1. What interventions did the PATCH trials test?
PATCH I was designed to test if low dose penicillin (250 mg) taken twice a day for 12 months could prevent further attacks in patients who suffer from repeat episodes of leg cellulitis. Patients who had had at least two episodes of leg cellulitis in the last three years were included in this trial.
PATCH II was almost identical to PATCH I, but this trial looked at just 6 months of low dose penicillin (250 mg) taken twice a day. Most patients (79%) included in the PATCH II trial had experienced just one episode of cellulitis before the trial.
In both PATCH I and PATCH II, patients remained in the trial for up to three years to see whether or not the penicillin was effective only whilst it was being taken, or whether there were longer term benefits after the antibiotics had been stopped.
2. How many patients took part?
These trials took place in 29 hospitals throughout the UK and Eire. In total, 274 patients took part in PATCH I, and 123 patients took part in PATCH II.
All the doctors and nurses who helped to recruit into the PATCH trials were members of the UK Dermatology Clinical Trials Network.
3.What were the main findings?
Both the PATCH I and PATCH II trials showed that taking low dose penicillin after an episode of cellulitis reduced the number of repeat episodes. But there were some differences in the findings of the two trials.
The PATCH I trial found that patients in the penicillin group were less likely to have another attack of cellulitis compared with the placebo (“dummy tablet”) group (22% compared with 37%). whilst taking the medication. However, this protection was then gradually lost after patients stopped taking the medication at 12 months. In fact, by three years, around half of all patients in both groups had suffered at least one further episode suggesting that longer-term antibiotics may be required to prevent further episodes in patients with recurrent cellulitis.
The PATCH II trial (mainly patients who have had only one episode of cellulitis) showed a similar reduction in the number of repeat episodes of cellulitis in the group that received the penicillin whilst taking the medication. However, unlike PATCH I, this trial showed that the preventative effect continued after the medication had stopped at 6 months. Overall, 20% of the participants who took penicillin had at least one repeat episode over the three years compared to 33% of those who received the placebo (dummy) tablets. These results require confirmation in future trials as there is an 8% chance that this effect was found simply by chance.
4. Does using prophylactic antibiotics promote antibiotic resistance?
The possibility of promoting antibiotic resistance should always be considered when prescribing interventions, for the treatment or prevention of disease. The need for antibiotics should be justified by evidence-based research wherever possible. The PATCH I and II trials have contributed to the body of evidence supporting the use of prophylactic antibiotics for the prevention of recurrent cellulitis.
For patients with recurrent cellulitis, the benefits of preventing future episodes of cellulitis generally outweighs the risks. Despite over 60 years of use, penicillin resistance has never been described in Group A streptococcus anywhere in the world.
Prophylactic penicillin is used for other indications (e.g. post splenectomy) and does not induce penicillin-resistant infections in such patients.
5. Why is this research important?
Cellulitis of the leg is extremely common, causes a lot of distress to patients, and results in time off work or other daily activities. By demonstrating that a simple, low cost and safe intervention such as low-dose penicillin taken for 6 to 12 months can reduce the number of repeat episodes, these trials will improve the lives of many thousands of patients, and could potentially reduce costs to the NHS by reducing hospital admissions.
Prior to the PATCH cellulitis trials there had been just three small trials published in the 1990’s that looked at the use of antibiotics for the prevention of recurrent cellulitis. These previous trials were all small (including 130 participants in total) and so were potentially misleading. By improving the evidence base on this topic patients and doctors can make more informed choices about the management and prevention of leg cellulitis.
6. How were the trials funded?