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

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ClinicalTrials.gov Identifier: NCT03576313
Recruitment Status : Recruiting
First Posted : July 3, 2018
Last Update Posted : November 29, 2018
Sponsor:
Collaborators:
Institute of Tropical Medicine, Belgium
National Malaria Control Programme, The Gambia
Liverpool School of Tropical Medicine
Radboud University
University of Durham
Imperial College London
Information provided by (Responsible Party):
London School of Hygiene and Tropical Medicine

Brief 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.

Condition or disease Intervention/treatment Phase
Malaria Drug: dihydroartemisinin-piperaquine (DP) Drug: ivermectin (IVM) Other: standard malaria control interventions only Phase 3

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  (Clinical Trial)
Estimated Enrollment : 6400 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: 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
Masking: Single (Outcomes Assessor)
Masking Description: Malaria prevalence will be determined by technicians blinded to the treatment arm
Primary Purpose: Prevention
Official Title: Mass Drug Administration of Ivermectin and Dihydroartemisinin-piperaquine as an Additional Intervention for Malaria Elimination
Actual Study Start Date : August 11, 2018
Estimated Primary Completion Date : August 2020
Estimated Study Completion Date : December 2021

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Malaria
Drug Information available for: Ivermectin

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
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

Drug: 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

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




Primary Outcome Measures :
  1. 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

  2. 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


Secondary Outcome Measures :
  1. 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

  2. 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

  3. 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

  4. 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

  5. mosquito density [ Time Frame: over 24 months after MDA ]
    Total number of mosquitoes collected during the study period across both intervention and control villages

  6. 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

  7. 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


Other Outcome Measures:
  1. 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



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Ages Eligible for Study:   6 Months and older   (Child, Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03576313


Contacts
Contact: Jane Achan, MD, PhD +220-4495443-6 ext 4006 jachan@mrc.gm
Contact: Umberto D'alessandro, MD, PhD +220-4495443-6 ext 4001 udalessandro@mrc.gm

Locations
Gambia
Basse Villages Recruiting
Basse Santa Su, Gambia
Contact: Onwuchekwa Chukwuemeka onwuchekwu, MD    +220-4495442-6 ext 2123    conwuchekwa@mrc.gm   
Sponsors and Collaborators
London School of Hygiene and Tropical Medicine
Institute of Tropical Medicine, Belgium
National Malaria Control Programme, The Gambia
Liverpool School of Tropical Medicine
Radboud University
University of Durham
Imperial College London
Investigators
Principal Investigator: Umberto D'alessandro, MD, PhD MRC @ LSHTM

Responsible Party: London School of Hygiene and Tropical Medicine
ClinicalTrials.gov Identifier: NCT03576313     History of Changes
Other Study ID Numbers: SCC 1593
First Posted: July 3, 2018    Key Record Dates
Last Update Posted: November 29, 2018
Last Verified: November 2018

Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by London School of Hygiene and Tropical Medicine:
transmission
reduction

Additional relevant MeSH terms:
Parasitic Diseases
Malaria
Protozoan Infections
Piperaquine
Dihydroartemisinin
Artemisinins
Ivermectin
Antimalarials
Antiprotozoal Agents
Antiparasitic Agents
Anti-Infective Agents