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Multiple-dose versus single-dose ivermectin for Strongyloides stercoralis infection (Strong Treat 1 to 4): a multicentre, open-label, phase 3, randomised controlled superiority trial

Strongyloides stercoralis infection is a neglected condition that places people who are immunocompromised at risk of hyperinfection and death. Ivermectin is the drug of choice for the treatment of S stercoralis infection, but there is no definitive evidence on the optimal dose. This trial aimed to a...

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Published in:The Lancet infectious diseases 2019-11, Vol.19 (11), p.1181-1190
Main Authors: Buonfrate, Dora, Salas-Coronas, Joaquin, Muñoz, José, Maruri, Begoña Trevino, Rodari, Paola, Castelli, Francesco, Zammarchi, Lorenzo, Bianchi, Leila, Gobbi, Federico, Cabezas-Fernández, Teresa, Requena-Mendez, Ana, Godbole, Gauri, Silva, Ronaldo, Romero, Marilena, Chiodini, Peter L, Bisoffi, Zeno
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cited_by cdi_FETCH-LOGICAL-c492t-261a62dfd751f6b9ee054607c0f1b14b171d006baf86eb28435f84f125c4fcf03
cites cdi_FETCH-LOGICAL-c492t-261a62dfd751f6b9ee054607c0f1b14b171d006baf86eb28435f84f125c4fcf03
container_end_page 1190
container_issue 11
container_start_page 1181
container_title The Lancet infectious diseases
container_volume 19
creator Buonfrate, Dora
Salas-Coronas, Joaquin
Muñoz, José
Maruri, Begoña Trevino
Rodari, Paola
Castelli, Francesco
Zammarchi, Lorenzo
Bianchi, Leila
Gobbi, Federico
Cabezas-Fernández, Teresa
Requena-Mendez, Ana
Godbole, Gauri
Silva, Ronaldo
Romero, Marilena
Chiodini, Peter L
Bisoffi, Zeno
description Strongyloides stercoralis infection is a neglected condition that places people who are immunocompromised at risk of hyperinfection and death. Ivermectin is the drug of choice for the treatment of S stercoralis infection, but there is no definitive evidence on the optimal dose. This trial aimed to assess whether multiple doses of ivermectin were superior to a single dose for the treatment of non-disseminated strongyloidiasis. Our study was designed as a multicentre, open-label, phase 3, randomised controlled superiority trial. Participants were enrolled in four centres in Italy, three in Spain, and two in the UK, and recruiting sites were predominantly hospitals. Eligible patients were older than 5 years, weighed more than 15 kg, were residents in an area not endemic for S stercoralis, and either were positive for S stercoralis in faecal tests and on serology (any titre) or had a positive serological test with high titres, irrespective of the result of faecal tests. Patients were randomly assigned (1:1) using a computer-generated, blinded allocation sequence (with randomly mixed block sizes of six, eight, and ten participants) to receive either one dose of ivermectin 200 μg/kg or four doses of ivermectin 200 μg/kg (given on days 1, 2, 15, and 16). The primary endpoint was the proportion of participants with clearance of S stercoralis infection at 12 months, which was assessed in all randomly assigned participants who were not lost to follow-up (modified full-analysis set) and in participants in the modified full-analysis set who did not deviate from the assigned treatment regimen (per-protocol set). All participants were included in the safety analysis. The trial was registered with ClinicalTrials.gov, NCT01570504, and is now closed for recruitment. Of the 351 patients assessed for eligibility, 309 recruited between March 26, 2013, and May 3, 2017, were randomly assigned to one dose (n=155) or four doses (n=154) of ivermectin. At 12 months in the modified full-analysis set, 86% (95% CI 79 to 91; 102 of 118 participants) had responded to treatment in the single-dose group compared with 85% (77 to 90; 96 of 113 participants) in the four-dose group (risk difference 1·48%, 95% CI −7·55 to 10·52; p=0·75); similar results were observed in the per-protocol set. Adverse events were generally of mild intensity and more frequent in the multiple-dose than in the single-dose group. The trial was terminated early due to futility. Multiple doses of ivermectin did not sh
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Ivermectin is the drug of choice for the treatment of S stercoralis infection, but there is no definitive evidence on the optimal dose. This trial aimed to assess whether multiple doses of ivermectin were superior to a single dose for the treatment of non-disseminated strongyloidiasis. Our study was designed as a multicentre, open-label, phase 3, randomised controlled superiority trial. Participants were enrolled in four centres in Italy, three in Spain, and two in the UK, and recruiting sites were predominantly hospitals. Eligible patients were older than 5 years, weighed more than 15 kg, were residents in an area not endemic for S stercoralis, and either were positive for S stercoralis in faecal tests and on serology (any titre) or had a positive serological test with high titres, irrespective of the result of faecal tests. Patients were randomly assigned (1:1) using a computer-generated, blinded allocation sequence (with randomly mixed block sizes of six, eight, and ten participants) to receive either one dose of ivermectin 200 μg/kg or four doses of ivermectin 200 μg/kg (given on days 1, 2, 15, and 16). The primary endpoint was the proportion of participants with clearance of S stercoralis infection at 12 months, which was assessed in all randomly assigned participants who were not lost to follow-up (modified full-analysis set) and in participants in the modified full-analysis set who did not deviate from the assigned treatment regimen (per-protocol set). All participants were included in the safety analysis. The trial was registered with ClinicalTrials.gov, NCT01570504, and is now closed for recruitment. Of the 351 patients assessed for eligibility, 309 recruited between March 26, 2013, and May 3, 2017, were randomly assigned to one dose (n=155) or four doses (n=154) of ivermectin. At 12 months in the modified full-analysis set, 86% (95% CI 79 to 91; 102 of 118 participants) had responded to treatment in the single-dose group compared with 85% (77 to 90; 96 of 113 participants) in the four-dose group (risk difference 1·48%, 95% CI −7·55 to 10·52; p=0·75); similar results were observed in the per-protocol set. Adverse events were generally of mild intensity and more frequent in the multiple-dose than in the single-dose group. The trial was terminated early due to futility. Multiple doses of ivermectin did not show higher efficacy and was tolerated less than a single dose. A single dose should therefore be preferred for the treatment of non-disseminated strongyloidiasis. 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Ivermectin is the drug of choice for the treatment of S stercoralis infection, but there is no definitive evidence on the optimal dose. This trial aimed to assess whether multiple doses of ivermectin were superior to a single dose for the treatment of non-disseminated strongyloidiasis. Our study was designed as a multicentre, open-label, phase 3, randomised controlled superiority trial. Participants were enrolled in four centres in Italy, three in Spain, and two in the UK, and recruiting sites were predominantly hospitals. Eligible patients were older than 5 years, weighed more than 15 kg, were residents in an area not endemic for S stercoralis, and either were positive for S stercoralis in faecal tests and on serology (any titre) or had a positive serological test with high titres, irrespective of the result of faecal tests. Patients were randomly assigned (1:1) using a computer-generated, blinded allocation sequence (with randomly mixed block sizes of six, eight, and ten participants) to receive either one dose of ivermectin 200 μg/kg or four doses of ivermectin 200 μg/kg (given on days 1, 2, 15, and 16). The primary endpoint was the proportion of participants with clearance of S stercoralis infection at 12 months, which was assessed in all randomly assigned participants who were not lost to follow-up (modified full-analysis set) and in participants in the modified full-analysis set who did not deviate from the assigned treatment regimen (per-protocol set). All participants were included in the safety analysis. The trial was registered with ClinicalTrials.gov, NCT01570504, and is now closed for recruitment. Of the 351 patients assessed for eligibility, 309 recruited between March 26, 2013, and May 3, 2017, were randomly assigned to one dose (n=155) or four doses (n=154) of ivermectin. At 12 months in the modified full-analysis set, 86% (95% CI 79 to 91; 102 of 118 participants) had responded to treatment in the single-dose group compared with 85% (77 to 90; 96 of 113 participants) in the four-dose group (risk difference 1·48%, 95% CI −7·55 to 10·52; p=0·75); similar results were observed in the per-protocol set. Adverse events were generally of mild intensity and more frequent in the multiple-dose than in the single-dose group. The trial was terminated early due to futility. Multiple doses of ivermectin did not show higher efficacy and was tolerated less than a single dose. A single dose should therefore be preferred for the treatment of non-disseminated strongyloidiasis. There was no funding source for this study.</abstract><cop>United States</cop><pub>Elsevier Ltd</pub><pmid>31558376</pmid><doi>10.1016/S1473-3099(19)30289-0</doi><tpages>10</tpages><oa>free_for_read</oa></addata></record>
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identifier ISSN: 1473-3099
ispartof The Lancet infectious diseases, 2019-11, Vol.19 (11), p.1181-1190
issn 1473-3099
1474-4457
language eng
recordid cdi_proquest_miscellaneous_2299136313
source ScienceDirect Freedom Collection
subjects Abdomen
Drug dosages
Funding
Hospitals
Infections
Infectious diseases
Ivermectin
Meta-analysis
Pain
Parasitic diseases
Patients
Pruritus
Randomization
Serology
Strongyloides stercoralis
Strongyloidiasis
Tropical diseases
title Multiple-dose versus single-dose ivermectin for Strongyloides stercoralis infection (Strong Treat 1 to 4): a multicentre, open-label, phase 3, randomised controlled superiority trial
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