ROAD Trial
Research type
Research Study
Full title
Rifaximin delayed release (400 mg tablet) for the prevention of recurrent acute diverticulitis and diverticular complications. A phase II, multicenter, double-blind, placebo-controlled, randomized clinical trial (The ROAD trial)
IRAS ID
237169
Contact name
Andrew Allison
Contact email
Sponsor organisation
Alfasigma S.p.A
Eudract number
2017-002708-28
Clinicaltrials.gov Identifier
Duration of Study in the UK
2 years, 4 months, 15 days
Research summary
Summary of Research
Diverticula are small pouches that form in the wall of the colon. These are not uncommon and, in the majority of cases do not cause any significant health problems. However, in a few cases, diverticula become inflamed and patients may present with belly pain and fever i.e. "acute diverticulitis".
Some will have a second (“recurrent”) episode of “acute diverticulitis” in the following months or years. Treatments aimed at preventing diverticular inflammation are still needed, and at present, there are no drugs approved for reducing the probability of recurrence (prophylactic use).
It has been hypothesised that changes in gut microflora may play a key role in the development and progression of acute diverticulitis. Previous clinical trials suggest that Rifaximin, an oral antibiotic, may be beneficial for the prevention of recurrence acute diverticulitis episodes by modulating the gut microflora.
The objective of the study is to look into the safety and efficacy of ‘Rifaximin delayed release tablets’ for the prevention of recurrent acute diverticulitis and diverticular complications.
The study will involve 882 patients (of whom approximately 32 are planned for inclusion in the UK), both male and female aged between 18 and 80 year of age who will be randomly divided into three groups. Two groups will be allocated to active drug treatment and one to placebo (inactive oral pill). To minimise bias, neither the patients nor the investigators will know what the treatment allocation is for any given patient.
Patients will be treated for 12 months and will be required to undergo periodic physical examinations, blood and urine tests and complete various questionnaires and diaries. The rate of recurrence of diverticulitis confirmed by either CT scanning or Ultrasonography will be compared between groups.
The study is expected to last 26 months overall, with patients being in the study for approximately 14 months.
Summary of Results
The study was prematurely interrupted due to a recruitment rate that was slower than the expected one, with a number of evaluable patients of about one quarter of the originally planned sample. Since the study was closed early, efficacy results are not considered definitive and no conclusion can be drawn on Rifaximin effect.
The results of the primary endpoint did not show differences between groups in rate of patients with recurrence of diverticulitis or diverticular complications over the 12-month treatment period.
No differences between groups were also observed for the key secondary endpoint rate of acute episode of prolonged left lower quadrant abdominal pain plus concomitant leukocytosis or elevation of serum CRP with or without CT or US imaging confirming acute diverticulitis.
Due to the low number of patients with episodes of recurrence of diverticulitis/diverticular complications and diverticulitis-associated fever, and of patients that required at least one hospitalization for diverticulitis, no differences between treatment groups could be detected for these endpoints.
Despite the reduced sample size, a superiority of Rifaximin over placebo, which was generally more evident with the higher dose level, was reported for parameters that evaluated the left-lower quadrant abdominal pain and for parameters that evaluated changes in bowel habits during the study.
Treatment with Rifaximin was also associated with significant improvements in quality of life compared to placebo.
Finally, in line with the conclusions of the DMB, following review of the safety data, Rifaximin EIR at both dose levels was well tolerated and safe. In particular, this study shows that 10-day repeat courses of the two doses Rifaximin-EIR followed by a 20-day wash-out period are well tolerated for 12 months. No relevant differences were observed between Rifaximin EIR treated groups and Placebo treated group in terms of adverse events, changes from baseline in laboratory parameters and findings at clinical examination.REC name
East Midlands - Leicester Central Research Ethics Committee
REC reference
18/EM/0236
Date of REC Opinion
28 Sep 2018
REC opinion
Further Information Favourable Opinion