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We aimed to compare the efficacy and safety of different doses of minocycline\u2010containing regimens with classical tetracycline\u2010based bismuth quadruple therapy.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      Refractory\n                      <jats:styled-content style=\"fixed-case\">\n                        <jats:italic>H. pylori<\/jats:italic>\n                      <\/jats:styled-content>\n                      \u2013infected participants with multiple treatment\u2010failure were randomly (1:1:1:1) allocated to receive 14\u2010day therapy with vonoprazan 20\u2009mg b.i.d, bismuth 220\u2009mg b.i.d, plus tetracycline 400\u2009mg q.i.d and metronidazole 500\u2009mg q.i.d (BQT), or minocycline 50\u2009mg\u2009t.i.d and metronidazole 400\u2009mg\u2009t.i.d (VBMn\n                      <jats:sub>3<\/jats:sub>\n                      M\n                      <jats:sub>3<\/jats:sub>\n                      ), or minocycline 50\u2009mg b.i.d and metronidazole 400\u2009mg q.i.d (VBMn\n                      <jats:sub>2<\/jats:sub>\n                      M\n                      <jats:sub>4<\/jats:sub>\n                      ), or minocycline 50\u2009mg b.i.d and metronidazole 400\u2009mg\u2009t.i.d (VBMn\n                      <jats:sub>2<\/jats:sub>\n                      M\n                      <jats:sub>3<\/jats:sub>\n                      ). Primary outcome was\n                      <jats:styled-content style=\"fixed-case\">\n                        <jats:italic>H. pylori<\/jats:italic>\n                      <\/jats:styled-content>\n                      eradication rate evaluated by\n                      <jats:sup>13<\/jats:sup>\n                      C\u2010urea breath test at least 6\u2009weeks after the end of treatment.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Totally, 480 participants were randomized. Eradication rates of BQT, VBMn\n                      <jats:sub>3<\/jats:sub>\n                      M\n                      <jats:sub>3<\/jats:sub>\n                      , VBMn\n                      <jats:sub>2<\/jats:sub>\n                      M\n                      <jats:sub>4<\/jats:sub>\n                      , and VBMn\n                      <jats:sub>2<\/jats:sub>\n                      M\n                      <jats:sub>3<\/jats:sub>\n                      were 90.0%, 92.5%, 90.8%, and 91.7% by intention\u2010to\u2010treat analysis; 97.3%, 97.4%, 97.3%, and 96.5% by modified intention\u2010to\u2010treat analysis; 98.2%, 97.4%, 97.2%, and 96.4% by per\u2010protocol analysis. There were no statistically significant differences in eradication rates among the regimens, and noninferiority of minocycline\u2010based regimens was confirmed (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.025). Metronidazole resistance did not affect the efficacy. VBMn\n                      <jats:sub>2<\/jats:sub>\n                      M\n                      <jats:sub>3<\/jats:sub>\n                      group achieved the lowest overall incidence of adverse events.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>\n                      Low\u2010dose minocycline\u2010containing quadruple therapy provided similar eradication rates, adherence, and lower adverse event rates compared with classical bismuth quadruple therapy, and may serve as a practical substitute strategy for\n                      <jats:styled-content style=\"fixed-case\">\n                        <jats:italic>H. pylori<\/jats:italic>\n                      <\/jats:styled-content>\n                      rescue treatment when tetracycline access is limited.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Trial Registration<\/jats:title>\n                    <jats:p>ClinicalTrials.gov: NCT06561711<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/jgh.70677","type":"journal-article","created":{"date-parts":[[2026,8,23]],"date-time":"2026-08-23T22:36:05Z","timestamp":1787524565000},"page":"3109-3117","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Optimization of Minocycline\u2010Containing Bismuth Quadruple Therapy for\n                    <scp>\n                      <i>Helicobacter pylori<\/i>\n                    <\/scp>\n                    Rescue Treatment: A Randomized Controlled Trial"],"prefix":"10.1111","volume":"41","author":[{"ORCID":"https:\/\/orcid.org\/0009-0009-4052-1162","authenticated-orcid":false,"given":"Yanan","family":"Gao","sequence":"first","affiliation":[{"name":"Division of Gastroenterology and Hepatology, Shanghai Institute of Digestive 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