Title: A randomised controlled trial to compare the safety and effectiveness of doxycycline (200 mg/day) with prednisolone (0.5 mg/kg/day) for initial treatment of bullous pemphigoid
Funder: Department of Health (England)

Abstract: DESIGNThis is a pragmatic 2-arm single blind parallel group prospective randomised controlled trial (RCT). It is designed to assess the risk / benefit ratio of systemic prednisolone versus doxycycline for the treatment of bullous pemphigoid (BP).The investigator will be blinded to treatment allocation for the initial induction of remission treatment phase (4 weeks). This is followed by an un-blinded treatment taper and follow-up phase (48 weeks) to allow the investigator to manage individual taper regimens effectively. Participants will be seen 2 and 4 weeks after starting the study medication monthly during the taper phase and while on treatment then every 3 months thereafter up to one year after starting the study.SETTINGSecondary care. Recruitment will be through the UK Dermatology Clinical Trials Network (UK DCTN) dermatologists and several centres in the Netherlands and Germany.TARGET POPULATIONNewly presenting adults with bullous pemphigoid who have received no previous treatment for this condition. Bullous pemphigoid is a severe autoimmune blistering disease associated with significant morbidity and mortality which cannot be left untreated.HEALTH TECHNOLOGIES BEING ASSESSEDPatients will be randomised to doxycycline (200mg/day) or prednisolone (0.5mg/kg/day) for the initial treatment of bullous pemphigoid. Clobetasol propionate cream / ointment prn applied once a day will be allowed for symptomatic relief of symptoms for the first 2 weeks due to the possible delayed onset of action of the study drugs. MEASUREMENT OF COSTS AND OUTCOMESPrimary outcome measure 1: .Proportion of patients who have five or less significant blisters at 4 weeks. Assessment of treatment success at 4 weeks has been used in previous studies and should allow sufficient time for the onset of action of the study drugs. A longer duration is likely to be unacceptable to patients if the treatment is not effective. The blister count will be carried out by the investigator whilst blinded to the treatment allocation. Primary outcome measure 2: Proportion of patients with grade 3 or above side effects (inc. mortality) at one year.Assessment of safety using grade 3 and above side effects over one year has been used previously for assessment of treatments for bullous pemphigoid. This outcome measure captures severe and life-threatening side effects plus mortality and is a straightforward and robust way of comparing the safety profile of the two treatments being studied.Health economic data relating to the overall cost to the NHS will be collected. Resource use (number type and duration of visits to healthcare professionals inpatient stays drug costs) will be used to calculate the average cost of the two regimens from an NHS perspective within the duration of the trial. These data will help establish whether any reduction in side-effects of doxycycline relative to prednisolone are associated with a subsequent reduction in costs to the NHS


Research activity codes: 6.1 PHARMACEUTICALS
Health categories: SKIN