The Bullous Pemphigoid Steroids and Tetracyclines Study
| ISRCTN | ISRCTN13704604 |
|---|---|
| DOI | https://doi.org/10.1186/ISRCTN13704604 |
| Secondary identifying numbers | HTA 06/403/51; 8024 |
- Submission date
- 11/11/2008
- Registration date
- 12/11/2008
- Last edited
- 18/04/2017
- Recruitment status
- No longer recruiting
- Overall study status
- Completed
- Condition category
- Skin and Connective Tissue Diseases
Plain English summary of protocol
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
Contact information
Scientific
Centre for Evidence Based Dermatology
Kings Meadow Campus
University of Nottingham
Nottingham
NG7 2NR
United Kingdom
Study information
| Study design | Prospective two-arm single-blind parallel-group multi-centre randomised controlled trial |
|---|---|
| Primary study design | Interventional |
| Secondary study design | Randomised parallel trial |
| Study setting(s) | Hospital |
| Study type | Treatment |
| Participant information sheet | Not available in web format, please use the contact details to request a patient information sheet |
| 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 acronym | BLISTER |
| Study objectives | 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(s) | Central Manchester Research Ethics Committee, 12/11/2008, ref: 08/H1008/174 |
| Health condition(s) or problem(s) studied | 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 |
| Pharmaceutical study type(s) | |
| Phase | Not Applicable |
| Drug / device / biological / vaccine name(s) | 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 study start date | 01/10/2008 |
| Completion date | 30/09/2013 |
Eligibility
| Participant type(s) | Patient |
|---|---|
| Age group | Adult |
| Lower age limit | 18 Years |
| Sex | Both |
| Target number of participants | 256 |
| Key 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 |
| Key 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 |
| Date of first enrolment | 30/03/2009 |
| Date of final enrolment | 30/09/2013 |
Locations
Countries of recruitment
- England
- Germany
- United Kingdom
Study participating centre
NG7 2NR
United Kingdom
Sponsor information
University/education
University Park
Nottingham
NG7 2RD
England
United Kingdom
| Website | http://www.nottingham.ac.uk |
|---|---|
"ROR" |
https://ror.org/01ee9ar58 |
Funders
Funder type
Government
Government organisation / National government
- Alternative name(s)
- NIHR Health Technology Assessment Programme, HTA
- Location
- United Kingdom
Results and Publications
| Intention to publish date | 01/03/2016 |
|---|---|
| Individual participant data (IPD) Intention to share | No |
| IPD sharing plan summary | Not provided at time of registration |
| Publication and dissemination plan | Not provided at time of registration |
| IPD sharing plan |
Study outputs
| Output type | Details | Date created | Date added | Peer reviewed? | Patient-facing? |
|---|---|---|---|---|---|
| Protocol article | protocol | 01/07/2015 | Yes | No | |
| Results article | results | 01/03/2017 | Yes | No | |
| Results article | results | 22/04/2017 | Yes | No | |
| HRA research summary | 28/06/2023 | No | No |
Editorial Notes
18/04/2017: Publication reference added.
13/03/2017: Publication reference added.
21/04/2016: Plain English summary added.
14/04/2016: Publication reference added.
11/05/2009: The overall trial start and end dates were changed from 01/10/2008 and 30/09/2013 to 05/01/2009 and 31/12/2012, respectively.
