Spironolactone for adult female acne (SAFA): protocol for a double-blind, placebo-controlled, phase III randomised study of spironolactone as systemic therapy for acne in adult women

Abstract

IntroductionAcne is one of the most common inflammatory skin diseases worldwide and can have significant psychosocial impact and cause permanent scarring. Spironolactone, a potassium-sparing diuretic, has antiandrogenic properties, potentially reducing sebum production and hyperkeratinisation in acne-prone follicles. Dermatologists have prescribed spironolactone for acne in women for over 30 years, but robust clinical study data are lacking. This study seeks to evaluate whether spironolactone is clinically effective and cost-effective in treating acne in women.Methods and analysisWomen (≥18 years) with persistent facial acne requiring systemic therapy are randomised to receive one tablet per day of 50 mg spironolactone or a matched placebo until week 6, increasing to up to two tablets per day (total of 100 mg spironolactone or matched placebo) until week 24, along with usual topical therapy if desired. Study treatment stops at week 24; participants are informed of their treatment allocation and enter an unblinded observational follow-up period for up to 6 months (up to week 52 after baseline). Primary outcome is the Acne-specific Quality of Life (Acne-QoL) symptom subscale score at week 12. Secondary outcomes include Acne-QoL total and subscales; participant acne self-assessment recorded on a 6-point Likert scale at 6, 12, 24 weeks and up to 52 weeks; Investigator’s Global Assessment at weeks 6 and 12; cost and cost effectiveness are assessed over 24 weeks. Aiming to detect a group difference of 2 points on the Acne-QoL symptom subscale (SD 5.8, effect size 0.35), allowing for 20% loss to follow-up, gives a sample size of 398 participants.Ethics and disseminationThis protocol was approved by Wales Research Ethics Committee (18/WA/0420). Follow-up to be completed in early 2022. Findings will be disseminated to participants, peer-reviewed journals, networks and patient groups, on social media, on the study website and the Southampton Clinical Trials Unit website to maximise impact.Trial registration numberISRCTN12892056;Pre-results.

National Institute for Health and Care Excellence (NICE) acne guideline: what’s the latest for dermatologists?

“…To date, evidence for oral spironolactone is not robust, and this has not been recommended. A study, supported by the National Institute for Health Research Health Technology Assessment, of acne in adult female patients may provide evidence in the future 8 …”

“…A study, supported by the National Institute for Health Research Health Technology Assessment, of acne in adult female patients may provide evidence in the future. 8 A novel introduction is the recommendation to consider photodynamic therapy for adults with moderate-to-severe acne if other treatments are ineffective, not tolerated or contraindicated.…”

Effectiveness of spironolactone for women with acne vulgaris (SAFA) in England and Wales: pragmatic, multicentre, phase 3, double blind, randomised controlled trial

“…This design included a participant reported outcome measure and allowed concomitant use of topical treatments. The trial protocol paper has been published 17. We revised the target sample size (details later) and made amendments to allow retention of research participants during the covid-19 pandemic through flexible trial procedures, particularly through remote follow-up.…”

Factors that influence women’s enrolment and ongoing participation in a partially decentralised randomised controlled dermatology trial: a qualitative interview study with participants in the SAFA (Spironolactone for Adult Female Acne) trial

“…(12,13) Method Setting This was a qualitative sub-study conducted alongside a placebo-controlled trial of Spironolactone for persistent (at least six months) facial acne vulgaris for women aged 18 and over (Spironolactone for Adult Female Acne (SAFA) trial, Fig. 1) (14).…”