{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T17:57:30Z","timestamp":1790272650393,"version":"4.1.0"},"reference-count":67,"publisher":"SAGE Publications","issue":"1","license":[{"start":{"date-parts":[[2024,7,27]],"date-time":"2024-07-27T00:00:00Z","timestamp":1722038400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"funder":[{"name":"National Institute of Arthritis and Musculoskeletal and Skin Diseases of the National Institutes of Health","award":["U01AR079752-01"],"award-info":[{"award-number":["U01AR079752-01"]}]}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Clinical Trials"],"published-print":{"date-parts":[[2025,2]]},"abstract":"<jats:sec>\n                    <jats:title>Background\/aims:<\/jats:title>\n                    <jats:p>Excessive use of antibiotics has led to development of antibiotic resistance and other antibiotic-associated complications. Dermatologists prescribe more antibiotics per clinician than any other major specialty, with much of this use for acne. Alternative acne treatments are available but are used much less often than antibiotics, at least partially because dermatologists feel that they are less effective. Spironolactone, a hormonal therapy with antiandrogen effects that can address the hormonal pathogenesis of acne, may represent a therapeutic alternative to oral antibiotics for women with acne. However, the comparative effects of spironolactone and oral antibiotics in the treatment of acne have not been definitively studied. The Spironolactone versus Doxycycline for Acne: A Comparative Effectiveness, Noninferiority Evaluation (SD-ACNE) trial aims to answer whether spironolactone, in addition to standard topical therapy, is noninferior to doxycycline (an oral antibiotic) for women with acne. Several interesting challenges arose in the development of this study, including determining acceptability of the comparative regimens to participating dermatologists, identifying data to support a noninferiority margin, and establishing a process for unblinding participants after they completed the study while maintaining the blind for study investigators.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods:<\/jats:title>\n                    <jats:p>We present the scientific and clinical rationale for the decisions made in the design of the trial, including input from key stakeholders through a Delphi consensus process.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results:<\/jats:title>\n                    <jats:p>The Spironolactone versus Doxycycline for Acne: A Comparative Effectiveness, Noninferiority Evaluation trial (NCT04582383) is being conducted at a range of community and academic sites in the United States. To maximize external validity and inform clinical practice, the study is designed with broad eligibility criteria and no prohibition of use of topical medications. Participants in the trial will be randomized to receive either spironolactone 100\u2009mg\/day or doxycycline hyclate 100\u2009mg\/day for 16\u2009weeks. The primary outcome is the absolute decrease in inflammatory lesion count, and we have established a noninferiority margin of four inflammatory lesions. Secondary outcomes include the percentage of participants achieving Investigator Global Assessment success, change in quality of life, and microbiome changes and diversity.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions:<\/jats:title>\n                    <jats:p>The Spironolactone versus Doxycycline for Acne: A Comparative Effectiveness, Noninferiority Evaluation trial will have substantial implications for the treatment of acne and antibiotic stewardship. In addition, this study will provide important information on the effect of these systemic agents on the development of changes to the microbiome and antibiotic resistance in a healthy population of patients.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1177\/17407745241265094","type":"journal-article","created":{"date-parts":[[2024,7,27]],"date-time":"2024-07-27T06:06:04Z","timestamp":1722060364000},"page":"66-76","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":3,"title":["Challenges in designing a randomized, double-blind noninferiority trial for treatment of acne: The SD-ACNE trial"],"prefix":"10.1177","volume":"22","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5467-4102","authenticated-orcid":false,"given":"John S","family":"Barbieri","sequence":"first","affiliation":[{"name":"Department of Dermatology, Brigham and Women\u2019s Hospital, Boston, MA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2364-5253","authenticated-orcid":false,"given":"Susan","family":"Ellenberg","sequence":"additional","affiliation":[{"name":"Center for Clinical Epidemiology and Biostatistics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elizabeth","family":"Grice","sequence":"additional","affiliation":[{"name":"Department of Dermatology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6912-4197","authenticated-orcid":false,"given":"Ann","family":"Tierney","sequence":"additional","affiliation":[{"name":"Center for Clinical Epidemiology and Biostatistics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-7227-6420","authenticated-orcid":false,"given":"Suzette Baez","family":"VanderBeek","sequence":"additional","affiliation":[{"name":"Department of Dermatology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maryte","family":"Papadopoulos","sequence":"additional","affiliation":[{"name":"Department of Dermatology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jennifer","family":"Mason","sequence":"additional","affiliation":[{"name":"Department of Dermatology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anabel","family":"Mason","sequence":"additional","affiliation":[{"name":"Department of Dermatology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James","family":"Dattilo","sequence":"additional","affiliation":[{"name":"Center for Clinical Epidemiology and Biostatistics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David J","family":"Margolis","sequence":"additional","affiliation":[{"name":"Department of Dermatology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2024,7,27]]},"reference":[{"key":"bibr1-17407745241265094","doi-asserted-by":"publisher","DOI":"10.1111\/j.1440-0960.1997.tb01126.x"},{"key":"bibr2-17407745241265094","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaad.2007.06.045"},{"key":"bibr3-17407745241265094","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaad.2015.12.037"},{"key":"bibr4-17407745241265094","doi-asserted-by":"publisher","DOI":"10.1007\/s40257-016-0245-x"},{"key":"bibr5-17407745241265094","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2133.1984.tb04045.x"},{"key":"bibr6-17407745241265094","doi-asserted-by":"publisher","DOI":"10.1111\/j.1468-3083.2005.01072.x"},{"key":"bibr7-17407745241265094","volume":"2","author":"Brown J","year":"2009","journal-title":"Cochrane Database Syst Rev"},{"key":"bibr8-17407745241265094","doi-asserted-by":"publisher","DOI":"10.1001\/jamadermatol.2014.709"},{"key":"bibr9-17407745241265094","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijwd.2016.12.002"},{"key":"bibr10-17407745241265094","doi-asserted-by":"publisher","DOI":"10.1136\/bmjopen-2015-008085"},{"key":"bibr11-17407745241265094","unstructured":"Committee on Comparative Effectiveness Research Prioritization. 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