Condition category
Skin and Connective Tissue Diseases
Date applied
Date assigned
Last edited
Prospectively registered
Overall trial status
Recruitment status
No longer recruiting

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

Contact information



Primary contact

Prof Hywel Williams


Contact details

Centre for Evidence Based Dermatology
Kings Meadow Campus
University of Nottingham
United Kingdom

Additional identifiers

EudraCT number 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



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

Details of this project can also be found at:
Protocol can be found at:

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


Secondary study design

Randomised parallel trial

Trial setting


Trial type


Patient information sheet

Not available in web format, please use the contact details below to request a patient information sheet


Bullous pemphigoid


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



Not Applicable

Drug names

Prednisolone, doxycycline

Primary outcome measures

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


Overall trial end date


Reason abandoned


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


Age group




Target number of participants


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


Recruitment end date



Countries of recruitment

Germany, United Kingdom

Trial participating centre

University of Nottingham
United Kingdom

Sponsor information


University of Nottingham (UK)

Sponsor details

University Park
United Kingdom

Sponsor type




Funder type


Funder name

NIHR Health Technology Assessment Programme - HTA (UK)

Alternative name(s)

Funding Body Type

Funding Body Subtype


Results and Publications

Publication and dissemination plan

Not provided at time of registration

Intention to publish date


Participant level data

Not provided at time of registration

Results - basic reporting

Publication summary

2015 protocol in:

Publication citations

Additional files

Editorial Notes

21/04/2016: Plain English summary added. 14/04/2016: Publication reference added. On 11/05/2009 the overall trial start and end dates were updated from 01/10/2008 and 30/09/2013 to 05/01/2009 and 31/12/2012, respectively.