TY - JOUR
T1 - Single dose moxidectin versus ivermectin for Onchocerca volvulus infection in Ghana, Liberia, and the Democratic Republic of the Congo
T2 - a randomised, controlled, double-blind phase 3 trial
AU - Opoku, Nicholas O.
AU - Bakajika, Didier K.
AU - Kanza, Eric M.
AU - Howard, Hayford
AU - Mambandu, Germain L.
AU - Nyathirombo, Amos
AU - Nigo, Maurice M.
AU - Kasonia, Kambale
AU - Masembe, Safari L.
AU - Mumbere, Mupenzi
AU - Kataliko, Kambale
AU - Larbelee, Jemmah P.
AU - Kpawor, Mawolo
AU - Bolay, Kpehe M.
AU - Bolay, Fatorma
AU - Asare, Sampson
AU - Attah, Simon K.
AU - Olipoh, George
AU - Vaillant, Michel
AU - Halleux, Christine M.
AU - Kuesel, Annette C.
N1 - Funding Information:
TDR funded this study, utilising contributions from the African Programme for Onchocerciasis Control, US$6?3 million from Wyeth and, following its acquisition by Pfizer, Pfizer, and TDR donor countries. Wyeth provided drug for this study and contributed to the study protocol. Wyeth (Pfizer) prepared the submissions to the Ministries of Health and provided data management services until July 3, 2011. Pfizer was not further involved in this study in any way, including data verification or analysis and has not commented on this manuscript. For input into study design, protocol, preparation, review of blinded progress reports, and advice during study conduct we thank M M Homeida (Academy of Medical Sciences and Technology, Khartoum, Sudan), J Gyapong (Ghana Health Service, Accra, Ghana), E Ottesen (Taskforce for Global Health, Atlanta, GA, USA), I Murdoch (Moorfields Eye Hospital, London, UK), H R Taylor (University of Melbourne, Melbourne, VIC, Australia), B Boatin (TDR, Geneva, Switzerland), and the late K Awadzi (Onchocerciasis Chemotherapy Research Center, Hohoe, Ghana). T Ukety (WHO, Geneva, Switzerland) and J Lazdins (TDR, Geneva, Switzerland) provided advice during capacity building at the sites and study design. P L Olliaro (TDR, Geneva, Switzerland) provided advice during study conduct and manuscript preparation. We thank all study participants, staff at the study sites (M Gayflor, J B Koryon, M Sesay, A Boakai, D Kollie, G S Flomo [Liberia], F Ngave Nyisi, G Abhafule Masikini, F Nzale Ndsedhasi, T Biriema, T Kumba Kabona, R D Ucima Wonya, J Mande Lonema, C Ucwala, J Ugen Walu, L B Havileo, J P Lotsima Tchatchu, Kpambu Lailo, K Pengeza, G K Wahotirwe, M Mambo-Yabo, R K Muhndo, J P K Sikuli, C K Kambere, L K Sivowa, M Vihamba, F Kavugho, I Kasereka, S Mbambu, M Katungu, K Yalala, J G Mateso, G Kiusa, J Ntumba, M R Batoto Valinda [Democratic Republic of the Congo], G Mawunya, C Agbalekpor, V Gantuah, A Kpogoh, V Quist, D G Makaful, S Dinah, S Adaletey, and S Wussah [Ghana]), blinded monitors (in particular J Kealy and M Mandro), and Data Monitoring Committee members (A Abiose and N Twum-Danso).
Funding Information:
Between April, 2009, and May, 2012, we did a randomised, double-blind, single oral dose, ivermectin-controlled study of moxidectin for superiority in onchocerciasis endemic areas in Ghana (Nkwanta district), Liberia (Lofa county), and the Democratic Republic of the Congo (Nord Ituri and Nord Kivu) without loiasis or previous CDTI. We enrolled male and female volunteers aged 12 years or older, weighing 30 kg or more, who had 10 or more microfilariae per mg of skin. Participants with loiasis or lymphatic filariasis with an intensity of infection greater than 100 microfilariae per mL were to be excluded. Full eligibility criteria are shown in the appendix . Volunteers gave consent or assent (with parental consent) through signature or thumbprint in the presence of a literate witness. SmfD was measured in the villages or nearby health clinics by study staff. Volunteers who qualified for further screening were brought to one of the research centres (Hohoe, Ghana; Bolahun, Liberia; Rethy, Nord Ituri and Butembo, Nord Kivu, Democratic Republic of the Congo) for 3 days of screening. Those who were eligible stayed another 5 days for treatment and initial follow-up, and were brought to the centre for 1–2 days for each follow-up visit. This study was approved by the Ghana Food and Drugs Authority; Ghana Health Service Ethics Review Committee; Liberia Ministry of Health and Social Welfare; Ethics Committee of the Liberia Institute for Biomedical Research; Ministère de la Santé Publique of the Democratic Republic of the Congo; Ethics Committee of the Ecole de la Santé Publique Université de Kinshasa Democratic Republic of the Congo; and the WHO Ethics Review Committee. Study compliance with International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use Good Clinical Practice guidelines was monitored. 7
Publisher Copyright:
© 2018 World Health Organization
PY - 2018/10/6
Y1 - 2018/10/6
N2 - Background: The morbidity and socioeconomic effects of onchocerciasis, a parasitic disease that is primarily endemic in sub-Saharan Africa, have motivated large morbidity and transmission control programmes. Annual community-directed ivermectin treatment has substantially reduced prevalence. Elimination requires intensified efforts, including more efficacious treatments. We compared parasitological efficacy and safety of moxidectin and ivermectin. Methods: This double-blind, parallel group, superiority trial was done in four sites in Ghana, Liberia, and the Democratic Republic of the Congo. We enrolled participants (aged ≥12 years) with at least 10 Onchocerca volvulus microfilariae per mg skin who were not co-infected with Loa loa or lymphatic filariasis microfilaraemic. Participants were randomly allocated, stratified by sex and level of infection, to receive a single oral dose of 8 mg moxidectin or 150 μg/kg ivermectin as overencapsulated oral tablets. The primary efficacy outcome was skin microfilariae density 12 months post treatment. We used a mixed-effects model to test the hypothesis that the primary efficacy outcome in the moxidectin group was 50% or less than that in the ivermectin group. The primary efficacy analysis population were all participants who received the study drug and completed 12-month follow-up (modified intention to treat). This study is registered with ClinicalTrials.gov, number NCT00790998. Findings: Between April 22, 2009, and Jan 23, 2011, we enrolled and allocated 998 participants to moxidectin and 501 participants to ivermectin. 978 received moxidectin and 494 ivermectin, of which 947 and 480 were included in primary efficacy outcome analyses. At 12 months, skin microfilarial density (microfilariae per mg of skin) was lower in the moxidectin group (adjusted geometric mean 0·6 [95% CI 0·3–1·0]) than in the ivermectin group (4·5 [3·5–5·9]; difference 3·9 [3·2–4·9], p<0·0001; treatment difference 86%). Mazzotti (ie, efficacy-related) reactions occurred in 967 (99%) of 978 moxidectin-treated participants and in 478 (97%) of 494 ivermectin-treated participants, including ocular reactions (moxidectin 113 [12%] participants and ivermectin 47 [10%] participants), laboratory reactions (788 [81%] and 415 [84%]), and clinical reactions (944 [97%] and 446 [90%]). No serious adverse events were considered to be related to treatment. Interpretation: Skin microfilarial loads (ie, parasite transmission reservoir) are lower after moxidectin treatment than after ivermectin treatment. Moxidectin would therefore be expected to reduce parasite transmission between treatment rounds more than ivermectin could, thus accelerating progress towards elimination. Funding: UNICEF/UNDP/World Bank/WHO Special Programme for Research and Training in Tropical Diseases.
AB - Background: The morbidity and socioeconomic effects of onchocerciasis, a parasitic disease that is primarily endemic in sub-Saharan Africa, have motivated large morbidity and transmission control programmes. Annual community-directed ivermectin treatment has substantially reduced prevalence. Elimination requires intensified efforts, including more efficacious treatments. We compared parasitological efficacy and safety of moxidectin and ivermectin. Methods: This double-blind, parallel group, superiority trial was done in four sites in Ghana, Liberia, and the Democratic Republic of the Congo. We enrolled participants (aged ≥12 years) with at least 10 Onchocerca volvulus microfilariae per mg skin who were not co-infected with Loa loa or lymphatic filariasis microfilaraemic. Participants were randomly allocated, stratified by sex and level of infection, to receive a single oral dose of 8 mg moxidectin or 150 μg/kg ivermectin as overencapsulated oral tablets. The primary efficacy outcome was skin microfilariae density 12 months post treatment. We used a mixed-effects model to test the hypothesis that the primary efficacy outcome in the moxidectin group was 50% or less than that in the ivermectin group. The primary efficacy analysis population were all participants who received the study drug and completed 12-month follow-up (modified intention to treat). This study is registered with ClinicalTrials.gov, number NCT00790998. Findings: Between April 22, 2009, and Jan 23, 2011, we enrolled and allocated 998 participants to moxidectin and 501 participants to ivermectin. 978 received moxidectin and 494 ivermectin, of which 947 and 480 were included in primary efficacy outcome analyses. At 12 months, skin microfilarial density (microfilariae per mg of skin) was lower in the moxidectin group (adjusted geometric mean 0·6 [95% CI 0·3–1·0]) than in the ivermectin group (4·5 [3·5–5·9]; difference 3·9 [3·2–4·9], p<0·0001; treatment difference 86%). Mazzotti (ie, efficacy-related) reactions occurred in 967 (99%) of 978 moxidectin-treated participants and in 478 (97%) of 494 ivermectin-treated participants, including ocular reactions (moxidectin 113 [12%] participants and ivermectin 47 [10%] participants), laboratory reactions (788 [81%] and 415 [84%]), and clinical reactions (944 [97%] and 446 [90%]). No serious adverse events were considered to be related to treatment. Interpretation: Skin microfilarial loads (ie, parasite transmission reservoir) are lower after moxidectin treatment than after ivermectin treatment. Moxidectin would therefore be expected to reduce parasite transmission between treatment rounds more than ivermectin could, thus accelerating progress towards elimination. Funding: UNICEF/UNDP/World Bank/WHO Special Programme for Research and Training in Tropical Diseases.
UR - http://www.scopus.com/inward/record.url?scp=85040638593&partnerID=8YFLogxK
U2 - 10.1016/S0140-6736(17)32844-1
DO - 10.1016/S0140-6736(17)32844-1
M3 - Article
C2 - 29361335
AN - SCOPUS:85040638593
SN - 0140-6736
VL - 392
SP - 1207
EP - 1216
JO - The Lancet
JF - The Lancet
IS - 10154
ER -