Mass Drug Administration of Ivermectin and Dihydroartemisinin-piperaquine as an Additional Intervention for Malaria Elimination

Malaria Clinical Trial

— MASSIV  

Official title:

Mass Drug Administration of Ivermectin and Dihydroartemisinin-piperaquine as an Additional Intervention for Malaria Elimination

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03576313
• Other study ID #: SCC 1593
• Status: Completed
• Phase: Phase 3
• Start date: August 11, 2018
• Est. completion date: July 31, 2021

Study information

• Verified date: March 2022
• Source: London School of Hygiene and Tropical Medicine
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This is a community-based cluster-randomized trial in which a novel approach to interrupt residual malaria transmission by mass drug administration (MDA) with ivermectin (IVM) combined with dihydroartemisinin-piperaquine (DP) will be tested. This cluster-randomized trial will involve 32 villages in the Upper River Region of The Gambia that will be randomized to MDA with IVM and DP or to standard of care in a ratio 1:1. This trial aims at establishing whether MDA with IVM and DP can reduce or interrupt malaria transmission in medium to low transmission settings by reducing vector survival and the human reservoir of infection. MDA with IVM and DP will be implemented in the intervention villages and all human settlements in the buffer zone, with the aim of minimizing spillover effects. Control clusters will receive standard malaria control interventions as implemented by the National Malaria Control Program. The primary outcomes will be the prevalence of malaria infection determined by molecular methods in all age groups at the peak of the second transmission season (November-December 2019) and the vector's parous rate 7-14 days after MDA.

Description:

The hypothesis of this project is that mass drug administration (MDA) with ivermectin (IVM) and dihydroartemisinin-piperaquine (DP) can reduce or interrupt malaria transmission in medium to low transmission settings by reducing vector survival and the human reservoir of infection. The research questions include the following: 1. Will MDA with IVM plus DP (3 rounds per transmission season) in communities with high coverage of vector control interventions further reduce malaria transmission (up to local elimination)? 2. Will MDA with IVM suppress the vector population? 3. What is the most socially acceptable and sustainable way of achieving and maintaining high coverage of MDA with IVM and DP, and of embedding it within local communities and stakeholders? 4. What is the impact of MDA with IVM on prevalence of ectoparasites and helminths 5. What is the cost and cost-effectiveness of this intervention compared to standard malaria control measures?

Recruitment information / eligibility

• Status: Completed
• Enrollment: 4939
• Est. completion date: July 31, 2021
• Est. primary completion date: December 31, 2019
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 6 Months and older

Eligibility

Inclusion Criteria

• Age/anthropometry

1. For IVM: weight = 15kg or height =90 cm;

2. For DP: age > 6 months

• Willingness to comply with trial procedures
• Individual written informed consent obtained at the beginning of the study

Exclusion Criteria:

• Exclusion criteria for both IVM and DP will include the following:
• Known chronic illness (eg HIV, TB, hepatitis and severe malnutrition).

Additionally for IVM:

1. Pregnancy (any trimester) and breast feeding

2. Hypersensitivity to IVM

3. Travel to Loa loa endemic countries (e.g. Central Africa)

Additionally for DP:

1. First trimester pregnancy

2. Hypersensitivity to DP

3. Taking drugs that influence cardiac function or prolong QTc interval

Related Conditions & MeSH terms

• Malaria

Intervention

Drug:
• dihydroartemisinin-piperaquine (DP)
DP will be available as tablets of 320/40mg and 160/20mg piperaquine/ dihydroartemisinin per tablet. Administration of a full course of DP will be done as per manufacturer's guidelines once daily for 3 days and according to body weight. DP will be taken orally with water and without food
• ivermectin (IVM)
IVM will be available as tablets of 3mg or 6mg strength. It will be given at 300-400µg/kg/day over 3 days (to the nearest whole tablet). IVM will also be taken on an empty stomach with water

Other:
• standard malaria control interventions only
this is the standard malaria control interventions in the Gambia

Locations

Country	Name	City	State
Gambia	Basse Villages	Basse Santa Su

Sponsors (7)

Lead Sponsor	Collaborator
London School of Hygiene and Tropical Medicine	Imperial College London, Institute of Tropical Medicine, Belgium, Liverpool School of Tropical Medicine, National Malaria Control Programme, The Gambia, Radboud University Medical Center, University of Durham

Country where clinical trial is conducted

Gambia, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	drug resistance markers	prevalence of drug resistance markers in the number of malaria parasites with drug-resistance markers divided by the total number of samples tested	after MDA 6 months
Primary	prevalence of malaria infection	Prevalence of malaria infection determined by molecular methods number of participants with a positive varATS quantitative PCR divided by the total number of participants sampled	at 12 months
Primary	Vector's parous rate	Malaria prevalence will be used as an indicator of on-going malaria transmission, while vector's parous rate will quantify the effect of IVM on vector survival and mosquito population age structure. Proportion: number of parous vectors divided by the total number of collected vectors	7-14 days after mass drug administration (MDA)
Secondary	malaria prevalence	malaria prevalence at the peak of the first transmission season of number of participants with a positive varATS quantitative PCR divided by the total number of participants sampled	at 6 months
Secondary	incidence of clinical (laboratory confirmed) malaria cases	incidence of clinical (laboratory confirmed) malaria cases at health facilities of Number of clinical malaria cases observed divided by person-years of follow-up	after MDA over 6 months period
Secondary	serological markers of recent malaria	serological markers of recent malaria infection by Mean Fluorescent Intensity of the different antigens will be determined and presented as a geometric mean	after MDA over 6 months period
Secondary	serological markers of recent Anopheles exposure	serological markers of recent Anopheles exposure by Mean Fluorescent Intensity of the different antigens will be determined and presented as a geometric mean	after MDA over 6 months period
Secondary	mosquito density	Total number of mosquitoes collected during the study period across both intervention and control villages	over 24 months after MDA
Secondary	mosquito mortality	mosquito mortality after feeding on IVM treated individuals Number of mosquitoes that die after a blood meal 21 days post-treatment divided by total number of mosquitoes blood fed	21 days post treatment
Secondary	sporozoite rates in field-caught mosquitoes	Number of P. falciparum circumsporozoite antibody (CSP) positive mosquitoes divided by the total number of mosquitoes caught	over 24 months after MDA