Clinical trial NCT03334682: Randomized Double-blind Study on the Benefit of Spironolactone for Treating Acne of Adult Woman.
Official title: Randomized Double-blind Study on the Benefit of Spironolactone for Treating Acne of Adult Woman.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Acne Vulgaris
Lead sponsor: Nantes University Hospital
Sponsor class: OTHER
First posted: 2017-11-07
Enrollment: 158
Sex: FEMALE
Minimum age (years): 20
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility criteria: Inclusion Criteria:

* 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

Exclusion Criteria:

* 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

Primary outcomes:
measure: Treatment efficacy
timeFrame: Month 4 and Month 6
Secondary outcomes:
measure: Clinical adverse events
timeFrame: Within 12 months after randomization
measure: Sodium abnormal values (biological adverse events)
timeFrame: From 30 days to 7 days before randomization visit, Month 2, Month 4, Month 9
measure: Potassium abnormal values (biological adverse events)
timeFrame: From 30 days to 7 days before randomization visit, Month 2, Month 4, Month 9
measure: Chlore abnormal values (biological adverse events)
timeFrame: From 30 days to 7 days before randomization visit, Month 2, Month 4, Month 9
measure: Calcium abnormal values (biological adverse events)
timeFrame: From 30 days to 7 days before randomization visit, Month 2, Month 4, Month 9
measure: AFAST score 1 (GEA) at 0 or 1
timeFrame: Month 2, Month 4, Month 6, Month 9 and Month 12
measure: AFAST score 2 (Mandibular) at 0 or 1
timeFrame: Month 2, Month 4, Month 6, Month 9 and Month 12
measure: AFAST score 1 associated with AFAST score 2 at 0 or 1
timeFrame: M2, M4, M6, M9 and M12
measure: Quality of life (cost-utility assessment and general quality of life assessment)
timeFrame: Month 2, Month 4, Month 6, Month 9 and Month 12
measure: Quality of life (specific to acne)
timeFrame: Month 2, Month 4, Month 6, Month 9 and Month 12
measure: Bacterial and parasital evaluations
timeFrame: Day 0 (baseline) and Month 4
measure: Inflammatory lesions of the face
timeFrame: Day 0 (baseline), Month 2, Month 4, Month 6, Month 9 and Month 12
measure: retentional lesions of the face
timeFrame: Day 0 (baseline), Month 2, Month 4, Month 6, Month 9 and Month 12
measure: Face lesions
timeFrame: Day 0 (baseline), Month 2, Month 4, Month 6, Month 9 and Month 12
measure: Trunk lesions
timeFrame: Day 0 (baseline), Month 2, Month 4, Month 6, Month 9 and Month 12
measure: Relapse
timeFrame: Month 4 and Month 6
measure: Reappearance of 10% and more of inflammatory lesions.
timeFrame: Month 6
measure: Incremental cost-effectiveness ratio (cost per Quality-Adjusted Life-Year, QALY) of the comparison between the spironolactone and cycline.
timeFrame: Month 6
Other outcomes:
Locations:
city: Brest
country: France
facility: Chru Brest
city: Caen
country: France
facility: CHU Caen
city: Grenoble
country: France
facility: CHU Grenoble
city: La Rochelle
country: France
facility: CH La Rochelle
city: Le Mans
country: France
facility: CH Le Mans
city: Nantes
country: France
facility: CHU de Nantes - Dermatologie
city: Poitiers
country: France
facility: CHU Poitiers
city: Tours
country: France
facility: Cabinet du Dr Jean-Paul Claudel
city: Tours
country: France
facility: CHRU Tours
Study officials:
References:
citation: 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.