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
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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. / Ekoka Mbassi, Dorothea; Mombo-Ngoma, Ghyslain; Held, Jana; Okwu, Dearie Glory; Ndzebe-Ndoumba, Wilfrid; Kalkman, Laura Charlotte; Ekoka Mbassi, Franck Aurelien; Pessanha de Carvalho, Lais; Inoue, Juliana; Akinosho, Malik Azeez; Dimessa Mbadinga, Lia Betty; Yovo, Emmanuel Koffi; Mordmüller, Benjamin; Kremsner, Peter Gottfried; Adegnika, Ayôla Akim; Ramharter, Michael; Zoleko-Manego, Rella.
In: EBIOMEDICINE, Vol. 97, 11.2023, p. 104814.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
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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 -