Condition category
Skin and Connective Tissue Diseases
Date applied
09/10/2018
Date assigned
15/10/2018
Last edited
24/10/2018
Prospective/Retrospective
Prospectively registered
Overall trial status
Ongoing
Recruitment status
Not yet recruiting

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. Chelsea and Westminster Hospital NHS Foundation Trust
4. Poole Hospital NHS Foundation Trust
5. Portsmouth Hospitals NHS Trust, St Marys Hospital

When is the study starting and how long is it expected to run for?
April 2018 to March 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

Planning to submit to HRA South Central Hampshire B, committee meeting date 28/11/2018

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

31/03/2021

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

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

Recruitment start date

01/02/2019

Recruitment end date

31/03/2021

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

Chelsea and Westminster Hospital NHS Foundation Trust
369 Fulham Rd, Chelsea
London
SW10 9NH
United Kingdom

Trial participating centre

University Hospitals Bristol NHS Foundation Trust
Bristol Royal Infirmary, Bristol Dermatology Centre
Bristol
BS6 7EL
United Kingdom

Sponsor information

Organisation

University of Southampton

Sponsor details

B28/2027
Highfield
Southampton
SO17 1BJ
United Kingdom

Sponsor type

University/education

Website

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

Federal/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

31/03/2022

Participant level data

To be made available at a later date

Basic results (scientific)

Publication list

Publication citations

Additional files

Editorial Notes

24/10/2018: Internal review.