{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,18]],"date-time":"2026-07-18T06:02:43Z","timestamp":1784354563184,"version":"3.55.0"},"reference-count":39,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2021,12,1]],"date-time":"2021-12-01T00:00:00Z","timestamp":1638316800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The Journal of Dermatology"],"published-print":{"date-parts":[[2022,3]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Topical metronidazole is not currently approved in Japan as a treatment for the indication of rosacea, although 0.75% metronidazole gel was authorized in 2014 for the management of cancerous skin ulcers. We conducted a randomized, double\u2010blind, vehicle\u2010controlled study to evaluate the efficacy and safety of 0.75% metronidazole gel in Japanese patients with inflammatory lesions (papules\/pustules) and erythema associated with moderate to severe rosacea. Overall, 130 patients were randomly assigned to receive 0.75% metronidazole gel (n\u00a0=\u00a065) or vehicle (n\u00a0=\u00a065), and 120 patients completed 12\u00a0weeks of treatment. The primary efficacy outcome was the proportion of patients who achieved both of the following at week 12: an improvement of &gt;50% in the number of inflammatory lesions (papules\/pustules) and a positive change of at least one degree in erythema severity. This composite outcome was achieved by 72.3% of metronidazole\u2010treated patients versus 36.9% of vehicle\u2010treated patients, with the between\u2010group difference demonstrating significant improvement with 0.75% metronidazole gel (<jats:italic>p<\/jats:italic>\u00a0&lt;\u00a00.0001). All secondary efficacy endpoints (patients achieving a score of \u22653 for percent change in the number of inflammatory lesions at week 12; patients achieving a score of \u22653 for change in erythema severity at week 12; patients achieving an Investigator\u2019s Global Assessment score of 0 or 1 at week 12; percent change over time in the number of inflammatory lesions; change over time in erythema severity) also showed improvement in the 0.75% metronidazole gel group. The incidence of adverse events was higher with metronidazole (40.0%) than with vehicle (29.2%). Of these, treatment\u2010related, treatment\u2010emergent adverse events occurred in 9.2% and 6.2% in the metronidazole and the vehicle group, respectively, but there were no new safety concerns. Overall, the results of this study have confirmed the efficacy and safety of 0.75% metronidazole gel in Japanese patients with rosacea.<\/jats:p>","DOI":"10.1111\/1346-8138.16254","type":"journal-article","created":{"date-parts":[[2021,12,2]],"date-time":"2021-12-02T04:36:18Z","timestamp":1638419778000},"page":"330-340","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["Metronidazole gel (0.75%) in Japanese patients with rosacea: A\u00a0randomized, vehicle\u2010controlled, phase 3 study"],"prefix":"10.1111","volume":"49","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1861-8071","authenticated-orcid":false,"given":"Yoshiki","family":"Miyachi","sequence":"first","affiliation":[{"name":"Graduate School of Public Health Shizuoka Graduate University of Public Health  Shizuoka Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5495-4956","authenticated-orcid":false,"given":"Kenshi","family":"Yamasaki","sequence":"additional","affiliation":[{"name":"Department of Dermatology Tohoku University Graduate School of Medicine  Sendai Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tomomitsu","family":"Fujita","sequence":"additional","affiliation":[{"name":"Clinical Development Department Maruho Co., Ltd  Kyoto Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chie","family":"Fujii","sequence":"additional","affiliation":[{"name":"Clinical Development Department Maruho Co., Ltd  Kyoto Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2021,12]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1111\/bjd.16481"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaad.2018.08.049"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1111\/1346-8138.15301"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1346-8138.2011.01209.x"},{"key":"e_1_2_7_6_1","first-page":"348","article-title":"Burden of disease: the psychosocial impact of rosacea on a patient\u2019s quality of life","volume":"6","author":"Huynh TT","year":"2013","journal-title":"Am Health Drug Benefits"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1007\/s40257-021-00595-7"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1067\/mjd.2002.120625"},{"key":"e_1_2_7_9_1","first-page":"888","article-title":"Recognizing rosacea: tips on differential diagnosis","volume":"18","author":"Johnson SM","year":"2019","journal-title":"J Drugs Dermatol"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaad.2017.08.037"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1111\/bjd.15122"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaad.2020.01.077"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.1038\/nm1616"},{"key":"e_1_2_7_14_1","first-page":"11","article-title":"Antimicrobial peptides in human skin disease","volume":"18","author":"Yamasaki K","year":"2008","journal-title":"Eur J Dermatol"},{"key":"e_1_2_7_15_1","doi-asserted-by":"publisher","DOI":"10.1038\/jidsymp.2011.4"},{"key":"e_1_2_7_16_1","doi-asserted-by":"publisher","DOI":"10.1038\/jid.2010.351"},{"key":"e_1_2_7_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jdermsci.2020.08.011"},{"key":"e_1_2_7_18_1","doi-asserted-by":"publisher","DOI":"10.1007\/978-3-319-49274-2"},{"key":"e_1_2_7_19_1","doi-asserted-by":"publisher","DOI":"10.1007\/s13555-019-00322-5"},{"key":"e_1_2_7_20_1","doi-asserted-by":"publisher","DOI":"10.1111\/ced.13919"},{"key":"e_1_2_7_21_1","doi-asserted-by":"publisher","DOI":"10.1111\/1346-8138.14355"},{"key":"e_1_2_7_22_1","doi-asserted-by":"publisher","DOI":"10.1177\/106002808702100410"},{"key":"e_1_2_7_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(76)92160-7"},{"key":"e_1_2_7_24_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00520-015-3067-0"},{"key":"e_1_2_7_25_1","doi-asserted-by":"publisher","DOI":"10.12968\/hmed.2020.0417"},{"key":"e_1_2_7_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.intimp.2007.10.018"},{"key":"e_1_2_7_27_1","doi-asserted-by":"publisher","DOI":"10.1007\/s101560200036"},{"key":"e_1_2_7_28_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2133.1986.tb02802.x"},{"key":"e_1_2_7_29_1","doi-asserted-by":"publisher","DOI":"10.1111\/ics.12736"},{"key":"e_1_2_7_30_1","doi-asserted-by":"publisher","DOI":"10.1211\/jpp.59.8.0010"},{"key":"e_1_2_7_31_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2133.1983.tb03972.x"},{"key":"e_1_2_7_32_1","doi-asserted-by":"publisher","DOI":"10.1067\/mjd.2001.116219"},{"key":"e_1_2_7_33_1","doi-asserted-by":"publisher","DOI":"10.1111\/bjd.13408"},{"key":"e_1_2_7_34_1","doi-asserted-by":"publisher","DOI":"10.1186\/1477-7525-4-46"},{"key":"e_1_2_7_35_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1346-8138.2002.tb00205.x"},{"key":"e_1_2_7_36_1","doi-asserted-by":"publisher","DOI":"10.1159\/000365390"},{"key":"e_1_2_7_37_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.jid.5700740"},{"key":"e_1_2_7_38_1","doi-asserted-by":"publisher","DOI":"10.2165\/00128071-200001030-00007"},{"key":"e_1_2_7_39_1","doi-asserted-by":"publisher","DOI":"10.1177\/2042098614554919"},{"key":"e_1_2_7_40_1","first-page":"277","article-title":"The antibiotic resistance crisis: Part 1: causes and threats","volume":"40","author":"Ventola CL","year":"2015","journal-title":"P T"}],"container-title":["The Journal of Dermatology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/1346-8138.16254","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/1346-8138.16254","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/1346-8138.16254","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,8,27]],"date-time":"2023-08-27T05:45:41Z","timestamp":1693115141000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/1346-8138.16254"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,12]]},"references-count":39,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2022,3]]}},"alternative-id":["10.1111\/1346-8138.16254"],"URL":"https:\/\/doi.org\/10.1111\/1346-8138.16254","archive":["Portico"],"relation":{},"ISSN":["0385-2407","1346-8138"],"issn-type":[{"value":"0385-2407","type":"print"},{"value":"1346-8138","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,12]]},"assertion":[{"value":"2021-08-25","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2021-11-14","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2021-12-01","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}