Delaney BC, Qumw M, Moayyedi P, et al. Helicobacter pylori test and treat versus proton pump inhibitor in initial management of dyspepsia in primary care: multicentre randomised controlled trial (MRC-CUBE trial). BMJ, doi:10.1136/bmj.39479.640486.AE (published 29 February 2008)
What is the background to this?
The 2004 guideline from the National Institute for Clinical Excellence (NICE) on the management of dyspepsia in adults recommends that either testing for H. pylori and eradication if positive (test-and-treat) or treatment with a proton pump inhibitor (PPI) is appropriate for the initial management for dyspepsia in primary care, on the grounds of a lack of evidence as to their relative cost effectiveness. A pragmatic clinical trial (MRC-CUBE: carbon-13 urea breath test and eradication study) was carried out in primary care to determine the cost effectiveness of test-and-treat compared with empirical PPI treatment in the initial management of people with dyspepsia (either epigastric pain, heartburn, or both).
What does this study claim?
At 12 months, no significant differences existed between the two strategies tested in terms of cost-effectiveness, costs or dyspeptic symptoms. Minor reductions in costly resource use (e.g. additional H. pylori tests) over the year in the test-and-treat group “paid back” the initial cost of the intervention. This study also found from subgroup analysis that there was no difference between the outcomes for heartburn predominant and epigastric pain predominant patients, although it must be noted that there were insufficient numbers of patients in these groups to rule out the possibility of a difference with certainty.
How does this relate to other studies?
This is the first study conducted in the UK which evaluated the test-and-treat strategy against empirical PPI treatment for the initial management of dyspepsia in primary care and, importantly, has compared their cost effectiveness.
The study supports the 2004 NICE guidelines, which do not recommend an H. pylori test-and-treat strategy over a PPI for the initial management of dyspepsia in primary care. This is not because test-and-treat is less effective or more costly than empirical acid suppression treatment, but because it offers no significant advantage at this point in a patient’s management. Although the results are less certain, results from subgroup analysis also support the NICE guideline in not separating gastro-oesophageal reflux disease and dyspepsia in uninvestigated patients.
Where initial acid suppression treatment fails, test-and-treat is more cost effective than endoscopy-based management (e.g., see Ford et al 2005). The authors point out that the MRC-CUBE study found that the costs of initial test-and-treat were “paid back” by other savings over the first year, and there was no point which it is “too early” for test-and-treat to be used and not be at least as cost effective as PPI alone. Waiting until the patient has persistent symptoms favours a test-and-treat strategy. At which point between “initial presentation” and “persistent symptoms” test and treat should be used is a matter for discussion with the individual patient.
Prescribers should continue to follow the NICE clinical guideline for the management of dyspepsia in primary care. Patients should be fully informed of the options for treatments, and this includes the decision of when or if to use a H. pylori test-and-treat strategy.
Study details – This was a publicly funded, randomised controlled trial across
80 general practices in the UK of adults (n=699, aged 18-65 years) who presented to their general practitioner with epigastric pain, heartburn, or both without “alarm symptoms” for malignancy. The study compared H. pylori 13C urea breath test plus eradication treatment if positive or PPI alone, with subsequent management at the general practitioner’s discretion. Patients who tested positive were offered H. pylori eradication with one week of omeprazole 20mg once daily, clarithromycin 250mg twice daily, and metronidazole 400 mg twice daily, followed by three weeks of omeprazole 20mg once daily. Patients who tested negative received omeprazole 20mg once daily for four weeks. Patients randomised to empirical acid suppression received omeprazole 20mg once daily for four weeks. No participants were taking non-steroidal anti-inflammatory drugs. Quality of life was measured with the EuroQol EQ-5D, which enabled cost-effectiveness to be estimated as cost per quality adjusted life year (QALY). The effect on dyspeptic symptoms at one year was measured with the short form Leeds dyspepsia questionnaire. 343 patients were randomised to testing for H pylori, and 100 were positive. The successful eradication rate was 78%. 356 patients received PPI for 28 days. The test-and-treat strategy did not significantly reduce the number of patients with symptoms of dyspepsia at one year — 82% test-and-treat vs. 83% PPI (absolute risk reduction 1%, 95% confidence intervals –5% to +7%). There was no significant difference in quality of life or costs in the whole group or in either of the pre-specified subgroups. Although the study was sufficiently powered to draw the conclusions of no difference between treatments for the primary outcome, a failure to recruit the 2000 patients originally intended limited its ability to demonstrate possible differences between treatments in the subgroups.
Further information on the treatment of dyspepsia can be found on NPC