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

NCT04864444 | Completed DMC

• 1 other identifier: 20-29886
• Study Type: interventional
• Target: 10,715
• Locations: 1 country
• Sites: 1

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)).

Conditions

Malaria,Falciparum; Malaria

Keywords

Antimalarials; Mass drug administration; Dihydroartemsinin; Piperaquine; Primaquine; Parasitic Diseases

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (5)

• Difference in parasite prevalence by microscopy during high malaria transmission season

  3 months after last round of MDA

• Difference in parasite prevalence by polymerase chain reaction (PCR) during high malaria transmission season

  3 months after last round of MDA

• Difference in serological markers of recent infection

  3 months after last round of MDA

• Difference in the change in prevalence of drug resistance markers

  Change from baseline to endline; 1 year period

• Difference in the change in prevalence of parasite population dynamics

  Change from baseline to endline; 1 year period

Other Outcomes (2)

• Population coverage of MDA

  Up to 18 weeks

• Difference in the cost-effectiveness of MDA versus SMC

  Up to 24 months

Study Arms (2)

MDA with DHA-PPQ + SLD-PQ

EXPERIMENTAL

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; Drug: Primaquine

Standard malaria control interventions

NO INTERVENTION

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.

Interventions

Dihydroartemisinin-piperaquine DRUG

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.

Also known as: Duo-Cotecxin

MDA with DHA-PPQ + SLD-PQ

Primaquine DRUG

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.

MDA with DHA-PPQ + SLD-PQ

Eligibility Criteria

• Age: 3 Months+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

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

You may not qualify if:

• Severe illness or self-reported chronic illness (e.g., HIV, tuberculosis, heart/liver/kidney disease, and severe malnutrition)
• Known hypersensitivity to study drug
• 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
• Pregnancy (any trimester) or currently breastfeeding an infant \<6 months of age assessed by history and/or urine pregnancy testing
• \<2 years of age

Sponsors & Collaborators

• University of California, San Francisco: lead
• L'université de Thiès: collaborator
• Programme National de Lutte contre le Paludisme (PNLP), Senegal: collaborator
• Population Services International: collaborator
• Centers for Disease Control and Prevention: collaborator
• US President's Malaria Initiative: collaborator

Study Sites (1)

Tambacounda Health District

Tambacounda, Senegal

Location

Related Publications (2)

• Ba EKC, Roh ME, Diallo A, Gadiaga T, Seck A, Thiam S, Fogelson A, Gaye S, Diallo I, Lo AC, Diouf E, Ba OG, Gueye AB, Wu X, Milligan P, Kibuka T, Hama M, Eckert E, Thwing J, Bennett A, Gosling R, Hwang J, Sene D, Ba F, Cisse B, Sturm-Ramirez K, Hsiang MS, Ndiaye JL. Effect of mass drug administration on malaria incidence in southeast Senegal during 2020-22: a two-arm, open-label, cluster-randomised controlled trial. Lancet Infect Dis. 2025 Jun;25(6):656-667. doi: 10.1016/S1473-3099(24)00741-2. Epub 2025 Jan 9.

  PMID: 39799956 DERIVED

• Ba Konko Cire EH, Roh ME, Diallo A, Gadiaga T, Seck A, Thiam S, Gaye S, Diallo I, Lo AC, Diouf E, Ba OG, Gueye AB, Fogelson A, Wu X, Milligan P, Kibuka T, Hama M, Eckert E, Thwing J, Bennett A, Gosling R, Hwang J, Sene D, Ba F, Cisse B, Sturm-Ramirez K, Hsiang MS, Ndiaye JL. Mass drug administration to reduce malaria incidence in a low-to-moderate endemic setting: short-term impact results from a cluster randomised controlled trial in Senegal. medRxiv [Preprint]. 2024 Jul 18:2024.07.17.24310593. doi: 10.1101/2024.07.17.24310593.

  PMID: 39072042 DERIVED

MeSH Terms

Conditions

Malaria, Falciparum; Malaria; Parasitic Diseases

Interventions

Primaquine

Condition Hierarchy (Ancestors)

Protozoan Infections; Infections; Mosquito-Borne Diseases; Vector Borne Diseases

Intervention Hierarchy (Ancestors)

Aminoquinolines; Quinolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Study Officials

• 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

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: 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

Study Record Dates

• First Submitted: April 22, 2021
• First Posted: April 28, 2021
• Study Start: June 19, 2021
• Primary Completion: December 31, 2022
• Study Completion: June 30, 2023
• Last Updated: June 24, 2024

Record last verified: 2024-06

Data Sharing

• IPD Sharing: Will not share

Locations

SE (1)