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

Malaria Clinical Trial

— IVERMAL  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02511353
• Other study ID #: 14.002
• Secondary ID: 27756720
• Status: Completed
• Phase: Phase 2
• Start date: July 2015
• Est. completion date: July 2016

Study information

• Verified date: August 2018
• Source: Liverpool School of Tropical Medicine
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 141
• Est. completion date: July 2016
• Est. primary completion date: July 2016
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 50 Years

Eligibility

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

Related Conditions & MeSH terms

• Malaria

Intervention

Drug:
• ivermectin

• placebo
Placebo for ivermectin.
• dihydroartemisinin-piperaquine

Locations

Country	Name	City	State
Kenya	Jaramogi Oginga Odinga Teaching and Referral Hospital	Kisumu

Sponsors (3)

Lead Sponsor	Collaborator
Liverpool School of Tropical Medicine	Centers for Disease Control and Prevention, Kenya Medical Research Institute

Country where clinical trial is conducted

Kenya, 

References & Publications (3)

Smit MR, Ochomo E, Aljayyoussi G, Kwambai T, Abong'o B, Bayoh N, Gimnig J, Samuels A, Desai M, Phillips-Howard PA, Kariuki S, Wang D, Ward S, Ter Kuile FO. Efficacy and Safety of High-Dose Ivermectin for Reducing Malaria Transmission (IVERMAL): Protocol for a Double-Blind, Randomized, Placebo-Controlled, Dose-Finding Trial in Western Kenya. JMIR Res Protoc. 2016 Nov 17;5(4):e213. — View Citation

Smit MR, Ochomo EO, Aljayyoussi G, Kwambai TK, Abong'o BO, Chen T, Bousema T, Slater HC, Waterhouse D, Bayoh NM, Gimnig JE, Samuels AM, Desai MR, Phillips-Howard PA, Kariuki SK, Wang D, Ward SA, Ter Kuile FO. Safety and mosquitocidal efficacy of high-dose — View Citation

Smit MR, Ochomo EO, Waterhouse D, Kwambai TK, Abong'o BO, Bousema T, Bayoh NM, Gimnig JE, Samuels AM, Desai MR, Phillips-Howard PA, Kariuki SK, Wang D, Ter Kuile FO, Ward SA, Aljayyoussi G. Pharmacokinetics-Pharmacodynamics of High-Dose Ivermectin with Di — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Mosquito survival		Survival of mosquitoes at 14 days after feeding on blood taking from study participants who started the 3-day ivermectin and DP regimen 7 days earlier.
Secondary	Mosquito survival		Survival of mosquitoes at each day up to day 21 or 28 after each feeding experiments performed at 0, 2 day+4h, 10, 14, 21, 28 days after start of treatment.
Secondary	Number of patients with malaria clinical and parasitological treatment response		Up to day 28.
Secondary	Area under the plasma concentration versus time curve (AUC) of ivermectin		Up to day 28.
Secondary	Area under the plasma concentration versus time curve (AUC) of piperaquine	Dihydroartemisinin-piperaquine is a combination drug. As dihydroartemisinin has a very short elimination time, only the AUC for the longer acting piperaquine component will be determined.	Up to day 28.
Secondary	Peak plasma Concentration (Cmax) of ivermectin		Up to day 28.
Secondary	Peak plasma Concentration (Cmax) of piperaquine	Dihydroartemisinin-piperaquine is a combination drug. As dihydroartemisinin has a very short elimination time, only the Cmax for the longer acting piperaquine component will be determined.	Up to day 28.
Secondary	Tolerability as assessed by adverse events reported in a general toxicity questionnaire		Up to day 28.
Secondary	CNS adverse events		Up to day 28.
Secondary	Serious adverse events		Up to day 28.
Secondary	Haemoglobin concentrations		Up to day 28.
Secondary	QTc interval		At 52 hours.
Secondary	Mydriasis quantitated by pupillometry		Up to day 28.