NCT04844905

Brief Summary

This is a cluster-randomized placebo-controlled clinical trial to evaluate the additive benefit of Ivermectin (IVM) (or Placebo) mass drug administration (MDA) to dihydroartemisinin-piperaquine (DP) MDA for malaria control in a moderate to low malaria-endemic setting as an adjunctive strategy to existing programmatic malaria control measures. The regime of DP and IVM will target both human reservoirs of Plasmodium falciparum and the Anopheles gambiae vector respectively, with the aim of interrupting transmission. The trial will be conducted on the Bijagos Archipelago, where islands (clusters) will be randomised to receive seasonal DP and IVM or DP and Placebo MDA. The primary outcome will be the prevalence of infection with Plasmodium falciparum in all age groups detected by nucleic acid amplification testing during the peak malaria transmission season after two years of intervention.

Trial Health

43
At Risk

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Trial has exceeded expected completion date
Enrollment
24,000

participants targeted

Target at P75+ for phase_3

Timeline
Completed

Started May 2021

Geographic Reach
1 country

1 active site

Status
unknown

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

March 17, 2021

Completed
28 days until next milestone

First Posted

Study publicly available on registry

April 14, 2021

Completed
19 days until next milestone

Study Start

First participant enrolled

May 3, 2021

Completed
1.8 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

March 1, 2023

Completed
5 months until next milestone

Study Completion

Last participant's last visit for all outcomes

August 1, 2023

Completed
Last Updated

February 24, 2022

Status Verified

February 1, 2022

Enrollment Period

1.8 years

First QC Date

March 17, 2021

Last Update Submit

February 22, 2022

Conditions

Keywords

Vector ControlMass Drug AdministrationIntegrated Disease ControlMalariaGuinea BissauWest AfricaAntimalarialsIvermectinDihydroartemisininPiperaquine

Outcome Measures

Primary Outcomes (1)

  • Prevalence of infection with Plasmodium falciparum

    Prevalence of infection with Plasmodium falciparum in all age groups estimated using a cross-sectional survey sample conducted during peak transmission season after 2 years of intervention

    2 years

Secondary Outcomes (12)

  • Vector parous rate

    7-14 days post-MDA

  • Prevalence of infection with Plasmodium falciparum

    1 year

  • Incidence of clinical malaria (Passive Case Detection)

    For six months during the malaria transmission season

  • Incidence of clinical malaria (Active Case Detection)

    For six months during the malaria transmission season

  • Age-adjusted prevalence of recent exposure to Plasmodium falciparum

    Peak transmission season at 1 year and 2 years

  • +7 more secondary outcomes

Study Arms (2)

Ivermectin Mass Drug Administration

EXPERIMENTAL

Ivermectin and Dihydroartemisinin-piperaquine MDA will be given to all eligible participants in each cluster (island) in addition to the standard national malaria control programme interventions.

Drug: IvermectinDrug: Dihydroartemisinin-piperaquine

Placebo Mass Drug Administration

PLACEBO COMPARATOR

Placebo and Dihydroartemisinin-piperaquine MDA will be given to all eligible participants in each cluster (island) in addition to the standard national malaria control programme interventions.

Drug: PlaceboDrug: Dihydroartemisinin-piperaquine

Interventions

Ivermectin will be given as tablets of 3 or 6mg. It will be given at 300-400μg/kg/day for 3 days (to the nearest whole tablet) each month for 3 months. It will be taken on an empty stomach with water.

Ivermectin Mass Drug Administration

Placebo will be given as tablets of 3 or 6mg (identical to Ivermectin in colour, size, shape and packaging). It will be given at 300-400μg/kg/day for 3 days (to the nearest whole tablet) each month for 3 months. It will be taken by mouth with water and without food.

Placebo Mass Drug Administration

Dihydroartemisinin-piperaquine will be given as tablets of 320/40mg (adult) and 160/20mg (child) piperaquine/dihydroartemisinin per tablet. Administration of a full course of dihydroartemisinin-piperaquine will be given in accordance with the manufacturer's guidelines once daily for 3 days each month for 3 months according to body weight. Dihydroartemisinin-piperaquine will be taken by mouth with water and without food.

Also known as: Eurartesim
Ivermectin Mass Drug AdministrationPlacebo Mass Drug Administration

Eligibility Criteria

Age6 Months+
Sexall
Healthy VolunteersYes
Age GroupsChild (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

  • Age over six months to receive dihydroartemisinin-piperaquine
  • Height over 90cm or weight over 15kg to receive ivermectin or placebo
  • Willingness to adhere to trial procedures
  • Individual written, informed consent from the participant or parent/guardian in the case of participants below the age of 18 years (and assent in young people between the ages of 12 and 17 years of age)

You may not qualify if:

  • Known severe chronic illness (AIDS, Tuberculosis, chronic malnutrition)
  • Known hypersensitivity to either dihydroartemisinin-piperaquine or ivermectin
  • Pregnancy (any trimester) and breastfeeding (for ivermectin (or placebo)) and pregnancy (first trimester only) (for dihydroartemisinin-piperaquine)
  • Travel to a Loa loa endemic country (eg Central African Republic) (for ivermectin (or placebo))
  • Concomitant drugs that influence cardiac function or affect the corrected QT interval (for dihydroartemisinin-piperaquine)

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

Bijagos Archipelago (islands)

Bissau, Guinea-Bissau

RECRUITING

Related Publications (2)

  • Hutchins H, Pretorius E, Bradley J, Teixeira da Silva E, Vasileva H, Ndiath MO, Jones RT, Soumare HDM, Nyang H, Prom A, Sambou S, Ceesay F, Ceesay S, Moss S, Mabey D, Djata P, Nante JE, Martins C, Logan JG, Slater H, Tetteh K, Drakeley C, D'Alessandro U, Rodrigues A, Last A. Adjunctive ivermectin mass drug administration for malaria control on the Bijagos Archipelago of Guinea-Bissau (MATAMAL): a quadruple-blinded, cluster-randomised, placebo-controlled trial. Lancet Infect Dis. 2025 Apr;25(4):424-434. doi: 10.1016/S1473-3099(24)00580-2. Epub 2024 Nov 14.

  • Hutchins H, Bradley J, Pretorius E, Teixeira da Silva E, Vasileva H, Jones RT, Ndiath MO, Dit Massire Soumare H, Mabey D, Nante EJ, Martins C, Logan JG, Slater H, Drakeley C, D'Alessandro U, Rodrigues A, Last AR. Protocol for a cluster randomised placebo-controlled trial of adjunctive ivermectin mass drug administration for malaria control on the Bijagos Archipelago of Guinea-Bissau: the MATAMAL trial. BMJ Open. 2023 Jul 7;13(7):e072347. doi: 10.1136/bmjopen-2023-072347.

MeSH Terms

Conditions

Malaria, FalciparumNeglected DiseasesStrongyloidiasisElephantiasis, FilarialScabiesAncylostomiasisMalaria

Interventions

Ivermectin

Condition Hierarchy (Ancestors)

Protozoan InfectionsParasitic DiseasesInfectionsMosquito-Borne DiseasesVector Borne DiseasesDisease AttributesPathologic ProcessesPathological Conditions, Signs and SymptomsRhabditida InfectionsSecernentea InfectionsNematode InfectionsHelminthiasisFilariasisSpirurida InfectionsLymphedemaLymphatic DiseasesHemic and Lymphatic DiseasesMite InfestationsEctoparasitic InfestationsSkin Diseases, ParasiticSkin Diseases, InfectiousSkin DiseasesSkin and Connective Tissue DiseasesHookworm InfectionsStrongylida Infections

Intervention Hierarchy (Ancestors)

MacrolidesPolyketidesLactonesOrganic Chemicals

Study Officials

  • Anna R Last, MBChB PhD

    London School of Hygiene and Tropical Medicine

    PRINCIPAL INVESTIGATOR

Central Study Contacts

Anna R Last, MBChB PhD

CONTACT

David CW Mabey

CONTACT

Study Design

Study Type
interventional
Phase
phase 3
Allocation
RANDOMIZED
Masking
QUADRUPLE
Who Masked
PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
Masking Details
An independent statistician will randomize the clusters to DP+IVM or DP+Placebo. The Placebo is identical in size, shape and colour and packaging. An independent pharmacist at Medical Research Council Unit The Gambia @ London School of Hygiene and Tropical Medicine will label the IVM and Placebo according to the statistician's designation and maintain the masking from all other investigators. Specifically generated masking codes will be generated and saved in three separate encrypted locations securely. Only the statistician and the pharmacist will have access to the encryption key.
Purpose
TREATMENT
Intervention Model
PARALLEL
Model Details: Two arms with clusters randomized to DP+IVM or DP+Placebo with a 1:1 ratio
Sponsor Type
OTHER
Responsible Party
SPONSOR

Study Record Dates

First Submitted

March 17, 2021

First Posted

April 14, 2021

Study Start

May 3, 2021

Primary Completion

March 1, 2023

Study Completion

August 1, 2023

Last Updated

February 24, 2022

Record last verified: 2022-02

Data Sharing

IPD Sharing
Will share

There is a manuscript in preparation detailing the study protocol and statistical analysis plan. The participant information and and informed consent form may be requested from the trial research team. Results and a clinical study report will be made available within six months of completion of the trial. Analytic code will be made available under a Creative Commons license. Publication of results will be open-access and available in pre-print on MedRxiv (The Preprint Server for Health Sciences).

Shared Documents
STUDY PROTOCOL, SAP, ICF, CSR, ANALYTIC CODE
Time Frame
The study protocol and Statistical Analysis Plan (SAP) will be made available on acceptance of the manuscript for publication. Participant information and Informed Consent Form (ICF) will be made available from recruitment. Results (including Clinical Study Report (CSR)) will be made available within six months of completion of the trial.
Access Criteria
Study Protocol and Statistical Analysis Plan (SAP) will be published in an Open Access peer-reviewed journal. The participant information and and informed consent form may be requested from the trial research team. Results and a clinical study report will be made available within six months of completion of the trial. Analytic code will be made available under a Creative Commons license. Publication of results will be Open-Access and available in pre-print on MedRxiv (The Preprint Server for Health Sciences).

Locations