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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

Tracking Information
First Submitted Date  ICMJE May 31, 2018
First Posted Date  ICMJE July 3, 2018
Last Update Posted Date November 29, 2018
Actual Study Start Date  ICMJE August 11, 2018
Estimated Primary Completion Date August 2020   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: July 2, 2018)
  • 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
  • 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
Original Primary Outcome Measures  ICMJE Same as current
Change History Complete list of historical versions of study NCT03576313 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: July 2, 2018)
  • 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
  • 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
  • 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
  • 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
  • mosquito density [ Time Frame: over 24 months after MDA ]
    Total number of mosquitoes collected during the study period across both intervention and control villages
  • 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
  • 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
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures
 (submitted: July 2, 2018)
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
Original Other Pre-specified Outcome Measures Same as current
 
Descriptive Information
Brief Title  ICMJE Mass Drug Administration of Ivermectin and Dihydroartemisinin-piperaquine as an Additional Intervention for Malaria Elimination
Official Title  ICMJE Mass Drug Administration of Ivermectin and Dihydroartemisinin-piperaquine as an Additional Intervention for Malaria Elimination
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.
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  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE 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
Condition  ICMJE Malaria
Intervention  ICMJE
  • 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
Study Arms  ICMJE
  • 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
    Interventions:
    • Drug: dihydroartemisinin-piperaquine (DP)
    • Drug: ivermectin (IVM)
    • Other: standard malaria control interventions only
  • 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
    Intervention: Other: standard malaria control interventions only
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: July 2, 2018)
6400
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE December 2021
Estimated Primary Completion Date August 2020   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 6 Months and older   (Child, Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE Yes
Contacts  ICMJE
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
Listed Location Countries  ICMJE Gambia
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03576313
Other Study ID Numbers  ICMJE SCC 1593
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE Not Provided
Responsible Party London School of Hygiene and Tropical Medicine
Study Sponsor  ICMJE London School of Hygiene and Tropical Medicine
Collaborators  ICMJE
  • 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  ICMJE
Principal Investigator: Umberto D'alessandro, MD, PhD MRC @ LSHTM
PRS Account London School of Hygiene and Tropical Medicine
Verification Date November 2018

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP