Randomized Double-blind Study on the Benefit of Spironolactone for Treating Acne of Adult Woman.

NCT03334682 | Completed Phase 3 DMC

• 1 other identifier: RC16_0467
• Study Type: interventional
• Target: 158
• Locations: 1 country
• Sites: 9

Brief Summary

Acne vulgaris of adult woman has increased over the past 10 years; it affects currently 20% to 30% of adult women. The physiopathology of adult woman acne is distinguished from the teenager one by essentially 2 factors:

• hormonal factor with a peripheral hyperandrogenism coupled with an hypersensibility of cutaneous androgens receptors of these women. But this point is still at the stage of hypothesis.
• inflammatory factor linked with Propionibacterium Aces ; indeed these women received most of the time many cures of local and systematic antibiotics at the origin of resistant Propionibacterium Aces strains which lead to a chronical activation of cutaneous innate immunity. On a therapeutic plan, four types of systemic treatment, approved in this indication are:
• Tetracyclines which are problematic for the bacterial resistance and consequently constant relapse when they are stopped.
• Zinc salts which target only the inflammatory lesions and were shown less effective than cycline
• Antiandrogens, with acetate of cyproterone associated with risks of phlebitis and pulmonary embolism, and increase risk of triglycerides, cholesterol and hepatic balance.
• The last alternative is represented by isotretinoin but the use in women of childbearing potential is binding because of the teratogen risks and the hyperandrogenism represents an identified risk of relapse. In this context, the spironolactone could represent an interesting alternative. It blocks the 5-alpha-reductase receptors at sebaceous gland and inhibits Luteinizing hormone (LH) production at the pituitary level. It is not submitted to isotretinoin constraints, does not lead to bacterial resistance and targets the peripheral hyperandrogenism. Currently, very few studies have been performed and on a weak number of patients but they showed that at low doses (lower than 200mg/day), spironolactone can be effective against acne. In that context, it seemed clearly interesting to perform the first double-blind randomized study spironolactone vs cyclines which remains the moderate acne reference treatment and to demonstrate the superiority of spironolactone's efficacy in order to establish it as alternative way to cycline.

Conditions

Acne Vulgaris

Outcome Measures

Primary Outcomes (1)

• Treatment efficacy

  The treatment's efficacy will be determined by the rate of success in each arm. The best rate of success between Month 4 and Month 6 will be chosen for the final result. Rate of success, defined by a decrease of both Adult Female Acne Scoring Tool (AFAST) scores 1 and 2: 1. AFAST score 1: decrease of at least 2 grades compared to baseline or to grade 0 if the baseline was at 1 and 2. AFAST score 2: decrease to grade 1 if baseline was \> 1 or to grade 0 if the baseline was at 1 AFAST 1 (also called GEA) assesses the comedones (open and closed), the non-inflammatory lesions, the papules and pustules and the nodules. The stage is defined according to a global evaluation of severity of acne and ranges from Grade 0 (no acne) to Grade 5 (the worse situation). AFAST 2 assesses acne on an area from the left and right mandibular zone to the upper edge of the trunk and ranges from Grade 0 (no acne) to Grade 3 (the worse situation).

  Month 4 and Month 6

Secondary Outcomes (18)

• Clinical adverse events

  Within 12 months after randomization

• Sodium abnormal values (biological adverse events)

  From 30 days to 7 days before randomization visit, Month 2, Month 4, Month 9

• Potassium abnormal values (biological adverse events)

  From 30 days to 7 days before randomization visit, Month 2, Month 4, Month 9

• Chlore abnormal values (biological adverse events)

  From 30 days to 7 days before randomization visit, Month 2, Month 4, Month 9

• Calcium abnormal values (biological adverse events)

  From 30 days to 7 days before randomization visit, Month 2, Month 4, Month 9

Study Arms (2)

spironolactone

EXPERIMENTAL

Spironolactone ARROW ® 75 mg, 150mg, orally, once a day during all the trial (12 months: 6 months on double-blinded spironolactone then 6 months on open-label spironolactone), + topical therapy during all the trial (benzoyl peroxide 5%)

Drug: spironolactone

doxycycline

ACTIVE COMPARATOR

(Doxycycline Sandoz 100 mg), 100mg/day during 3 months followed by placebo during 3 months, on double-blinded + topical therapy during all the trial (benzoyl peroxide 5%

Drug: Doxycycline

Interventions

spironolactone DRUG

Dispensation of spironolactone at each visit according to the arm description described above.

spironolactone

Doxycycline DRUG

Dispensation of doxycycline then placebo, at each visit according to the arm description described above.

doxycycline

Eligibility Criteria

• Age: 20 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patient with acne, with at least 10 inflammatory lesions and no more than 3 nodules
• Patient who already had one cycline course for her acne treatment with a 3 months\* wash out or who never had any cycline
• Patient having signed an informed consent
• Absence of use of oral antibiotics and Zinc salts in the last 30 days
• Absence of use of systemic isotretinoin and antiandrogens in the last 6 months
• Absence of microphysiotherapy in the last 15 da
• Women of child-bearing age under contraception since 3 months (oral contraception, implant or IUD).
• Patients with social security

You may not qualify if:

• Patient affected by active /progressive diseases, as infections including Hidradenitis suppurativa, cancers, or endocrine syndrome (eg polycystic ovary syndrome), Addison's disease)
• Patient affected by Rosacea
• Patient with contra-indication to the use of one of the investigational products or auxiliary :
• Patient with intolerance or hypersensitivity to cyclin's, spironolactone or to any ingredient present in associated benzoyl peroxide gel
• Patient with significant impairment of renal excretory function, acute or chronic renal failure, anuria.
• Patient with life-threatening or very severe hepatic impairment.(grade III or IV)
• Patient with hyperkalaemia or strongly requiring potassium-sparing diuretics (eg amiloride, canrenoate, eplerenone, triamterene), or treated continuously with Angiotensin-converting-enzyme (ACE) inhibitors, angiotensin II antagonist, NSAIDs, heparin and molecular weight heparin, ciclosporin and tacrolimus.
• Patient requiring topical isotretinoin or who stopped this drug since less than 2 weeks
• Patient previously treated with spironolactone
• Pregnant woman or likely to become pregnant or nursing and refusing to use an effective contraceptive method
• Patient participating in another interventional clinical trial
• Patient under guardianship or trusteeship

Sponsors & Collaborators

• Nantes University Hospital: lead

Study Sites (9)

Chru Brest

Brest, France

Location

CHU Caen

Caen, France

Location

CHU Grenoble

Grenoble, France

Location

CH La Rochelle

La Rochelle, France

Location

CH Le Mans

Le Mans, France

Location

CHU de Nantes - Dermatologie

Nantes, France

Location

CHU Poitiers

Poitiers, France

Location

Cabinet du Dr Jean-Paul Claudel

Tours, France

Location

CHRU Tours

Tours, France

Location

Related Publications (1)

• Poinas A, Lemoigne M, Le Naour S, Nguyen JM, Schirr-Bonnans S, Riche VP, Vrignaud F, Machet L, Claudel JP, Leccia MT, Hainaut E, Beneton N, Dert C, Boisrobert A, Flet L, Chiffoleau A, Corvec S, Khammari A, Dreno B. FASCE, the benefit of spironolactone for treating acne in women: study protocol for a randomized double-blind trial. Trials. 2020 Jun 25;21(1):571. doi: 10.1186/s13063-020-04432-w.

  PMID: 32586344 DERIVED

MeSH Terms

Conditions

Acne Vulgaris

Interventions

Spironolactone; Doxycycline

Condition Hierarchy (Ancestors)

Acneiform Eruptions; Skin Diseases; Skin and Connective Tissue Diseases; Sebaceous Gland Diseases

Intervention Hierarchy (Ancestors)

Lactones; Organic Chemicals; Pregnenes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Tetracyclines; Naphthacenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Masking Details: The products used in both arms will be over-encapsulated by the Pharmacy of Nantes University Hospital
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 30, 2017
• First Posted: November 7, 2017
• Study Start: January 31, 2018
• Primary Completion: February 3, 2023
• Study Completion: July 4, 2023
• Last Updated: July 18, 2023

Record last verified: 2023-07

Data Sharing

• IPD Sharing: Will not share

Locations

FR (9)