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

NCT03576313 | Completed Phase 3 DMC

• 1 other identifier: SCC 1593
• Study Type: interventional
• Target: 4,939
• Locations: 1 country
• Sites: 1

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.

Conditions

Malaria

Keywords

transmission; reduction

Outcome Measures

Primary Outcomes (2)

• 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

• 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 Outcomes (7)

• malaria prevalence

  at 6 months

• incidence of clinical (laboratory confirmed) malaria cases

  after MDA over 6 months period

• serological markers of recent malaria

  after MDA over 6 months period

• serological markers of recent Anopheles exposure

  after MDA over 6 months period

• mosquito density

  over 24 months after MDA

Other Outcomes (1)

• drug resistance markers

  after MDA 6 months

Study Arms (2)

intervention: IVM and DP

EXPERIMENTAL

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); Drug: ivermectin (IVM); Other: standard malaria control interventions only

control: standard malaria control intervetions

ACTIVE COMPARATOR

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

Interventions

dihydroartemisinin-piperaquine (DP) DRUG

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

intervention: IVM and DP

ivermectin (IVM) DRUG

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

intervention: IVM and DP

standard malaria control interventions only OTHER

this is the standard malaria control interventions in the Gambia

control: standard malaria control intervetions; intervention: IVM and DP

Eligibility Criteria

• Age: 6 Months+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Age/anthropometry
• For IVM: weight ≥ 15kg or height ≥90 cm;
• For DP: age \> 6 months
• Willingness to comply with trial procedures
• Individual written informed consent obtained at the beginning of the study

You may not qualify if:

• Known chronic illness (eg HIV, TB, hepatitis and severe malnutrition).
• Additionally for IVM:
• Pregnancy (any trimester) and breast feeding
• Hypersensitivity to IVM
• Travel to Loa loa endemic countries (e.g. Central Africa)
• Additionally for DP:
• First trimester pregnancy
• Hypersensitivity to DP
• Taking drugs that influence cardiac function or prolong QTc interval

Sponsors & Collaborators

• London School of Hygiene and Tropical Medicine: lead
• Institute of Tropical Medicine, Belgium: collaborator
• National Malaria Control Programme, The Gambia: collaborator
• Liverpool School of Tropical Medicine: collaborator
• Radboud University Medical Center: collaborator
• University of Durham: collaborator
• Imperial College London: collaborator

Study Sites (1)

Basse Villages

Basse Santa Su, The Gambia

Location

Related Publications (4)

• Kositz C, Vasileva H, Mohammed N, Achan J, Dabira ED, D'Alessandro U, Bradley J, Marks M. Risk factors for non-participation in ivermectin and dihydroartemisinin-piperaquine mass drug administration for malaria control in the MASSIV trial. Malar J. 2024 Feb 22;23(1):54. doi: 10.1186/s12936-024-04878-2.

  PMID: 38383367 DERIVED

• Fehr A, Nieto-Sanchez C, Muela J, Manneh E, Baldeh D, Ceesay O, D'Alessandro U, Dabira E, Kingori P, Peeters Grietens K, Bardaji A, Bunders-Aelen J, Zuiderent-Jerak T. Doing 'reciprocity work': The role of fieldworkers in a mass drug administration trial in the Gambia. Glob Public Health. 2022 Dec;17(12):4116-4128. doi: 10.1080/17441692.2022.2125998. Epub 2022 Oct 2.

  PMID: 36183416 DERIVED

• Dabira ED, Soumare HM, Conteh B, Ceesay F, Ndiath MO, Bradley J, Mohammed N, Kandeh B, Smit MR, Slater H, Peeters Grietens K, Broekhuizen H, Bousema T, Drakeley C, Lindsay SW, Achan J, D'Alessandro U. Mass drug administration of ivermectin and dihydroartemisinin-piperaquine against malaria in settings with high coverage of standard control interventions: a cluster-randomised controlled trial in The Gambia. Lancet Infect Dis. 2022 Apr;22(4):519-528. doi: 10.1016/S1473-3099(21)00557-0. Epub 2021 Dec 15.

  PMID: 34919831 DERIVED

• Dabira ED, Soumare HM, Lindsay SW, Conteh B, Ceesay F, Bradley J, Kositz C, Broekhuizen H, Kandeh B, Fehr AE, Nieto-Sanchez C, Ribera JM, Peeters Grietens K, Smit MR, Drakeley C, Bousema T, Achan J, D'Alessandro U. Mass Drug Administration With High-Dose Ivermectin and Dihydroartemisinin-Piperaquine for Malaria Elimination in an Area of Low Transmission With High Coverage of Malaria Control Interventions: Protocol for the MASSIV Cluster Randomized Clinical Trial. JMIR Res Protoc. 2020 Nov 19;9(11):e20904. doi: 10.2196/20904.

  PMID: 33211022 DERIVED

MeSH Terms

Conditions

Malaria

Interventions

Ivermectin

Condition Hierarchy (Ancestors)

Protozoan Infections; Parasitic Diseases; Infections; Mosquito-Borne Diseases; Vector Borne Diseases

Intervention Hierarchy (Ancestors)

Macrolides; Polyketides; Lactones; Organic Chemicals

Study Officials

• Umberto D'alessandro, MD, PhD

  MRC @ LSHTM

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Masking Details: Malaria prevalence will be determined by technicians blinded to the treatment arm
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: 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

Study Record Dates

• First Submitted: May 31, 2018
• First Posted: July 3, 2018
• Study Start: August 11, 2018
• Primary Completion: December 31, 2019
• Study Completion: July 31, 2021
• Last Updated: March 14, 2022

Record last verified: 2022-03

Locations

TH (1)