Fixed-Dose Artesunate–Amodiaquine Combination vs Chloroquine for Treatment of Uncomplicated Blood Stage P. vivax Infection in the Brazilian Amazon: An Open-Label Randomized, Controlled Trial
Background. Despite increasing evidence of the development of Plasmodium vivax chloroquine (CQ) resistance, there have been no trials comparing its efficacy with that of artemisinin-based combination therapies (ACTs) in Latin America. Methods. This randomized controlled trial compared the antischizo...
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| Veröffentlicht in: | Clinical infectious diseases 2017-01, Vol.64 (2), p.166-174 |
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| creator | Siqueira, Andre M. Alencar, Aline C. Melo, Gisely C. Magalhaes, Belisa L. Machado, Kim Filho, Aristóteles C. Alencar Kuehn, Andrea Marques, Marly M. Manso, Monica Costa Felger, Ingrid Vieira, José L. F. Lameyre, Valerie Daniel-Ribeiro, Claudio T. Lacerda, Marcus V. G. |
| description | Background. Despite increasing evidence of the development of Plasmodium vivax chloroquine (CQ) resistance, there have been no trials comparing its efficacy with that of artemisinin-based combination therapies (ACTs) in Latin America. Methods. This randomized controlled trial compared the antischizontocidal efficacy and safety of a 3-day supervised treatment of the fixed-dose combination artesunate-amodiaquine Winthrop® (ASAQ) versus CQ for treatment of uncomplicated P. vivax infection in Manaus, Brazil. Patients were followed for 42 days. Primary endpoints were adequate clinical and parasitological responses (ACPR) rates at day 28. Genotype-adjustment was performed. Results. From 2012 to 2013, 380 patients were enrolled. In the per-protocol (PP) analysis, adjusted-ACPR was achieved in 100% (165/165) and 93.6% (161/172) of patients in the ASAQ and CQ arm (difference 6.4%, 95% CI 2.7%; 10.1%) at day 28 and in 97.4% (151/155) and 77.7% (129/166), respectively (difference 19.7%, 95% CI 12.9%; 26.5%), at day 42. Apart from ITT D28 assessment, superiority of ASAQ on ACPR was demonstrated. ASAQ presented faster clearance of parasitaemia and fever. Based on CQ blood level measurements, CQ resistance prevalence was estimated at 11.5% (95% CI: 7.5-17.3) up to day 42. At least one emergent adverse event (AE) was recorded for 79/190 (41×6%) in the ASAQ group and for 85/190 (44×7%) in the CQ group. Both treatments had similar safety profiles. Conclusions. ASAQ exhibited high efficacy against CQ resistant P. vivax and is an adequate alternative in the study area. Studies with an efficacious comparator, longer follow-up and genotype-adjustment can improve CQR characterization. Clinical Trials Registration. NCT01378286. |
| doi_str_mv | 10.1093/cid/ciw706 |
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Alencar ; Kuehn, Andrea ; Marques, Marly M. ; Manso, Monica Costa ; Felger, Ingrid ; Vieira, José L. F. ; Lameyre, Valerie ; Daniel-Ribeiro, Claudio T. ; Lacerda, Marcus V. G.</creator><creatorcontrib>Siqueira, Andre M. ; Alencar, Aline C. ; Melo, Gisely C. ; Magalhaes, Belisa L. ; Machado, Kim ; Filho, Aristóteles C. Alencar ; Kuehn, Andrea ; Marques, Marly M. ; Manso, Monica Costa ; Felger, Ingrid ; Vieira, José L. F. ; Lameyre, Valerie ; Daniel-Ribeiro, Claudio T. ; Lacerda, Marcus V. G.</creatorcontrib><description>Background. Despite increasing evidence of the development of Plasmodium vivax chloroquine (CQ) resistance, there have been no trials comparing its efficacy with that of artemisinin-based combination therapies (ACTs) in Latin America. Methods. This randomized controlled trial compared the antischizontocidal efficacy and safety of a 3-day supervised treatment of the fixed-dose combination artesunate-amodiaquine Winthrop® (ASAQ) versus CQ for treatment of uncomplicated P. vivax infection in Manaus, Brazil. Patients were followed for 42 days. Primary endpoints were adequate clinical and parasitological responses (ACPR) rates at day 28. Genotype-adjustment was performed. Results. From 2012 to 2013, 380 patients were enrolled. In the per-protocol (PP) analysis, adjusted-ACPR was achieved in 100% (165/165) and 93.6% (161/172) of patients in the ASAQ and CQ arm (difference 6.4%, 95% CI 2.7%; 10.1%) at day 28 and in 97.4% (151/155) and 77.7% (129/166), respectively (difference 19.7%, 95% CI 12.9%; 26.5%), at day 42. Apart from ITT D28 assessment, superiority of ASAQ on ACPR was demonstrated. ASAQ presented faster clearance of parasitaemia and fever. Based on CQ blood level measurements, CQ resistance prevalence was estimated at 11.5% (95% CI: 7.5-17.3) up to day 42. At least one emergent adverse event (AE) was recorded for 79/190 (41×6%) in the ASAQ group and for 85/190 (44×7%) in the CQ group. Both treatments had similar safety profiles. Conclusions. ASAQ exhibited high efficacy against CQ resistant P. vivax and is an adequate alternative in the study area. Studies with an efficacious comparator, longer follow-up and genotype-adjustment can improve CQR characterization. Clinical Trials Registration. NCT01378286.</description><identifier>ISSN: 1058-4838</identifier><identifier>EISSN: 1537-6591</identifier><identifier>DOI: 10.1093/cid/ciw706</identifier><identifier>PMID: 27988484</identifier><language>eng</language><publisher>United States: Oxford University Press</publisher><subject>Adolescent ; Adult ; Aged ; Amodiaquine - administration & dosage ; Antimalarials - administration & dosage ; Artemisinins - administration & dosage ; ARTICLES AND COMMENTARIES ; Brazil ; Child ; Child, Preschool ; Chloroquine - administration & dosage ; Clinical trials ; Drug Combinations ; Drug dosages ; Drug resistance ; Drug therapy ; Female ; Genotype ; Genotype & phenotype ; Humans ; Infant ; Kaplan-Meier Estimate ; Major ; Malaria ; Malaria, Vivax - drug therapy ; Malaria, Vivax - parasitology ; Malaria, Vivax - transmission ; Male ; Malària ; Middle Aged ; Parasitemia - drug therapy ; Parasitemia - parasitology ; Parasitic protozoa ; Plasmodium vivax ; Plasmodium vivax - drug effects ; Plasmodium vivax - genetics ; Prescription drugs ; Recurrence ; Treatment Failure ; Treatment Outcome ; Young Adult</subject><ispartof>Clinical infectious diseases, 2017-01, Vol.64 (2), p.166-174</ispartof><rights>Copyright © 2017 Oxford University Press on behalf of the Infectious Diseases Society of America</rights><rights>The Author 2016. Published by Oxford University Press for the Infectious Diseases Society of America.</rights><rights>Copyright Oxford University Press, UK Jan 15, 2017</rights><rights>cc by (c) Siqueira et al., 2017 info:eu-repo/semantics/openAccess <a href="http://creativecommons.org/licenses/by/3.0/es/">http://creativecommons.org/licenses/by/3.0/es/</a></rights><rights>The Author 2016. Published by Oxford University Press for the Infectious Diseases Society of America. 2016</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c503t-7123e8a63db31c8de812f3d17b546c4e456b3a10267abe937521d437f9b8fb5e3</citedby><cites>FETCH-LOGICAL-c503t-7123e8a63db31c8de812f3d17b546c4e456b3a10267abe937521d437f9b8fb5e3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.jstor.org/stable/pdf/26373739$$EPDF$$P50$$Gjstor$$H</linktopdf><linktohtml>$$Uhttps://www.jstor.org/stable/26373739$$EHTML$$P50$$Gjstor$$H</linktohtml><link.rule.ids>230,315,781,785,804,886,26979,27929,27930,58022,58255</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/27988484$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Siqueira, Andre M.</creatorcontrib><creatorcontrib>Alencar, Aline C.</creatorcontrib><creatorcontrib>Melo, Gisely C.</creatorcontrib><creatorcontrib>Magalhaes, Belisa L.</creatorcontrib><creatorcontrib>Machado, Kim</creatorcontrib><creatorcontrib>Filho, Aristóteles C. Alencar</creatorcontrib><creatorcontrib>Kuehn, Andrea</creatorcontrib><creatorcontrib>Marques, Marly M.</creatorcontrib><creatorcontrib>Manso, Monica Costa</creatorcontrib><creatorcontrib>Felger, Ingrid</creatorcontrib><creatorcontrib>Vieira, José L. F.</creatorcontrib><creatorcontrib>Lameyre, Valerie</creatorcontrib><creatorcontrib>Daniel-Ribeiro, Claudio T.</creatorcontrib><creatorcontrib>Lacerda, Marcus V. G.</creatorcontrib><title>Fixed-Dose Artesunate–Amodiaquine Combination vs Chloroquine for Treatment of Uncomplicated Blood Stage P. vivax Infection in the Brazilian Amazon: An Open-Label Randomized, Controlled Trial</title><title>Clinical infectious diseases</title><addtitle>Clin Infect Dis</addtitle><description>Background. Despite increasing evidence of the development of Plasmodium vivax chloroquine (CQ) resistance, there have been no trials comparing its efficacy with that of artemisinin-based combination therapies (ACTs) in Latin America. Methods. This randomized controlled trial compared the antischizontocidal efficacy and safety of a 3-day supervised treatment of the fixed-dose combination artesunate-amodiaquine Winthrop® (ASAQ) versus CQ for treatment of uncomplicated P. vivax infection in Manaus, Brazil. Patients were followed for 42 days. Primary endpoints were adequate clinical and parasitological responses (ACPR) rates at day 28. Genotype-adjustment was performed. Results. From 2012 to 2013, 380 patients were enrolled. In the per-protocol (PP) analysis, adjusted-ACPR was achieved in 100% (165/165) and 93.6% (161/172) of patients in the ASAQ and CQ arm (difference 6.4%, 95% CI 2.7%; 10.1%) at day 28 and in 97.4% (151/155) and 77.7% (129/166), respectively (difference 19.7%, 95% CI 12.9%; 26.5%), at day 42. Apart from ITT D28 assessment, superiority of ASAQ on ACPR was demonstrated. ASAQ presented faster clearance of parasitaemia and fever. Based on CQ blood level measurements, CQ resistance prevalence was estimated at 11.5% (95% CI: 7.5-17.3) up to day 42. At least one emergent adverse event (AE) was recorded for 79/190 (41×6%) in the ASAQ group and for 85/190 (44×7%) in the CQ group. Both treatments had similar safety profiles. Conclusions. ASAQ exhibited high efficacy against CQ resistant P. vivax and is an adequate alternative in the study area. Studies with an efficacious comparator, longer follow-up and genotype-adjustment can improve CQR characterization. Clinical Trials Registration. NCT01378286.</description><subject>Adolescent</subject><subject>Adult</subject><subject>Aged</subject><subject>Amodiaquine - administration & dosage</subject><subject>Antimalarials - administration & dosage</subject><subject>Artemisinins - administration & dosage</subject><subject>ARTICLES AND COMMENTARIES</subject><subject>Brazil</subject><subject>Child</subject><subject>Child, Preschool</subject><subject>Chloroquine - administration & dosage</subject><subject>Clinical trials</subject><subject>Drug Combinations</subject><subject>Drug dosages</subject><subject>Drug resistance</subject><subject>Drug therapy</subject><subject>Female</subject><subject>Genotype</subject><subject>Genotype & phenotype</subject><subject>Humans</subject><subject>Infant</subject><subject>Kaplan-Meier Estimate</subject><subject>Major</subject><subject>Malaria</subject><subject>Malaria, Vivax - drug therapy</subject><subject>Malaria, Vivax - parasitology</subject><subject>Malaria, Vivax - transmission</subject><subject>Male</subject><subject>Malària</subject><subject>Middle Aged</subject><subject>Parasitemia - drug therapy</subject><subject>Parasitemia - parasitology</subject><subject>Parasitic protozoa</subject><subject>Plasmodium vivax</subject><subject>Plasmodium vivax - drug effects</subject><subject>Plasmodium vivax - genetics</subject><subject>Prescription drugs</subject><subject>Recurrence</subject><subject>Treatment Failure</subject><subject>Treatment Outcome</subject><subject>Young Adult</subject><issn>1058-4838</issn><issn>1537-6591</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2017</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>XX2</sourceid><recordid>eNqNkstu1DAUhiMEoqWwYQ-yxAYhUuw4iR0WSNOBQqWRimC6thz7pOPKsQc7GcqseAdeiGfhSfB0huGyQrbly_nOb_voz7KHBB8T3NAXyug0PjNc38oOSUVZXlcNuZ3WuOJ5ySk_yO7FeIUxIRxXd7ODgjWcl7w8zL6fmmvQ-WsfAU3CAHF0coAfX79Neq-N_DQaB2jq-9akc-MdWkU0XVgf_DbU-YDmAeTQgxuQ79CFU75fWqOSjEYn1nuNPg7yEtD7Y7QyK3mNzlwH6kbMODQsAJ0EuTbWSIcmvVx79xJNHDpfgstnsgWLPkinfW_WoJ-nt7gheGuT-DwYae9ndzppIzzYzUfZxemb-fRdPjt_ezadzHJVYTrkjBQUuKypbilRXAMnRUc1YW1V1qqEsqpbKgkuapaubCirCqJLyrqm5V1bAT3KXm11l2Pbg1bpu0FasQyml-GL8NKIvyPOLMSlX4kklDpPAmQroOKoRAAFIdXoJnG_2YwCs0IULLUy5TzdXbqpN8RB9CYqsFY68GMUhNecFoxj_h9oRYqmLhua0Cf_oFd-DC5Vb0Nx3JBklEQ92703-BgDdPu_Eiw2vhPJd2LruwQ__rM6e_SX0RLwaAtcxcGH3_GastQa-hMcI-HA</recordid><startdate>20170115</startdate><enddate>20170115</enddate><creator>Siqueira, Andre M.</creator><creator>Alencar, Aline C.</creator><creator>Melo, Gisely C.</creator><creator>Magalhaes, Belisa L.</creator><creator>Machado, Kim</creator><creator>Filho, Aristóteles C. Alencar</creator><creator>Kuehn, Andrea</creator><creator>Marques, Marly M.</creator><creator>Manso, Monica Costa</creator><creator>Felger, Ingrid</creator><creator>Vieira, José L. F.</creator><creator>Lameyre, Valerie</creator><creator>Daniel-Ribeiro, Claudio T.</creator><creator>Lacerda, Marcus V. G.</creator><general>Oxford University Press</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7QL</scope><scope>7T2</scope><scope>7T7</scope><scope>7U7</scope><scope>7U9</scope><scope>8FD</scope><scope>C1K</scope><scope>FR3</scope><scope>H94</scope><scope>K9.</scope><scope>M7N</scope><scope>P64</scope><scope>7X8</scope><scope>7U2</scope><scope>XX2</scope><scope>5PM</scope></search><sort><creationdate>20170115</creationdate><title>Fixed-Dose Artesunate–Amodiaquine Combination vs Chloroquine for Treatment of Uncomplicated Blood Stage P. vivax Infection in the Brazilian Amazon: An Open-Label Randomized, Controlled Trial</title><author>Siqueira, Andre M. ; Alencar, Aline C. ; Melo, Gisely C. ; Magalhaes, Belisa L. ; Machado, Kim ; Filho, Aristóteles C. Alencar ; Kuehn, Andrea ; Marques, Marly M. ; Manso, Monica Costa ; Felger, Ingrid ; Vieira, José L. 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Alencar</creatorcontrib><creatorcontrib>Kuehn, Andrea</creatorcontrib><creatorcontrib>Marques, Marly M.</creatorcontrib><creatorcontrib>Manso, Monica Costa</creatorcontrib><creatorcontrib>Felger, Ingrid</creatorcontrib><creatorcontrib>Vieira, José L. F.</creatorcontrib><creatorcontrib>Lameyre, Valerie</creatorcontrib><creatorcontrib>Daniel-Ribeiro, Claudio T.</creatorcontrib><creatorcontrib>Lacerda, Marcus V. G.</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Bacteriology Abstracts (Microbiology B)</collection><collection>Health and Safety Science Abstracts (Full archive)</collection><collection>Industrial and Applied Microbiology Abstracts (Microbiology A)</collection><collection>Toxicology Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>Technology Research Database</collection><collection>Environmental Sciences and Pollution Management</collection><collection>Engineering Research Database</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Algology Mycology and Protozoology Abstracts (Microbiology C)</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>MEDLINE - Academic</collection><collection>Safety Science and Risk</collection><collection>Recercat</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Clinical infectious diseases</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Siqueira, Andre M.</au><au>Alencar, Aline C.</au><au>Melo, Gisely C.</au><au>Magalhaes, Belisa L.</au><au>Machado, Kim</au><au>Filho, Aristóteles C. Alencar</au><au>Kuehn, Andrea</au><au>Marques, Marly M.</au><au>Manso, Monica Costa</au><au>Felger, Ingrid</au><au>Vieira, José L. F.</au><au>Lameyre, Valerie</au><au>Daniel-Ribeiro, Claudio T.</au><au>Lacerda, Marcus V. G.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Fixed-Dose Artesunate–Amodiaquine Combination vs Chloroquine for Treatment of Uncomplicated Blood Stage P. vivax Infection in the Brazilian Amazon: An Open-Label Randomized, Controlled Trial</atitle><jtitle>Clinical infectious diseases</jtitle><addtitle>Clin Infect Dis</addtitle><date>2017-01-15</date><risdate>2017</risdate><volume>64</volume><issue>2</issue><spage>166</spage><epage>174</epage><pages>166-174</pages><issn>1058-4838</issn><eissn>1537-6591</eissn><abstract>Background. Despite increasing evidence of the development of Plasmodium vivax chloroquine (CQ) resistance, there have been no trials comparing its efficacy with that of artemisinin-based combination therapies (ACTs) in Latin America. Methods. This randomized controlled trial compared the antischizontocidal efficacy and safety of a 3-day supervised treatment of the fixed-dose combination artesunate-amodiaquine Winthrop® (ASAQ) versus CQ for treatment of uncomplicated P. vivax infection in Manaus, Brazil. Patients were followed for 42 days. Primary endpoints were adequate clinical and parasitological responses (ACPR) rates at day 28. Genotype-adjustment was performed. Results. From 2012 to 2013, 380 patients were enrolled. In the per-protocol (PP) analysis, adjusted-ACPR was achieved in 100% (165/165) and 93.6% (161/172) of patients in the ASAQ and CQ arm (difference 6.4%, 95% CI 2.7%; 10.1%) at day 28 and in 97.4% (151/155) and 77.7% (129/166), respectively (difference 19.7%, 95% CI 12.9%; 26.5%), at day 42. Apart from ITT D28 assessment, superiority of ASAQ on ACPR was demonstrated. ASAQ presented faster clearance of parasitaemia and fever. Based on CQ blood level measurements, CQ resistance prevalence was estimated at 11.5% (95% CI: 7.5-17.3) up to day 42. At least one emergent adverse event (AE) was recorded for 79/190 (41×6%) in the ASAQ group and for 85/190 (44×7%) in the CQ group. Both treatments had similar safety profiles. Conclusions. ASAQ exhibited high efficacy against CQ resistant P. vivax and is an adequate alternative in the study area. Studies with an efficacious comparator, longer follow-up and genotype-adjustment can improve CQR characterization. Clinical Trials Registration. NCT01378286.</abstract><cop>United States</cop><pub>Oxford University Press</pub><pmid>27988484</pmid><doi>10.1093/cid/ciw706</doi><tpages>9</tpages><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 1058-4838 |
| ispartof | Clinical infectious diseases, 2017-01, Vol.64 (2), p.166-174 |
| issn | 1058-4838 1537-6591 |
| language | eng |
| recordid | cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_5215218 |
| source | MEDLINE; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; JSTOR Archive Collection A-Z Listing; Oxford University Press Journals All Titles (1996-Current); Recercat; Alma/SFX Local Collection |
| subjects | Adolescent Adult Aged Amodiaquine - administration & dosage Antimalarials - administration & dosage Artemisinins - administration & dosage ARTICLES AND COMMENTARIES Brazil Child Child, Preschool Chloroquine - administration & dosage Clinical trials Drug Combinations Drug dosages Drug resistance Drug therapy Female Genotype Genotype & phenotype Humans Infant Kaplan-Meier Estimate Major Malaria Malaria, Vivax - drug therapy Malaria, Vivax - parasitology Malaria, Vivax - transmission Male Malària Middle Aged Parasitemia - drug therapy Parasitemia - parasitology Parasitic protozoa Plasmodium vivax Plasmodium vivax - drug effects Plasmodium vivax - genetics Prescription drugs Recurrence Treatment Failure Treatment Outcome Young Adult |
| title | Fixed-Dose Artesunate–Amodiaquine Combination vs Chloroquine for Treatment of Uncomplicated Blood Stage P. vivax Infection in the Brazilian Amazon: An Open-Label Randomized, Controlled Trial |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2024-12-14T20%3A18%3A05IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-jstor_pubme&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Fixed-Dose%20Artesunate%E2%80%93Amodiaquine%20Combination%20vs%20Chloroquine%20for%20Treatment%20of%20Uncomplicated%20Blood%20Stage%20P.%20vivax%20Infection%20in%20the%20Brazilian%20Amazon:%20An%20Open-Label%20Randomized,%20Controlled%20Trial&rft.jtitle=Clinical%20infectious%20diseases&rft.au=Siqueira,%20Andre%20M.&rft.date=2017-01-15&rft.volume=64&rft.issue=2&rft.spage=166&rft.epage=174&rft.pages=166-174&rft.issn=1058-4838&rft.eissn=1537-6591&rft_id=info:doi/10.1093/cid/ciw706&rft_dat=%3Cjstor_pubme%3E26373739%3C/jstor_pubme%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=1858091011&rft_id=info:pmid/27988484&rft_jstor_id=26373739&rfr_iscdi=true |