Plain English Summary
Background and study aims
Spironolactone reduces hormones called androgens, which increase grease production and cause changes in follicles in the skin, making them prone to acne. This study will measure whether spironolactone helps adult women with persistent acne that would normally be treated with oral antibiotics. If shown to be effective, spironolactone could reduce the use of antibiotics for acne, be cheaper than antibiotics, and would be more suitable for long-term use than other treatments taken by mouth (oral treatments).
Who can participate?
Adult women with acne
What does the study involve?
Participants will be randomly allocated to one of two groups. In addition to usual care, participants will take either spironolactone tablets or dummy tablets (placebo) once a day for 24 weeks.
During the first 12 weeks, participants may continue using topical treatments (creams, gels or lotions) as usual but not oral treatments for acne (apart from the contraceptive pill if they are already using it and have been on it for 3 months or more). The study will run for 52 weeks, but participants will be able to use all other treatments as usual after the first 24 weeks (apart from oral antibiotics, which may be used from 12 weeks onwards). After 24 weeks all participants and their GPs will be informed which tablets the participant received in the study. Participants in both arms may ask their GP to prescribe it. We will assess the result of the study by asking participants to complete a standardised questionnaire about acne.
What are the possible benefits and risks of participating?
Participants may see an improvement in their acne and avoid needing to use antibiotics or Roaccutane (isotretinoin), and will be helping to further our knowledge of how to treat adult female acne. This will benefit other women with the same condition in the future. However, a possible risk is that the study treatment may not control the participant’s acne, and there may be some side effects. There could be risks to a participant’s child if they become pregnant and remain on spironolactone. Participants will need to attend 3 clinic visits, provide a couple of blood samples and answer some questionnaires, which they would not do if they were not taking part in the study
Where is the study run from?
The study is being run from 5 dermatology clinics in hospitals in the UK:
1. Harrogate and District NHS Foundation Trust (lead site)
2. University Hospitals Bristol NHS Foundation Trust, Bristol Royal Infirmary, Bristol Dermatology Centre
3. Poole Hospital NHS Foundation Trust
4. Portsmouth Hospitals NHS Trust, St Marys Hospital
5. Epsom and St Helier University Hospitals NHS Trust
6. University Hospitals Birmingham NHS Foundation Trust
When is the study starting and how long is it expected to run for?
April 2018 to November 2021
Who is funding the study?
National Institute for Health Research (NIHR) Health Technology Assessment (HTA) Programme (UK)
Who is the main contact?
Dr Fay Chinnery
safa@soton.ac.uk
Trial website
Contact information
Type
Scientific
Primary contact
Dr Miriam Santer
ORCID ID
Contact details
Primary Care and Population Sciences
University of Southampton
Aldermoor Health Centre
Aldermoor Close
Southampton
SO16 5ST
United Kingdom
Type
Scientific
Additional contact
Dr Alison Layton
ORCID ID
Contact details
Harrogate & District NHS Foundation Trust
Lancaster Park Road
Harrogate
HG2 7SX
United Kingdom
Type
Public
Additional contact
Dr Fay Chinnery
ORCID ID
Contact details
Southampton Clinical Trials Unit
University of Southampton
Mailpoint 131
Southampton General Hospital
Southampton
SO16 6YD
United Kingdom
023 8120 5596
safa@soton.ac.uk
Additional identifiers
EudraCT number
2018-003630-33
ClinicalTrials.gov number
Protocol/serial number
HTA 16/13/02
Study information
Scientific title
Spironolactone for Adult Female Acne: a pragmatic multicentre double-blind randomised superiority trial to investigate the clinical and cost-effectiveness of spironolactone for moderate or severe persistent acne in women
Acronym
SAFA
Study hypothesis
The clinical effectiveness of adding spironolactone to standard topical treatment is greater than placebo and standard topical treatment, for moderate or severe persistent facial acne in adult women.
Ethics approval
Approved 10/01/2019, Wales REC 3 (Health and Care Research Wales Support and Delivery Centre, Castlebridge 4, 15-19 Cowbridge Road East, Cardiff CF11 9AB; Tel: +44 (0)29 2078 5741; Email: corinne.scott@wales.nhs.uk; helen.williams19@wales.nhs.uk), REC ref: 18/WA/0420
Study design
Interventional multi-centre double-blind randomised placebo-controlled superiority trial
Primary study design
Interventional
Secondary study design
Randomised controlled trial
Trial setting
Hospitals
Trial type
Treatment
Patient information sheet
Not available in web format, please use contact details to request a participant information sheet.
Condition
Acne
Intervention
Participants will be randomised to a patient pack which will contain either spironolactone or the placebo in a 1:1 ratio using an Interactive Web Response System (IWRS). Participants will be stratified by centre and by baseline severity (IGA <3 versus IGA ≥3). Participants will remain blinded and receive treatment for 24 weeks, followed by an unblinded follow-up to 52 weeks.
At the baseline, all participants will be given either spironolactone (50 mg) or a placebo, with one tablet to be taken once daily for 6 weeks.
At the 6 week visit, all participants have a 6 week dose escalation review, where either the dose will be kept at 50 mg (one tablet to be taken once daily for a further 6 weeks), or will be increased to 100 mg (two tablets to be taken once daily for a further 6 weeks).
At the 12 week visit, all participants will have a 12 week dose escalation review. Based on their current prescription, the dose will be kept at 50 mg (one tablet to be taken once daily for a further 12 weeks), or will be increased to 100 mg (two tablets to be taken once daily for a further 12 weeks).
All participants will complete their course of study drug at 24 weeks.
Participants who meet the eligibility criteria (as determined by the inclusion and exclusion criteria) for the study and for whom written consent has been obtained will be individually randomised (1:1 ratio) to either the active or the placebo treatment using an Interactive Web Response System (IWRS).
Intervention type
Drug
Phase
Phase III
Drug names
Spironolactone
Primary outcome measure
Quality of life, assessed using the Acne-QoL symptom subscale score at 12 weeks
Secondary outcome measures
1. Quality of life, assessed using the Acne-QoL symptom subscale score at 6 and 24 weeks
2. Emotional effect of the impact of facial acne, assessed using the role-emotional subscale of the Acne-QoL at 6, 12 and 24 weeks
3. Impact of facial acne on a respondent's intersocial relationships, assessed using the role-emotional subscale of the Acne-QoL at 6, 12 and 24 weeks
4. Self-perception of facial acne, assessed using the role-emotional subscale of the Acne-QoL at 6, 12 and 24 weeks
5. Participant self-assessed improvement,recorded on a 6-point Likert scale (with baseline photograph to assist recall) at 6, 12 and 24 weeks
6. Description of individual's acne, assessed by the treating clinician using the Investigator’s Global Assessment at 6 and 12 weeks, adjusted for baseline variables
7. Description of individual's acne, assessed by the individual themselves using the Participant’s Global Assessment at 6, 12 and 24 weeks, adjusted for baseline variables
8. Participant satisfaction with study treatment at 24 weeks (asked prior to unblinding), assessed using a 6-point Likert scale
9. Health-related quality of life, assessed using the EQ-5D-5L at 6, 12 and 24 weeks
10. Cost and cost-effectiveness, assessed using:
10.1. eCRF (case report form) regarding the intervention at the baseline and 6, 12, 24 and 52 weeks
10.2. Participant questionnaires regarding wider NHS resource use at the baseline and 6, 12, 24 and 52 weeks
10.3. EQ-5D-5L at the baseline and 6, 12, 24 and 52 weeks
10.4. Quality adjusted life years (QALYs), assessed using the EQ-5D-5L at the baseline and 6, 12, 24 and 52 weeks
The primary economic evaluation will be an Incremental cost utility analysis from an NHS perspective, as this enables the cost effectiveness to be compared across a range of health conditions and interventions such that decision makers can use the information to inform prioritisation of health care.
A detailed Health Economic Analysis Plan will be written and reviewed prior to the trial database being locked.
Overall trial start date
01/04/2018
Overall trial end date
30/11/2021
Reason abandoned (if study stopped)
Eligibility
Participant inclusion criteria
1. Female
2. Aged 18 years or over
3. Facial acne with symptoms present since at least 6 months
4. Acne of sufficient severity to warrant treatment with oral antibiotics, as judged by the study clinician
5. Women of childbearing potential at risk of pregnancy must be willing to use their usual hormonal or barrier method of contraception for the first 6 months of the study
6. Willing to be randomised to either study arm
7. Willing and able to give informed consent
8. Sufficient English to carry out primary outcome Acne-QoL (which has not been validated in other languages)
Participant type
Patient
Age group
Adult
Gender
Female
Target number of participants
434
Participant exclusion criteria
Current exclusion criteria as of 20/01/2020:
1. Hereditary problems of galactose intolerance, lactase deficiency or glucose-galactose malabsorption
2. Acne grade 0-1 using the Investigator’s Global Assessment (i.e. clear or almost clear)
3. Currently using any of the following:
3.1. Potassium-sparing diuretic
3.2. ACE inhibitor
3.3. Angiotensin II receptor blocker
3.4. Digoxin
4. Started, stopped or changed long-term (lasting more than 2 weeks) hormonal contraception, co-cyprindiol or other hormonal treatment within the past 3 months
5. Planning to start, stop or change long-term (lasting more than 2 weeks) hormonal
contraception, co-cyprindiol or other hormonal treatment within the next 3 months
6. Pregnant/breastfeeding
7. Intending to become pregnant in the next 6 months
8. Androgen-secreting adrenal or ovarian tumour
9. Cushing’s syndrome
10. Congenital adrenal hyperplasia
11. Oral antibiotic treatment (lasting longer than a week) for acne within the past month
12. Oral isotretinoin treatment within the past 6 months
13. Has ever used spironolactone
Blood tests will also be performed at baseline to determine participants’ serum potassium level and estimated glomerular filtration rate (eGFR). Participants may start the trial IMP before the test results are known.
STOPPING CRITERIA
Participants may commence treatment before blood test results are known, but if there is an abnormality (serum potassium level is above the upper limit of the reference range for the laboratory processing the sample, or the eGFR is below 60 ml/min/1.73m2), the participant must be contacted within 5 working days by telephone and told to stop taking the IMP. Participant will be considered a screen failure.
Previous exclusion criteria:
1. Serum potassium above the upper limit of the reference range for the laboratory processing the test (measured at the baseline clinic visit)
2. eGFR below 60 ml/min/1.73m²
3. Hereditary problems of galactose intolerance, lactase deficiency or glucose-galactose malabsorption
4. Acne grade 0-1 using the Investigator’s Global Assessment (i.e. clear or almost clear)
5. Currently using any of the following:
5.1. Potassium-sparing diuretic
5.2. ACE inhibitor
5.3. Angiotensin II receptor blocker
5.4. Digoxin
6. Started, stopped or changed long-term (lasting more than 2 weeks) hormonal contraception, co-cyprindiol or other hormonal treatment within the past 3 months
7. Planning to start, stop or change long-term (lasting more than 2 weeks) hormonal contraception, co-cyprindiol or other hormonal treatment within the next 3 months
8. Pregnant/breastfeeding
9. Intending to become pregnant in the next 6 months
10. Androgen-secreting adrenal or ovarian tumour
11. Cushing’s syndrome
12. Congenital adrenal hyperplasia
13. Oral antibiotic treatment (lasting longer than a week) for acne within the past month
14. Oral isotretinoin treatment within the past 6 months
Added 25/04/2019:
15. Has ever used spironolactone
Recruitment start date
15/06/2019
Recruitment end date
31/05/2021
Locations
Countries of recruitment
United Kingdom
Trial participating centre
Harrogate and District NHS Foundation Trust
Lancaster Park Road
Harrogate
HG2 7SX
United Kingdom
Trial participating centre
Poole Hospital NHS Foundation Trust
Longfleet Road
Poole
BH15 2JB
United Kingdom
Trial participating centre
Portsmouth Hospitals NHS Trust
St Marys Hospital, Milton Road
Portsmouth
PO3 6AD
United Kingdom
Trial participating centre
University Hospitals Bristol NHS Foundation Trust
Bristol Royal Infirmary, Bristol Dermatology Centre
Bristol
BS6 7EL
United Kingdom
Trial participating centre
Queen Elizabeth Hospital
University Hospitals Birmingham NHS Foundation Trust
Mindelsohn Way
Birmingham
B15 2GW
United Kingdom
Trial participating centre
St Helier Hospital
Epsom and St Helier University Hospitals NHS Trust
Wrythe Lane
Carshalton
SM5 1AA
United Kingdom
Funders
Funder type
Government
Funder name
Health Technology Assessment Programme
Alternative name(s)
NIHR Health Technology Assessment Programme, HTA
Funding Body Type
government organisation
Funding Body Subtype
National government
Location
United Kingdom
Results and Publications
Publication and dissemination plan
The study will be reported and disseminated via peer-reviewed scientific journals, internal reports and conference presentations.
We will send participants a summary of the study results, unless they have told us they prefer not to receive this. The summary will also be available on the Southampton Clinical Trial Unit SAFA website to members of the public.
The findings will also be published in updates to participants and through contacts with patient groups. Existing networks (email lists and social media) will be used to maximise impact.
No identifiable personal data will be published.
IPD sharing statement:
The data sharing plans for the current study are unknown and will be made available at a later date
Intention to publish date
31/05/2022
Participant level data
To be made available at a later date
Basic results (scientific)
Publication list