A randomized, double-blind, multi-center comparative effectiveness study of spironolactone versus doxycycline hyclate for the treatment of acne in women

螺内酯与盐酸强力霉素治疗女性痤疮的随机、双盲、多中心比较疗效研究

• 批准号: 10296086
• 负责人: David Margolis
• 金额: $ 104.05万
• 依托单位: UNIVERSITY OF PENNSYLVANIA
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-08-17 至 2026-07-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10296086
• 关键词: Acne; Address; Adolescent; Adult; Adverse event; Affect; Antibiotic Resistance; Antibiotic Therapy; Antibiotics; Antimicrobial Resistance; Area; Attention; Bacterial Antibiotic Resistance; Blood Vessels; Cardiovascular Diseases; Caring; Cellulitis; Centers for Disease Control and Prevention (U.S.); Clinical; Clinical Trials; Collagen; Colon Carcinoma; Comparative Effectiveness Research; Consensus; Dermatologist; Dermatology; Development; Disease; Diuretics; Double-Blind Method; Doxycycline; Drug Prescriptions; Effectiveness; Enrollment; Evaluation; Expert Opinion; Guidelines; Healthcare; Hormonal; Inflammatory; Inflammatory Bowel Diseases; Institute of Medicine (U.S.); International; Interview; Isotretinoin; Lesion; Measures; Medicine; Oral; Outcome; Outpatients; Pathogenesis; Patient-Focused Outcomes; Patients; Pharmaceutical Preparations; Pharyngitis; Policies; Potassium; Provider; Psoriasis; Quality of life; Questionnaires; Randomized; Randomized Clinical Trials; Research; Research Personnel; Retrospective Studies; Safety; Sampling; Spironolactone; Taxonomy; Tetracyclines; Therapeutic; Vascular Diseases; Woman; Work; adverse outcome; bacterial resistance; beta diversity; burden of illness; cohort; comparative effectiveness; comparative effectiveness study; compare effectiveness; evidence base; gut microbiome; improved; indexing; innovation; insight; interest; malignant breast neoplasm; medical specialties; meetings; melanoma; microbial; microbiome; off-label use; primary outcome; randomized trial; skin microbiome; therapy duration; trial comparing; trial design

Project Summary/Abstract Acne is one of the most common diseases worldwide, affecting 85% of adolescents and often persisting into adulthood. Acne is responsible for a greater global burden of disease than psoriasis, cellulitis, and melanoma. Although mild acne can usually be managed with topical medications, moderate to severe acne often requires treatment with systemic medications such as oral antibiotics, spironolactone, and isotretinoin. While these medications are a standard part of care, there are very few randomized clinical trials showing efficacy and none that show comparative effectiveness between these commonly used treatment options. The Institute of Medicine has identified this area as one of the top priorities for comparative effectiveness research. In addition, little is known about the effects of these different treatments on the microbiome. Previous work by our group has shown oral antibiotics are the most common systemic medication used in the treatment of acne and patients frequently use them for more than one year. In fact, dermatologists prescribe more antibiotics per capita than any other specialty. However, prolonged antibiotic use may be associated with a variety of adverse outcomes including bacterial antibiotic resistance, pharyngitis, collagen vascular illnesses, inflammatory bowel disease, and breast and colon cancer. As a result, there is growing international interest and attention specifically from the Centers for Disease Control regarding improving antibiotic stewardship in the outpatient setting and multiple clinical guidelines for acne have recommended reducing the use of antibiotics through the use of non-antimicrobial therapies and by limiting the duration of therapy. For women with moderate to severe acne, spironolactone may represent an effective, well-tolerated therapeutic alternative to oral antibiotics. Originally developed as a potassium-sparing diuretic, for many years it has also been used off-label for acne due to its potential impact on hormonal pathogenesis of this disease. However, despite expert opinion supporting the use of spironolactone in the treatment of acne, its use remains relatively uncommon and clinical evidence demonstrating the effectiveness of spironolactone is limited to small, often retrospective studies. Trials comparing the effectiveness of spironolactone to that of other medications such as oral antibiotics are lacking. In Specific Aim 1, we will conduct a double-blind randomized controlled non-inferiority comparative effectiveness study of spironolactone versus doxycycline for women with acne. Since oral tetracycline-class antibiotics like doxycycline are currently the most common systemic medication prescribed for acne, the results of this trial will have substantial implications for the treatment of acne. In Specific Aim 2, we will evaluate the impact of spironolactone versus doxycycline treatment on the microbiome, which will provide valuable insights regarding the relative effects of antibiotic (doxycycline) versus non-antibiotic (spironolactone) acne treatments on the microbiome. This trial will significantly influence healthcare practice with respect to the treatment of moderate to severe acne in women and inform policy regarding more appropriate use of antibiotics throughout medicine.

项目总结/摘要 痤疮是世界范围内最常见的疾病之一，影响85%的青少年，并且经常持续存在 长大成人痤疮是负责一个更大的全球疾病负担比牛皮癣，蜂窝织炎， 黑素瘤虽然轻度痤疮通常可以管理与外用药物，中度至重度痤疮 通常需要用全身性药物治疗，例如口服抗生素、螺内酯和异维甲酸。 虽然这些药物是护理的标准组成部分，但很少有随机临床试验显示 有效性，没有显示这些常用治疗方案之间的比较有效性。的 医学研究所已将这一领域确定为比较有效性研究的首要任务之一。 此外，人们对这些不同治疗对微生物组的影响知之甚少。 我们小组以前的工作表明，口服抗生素是最常见的全身性药物， 痤疮的治疗和患者经常使用它们超过一年。事实上，皮肤科医生 人均抗生素处方量超过其他任何专科。然而，长期使用抗生素可能会 与多种不良结局相关，包括细菌抗生素耐药性、咽炎、胶原蛋白 血管疾病、炎症性肠病、乳腺癌和结肠癌。因此， 国际关注和关注，特别是来自疾病控制中心关于改善 门诊抗生素管理和多个痤疮临床指南建议 通过使用非抗菌治疗和限制持续时间，减少抗生素的使用 疗法 对于中度至重度痤疮的女性，螺内酯可能是一种有效的，耐受性良好的药物， 替代口服抗生素的治疗方法。最初作为保钾利尿剂开发，多年来 由于其对这种疾病的激素发病机理的潜在影响，它也被用于痤疮的标签外。 然而，尽管专家意见支持使用安体舒通治疗痤疮，其使用仍然存在。 证明螺内酯有效性的临床证据相对少见，仅限于 小型的，通常是回顾性的研究。比较螺内酯与其他药物的有效性的试验 缺乏口服抗生素等药物。 在具体目标1中，我们将进行一项双盲随机对照非劣效性比较 螺内酯与强力霉素治疗女性痤疮疗效比较自口服四环素类 像强力霉素这样的抗生素是目前治疗痤疮最常见的全身性药物， 这项试验的结果将对痤疮的治疗产生重大影响。在具体目标2中，我们将评估 螺内酯与多西环素治疗对微生物组的影响，这将提供有价值的见解 关于抗生素（强力霉素）与非抗生素（螺内酯）痤疮治疗的相对效果 在微生物组上。这项试验将显著影响医疗保健实践方面的治疗 中度至重度痤疮的妇女，并告知政策，更适当地使用抗生素在整个 药