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

项目摘要/摘要 痤疮是世界范围内最常见的疾病之一，85%的青少年患有痤疮，而且经常持续存在 进入成年期。痤疮比牛皮癣、蜂窝织炎和 黑色素瘤。虽然轻度痤疮通常可以通过外用药物来治疗，但中度到重度痤疮 通常需要全身用药，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部分，但很少有随机临床试验表明 在这些常用的治疗方案中，疗效和无显示出比较的有效性。这个 医学研究所已将这一领域确定为比较有效性研究的最优先事项之一。 此外，人们对这些不同处理对微生物群的影响知之甚少。 我们小组之前的研究表明，口服抗生素是最常见的全身用药 痤疮的治疗和患者经常使用它们一年以上。事实上，皮肤科医生 人均开出的抗生素比其他任何专科都多。然而，长时间使用抗生素可能会 与各种不良后果有关，包括细菌耐药性、咽炎、胶原蛋白 血管疾病、炎症性肠病、乳腺癌和结肠癌。因此，有越来越多的 国际社会特别是疾病控制中心对改善 门诊环境中的抗生素管理和多个痤疮临床指南建议 通过使用非抗菌疗法减少抗生素的使用，并限制抗生素的使用时间 心理治疗。 对于患有中度到严重痤疮的女性，螺内酯可能代表着一种有效的、耐受性良好的 口服抗生素的治疗替代品。最初是作为一种节省钾的利尿剂开发的，多年来 它也被用于标签外的痤疮，因为它对这种疾病的激素发病机制的潜在影响。 然而，尽管专家意见支持使用螺内酯治疗痤疮，但它的使用仍然存在 相对少见的临床证据表明螺内酯的有效性仅限于 小型的，通常是回溯性的研究。螺内酯与其他药物的疗效比较试验 缺乏口服抗生素等药物。 在具体目标1中，我们将进行双盲随机对照非劣势比较 螺内酯与多西环素治疗女性痤疮的疗效比较。自口服四环素类 结果显示，像多西环素这样的抗生素是目前治疗痤疮最常见的全身用药 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(多西环素)与非抗生素(螺内酯)治疗痤疮的相对效果 在微生物组上。这项试验将对医疗实践产生重大影响，涉及到 女性中至重度痤疮，并告知有关在整个过程中更适当地使用抗生素的政策 医药。

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.