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.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
QUADRUPLE
Enrollment
141
Jaramogi Oginga Odinga Teaching and Referral Hospital
Kisumu, Kenya
Mosquito survival
Time frame: 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.
Mosquito survival
Time frame: 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.
Number of patients with malaria clinical and parasitological treatment response
Time frame: Up to day 28.
Area under the plasma concentration versus time curve (AUC) of ivermectin
Time frame: Up to day 28.
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.
Time frame: Up to day 28.
Peak plasma Concentration (Cmax) of ivermectin
Time frame: Up to day 28.
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.
Time frame: Up to day 28.
Tolerability as assessed by adverse events reported in a general toxicity questionnaire
Time frame: Up to day 28.
CNS adverse events
Time frame: Up to day 28.
Serious adverse events
Time frame: Up to day 28.
Haemoglobin concentrations
Time frame: Up to day 28.
QTc interval
Time frame: At 52 hours.
Mydriasis quantitated by pupillometry
Time frame: Up to day 28.
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