Clinical trial NCT03576313: Mass Drug Administration of Ivermectin and Dihydroartemisinin-piperaquine as an Additional Intervention for Malaria Elimination
Official title: Mass Drug Administration of Ivermectin and Dihydroartemisinin-piperaquine as an Additional Intervention for Malaria Elimination
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Malaria
Keywords: transmission
reduction
Lead sponsor: London School of Hygiene and Tropical Medicine
Sponsor class: OTHER
Collaborators: name: Institute of Tropical Medicine, Belgium
name: National Malaria Control Programme, The Gambia
name: Liverpool School of Tropical Medicine
name: Radboud University Medical Center
name: University of Durham
name: Imperial College London
First posted: 2018-07-03
Enrollment: 4939
Sex: ALL
Minimum age (years): 6
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
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
Primary purpose: PREVENTION

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?

Eligibility 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

Primary outcomes:
measure: prevalence of malaria infection
timeFrame: at 12 months
measure: Vector's parous rate
timeFrame: 7-14 days after mass drug administration (MDA)
Secondary outcomes:
measure: malaria prevalence
timeFrame: at 6 months
measure: incidence of clinical (laboratory confirmed) malaria cases
timeFrame: after MDA over 6 months period
measure: serological markers of recent malaria
timeFrame: after MDA over 6 months period
measure: serological markers of recent Anopheles exposure
timeFrame: after MDA over 6 months period
measure: mosquito density
timeFrame: over 24 months after MDA
measure: mosquito mortality
timeFrame: 21 days post treatment
measure: sporozoite rates in field-caught mosquitoes
timeFrame: over 24 months after MDA
Other outcomes:
measure: drug resistance markers
timeFrame: after MDA 6 months
Locations:
city: Basse Santa Su
country: Gambia
facility: Basse Villages
Study officials:
affiliation: MRC @ LSHTM
name: Umberto D'alessandro, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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.