Elsevier

The Lancet

Volume 352, Issue 9133, 26 September 1998, Pages 1016-1021
The Lancet

Articles
Randomised controlled trial of Helicobacter pylori eradication in patients on non-steroidal anti-inflammatory drugs: HELP NSAIDs study

https://doi.org/10.1016/S0140-6736(98)04206-8Get rights and content

Summary

Background

The effect of Helicobacter pylori in patients receiving non-steroidal anti-inflammatory drugs (NSAIDs) is unclear. We investigated the effects of H pylori eradication in patients with current or previous peptic ulceration, dyspepsia, or both who continued to use NSAIDs.

Methods

285 patients were randomly assigned omeprazole 20 mg, amoxycillin 1000 mg, and clarithromycin 500 mg, twice daily (n=142, H pylori eradication treatment), or omeprazole with placebo antibiotics (n=143, controls) for 1 week. All patients received omeprazole 20 mg once daily for 3 weeks until endoscopy, and, if the ulcer was not healed, 40 mg once daily until repeat endoscopy at 8 weeks. Ulcer-free patients with mild dyspepsia continued NSAIDs but not antiulcer treatment. We investigated ulcers with endoscopy at 1, 3, and 6 months and with carbon-13-labelled urea breath test at 3 months.

Findings

The estimated probability of being ulcer-free at 6 months was 0.56 (95% CI 0.47–0.65) on eradication treatment and 0·53 (0·44–0·62) on on control treatment (p=0·80). Time to treatment failure did not differ between groups for ulcers or dyspepsia alone, per-protocol analysis, or final H pylori status. 66% (58–74) of the eradication group compared with 14% (8–20) of the control group had a final negative H pylori result (p<0·001). Fewer baseline gastric ulcers healed among eradication-treatment patients than among controls (72 vs 100% at 8 weeks, p=0·006).

Interpretation

H pylori eradication in long-term users of NSAIDs with past or current peptic ulcer or troublesome dyspepsia led to impaired healing of gastric ulcers and did not affect the rate of peptic ulcers or dyspepsia over 6 months.

Introduction

Helicobacter pylori and non-steroidal anti-inflammatory drugs (NSAIDs) account for nearly all gastroduodenal ulcers and serious ulcer complications.1, 2, 3, 4 Endoscopic and epidemiological data are conflicting about whether H pylori infection increases the risks in NSAID users, has no effect, or is protective.5, 6, 7, 8, 9, 10

Eradication of H pylori substantially decreases the rate of recurrence of gastric and duodenal ulcers in patients not taking NSAIDs,11 but whether this effect occurs in patients on NSAIDs is unclear. In NSAID users, dyspepsia correlates poorly with ulceration but is common in patients infected with H pylori.12, 13

In a randomised controlled trial we investigated the hypothesis that H pylori eradication would decrease dyspepsia in patients taking NSAIDs but would have no effect on ulcer recurrence.

Section snippets

Methods

We did the HELP NSAIDs (Heliobacter Eradication for Lesion Prevention with NSAIDs) study in primary-care and secondary-care centres in Hungary, Poland, South Africa, Spain, and the UK. The study was approved by the ethics committees of the participating centres and all patients gave written, informed consent.

Patients

We randomly assigned 285 patients eradication treatment (n=142) or omeprazole plus placebo (n=143, figure 2). Six patients were excluded from the analysis by intention to treat, one because of non-compliance for NSAIDs and five because they did not return for further assessments. 23 patients were excluded from the perprotocol analysis, eight because of non-compliance with study medication, five because they did not meet the entry criteria, one because of a missed visit, and nine because of

Discussion

Our study was designed to investigate patients who had already experienced gastroduodenal ulceration and drug-associated dyspepsia, since a past history increases the risk of recurrence.2 Many of the patients in our study were old and more than 40% had had an endoscopically confirmed ulcer within the previous 5 years. Nearly a third of patients had active ulceration at the start of the study and half had moderate or severe dyspepsia. Our results confirmed previously reported higher rates of

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