Comparative Effectiveness Study of Spironolactone Versus Doxycycline for Acne

Study Overview
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Brief Summary
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Acne is common illness of adolescents and young adults which is associated with substantial morbidity. While topical treatments are often sufficient for mild acne, moderate to severe acne often requires treatment with systemic medications such as oral antibiotics, hormonal therapies such spironolactone, and isotretinoin. Sebum overproduction is fundamental to the pathogenesis of acne with associated disordered keratinization and subsequent microbial colonization and inflammation resulting in the clinical manifestations of acne. Given the influence of hormones on sebum production, therapies that address these underlying hormonal factors such as spironolactone and oral contraceptive pills represent an underutilized treatment option for women with acne and could help decrease the use of long-term oral antibiotics in this patient population. The purpose of this trial is to evaluate the comparative effectiveness of spironolactone versus doxycycline hyclate (tetracycline class antibiotic) for women with acne.

Official Title
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A Randomized, Double-Blind, Multi-Center Comparative Effectiveness Study of Spironolactone Versus Doxycycline Hyclate for the Treatment of Acne in Women

Conditions
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Acne

Intervention / Treatment
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* Drug: Spironolactone
* Drug: Doxycycline Hyclate


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Female sex assigned at birth Age 16-40 years old Acne defined as at least 10 inflammatory papules or pustules and an Investigator's Global Assessment (IGA) score of at least 2 as measured by the Comprehensive Acne Severity Scale Not currently pregnant or planning to become pregnant Exclusion Criteria: Pregnancy Heart disease Renal disease Liver disease Orthostatic hypotension Addison's disease History of hyperkalemia Allergy to tetracycline-class antibiotic Allergy to spironolactone Concomitant use of medications known to interact with spironolactone or doxycycline or that may increase the risk for hyperkalemia, including angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, eplerenone, nonsteroidal anti-inflammatory drugs, and digoxin. Treatment with spironolactone, an oral antibiotic, laser, photodynamic therapy, or chemical peel within the past 4 weeks Treatment with isotretinoin within the past 3 months Sebacia laser treatment within the past 12 months

Ages Eligible for Study
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Minimum Age: 16 Years
Maximum Age: 40 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: 200 participants will be randomized to treatment with spironolactone 100mg/day and 200 participants will be randomized to treatment with doxycycline hyclate 100mg/day.
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Spironolactone<br>In this arm, participants will receive spironolactone 100mg/day for the entirety of the study. To maximize the generalizability of the study, participants will be allowed to continue their current topical regimen as long as no changes were made in the 4 weeks prior to randomization. No additions to their topical regimen may be made during the study period. | Drug: Spironolactone<br>* Dispensation of spironolactone according to the arm description.<br>|
| Active Comparator: Doxycycline hyclate<br>This arm is an active-comparator arm in which participants will receive doxycycline hyclate 100mg/day for the entirety of the study. To maximize the generalizability of the study, participants will be allowed to continue their current topical regimen as long as no changes were made in the 4 weeks prior to randomization. No additions to their topical regimen may be made during the study period. | Drug: Doxycycline Hyclate<br>* Dispensation of doxycycline hyclate according to the arm description.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Absolute change in inflammatory papules and pustules | Difference in change in inflammatory papules and pustules between those randomized to spironolactone versus doxycycline hyclate | Baseline to Week 16 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage achieving Investigator Global Assessment (IGA) Success (IGA grade of clear or almost clear; grade 0 or 1) | Difference in percentage achieving IGA success between those randomized to spironolactone versus doxycycline hyclate | Baseline to Week 8, and Week 16 | 
| Change in comedonal lesions | Difference in change in comedonal lesions between those randomized to spironolactone versus doxycycline hyclate | Baseline to Week 8, and Week 16 | 
| Change in Acne-QoL, an acne-specific quality of life measure | Difference in change in Acne-QoL score between those randomized to spironolactone versus doxycycline hyclate. There are 4 subscales: self perception, scored 0-30; role social, scored 0-24; role-emotional, scored 0-30; and acne symptoms, scored 0-30. Higher scores indicate better quality of life. | Baseline to Week4, Week 8, Week 12, and Week 16 | 
| Change in Dermatology Life Quality Index (DLQI), a dermatology-specific quality of life measure | Difference in change in DLQI score between those randomized to spironolactone versus doxycycline hyclate. Scores range from 0-30, with lower scores indicated better quality of life. | Baseline to Week4, Week 8, Week 12, and Week 16 | 
| Patient global assessment | Difference in change in patient global assessment scores between those randomized to spironolactone versus doxycycline hyclate. | Baseline to Week4, Week 8, Week 12, and Week 16 | 
| Percentage on any topical medication at baseline who discontinued at least one of these topical medications (i.e. topical retinoid, benzoyl peroxide, and topical antibiotic) | Difference between those randomized to spironolactone versus doxycycline hyclate | Baseline to Week 16 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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spironolactone, doxycycline