Feasibility Study for a multi-centre trial studying treatments for pyoderma gangrenosum patients
Why we did the Study
Pyoderma gangrenosum (PG) is a rare, and mutilating skin condition that results in extremely painful and rapidly spreading ulcers. It can be an extremely difficult condition to treat and patients often require treatment with steroids or other medicines that suppress the immune system. Because of the relative rarity of the condition, there is very little evidence regarding its management.
In an effort to address this lack of evidence, the UK Dermatology Clinical Trials Network (UK DCTN) has designed a study for the first randomised controlled trial (RCT) comparing commonly used treatments for pyoderma gangrenosum. To assess the feasibility of conducting this trial, 3 pilot studies were conducted:
Pilot 1 - A casenote review looking at patients seen with pyoderma gangrenosum over the last 3 years. This took place in ten
Pilot 2 - A feasibility study looking at best ways of assessing improvements in the ulcers.
Pilot 3 - Focus group work to establish patients’ views of the proposed study
Results of the Study
Pilot 1 – Casenote review
There were 165 patients with confirmed or suspected PG treated in the 11 centres between September 2004 and August 2007. There were 188 documented episodes of PG in the 155 patients whose case notes were available. This equates to a mean of 6 episodes per centre per year.
One or more underlying condition such as inflammatory bowel disease or rheumatoid arthritis was evident in 86 patients (55%). Inflammatory bowel disease was the commonest underlying condition which was present in almost ⅓ of cases. This highlighted the need to engage with colleagues in other specialties (particularly gastroenterology) during the recruitment period to ensure the highest possible recruitment rate.
On average, each patient received two treatments for each episode of pyoderma gangrenosum. The initial treatment was an ointment in 68 episodes (36%), taken orally in 53 episodes (28%) and a combination of both in 55 episodes (29%).
Forty-two episodes (22%) were treated with ointments. Of these, 34 episodes were documented as having healed. The remaining 146 episodes (78%) were treated with treatments taken orally at some stage. The most commonly used systemic treatments were oral steroids and ciclosporin which were used in 56% and 29% or episodes respectively. These two treatments were therefore chosen as being the best treatments to compare in the future trial.
Only 105 episodes (56%) were documented as having healed at some point. The average time to healing was 8.4.months. The remaining 83 episodes (44%) either remained unhealed or were lost to follow up.
Pilot 2 – Imaging of the ulcer
The purpose of this work was to determine an appropriate method of recording the main study outcome – velocity of healing. In addition, the quality of images taken by patients using disposable cameras was assessed, to determine if this would be an appropriate method of monitoring the ulcer between trial visits.
The digital photographs taken at the start of the study and after 4 weeks were analysed (using Vista medical VeV Measurement Documentation version 1.1.14) to assess the change in ulcer size between the two images. This allowed us to specify the optimum image size and give guidance on how to take an image which is suitable for analysis.
The photographs taken by patients using disposable cameras were of poor quality. Therefore, this was not deemed an effective method of monitoring the ulcer between visits and will not be used during the main trial.
Pilot 3 – Assessing patients view’s
The main purpose of this work was to ensure that the future trial design was appropriate and relevant to patients’ needs. One focus group session and two structured interviews were conducted, including five patients in total. All participants had previously been treated for PG at Aberdeen Royal Infirmary.
As a result of this work, greater emphasis has been placed on the importance of capturing pain as an outcome measure, and details of discharge from the wound have been added to the severity assessment. Patients were generally very supportive of the trial and were keen to see research into the condition.
Three participants have since agreed to assist the trial team by contributing to a service user panel for the study. These patients are now helping us to finalise the wording of data collection tools (particularly the participants’ diary).
Implications for the future trial (See http://stopgaptrial.co.uk)
The STOP GAP trial has now been funded as part of an NIHR Programme Grant award to the Centre of Evidence Based Dermatology. This feasibility work provided vital support for this funding application. A total of 49 centres across the UK are recruiting to the study and, as of September 2009, 32 centres are open to recruitment with 7 patients recruited to the study.
Several important changes were made to the trial as a result of this feasibility work including:
The trial design and choice of interventions have been modified.
The timing of the primary outcome has been changed from four to six weeks.
Additional outcome measures have been included.
Study procedures have been modified (particularly with regard to images taken by participants and the need for a biopsy prior to inclusion in the study).
Recruitment into a trial of this kind will always be a challenge given the rarity of the condition, but these important first steps in ensuring that the trial design is appropriate and endorsed by the clinical community have been vital to ensuring that we get the best possible start.
Results of this work were presented during the plenary session at the annual BAD conference in July 2009, and results of the study will be published in a peer reviewed journal in due course.
Publication
Funding: British Skin Foundation
For further information see STOP GAP Website http://stopgaptrial.co.uk
