Efficacy and safety of ivermectin for the treatment of Plasmodium falciparum infections in asymptomatic male and female Gabonese adults - a pilot randomized, double-blind, placebo-controlled single-centre phase Ib/IIa clinical trial

TY - JOUR

T1 - Efficacy and safety of ivermectin for the treatment of Plasmodium falciparum infections in asymptomatic male and female Gabonese adults - a pilot randomized, double-blind, placebo-controlled single-centre phase Ib/IIa clinical trial

AU - Ekoka Mbassi, Dorothea

AU - Mombo-Ngoma, Ghyslain

AU - Held, Jana

AU - Okwu, Dearie Glory

AU - Ndzebe-Ndoumba, Wilfrid

AU - Kalkman, Laura Charlotte

AU - Ekoka Mbassi, Franck Aurelien

AU - Pessanha de Carvalho, Lais

AU - Inoue, Juliana

AU - Akinosho, Malik Azeez

AU - Dimessa Mbadinga, Lia Betty

AU - Yovo, Emmanuel Koffi

AU - Mordmüller, Benjamin

AU - Kremsner, Peter Gottfried

AU - Adegnika, Ayôla Akim

AU - Ramharter, Michael

AU - Zoleko-Manego, Rella

N1 - Copyright © 2023 The Author(s). Published by Elsevier B.V. All rights reserved.

PY - 2023/11

Y1 - 2023/11

N2 - BACKGROUND: Ivermectin's mosquitocidal effect and in vitro activity against Plasmodium falciparum asexual stages are known. Its in vivo blood-schizonticidal efficacy is unknown. Ivermectin's tolerability and efficacy against P. falciparum infections in Gabonese adults were assessed.METHODS: The study consisted of a multiple dose stage and a randomized, double-blind, placebo-controlled stage. Adults with asymptomatic P. falciparum parasitaemia (200-5000 parasites/μl) were enrolled. First, three groups of five participants received 200 μg/kg ivermectin once daily for one, two, and three days, respectively, and then 34 participants were randomized to 300 μg/kg ivermectin or placebo once daily for 3 days. Primary efficacy outcome was time to 90% parasite reduction. Primary safety outcomes were drug-related serious and severe adverse events (Trial registration: PACTR201908520097051).FINDINGS: Between June 2019 and October 2020, 49 participants were enrolled. Out of the 34 randomized participants, 29 (85%) completed the trial as per protocol. No severe or serious adverse events were observed. The median time to 90% parasite reduction was 24.1 vs. 32.0 h in the ivermectin and placebo groups, respectively (HR 1.38 [95% CI 0.64 to 2.97]).INTERPRETATION: Ivermectin was well tolerated in doses up to 300 μg/kg once daily for three days and asymptomatic P. falciparum asexual parasitaemia was reduced similarly with this dose of ivermectin compared to placebo. Further studies are needed to evaluate plasmodicidal effect of ivermectin at higher doses and in larger samples.FUNDING: This study was funded by the Centre de Recherches Médicales de Lambaréné and the Centre for Tropical Medicine of the Bernhard Nocht Institute for Tropical Medicine.

AB - BACKGROUND: Ivermectin's mosquitocidal effect and in vitro activity against Plasmodium falciparum asexual stages are known. Its in vivo blood-schizonticidal efficacy is unknown. Ivermectin's tolerability and efficacy against P. falciparum infections in Gabonese adults were assessed.METHODS: The study consisted of a multiple dose stage and a randomized, double-blind, placebo-controlled stage. Adults with asymptomatic P. falciparum parasitaemia (200-5000 parasites/μl) were enrolled. First, three groups of five participants received 200 μg/kg ivermectin once daily for one, two, and three days, respectively, and then 34 participants were randomized to 300 μg/kg ivermectin or placebo once daily for 3 days. Primary efficacy outcome was time to 90% parasite reduction. Primary safety outcomes were drug-related serious and severe adverse events (Trial registration: PACTR201908520097051).FINDINGS: Between June 2019 and October 2020, 49 participants were enrolled. Out of the 34 randomized participants, 29 (85%) completed the trial as per protocol. No severe or serious adverse events were observed. The median time to 90% parasite reduction was 24.1 vs. 32.0 h in the ivermectin and placebo groups, respectively (HR 1.38 [95% CI 0.64 to 2.97]).INTERPRETATION: Ivermectin was well tolerated in doses up to 300 μg/kg once daily for three days and asymptomatic P. falciparum asexual parasitaemia was reduced similarly with this dose of ivermectin compared to placebo. Further studies are needed to evaluate plasmodicidal effect of ivermectin at higher doses and in larger samples.FUNDING: This study was funded by the Centre de Recherches Médicales de Lambaréné and the Centre for Tropical Medicine of the Bernhard Nocht Institute for Tropical Medicine.

KW - Adult

KW - Female

KW - Humans

KW - Male

KW - Antimalarials/adverse effects

KW - Double-Blind Method

KW - Ivermectin/adverse effects

KW - Malaria, Falciparum/drug therapy

KW - Pilot Projects

KW - Plasmodium falciparum

U2 - 10.1016/j.ebiom.2023.104814

DO - 10.1016/j.ebiom.2023.104814

M3 - SCORING: Journal article

C2 - 37839134

VL - 97

SP - 104814

JO - EBIOMEDICINE

JF - EBIOMEDICINE

SN - 2352-3964

ER -