Adjunctive Ivermectin Mass Drug Administration for Malaria Control

Malaria,Falciparum Clinical Trial

— MATAMAL  

Official title:

Adjunctive Ivermectin Mass Drug Administration for Malaria Control on the Bijagos Archipelago of Guinea Bissau: A Cluster-randomized Placebo-controlled Trial

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04844905
• Other study ID #: 19156
• Status: Recruiting
• Phase: Phase 3
• Start date: May 3, 2021
• Est. completion date: August 2023

Study information

• Verified date: February 2022
• Source: London School of Hygiene and Tropical Medicine
• Contact: Anna R Last, MBChB PhD
• Phone: 0044(0)2072770
• Email: anna.last[@]lshtm.ac.uk
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 24000
• Est. completion date: August 2023
• Est. primary completion date: March 2023
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 6 Months and older

Eligibility

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)

Related Conditions & MeSH terms

• Filariasis
• Hook Worm
• Lymphatic Filariasis
• Malaria
• Malaria, Falciparum
• Malaria,Falciparum
• Neglected Tropical Diseases
• Scabies
• Soil Transmitted Helminths
• Strongyloidiasis

Intervention

Drug:
• Ivermectin
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.
• Placebo
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.
• Dihydroartemisinin-piperaquine
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.

Locations

Country	Name	City	State
Guinea-Bissau	Bijagos Archipelago (islands)	Bissau

Sponsors (5)

Lead Sponsor	Collaborator
London School of Hygiene and Tropical Medicine	Bandim Health Project, Instituto Nacional de Estudos e Pesquisas, Guinee-Bissau, Medical Research Council Unit, The Gambia, Ministerio de Saude Publica, Guinee-Bissau

Country where clinical trial is conducted

Guinea-Bissau, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Vector parous rate	Vector parous rate will be determined by assessment of mosquitoes trapped 7-14 days following MDA. Vector parity will be used to determine Anopheles gambiae age structure to estimate vector survival between arms.	7-14 days post-MDA
Secondary	Prevalence of infection with Plasmodium falciparum	Prevalence of infection with Plasmodium falciparum in all age groups estimated using a cross-sectional survey sample conducted after the first year of intervention	1 year
Secondary	Incidence of clinical malaria (Passive Case Detection)	Incidence of clinical malaria diagnosed at health facilities confirmed by malaria Rapid Diagnostic Test	For six months during the malaria transmission season
Secondary	Incidence of clinical malaria (Active Case Detection)	Incidence of clinical malaria confirmed by malaria Rapid Diagnostic Test in a cohort of 50 children per cluster aged 5-14 years	For six months during the malaria transmission season
Secondary	Age-adjusted prevalence of recent exposure to Plasmodium falciparum	Mean Median Fluorescence Intensity of serological markers associated with recent exposure to Plasmodium falciparum in all age groups estimated using a cross-sectional survey sample during peak transmission season after each year of intervention	Peak transmission season at 1 year and 2 years
Secondary	Vector density	Total number of trapped mosquitoes per cluster	For six months during the malaria transmission season
Secondary	Vector species composition	Species characterisation using nucleic acid amplification tests as a proportion of total mosquitoes caught in traps	For six months during the malaria transmission season
Secondary	Prevalence of exposure to Anopheles exposure	Mean Median Fluorescence Intensity of serological markers associated with exposure to Anopheles salivary antigen in all age groups estimated using a cross-sectional survey sample	Peak transmission season at 1 year and 2 years
Secondary	Vector sporozoite rates	Proportion of Plasmodium falciparum circumsporozoite antibody (CSP) positive mosquitoes caught in traps	For six months during the malaria transmission season
Secondary	Prevalence of Ivermectin-susceptible Neglected Tropical Diseases (NTDs)	Prevalence of IVM-susceptible NTDs (scabies, strongyloides, other soil-transmitted helminths and lymphatic filariasis) and head lice using clinical and serological parameters estimated using a cross-sectional survey sample during the dry season after two years of intervention.	2 years
Secondary	MDA coverage estimates	Cluster level coverage estimates calculated from MDA distribution and denominator census	During MDA in year 1 and year 2
Secondary	Prevalence of resistance to artemisinin and partner drugs in humans	Prevalence of resistance to artemisinin and partner drugs in humans using molecular markers of resistance in all age groups estimated using a cross-sectional survey sample	Peak transmission season at 1 year and at 2 years