Efficacy and Safety of High-dose Ivermectin for Reducing Malaria Transmission: A Dose Finding Study
Information source: Liverpool School of Tropical Medicine
ClinicalTrials.gov processed this data on August 23, 2015
Link to the current ClinicalTrials.gov record.
Condition(s) targeted: Malaria
Intervention: ivermectin (Drug); placebo (Drug); dihydroartemisinin-piperaquine (Drug)
Phase: Phase 2
Status: Recruiting
Sponsored by: Liverpool School of Tropical Medicine Official(s) and/or principal investigator(s):
Menno R. Smit, MD, MPH, Principal Investigator, Affiliation: Liverpool School of Tropical Medicine
Feiko ter Kuile, Prof., Principal Investigator, Affiliation: Liverpool School of Tropical Medicine
Overall contact:
Menno R. Smit, MD, MPH, Phone: +254703991513, Email: menno.smit@liverpool.ac.uk
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.
Clinical Details
Official title: Efficacy and Safety of High-dose Ivermectin for Reducing Malaria Transmission: A Dose Finding Study (IVERMAL)
Study design: Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment
Primary outcome: Mosquito survival
Secondary outcome: Mosquito survivalNumber of patients with malaria clinical and parasitological treatment response Area under the plasma concentration versus time curve (AUC) of ivermectin Area under the plasma concentration versus time curve (AUC) of piperaquine Peak plasma Concentration (Cmax) of ivermectin Peak plasma Concentration (Cmax) of piperaquine Tolerability as assessed by adverse events reported in a general toxicity questionnaire CNS adverse events Serious adverse events Haemoglobin concentrations QTc interval Mydriasis quantitated by pupillometry
Eligibility
Minimum age: 18 Years.
Maximum age: 50 Years.
Gender(s): Both.
Criteria:
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
Locations and Contacts
Menno R. Smit, MD, MPH, Phone: +254703991513, Email: menno.smit@liverpool.ac.uk
Jaramogi Oginga Odinga Teaching and Referral Hospital, Kisumu 40100, Kenya; Recruiting
Menno R. Smit, MD, MPH, Phone: +254703991513, Email: menno.smit@liverpool.ac.uk
Feiko ter Kuile, Prof., Phone: +254708739228, Email: Feiko.TerKuile@lstmed.ac.uk
Additional Information
Starting date: July 2015
Last updated: July 27, 2015
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