The BLISTER Study

(Bullous Pemphigoid Steroids and Tetracyclines Study)

A randomised controlled trial to compare the safety and effectiveness of doxycycline (200 mg/day) with prednisolone (0.5 mg/kg bodyweight/day) for initial treatment of bullous pemphigoid Joanne Chalmers

Senior Clinical Trials Manager, UK Dermatology Clinical Trials Network

The UK Dermatology Clinical Trials Network (UK DCTN)

• Membership • Structure • Meetings • Co-ordinating Centre • Trial development

Study Development

 Suggested by Professor Fenella Wojnarowska  Important clinical question (UK DCTN and patients).

 Study developed by UK DCTN  Funded by UK Department of Health (NIHR Health Technology Assessment (HTA) Programme).

Treatments for Bullous pemphigoid

 Oral prednisolone most common 1st line treatment in UK  Many side effects especially in elderly population  Clobetasol propionate cream (40g / day) (Joly et al 2002)  Topical therapy difficult for some patients  Safer alternative oral treatment needed  Possible role for tetracycline & nicotinamide (Fivenson et al 1994)  Further research needed

Rationale for the study design

 Prednisolone dose 0.5mg/kg/day  Choice of tetracycline doxycycline  Included topical betnovate as rescue medication  Nicotinamide not included in study

Hypotheses

Likely to be:

↑ safety ↓ effectiveness 1.

Doxycycline is not inferior in effectiveness to prednisolone in treating bullous pemphigoid given an accepted non-inferiority margin.

2.

Doxycycline has a better safety profile than prednisolone.

Primary Outcome Measures

Two needed:

Effectiveness:

Blister count after 6 weeks treatment. Five or less significant blisters will be considered to be a treatment success.

Safety:

Number of severe adverse events after 1 year.

Grade 3, 4 and 5 (death) adverse reactions using the common toxicity criteria.

Secondary Outcome Measures

Effectiveness

    Long term effectiveness  treatment success at 3 & 12 months Speed of onset of action  treatment success at 3 weeks Proportion of patients completely blister free at 6 weeks. Relapse rates over one year.

Safety

  Survival rate at one year. Incidence of grade 1 and 2 adverse events.



Comp osite

Treatment success at 6 weeks

and

alive at 1 year .

Other

 Quality of life.  Costs to the NHS

Study Design

 Multi-centre randomised controlled trial, pragmatic design  Recruiting in UK, Germany and the Netherlands  Sample size = 256 patients  Patients in study for 1 year

Inclusion Criteria

 Clinical features consistent with bullous pemphigoid  At least 3 recent blisters at 2 or more body sites  Positive direct

or

fluorescence indirect immuno  Free of blisters and treatment for BP for at least 1 year prior to this episode

Main Exclusion Criteria

 Received prior oral therapy  Received > 1 week of topical therapy  Mucosal bullous pemphigoid  Allergy to tetracyclines  Unable to give informed consent

effective prednisolone 0.5 mg/kg/day + betamethasone

not

effective Study entry and rando misati on Week 0 effective Doxycycline 200mg / day + betamethasone

not

effective Week 6 Continue & taper Switch / increase dose / add in other treatment Continue & reduce dose Switch / add in other treatment Continue for further 46 weeks (total 1 year).

Follow-up 3 monthly plus other visits as per clinical need 1 year

In summary…

 Comparing safety and effectiveness of doxycycline and prednisolone.

 Hypothesis= ↑ safety ↓ effectiveness .

 In study for 1 year.

 Treatment fixed for 6 weeks (primary effectiveness outcome).

 Adverse events recorded over 1 year.

Study Team

   Lead Clinician: Chief Investigator: Clinical Expert:    Statistician: Health Economist: Trial Manager: Professor Fenella Wojnarowska Professor Hywel Williams Dr Gudula Kirtschig (& co ordinates European centres) Professor Andrew Nunn Professor James Mason Dr Joanne Chalmers For more information about the study or if you are interested in becoming a recruiting centre please contact (details in delegate pack): [email protected]