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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

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
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
Introduction: acne 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 analysis: women (≥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 dissemination: this 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 number ISRCTN12892056;Pre-results.
Acne Vulgaris/drug therapy, Adult, Clinical Trials, Phase III as Topic, Double-Blind Method, Female, Humans, Quality of Life, Randomized Controlled Trials as Topic, Spironolactone/therapeutic use, Treatment Outcome
2044-6055
Renz, Susanne
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Chinnery, Fay
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Stuart, Beth
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Day, Laura
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Muller, Ingrid
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Soulsby, Irene
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Nuttall, Jacqui
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Thomas, Karen
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Thomas, Kim Suzanne
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Sach, Tracey
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Stanton, Louise
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Ridd, Matthew J
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Francis, Nick
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Little, Paul
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Eminton, Zina
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Griffiths, Gareth
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Layton, Alison M
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Santer, Miriam
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Renz, Susanne
36c29f10-0c7b-4c5f-85c0-4d6828696853
Chinnery, Fay
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Stuart, Beth
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Day, Laura
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Muller, Ingrid
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Soulsby, Irene
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Nuttall, Jacqui
154aec0a-05f2-4379-918e-9c36767fdc4c
Thomas, Karen
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Thomas, Kim Suzanne
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Sach, Tracey
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Stanton, Louise
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Ridd, Matthew J
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Francis, Nick
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Little, Paul
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Eminton, Zina
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Griffiths, Gareth
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Layton, Alison M
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Santer, Miriam
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Renz, Susanne, Chinnery, Fay, Stuart, Beth, Day, Laura, Muller, Ingrid, Soulsby, Irene, Nuttall, Jacqui, Thomas, Karen, Thomas, Kim Suzanne, Sach, Tracey, Stanton, Louise, Ridd, Matthew J, Francis, Nick, Little, Paul, Eminton, Zina, Griffiths, Gareth, Layton, Alison M and Santer, Miriam (2021) 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. BMJ Open, 11 (8), [e053876]. (doi:10.1136/bmjopen-2021-053876).

Record type: Article

Abstract

Introduction: acne 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 analysis: women (≥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 dissemination: this 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 number ISRCTN12892056;Pre-results.

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e053876.full - Version of Record
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Accepted/In Press date: 20 July 2021
Published date: 26 August 2021
Additional Information: Funding This project is funded by the National Institute for Health Research (NIHR) Health Technology Assessment (HTA) programme (grant reference number 16/13/02) and supported by NIHR CTU support funding at Southampton CTU. The views expressed are those of the authors and not necessarily those of the NIHR or the Department of Health and Social Care. The NIHR HTA funder will play no role in the execution, analysis, interpretation of data or study publication. The study is registered on the UK NIHR study portfolio, meaning there are research nurses based at UK hospitals who help in screening potential patients to identify those eligible for the study. Southampton CTU, an NIHR CTU support funded UK Clinical Research Collaboration registered CTU, is coordinating the study. University of Southampton is the sponsor for the study. Acknowledgments The authors thank the virtual patient panel (brought together by NIHR INVOLVE) for their advice on the study design. The study was developed with support from the UK Dermatology Clinical Trials Network (UK DCTN). The UK DCTN is grateful to the British Association of Dermatologists and the University of Nottingham for financial support of the Network. UK DCTN conducted surveys among patients with acne and health professionals managing acne to inform the study design, promoting the study and identifying and advising on potential hospital sites delivering the study. The authors also thank Wessex CRN for funding the initial social media advertising campaign; Jessica Boxall and Liz Allaway for management of the study social media accounts as well as running and coordinating the social media adverts; hospital dermatology centres recruiting for the study: Queen Elizabeth Hospital, Birmingham; Bristol Royal Infirmary Dermatology Centre, Bristol; University Hospital of Wales, Cardiff; General Hospital, Epsom; District Hospital, Harrogate; St Mary’s Hospital (Imperial College NHS Healthcare Trust), London; Queen’s Medical Centre, Nottingham; General Hospital, Poole; St Mary’s General Hospital Dermatology Centre, Portsmouth; Swansea Bay University Health Board, Swansea; participant identification centres (PICs) for searching their patient lists and mail outs and clinical research networks for helping to identify potential PICs.
Keywords: Acne Vulgaris/drug therapy, Adult, Clinical Trials, Phase III as Topic, Double-Blind Method, Female, Humans, Quality of Life, Randomized Controlled Trials as Topic, Spironolactone/therapeutic use, Treatment Outcome

Identifiers

Local EPrints ID: 452496
URI: http://eprints.soton.ac.uk/id/eprint/452496
ISSN: 2044-6055
PURE UUID: f3c85d85-4ce1-4f4a-bfd9-2016bd911839
ORCID for Fay Chinnery: ORCID iD orcid.org/0000-0002-8082-9016
ORCID for Beth Stuart: ORCID iD orcid.org/0000-0001-5432-7437
ORCID for Ingrid Muller: ORCID iD orcid.org/0000-0001-9341-6133
ORCID for Tracey Sach: ORCID iD orcid.org/0000-0002-8098-9220
ORCID for Louise Stanton: ORCID iD orcid.org/0000-0001-8181-840X
ORCID for Nick Francis: ORCID iD orcid.org/0000-0001-8939-7312
ORCID for Paul Little: ORCID iD orcid.org/0000-0003-3664-1873
ORCID for Gareth Griffiths: ORCID iD orcid.org/0000-0002-9579-8021
ORCID for Miriam Santer: ORCID iD orcid.org/0000-0001-7264-5260

Catalogue record

Date deposited: 11 Dec 2021 11:20
Last modified: 12 Jul 2024 02:14

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Contributors

Author: Susanne Renz
Author: Fay Chinnery ORCID iD
Author: Beth Stuart ORCID iD
Author: Laura Day
Author: Ingrid Muller ORCID iD
Author: Irene Soulsby
Author: Jacqui Nuttall
Author: Karen Thomas
Author: Kim Suzanne Thomas
Author: Tracey Sach ORCID iD
Author: Louise Stanton ORCID iD
Author: Matthew J Ridd
Author: Nick Francis ORCID iD
Author: Paul Little ORCID iD
Author: Zina Eminton
Author: Alison M Layton
Author: Miriam Santer ORCID iD

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