Plain English Summary
Background and study aims
Bullous pemphigoid (BP) is a skin condition affecting mainly the elderly, which causes tense, itchy blisters and painful skin erosions that can affect the whole body. Between 20% and 40% of patients die within 1 year of diagnosis. It is an auto-immune disease, which means that the immune system makes antibodies against parts of the skin in error. In BP, these antibodies are directed at the basement membrane zone - the area between the top layer of skin (the epidermis) and the next layer (the dermis). BP is usually treated with long-term prednisolone tablets (a corticosteroid), which can cause many unwanted side effects such as high blood pressure, osteoporosis (brittle bones), infections and diabetes. It is thought that these side effects are at least in part responsible for the deaths of some BP patients. A safer alternative treatment is sought for this condition. Tetracyclines might be effective in treating BP, but a larger study is needed to confirm if this is the case. Tetracyclines are readily available, cheap and are likely to have a better safety profile than prednisolone, but may be slightly less effective. This study will determine whether doxycycline (a member of the tetracycline family) would be a good alternative to prednisolone for treating BP - i.e. whether the benefits of less severe side effects outweigh any reduction in effectiveness.
Who can participate?
Patients aged 18 or over with bullous pemphigoid
What does the study involve?
Participants are randomly allocated to be treated with either prednisolone or doxycycline. After 4 weeks the investigator counts the number of blisters that remain to see if the treatment has worked. The medication dose is then reduced every few weeks until the blisters have virtually all cleared. To assess which drug is safer, all adverse events, including deaths, are recorded for up to a year after starting the study.
What are the possible benefits and risks of participating?
Not provided at time of registration
Where is the study run from?
The study will be carried out in hospitals by dermatologists in the UK, the Netherlands and Germany. It will be run through the UK Dermatology Clinical Trials Network with the support of the University of Nottingham Clinical Trials Support Unit.
When is the study starting and how long is it expected to run for?
October 2008 to September 2013
Who is funding the study?
NIHR Health Technology Assessment Programme - HTA (UK)
Who is the main contact?
Prof Hywel Williams
Trial website
http://www.nottingham.ac.uk/research/groups/cebd/projects/5rareandother/blistertrial.aspx
Additional identifiers
EudraCT number
ClinicalTrials.gov number
Protocol/serial number
HTA 06/403/51; 8024
Study information
Scientific 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
Acronym
BLISTER
Study hypothesis
1. Doxycycline is not inferior in effectiveness to prednisolone in treating bullous pemphigoid given an accepted non-inferiority margin
2. Doxycycline is less likely to result in severe adverse reactions than prednisolone
Ethics approval
Central Manchester Research Ethics Committee, 12/11/2008, ref: 08/H1008/174
Study design
Prospective two-arm single-blind parallel-group multi-centre randomised controlled trial
Primary study design
Interventional
Secondary study design
Randomised parallel trial
Trial setting
Hospitals
Trial type
Treatment
Patient information sheet
Not available in web format, please use the contact details to request a patient information sheet
Condition
Bullous pemphigoid
Intervention
Prednisolone (0.5 mg/kg/day; oral) vs doxycycline (200 mg/day; oral)
The initial clinician-blinded phase will last for 6 weeks when participants will receive one of either prednisolone or doxycycline. After this 6 weeks the clinician will be able to adjust the dose of the medication and will prescribe for as long as is clinically necessary. However, the patient will be followed up for 1 year from randomisation.
Intervention type
Drug
Phase
Not Applicable
Drug names
Prednisolone, doxycycline
Primary outcome measure
Current primary outcome measure(s) as of 05/04/2012:
Absolute differences in the two treatment arms in the:
1. Proportion of participants classed as treatment success (3 or less significant blisters present on examination) at 6 weeks
2. Number of reported grade 3, 4 and 5 (mortality) adverse events for one year
Previous primary outcome measure(s):
Differences in the two treatment arms in the:
1. Proportion of participants classed as treatment success (3 or less significant blisters present on examination) at 6 weeks
2. Number of reported grade 3, 4 and 5 (mortality) adverse events for one year
Secondary outcome measures
Differences in the two treatment arms in the:
1. Proportion of participants classed as treatment success (3 or less significant blisters present on examination) at 6 weeks and are alive at one year
2. Proportion of participants classed as treatment success (3 or less significant blisters present on examination) after 3 and 12 months of treatment
3. Proportion of participants who have a further episode of bullous pemphigoid during their participation in the study after previously being classed as a treatment success
4. Number of reported grade 1 and 2 adverse events for one year following the start of study treatment
5. Cost-effectiveness
Overall trial start date
01/10/2008
Overall trial end date
30/09/2013
Reason abandoned (if study stopped)
Eligibility
Participant inclusion criteria
1. Both males and females, aged at least 18 years old
2. Able to provide written informed consent
3. Clinical features consistent with bullous pemphigoid
4. Either a direct or indirect (serum) immuno-fluorescence (linear IgG/C3 at epidermal basement membrane zone) positive for bullous pemphigoid
5. At least three significant blisters spread over two or more body sites that have appeared in the week prior to study enrolment
6. Free of blisters and any treatment for previous episodes of bullous pemphigoid for at least one year
Participant type
Patient
Age group
Adult
Gender
Both
Target number of participants
256
Participant exclusion criteria
1. Received any of the study medications or other recognised systemic medications for the treatment of this episode of bullous pemphigoid prior to study entry. Prior topical treatment for this episode is permitted.
2. Recent administration of a live virus vaccine
3. Mainly or entirely mucosal pemphigoid
4. Known allergy to tetracyclines
5. Presence of any condition which precludes the use of either of the study drugs
6. Women of childbearing potential who are not taking adequate contraception or who are pregnant, plan to become pregnant during the study duration or lactating
7. Has active cancer (apart from basal cell carcinoma and Bowen's disease)
8. Has any other condition which would, in the Investigator's opinion, deem the patient unsuitable for participation in the study
9. Taking part in any other intervention study
Recruitment start date
30/03/2009
Recruitment end date
30/09/2013
Locations
Countries of recruitment
Germany, United Kingdom
Trial participating centre
University of Nottingham
Nottingham
NG7 2NR
United Kingdom
Sponsor information
Organisation
University of Nottingham (UK)
Sponsor details
University Park
Nottingham
NG7 2RD
United Kingdom
Sponsor type
University/education
Website
Funders
Funder type
Government
Funder name
Health Technology Assessment Programme
Alternative name(s)
NIHR Health Technology Assessment Programme, HTA
Funding Body Type
government organisation
Funding Body Subtype
National government
Location
United Kingdom
Results and Publications
Publication and dissemination plan
Not provided at time of registration
Intention to publish date
01/03/2016
Participant level data
Not provided at time of registration
Basic results (scientific)
Publication list
2015 protocol in: http://www.ncbi.nlm.nih.gov/pubmed/25683592
2017 results in: https://www.ncbi.nlm.nih.gov/pubmed/28279484
2017 results in: https://www.ncbi.nlm.nih.gov/pubmed/28406394