Efficacy and Safety of High-dose Ivermectin for Reducing Malaria Transmission: A Dose Finding Study
- Conditions
- Malaria
- Interventions
- Registration Number
- NCT02511353
- Lead Sponsor
- Liverpool School of Tropical Medicine
- Brief 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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 141
- 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
- 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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description ivermectin 300 mcg/kg placebo 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. ivermectin 600 mcg/kg dihydroartemisinin-piperaquine Standard 3-day course of dihydroartemisinin-piperaquine, plus once a day for 3 days: ivermectin 600 mcg/kg/day. placebo dihydroartemisinin-piperaquine Standard 3-day course of dihydroartemisinin-piperaquine, plus once a day for 3 days: placebo 600 mcg/kg/day. placebo placebo Standard 3-day course of dihydroartemisinin-piperaquine, plus once a day for 3 days: placebo 600 mcg/kg/day. ivermectin 300 mcg/kg dihydroartemisinin-piperaquine 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. ivermectin 300 mcg/kg ivermectin 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. ivermectin 600 mcg/kg ivermectin Standard 3-day course of dihydroartemisinin-piperaquine, plus once a day for 3 days: ivermectin 600 mcg/kg/day.
- Primary Outcome Measures
Name Time Method 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 Outcome Measures
Name Time Method Peak plasma Concentration (Cmax) of ivermectin Up to day 28. Peak plasma Concentration (Cmax) of piperaquine Up to day 28. 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.
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. Tolerability as assessed by adverse events reported in a general toxicity questionnaire Up to day 28. Area under the plasma concentration versus time curve (AUC) of ivermectin Up to day 28. CNS adverse events Up to day 28. Number of patients with malaria clinical and parasitological treatment response Up to day 28. Haemoglobin concentrations Up to day 28. Mydriasis quantitated by pupillometry Up to day 28. Area under the plasma concentration versus time curve (AUC) of piperaquine Up to day 28. 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.
QTc interval At 52 hours. Serious adverse events Up to day 28.
Trial Locations
- Locations (1)
Jaramogi Oginga Odinga Teaching and Referral Hospital
🇰🇪Kisumu, Kenya