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

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.

Study Overview

Detailed 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?

Study Type

Interventional

Enrollment (Actual)

4939

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

      • Basse Santa Su, Gambia
        • Basse Villages

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

6 months and older (Child, Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Prevention
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Single

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: intervention: IVM and DP
Mass Drug Administration with ivermectin (IVM) and dihydroartemisinin-piperaquine (DP) will be given to participants in the intervention villages plus the NMCP standard malaria control intervention
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
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
this is the standard malaria control interventions in the Gambia
Active Comparator: control: standard malaria control intervetions
Participants in the control clusters will receive only standard malaria control interventions such as Artemether Lumefantrine, LLINs, IRS, SMC and IPTp as implemented by the National Malaria Control Program (NMCP) of the Gambia
this is the standard malaria control interventions in the Gambia

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
prevalence of malaria infection
Time Frame: at 12 months
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
Vector's parous rate
Time Frame: 7-14 days after mass drug administration (MDA)
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 Outcome Measures

Outcome Measure
Measure Description
Time Frame
malaria prevalence
Time Frame: at 6 months
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
incidence of clinical (laboratory confirmed) malaria cases
Time Frame: after MDA over 6 months period
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
serological markers of recent malaria
Time Frame: after MDA over 6 months period
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
serological markers of recent Anopheles exposure
Time Frame: after MDA over 6 months period
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
mosquito density
Time Frame: over 24 months after MDA
Total number of mosquitoes collected during the study period across both intervention and control villages
over 24 months after MDA
mosquito mortality
Time Frame: 21 days post treatment
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
sporozoite rates in field-caught mosquitoes
Time Frame: over 24 months after MDA
Number of P. falciparum circumsporozoite antibody (CSP) positive mosquitoes divided by the total number of mosquitoes caught
over 24 months after MDA

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
drug resistance markers
Time Frame: after MDA 6 months
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

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

August 11, 2018

Primary Completion (Actual)

December 31, 2019

Study Completion (Actual)

July 31, 2021

Study Registration Dates

First Submitted

May 31, 2018

First Submitted That Met QC Criteria

July 2, 2018

First Posted (Actual)

July 3, 2018

Study Record Updates

Last Update Posted (Actual)

March 14, 2022

Last Update Submitted That Met QC Criteria

March 11, 2022

Last Verified

March 1, 2022

More Information

Terms related to this study

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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