ACTIVE: Trial of Artemether-Lumefantrine Alone and in Combination With Ivermectin to Reduce Post-Treatment Malaria Transmission

Sponsor

London School of Hygiene and Tropical Medicine (Other)

Overall Status

Completed

CT.gov ID

NCT01603251

Collaborator

Radboud University Medical Center (Other), Centre national de recherche et de formation sur le paludisme (Other)

120

Enrollment

Location

Arms

Duration (Months)

40.6

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The purpose of this study is to determine the safety and impact of ivermectin, administered as single or repeated dose, in combination with artemether-lumefantrine in reducing the proportion of mosquitoes that survive and become infected after feeding on a blood meal from a malaria-infected individual.

Condition or Disease	Intervention/Treatment	Phase
Malaria	Drug: Artemether-lumefantrine combination Drug: Artemether-lumefantrine combination + single dose Ivermectin Drug: Artemether-lumefantrine combination + repeated dose Ivermectin	Phase 1/Phase 2

Study Design

Study Type:

Interventional

Actual Enrollment :

120 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Primary Purpose:

Treatment

Official Title:

A Double Blind Randomized Controlled Trial of Artemether-Lumefantrine Alone and in Combination With Ivermectin to Reduce Post-Treatment Malaria Transmission

Study Start Date :

Jan 1, 2013

Actual Primary Completion Date :

Apr 1, 2013

Actual Study Completion Date :

Apr 1, 2013

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Artemether-Lumefantrine	Drug: Artemether-lumefantrine combination Artemether-Lumefantrine (AL)combination; a placebo is given together with the first and fifth dose of AL
Experimental: Artemether-Lumefantrine + single dose Ivermectin	Drug: Artemether-lumefantrine combination + single dose Ivermectin Artemether-lumefantrine (AL) combination + Ivermectin (200ug/kg) given once together with the first dose of AL. A placebo is given together with the fifth dose of AL.
Experimental: Artemether-Lumefantrine + repeated dose Ivermectin	Drug: Artemether-lumefantrine combination + repeated dose Ivermectin Artemether-lumefantrine (AL) combination + Ivermectin (200ug/kg) given together with the first and fifth dose of AL.

Arm

Intervention/Treatment

Active Comparator: Artemether-Lumefantrine

Drug: Artemether-lumefantrine combination

Artemether-Lumefantrine (AL)combination; a placebo is given together with the first and fifth dose of AL

Experimental: Artemether-Lumefantrine + single dose Ivermectin

Drug: Artemether-lumefantrine combination + single dose Ivermectin

Artemether-lumefantrine (AL) combination + Ivermectin (200ug/kg) given once together with the first dose of AL. A placebo is given together with the fifth dose of AL.

Experimental: Artemether-Lumefantrine + repeated dose Ivermectin

Drug: Artemether-lumefantrine combination + repeated dose Ivermectin

Artemether-lumefantrine (AL) combination + Ivermectin (200ug/kg) given together with the first and fifth dose of AL.

Outcome Measures

Primary Outcome Measures

Safety [8 days]
The number of adverse events; number of participants with abnormal haemoglobin, biochemistry or full blood count values

Secondary Outcome Measures

Mosquitocidal activity [feeding experiments performed up to 8 days after enrolment; survival of mosquitoes determined up to day 10 after feeding]
Daily mortality rates of (malaria-infected) Anopheles gambiae s.s. and An. funestus mosquitoes after taking a blood meal 1, 3 or 7 days after initiation of treatment

Eligibility Criteria

Criteria

Ages Eligible for Study:

15 Years to 25 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Yes

Inclusion Criteria:

asymptomatically infected individuals with any P. falciparum parasite density

Exclusion Criteria:

age < 15 years or > 25 years
malaria parasite density ≥ 10,000 parasites/µL
clinical symptoms indicating severe malaria
axillary temperature ≥ 37.5°C
Body Mass Index (BMI) below 18 or above 32 kg/m2
haemoglobin concentration below 11 g/dL
taken ivermectin in the last three months
Loa loa as assessed by questionnaire, clinical examination and parasitological assessments
for women: pregnancy or lactation
known hypersensitivity to AL or IVM
history and/or symptoms indicating chronic illness
current use of tuberculosis or anti-retroviral medication
unable to give written informed consent
unwillingness to participate in two membrane feeding assays
travel history to Angola, Cameroon, Chad, Central African Republic, Congo, DR Congo, Equatorial Guinea, Ethiopia, Gabon, Nigeria and Sudan. If a potential participant has ever visited one or more of these countries, he or she will not be eligible for enrolment.
history of cardiovascular disease.
taking drugs that are known to influence cardiac function and to prolong QTc interval, such as class IA and III: neuroleptics, antidepressant agents, certain antibiotics including some agents of the following classes - macrolides, fluoroquinolones, imidazole, and triazole antifungal agents, certain non-sedating antihistaminics (terfenadine, astemizole) and cisapride.
known disturbances of electrolyte balance, e.g. hypokalaemia or hypomagnesaemia.
taking drugs which may be metabolized by cytochrome enzyme CYP2D6 (e.g., flecainide, metoprolol, imipramine, amitriptyline, clomipramine).