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| ID | Type | Description | Link |
|---|---|---|---|
| 2775 | Other Identifier | Kenya Medical Research Institute | |
| 6720 | Other Identifier | Centers for Disease Control and Prevention |
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| Name | Class |
|---|---|
| Kenya Medical Research Institute | OTHER |
| Centers for Disease Control and Prevention | FED |
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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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| placebo | Placebo Comparator | Standard 3-day course of dihydroartemisinin-piperaquine, plus once a day for 3 days: placebo 600 mcg/kg/day. |
|
| ivermectin 300 mcg/kg | Experimental | 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 | Experimental | Standard 3-day course of dihydroartemisinin-piperaquine, plus once a day for 3 days: ivermectin 600 mcg/kg/day. |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| ivermectin | Drug |
| ||
| placebo |
| Measure | Description | Time Frame |
|---|---|---|
| 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. |
| Measure | Description | Time Frame |
|---|---|---|
| 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. | |
| Number of patients with malaria clinical and parasitological treatment response |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Menno R. Smit, MD, MPH | Liverpool School of Tropical Medicine | Principal Investigator |
| Feiko ter Kuile, Prof. | Liverpool School of Tropical Medicine | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Jaramogi Oginga Odinga Teaching and Referral Hospital | Kisumu | 40100 | Kenya |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 27856406 | Background | 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. doi: 10.2196/resprot.6617. | |
| 29602751 |
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| ID | Term |
|---|---|
| D008288 | Malaria |
| ID | Term |
|---|---|
| D011528 | Protozoan Infections |
| D010272 | Parasitic Diseases |
| D007239 | Infections |
| D000096724 | Mosquito-Borne Diseases |
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| ID | Term |
|---|---|
| D007559 | Ivermectin |
| ID | Term |
|---|---|
| D018942 | Macrolides |
| D061065 | Polyketides |
| D007783 | Lactones |
| D009930 | Organic Chemicals |
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| Drug |
Placebo for ivermectin. |
|
| dihydroartemisinin-piperaquine | Drug |
|
| Up to day 28. |
| Area under the plasma concentration versus time curve (AUC) of ivermectin | 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. | Up to day 28. |
| Peak plasma Concentration (Cmax) of ivermectin | 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. | Up to day 28. |
| Tolerability as assessed by adverse events reported in a general toxicity questionnaire | Up to day 28. |
| CNS adverse events | Up to day 28. |
| Serious adverse events | Up to day 28. |
| Haemoglobin concentrations | Up to day 28. |
| QTc interval | At 52 hours. |
| Mydriasis quantitated by pupillometry | Up to day 28. |
| Result |
| 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 ivermectin when co-administered with dihydroartemisinin-piperaquine in Kenyan adults with uncomplicated malaria (IVERMAL): a randomised, double-blind, placebo-controlled trial. Lancet Infect Dis. 2018 Jun;18(6):615-626. doi: 10.1016/S1473-3099(18)30163-4. Epub 2018 Mar 27. |
| 30125353 | Result | 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 Dihydroartemisinin-Piperaquine on Mosquitocidal Activity and QT-Prolongation (IVERMAL). Clin Pharmacol Ther. 2019 Feb;105(2):388-401. doi: 10.1002/cpt.1219. Epub 2018 Oct 9. |
| 30590537 | Derived | Smit MR, Ochomo EO, Aljayyoussi G, Kwambai TK, Abong'o BO, Bousema T, Waterhouse D, Bayoh NM, Gimnig JE, Samuels AM, Desai MR, Phillips-Howard PA, Kariuki SK, Wang D, Ward SA, Ter Kuile FO. Human Direct Skin Feeding Versus Membrane Feeding to Assess the Mosquitocidal Efficacy of High-Dose Ivermectin (IVERMAL Trial). Clin Infect Dis. 2019 Sep 13;69(7):1112-1119. doi: 10.1093/cid/ciy1063. |
| D000079426 |
| Vector Borne Diseases |