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

Malaria Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04864444
• Other study ID #: 20-29886
• Status: Completed
• Phase: N/A
• Start date: June 19, 2021
• Est. completion date: June 30, 2023

Study information

• Verified date: August 2023
• Source: University of California, San Francisco
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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)).

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 10715
• Est. completion date: June 30, 2023
• Est. primary completion date: December 31, 2022
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 3 Months and older

Eligibility

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

Related Conditions & MeSH terms

• Malaria
• Malaria, Falciparum
• Malaria,Falciparum

Intervention

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.
• 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.

Locations

Country	Name	City	State
Senegal	Tambacounda Health District	Tambacounda

Sponsors (6)

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

Country where clinical trial is conducted

Senegal, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	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
Other	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
Primary	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	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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