dihydroartemisinin-piperaquine and Primaquine to Reduce Malaria in a Moderate-low Transmission Setting in Senegal: A Cluster Randomized Controlled Trial

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)).

Study Overview

• Status: Completed
• Conditions: Malaria; Malaria,Falciparum
• Intervention / Treatment: Drug: Dihydroartemisinin-piperaquine; Drug: Primaquine

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.

• Study Type: Interventional
• Enrollment (Actual): 10715
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Senegal
  • Tambacounda, Senegal
    • Tambacounda Health District

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 3 months and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: MDA with DHA-PPQ + SLD-PQ; Participants in intervention villages will be given three rounds of MDA with DHA-PPQ and SLD-PQ. Prior to the intervention, participants will have received piperonyl butoxide (PBO) treated LLINs and proactive community case management. Unlike control villages, MDA-randomized villages will not receive SMC.	Drug: Dihydroartemisinin-piperaquine; DHA-PPQ will be given over the course of three consecutive days using 160mg/20mg or 320mg/40mg of dihydroartemisinin/piperaquine tablets. DHA-PPQ will be administered via age-based dosing. All three doses will be directly observed and given orally with water and without food.; Other Names: Duo-Cotecxin; Drug: Primaquine; Primaquine will be given once with the first dose of DHA-PPQ. Primaquine will be administered in an aqueous solution according to age-based dosing guidelines.
No Intervention: Standard malaria control interventions; Participants in the control villages will receive standard malaria control interventions as implemented by the Senegal PNLP. This will include the distribution of PBO LLINs, proactive case management, and SMC.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Difference in village-level confirmed incidence of malaria	Village-level malaria incidence will be defined as the number of individuals diagnosed with malaria through proactive case detection and passive malaria surveillance at the health facility-level over the total village population measured during census.	one year post-MDA

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Difference in parasite prevalence by microscopy during high malaria transmission season	Parasite prevalence will be assessed via microscopy from samples obtained during cross-sectional survey conducted at the end of the transmission season.	3 months after last round of MDA
Difference in parasite prevalence by polymerase chain reaction (PCR) during high malaria transmission season	Parasite prevalence will be assessed via polymerase chain reaction from samples obtained during cross-sectional survey conducted at the end of the transmission season.	3 months after last round of MDA
Difference in serological markers of recent infection	Difference in seroprevalence from samples obtained during cross-sectional survey conducted at the end of the transmission season.	3 months after last round of MDA
Difference in the change in prevalence of drug resistance markers	Prevalence of drug resistance markers (K13 and plasmepsin copy number) will be assessed from samples taken during the baseline and endline cross-sectional surveys.	Change from baseline to endline; 1 year period
Difference in the change in prevalence of parasite population dynamics	Prevalence of parasite population dynamics (multiplicity of infection) will be assessed from samples taken during the baseline and endline cross-sectional surveys.	Change from baseline to endline; 1 year period

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Population coverage of MDA	Coverage will be measured as the proportion of people who received MDA divided by the total number of persons in the population at each MDA round.	Up to 18 weeks
Difference in the cost-effectiveness of MDA versus SMC	Costs of MDA and optimized control will be collected throughout the study period. The incremental cost-effectiveness ratio (ICER) will be used to compare MDA to SMC.	Up to 24 months

Collaborators and Investigators

• Sponsor: University of California, San Francisco
• Collaborators: Centers for Disease Control and Prevention; Population Services International; L'université de Thiès; Programme National de Lutte contre le Paludisme (PNLP), Senegal; US President's Malaria Initiative
• Investigators: Principal Investigator: Jean Louis Ndiaye, MD PhD, Université de Thiès; Principal Investigator: Michelle Hsiang, MD MSc, University of California, San Francisco; Principal Investigator: Doudou Séne, MD, Senegal Programme National de Lutte contre le Paludisme (PNLP); Principal Investigator: Katharine Sturm-Ramirez, PhD, US President's Malaria Initiative/CDC

Study record dates

Study Major Dates

• Study Start (Actual): June 19, 2021
• Primary Completion (Actual): December 31, 2022
• Study Completion (Actual): June 30, 2023

Study Registration Dates

• First Submitted: April 22, 2021
• First Submitted That Met QC Criteria: April 26, 2021
• First Posted (Actual): April 28, 2021

Study Record Updates

• Last Update Posted (Actual): June 24, 2024
• Last Update Submitted That Met QC Criteria: June 20, 2024
• Last Verified: June 1, 2024

More Information

Terms related to this study

• Keywords: Parasitic Diseases; Mass drug administration; Piperaquine; Primaquine; Antimalarials; Dihydroartemsinin
• Additional Relevant MeSH Terms: Infections; Vector Borne Diseases; Parasitic Diseases; Protozoan Infections; Mosquito-Borne Diseases; Malaria; Malaria, Falciparum; Anti-Infective Agents; Antiprotozoal Agents; Antiparasitic Agents; Antimalarials; Primaquine; Piperaquine; Artenimol
• Other Study ID Numbers: 20-29886

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No