The BLISTER Study Bullous Pemphigoid Steroids and Tetracyclines Study A randomised controlled trial

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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 pemphigoidJoanne ChalmersSenior
Clinical Trials Manager, UK Dermatology Clinical
Trials Network
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The UK Dermatology Clinical Trials Network (UK
DCTN)

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

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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).
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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

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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

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Hypotheses

• Likely to be ? safety ? effectiveness
• Doxycycline is not inferior in effectiveness to
  prednisolone in treating bullous pemphigoid given
  an accepted non-inferiority margin.
• Doxycycline has a better safety profile than
  prednisolone.

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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.
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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.

• Composite
• Treatment success at 6 weeks and alive at 1 year.

• Other
• Quality of life.
• Costs to the NHS

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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

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Inclusion Criteria

• Clinical features consistent
• with bullous pemphigoid
• At least 3 recent blisters at
  2 or more body sites
• Positive direct or indirect immuno-fluorescence
• Free of blisters and treatment for BP for at
  least 1 year prior to this episode

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Main Exclusion Criteria

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

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Continue taper
effective
prednisolone 0.5 mg/kg/day betamethasone
Switch / increase dose / add in other treatment
Study entry and randomisation
not effective
Continue for further 46 weeks (total 1
year). Follow-up 3 monthly plus other visits as
per clinical need
Continue reduce dose
effective
Doxycycline 200mg / day betamethasone
Switch / add in other treatment
not effective
Week 6
1 year
Week 0
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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.

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Study Team

• Lead Clinician Professor Fenella Wojnarowska
• Chief Investigator Professor Hywel Williams
• Clinical Expert Dr Gudula Kirtschig (
  co- ordinates European centres)
• Statistician Professor Andrew Nunn
• Health Economist Professor James Mason
• Trial Manager 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)
joanne.chalmers_at_nottingham.ac.uk