Clinical trial NCT04844905: Adjunctive Ivermectin Mass Drug Administration for Malaria Control
Official title: Adjunctive Ivermectin Mass Drug Administration for Malaria Control on the Bijagos Archipelago of Guinea Bissau: A Cluster-randomized Placebo-controlled Trial
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE3
Conditions: Malaria,Falciparum
Neglected Tropical Diseases
Strongyloidiasis
Lymphatic Filariasis
Scabies
Hook Worm
Soil Transmitted Helminths
Keywords: Vector Control
Mass Drug Administration
Integrated Disease Control
Malaria
Guinea Bissau
West Africa
Antimalarials
Ivermectin
Dihydroartemisinin
Piperaquine
Lead sponsor: London School of Hygiene and Tropical Medicine
Sponsor class: OTHER
Collaborators: name: Medical Research Council Unit, The Gambia
name: Ministerio de Saude Publica, Guinee-Bissau
name: Bandim Health Project
name: Instituto Nacional de Estudos e Pesquisas, Guinee-Bissau
First posted: 2021-04-14
Enrollment: 24000
Sex: ALL
Minimum age (years): 6
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Two arms with clusters randomized to DP+IVM or DP+Placebo with a 1:1 ratio
Primary purpose: TREATMENT

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.

Detailed description: The objectives of this trial are

1. To evaluate the impact of adjunctive IVM to DP MDA on malaria transmission in communities with high ITN coverage.
2. To evaluate the impact of IVM MDA on An. gambiae population density and age-structure.
3. To evaluate the impact of IVM MDA on the prevalence of co-endemic IVM-susceptible Neglected Tropical Diseases (lymphatic filariasis, soil transmitted helminths and scabies)
4. To evaluate acceptability, feasibility and access to MDA as a strategy for malaria control and to identify the most acceptable way of achieving and sustaining high coverage MDA with IVM and DP.

This cluster-randomized placebo-controlled trial has two arms. A total of 24 clusters will be randomly assigned to receive DP + IVM MDA or DP+ Placebo MDA using computer-generated random numbers. To mitigate against contamination effects, the majority of clusters will be separate islands and will be separated by distances greater than 2km. On the two islands that are divided (each into two clusters), a buffer zone of 2km between each cluster will be ensured. The total population of the archipelago is 24,000. The investigators will ensure balance between trial arms with respect to population size, baseline Plasmodium falciparum prevalence and access to health care. All clusters will receive the standard programmatic malaria control interventions implemented by the National Malaria Control Programme which includes insecticide-treated nets (ITN), intermittent preventative treatment in pregnancy (IPTp), seasonal malarial chemoprophylaxis (SMC) for children aged 3-59 months and case diagnosis and treatment (CDT) with Artemether-lumefantrine.

Eligibility criteria: Inclusion Criteria:

1. Age over six months to receive dihydroartemisinin-piperaquine
2. Height over 90cm or weight over 15kg to receive ivermectin or placebo
3. Willingness to adhere to trial procedures
4. 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)

Exclusion Criteria:

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

Primary outcomes:
measure: Prevalence of infection with Plasmodium falciparum
timeFrame: 2 years
Secondary outcomes:
measure: Vector parous rate
timeFrame: 7-14 days post-MDA
measure: Prevalence of infection with Plasmodium falciparum
timeFrame: 1 year
measure: Incidence of clinical malaria (Passive Case Detection)
timeFrame: For six months during the malaria transmission season
measure: Incidence of clinical malaria (Active Case Detection)
timeFrame: For six months during the malaria transmission season
measure: Age-adjusted prevalence of recent exposure to Plasmodium falciparum
timeFrame: Peak transmission season at 1 year and 2 years
measure: Vector density
timeFrame: For six months during the malaria transmission season
measure: Vector species composition
timeFrame: For six months during the malaria transmission season
measure: Prevalence of exposure to Anopheles exposure
timeFrame: Peak transmission season at 1 year and 2 years
measure: Vector sporozoite rates
timeFrame: For six months during the malaria transmission season
measure: Prevalence of Ivermectin-susceptible Neglected Tropical Diseases (NTDs)
timeFrame: 2 years
measure: MDA coverage estimates
timeFrame: During MDA in year 1 and year 2
measure: Prevalence of resistance to artemisinin and partner drugs in humans
timeFrame: Peak transmission season at 1 year and at 2 years
Other outcomes:
Locations:
city: Bissau
country: Guinea-Bissau
facility: Bijagos Archipelago (islands)
Study officials:
affiliation: London School of Hygiene and Tropical Medicine
name: Anna R Last, MBChB PhD
role: PRINCIPAL_INVESTIGATOR
References: