Efficacy and Safety of High-dose Ivermectin for Reducing Malaria Transmission: A Dose Finding Study (IVERMAL)

Liverpool School of Tropical Medicine

Status and phase: Completed; Phase 2

Conditions: Malaria

Treatments: Drug: dihydroartemisinin-piperaquine; Drug: ivermectin; Drug: placebo

Study type: Interventional

Funder types: Other; Other U.S. Federal agency

Identifiers

NCT02511353

2775 (Other Identifier)

6720 (Other Identifier)

14.002

Details and patient eligibility

About

In western Kenya the prevalence of malaria in <5 year olds has fallen from 70% in 1997 to 40% in 2008, where it has now stagnated. Innovative approaches are needed to continue towards elimination. Ivermectin is a broad spectrum antiparasitic endectocide widely used for the control of onchocerciasis and lymphatic filariasis at a dose of 150-200 mcg/kg. Ivermectin at this dose has a potent, but short-lived effect for 6-11 days on mosquito survival, egg-laying, and parasite sporogony. Higher doses are needed to prolong its mosquitocidal effects. Previous studies have shown ivermectin is very well tolerated and safe even up to 2,000 mcg/kg. This dose finding study will evaluate the transmission blocking effect of high-dose ivermectin to define the optimal dose for future use of ivermectin in combination with artemisinin-based combination therapy (ACT) for mass drug administration (MDA). It explores a research question of global relevance. A prolonged transmission blocking effect of ivermectin could have substantial consequences for malaria control in the next decades. The results are expected to inform national malaria control programs in malaria endemic countries, to inform WHO guidelines, and to contribute to the regulatory process.

Enrollment: 141 patients

Sex: All

Ages: 18 to 50 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Symptomatic, uncomplicated Plasmodium falciparum infection
• Positive malaria microscopy or malaria RDT (pLDH)
• Age: 18-50 years
• Provide written informed consent
• Agree to be able to travel to clinic on days: 1, 2, 7, 10, 14, 21, and 28

Exclusion criteria

• Signs or symptoms of severe malaria
• Unable to provide written informed consent
• For women: pregnancy or lactation
• Hypersensitivity to ivermectin or DP
• QTc >460 ms on ECG
• Body Mass Index (BMI) below 16 or above 32 kg/m2
• Haemoglobin concentration below 9 g/dL
• Taken ivermectin in the last month
• Taken dihydroartemisinin-piperaquine in the last 12 weeks
• Loa loa as assessed by travel history to Angola, Cameroon, Chad, Central African Republic, Congo, DR Congo, Equatorial Guinea, Ethiopia, Gabon, Nigeria and Sudan
• History and/or symptoms indicating chronic illness
• Current use of tuberculosis or anti-retroviral medication
• Previously enrolled in the same study

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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141 participants in 3 patient groups, including a placebo group

placebo

Placebo Comparator group

Description:

Standard 3-day course of dihydroartemisinin-piperaquine, plus once a day for 3 days: placebo 600 mcg/kg/day.

Treatment:

Drug: placebo

Drug: dihydroartemisinin-piperaquine

ivermectin 300 mcg/kg

Experimental group

Description:

Standard 3-day course of dihydroartemisinin-piperaquine, plus once a day for 3 days: ivermectin 300 mcg/kg/day and placebo 300 mcg/kg/day.

Treatment:

Drug: ivermectin

Drug: placebo

Drug: dihydroartemisinin-piperaquine

ivermectin 600 mcg/kg

Experimental group

Description:

Standard 3-day course of dihydroartemisinin-piperaquine, plus once a day for 3 days: ivermectin 600 mcg/kg/day.

Treatment:

Drug: ivermectin

Drug: dihydroartemisinin-piperaquine