IASO
Research type
Research Study
Full title
A phase II randomised placebo controlled double blinded trial of Interleukin 1 blockade in Acute Severe Colitis
IRAS ID
201505
Contact name
Arthur Kaser
Contact email
Sponsor organisation
Cambridge University hospitals NHS Foundation Trust & University of Cambridge
Eudract number
2017-001389-10
Duration of Study in the UK
5 years, 2 months, 31 days
Research summary
Summary of Research
Ulcerative colitis is a condition in which the body’s large intestine, known as the colon, becomes inflamed. In most patients, ulcerative colitis involves some periods without strong symptoms but also periods (called flares) where the symptoms become more severe.
Sometimes, the intensity of the symptoms means that a patient needs to be admitted to hospital. If this happens, the patient will be given drugs called corticosteroids to reduce the inflammation and alleviate symptoms. If these make the patient better, the patient can then leave hospital after a few days.
If the corticosteroids aren’t making the condition better, other medicines can be given. This would be either a drug called infliximab or ciclosporin. Either drug can be used and both are equally effective.
If these treatments still don’t work, then doctors and the patient will discuss surgery to remove the colon. This is called a colectomy.
Currently, we know that around half of patients given the initial treatment (corticosteroids) will get better, whilst the other half will go on to need one of the other medications, and some patients will still need to go on to surgery.
This trial will test whether giving patients another medicine, called anakinra, in addition to the initial treatment with corticosteroids will increase the number of patients who get better without needing to go on to receive additional medical treatments or surgery. We will test this possibility by taking 214 patients and randomly allocating them to receive either the anakinra, or a placebo (dummy drug). Patients and their doctors will not know which group they are in. We will compare differences in several outcomes between the 2 groups of patients to test whether giving anakinra gives benefit to patients with this condition.
Summary of Final Report
Background Acute severe ulcerative colitis (ASUC) is an inflammatory condition of the colon associated with diarrhoea, rectal bleeding and abdominal pain. This requires urgent hospital treatment. Treatment for ASUC involves giving steroids, which resolves inflammation in about half of the patients treated. For those who don’t respond to steroid therapy, there are other medical treatment options (so called “rescue therapy”). Despite these treatments, around 20% of patients will require emergency surgical removal of the colon (colectomy) during the same hospital admission. Scientific studies have identified a molecule known as interleukin-1 as potentially important in ASUC. This has led to suggestions that blocking IL-1 might benefit patients with this condition.
Design
This study was designed to find out if blocking IL-1 effects using a drug called anakinra is an effective treatment for patients with ASUC. The trial compared the effects of anakinra with dummy drug (placebo) when given in addition to current standard care.
We planned to recruit 214 patients. To make sure that the study was safe, we planned a series of early analyses of the findings. At the point when 113 patients had been recruited, we found evidence that the drug was not effective and therefore we stopped the study early.Trial results
More patients treated with anakinra than with placebo needed further medical or surgical treatment for their disease. More safety problems were seen in the patients treated with placebo than in the group who received anakinra. However, there was no clear evidence to suggest that any of the outcomes we measured were meaningfully different between the treatment groups.
Conclusion
Although prior scientific studies had suggested the IL-1 might be important in driving ASUC, this study suggests that in patients with ASUC, using anakinra to target IL-1 does not lead to better patient outcomes.REC name
East of England - Cambridge Central Research Ethics Committee
REC reference
17/EE/0347
Date of REC Opinion
21 Sep 2017
REC opinion
Favourable Opinion