Investigating the benefits and harms of reduced daily dose oral isotretinoin in the treatment of acne: a parallel group, assessor blind, non-inferiority, multicentre randomised controlled trial, with an internal pilot
Acne
This trial is a comparison of two dosing strategies. Low-dose strategy (intervention): Oral isotretinoin 0.25 mg/kg/day (within a range of 0.2-0.3 mg/kg/day). At 6 months, if there has been insufficient improvement, the dose can be increased to <0.5 mg/kg/day. Low-dose strategy may have a longer treatment duration (anticipated 6-12 months). Standard-dose strategy (comparator) Oral isotretinoin ≥0.5 mg/kg day and dose titration up to 1 mg/kg/day over 1-2 months, unless clinically contraindicated. Aim for a minimum of 0.7 mg/kg/day. The typical treatment duration for the standard-dose strategy is 6 months. The end of the treatment course for each strategy will be when the first of the following criteria is met: 1. Participants have no new inflammatory lesions for a minimum of 4 weeks; this is a shared decision between the participant and a health professional or 2. A maximum cumulative dose of 150 mg/kg is reached or 3. A total of 12 months duration on the medication or 4. A participant and/or clinician decision to stop isotretinoin even when there has not been a satisfactory outcome e.g. due to side effects 5. A participant becomes pregnant Participants who reach 150 mg/kg/day cumulative dose or 12 months duration of treatment and continue to have new inflammatory lesions will be treated according to routine clinical care.
Current inclusion criteria as of 22/08/2025: 1. Age 12 years to 24 years. 2. Acne of the face +/- trunk. 3. Meets the MHRA definition of severe forms of acne (including acne at risk of permanent scarring). 4. Able to give consent or child assent with parental consent 5. Clinical decision to start treatment with oral isotretinoin 6. Medicines and Healthcare products Regulatory Agency (MHRA) risk acknowledgment form completed by the treating clinician 7. Willing to be randomised to either treatment group 8. Willing and able to complete the trial questionnaires _____ Previous inclusion criteria: 1. Clinical diagnosis of severe acne (including acne at risk of scarring) of the face +/- trunk 2. Acne that has failed to respond to at least one 12-week minimum course of oral antibiotics in combination with a topical treatment 3. Age ≥12 years to <25 years 4. Able to give consent or child assent with parental consent 5. Clinical decision to start treatment with oral isotretinoin 6. Medicines and Healthcare products Regulatory Agency (MHRA) risk acknowledgment form completed by the treating clinician 7. Willing to be randomised to either treatment group 8. Willing and able to complete the trial questionnaires
1. Contraindication to isotretinoin as per clinician assessment in routine care (e.g. severe mood concerns on screening, refusal to sign the Acknowledgement of Risk Form and enter the Pregnancy Prevention Programme if has childbearing potential (pregnant, or breastfeeding or Intention to become pregnant), concomitant medications with an interaction with isotretinoin) 2. Acne fulminans, acne conglobata or other acne subtype unsuitable for higher dose strategy 3. Previously been treated with oral isotretinoin 4. Known allergy or sensitivity to isotretinoin or any of its excipients