Short course acid suppressive treatment for patients with functional dyspepsia: results depend on Helicobacter pylori status. The Frosch Study Group

Abstract

Background and aims: Treatment of functional dyspepsia with acid inhibitors is controversial and it is not known if the presence of Helicobacter pylori infection influences the response.

Methods: After a complete diagnostic workup, 792 patients with functional dyspepsia unresponsive to one week of low dose antacid treatment were randomised to two weeks of treatment with placebo, ranitidine 150 mg, omeprazole 10 mg, or omeprazole 20 mg daily. Individual dyspeptic and other abdominal symptoms were evaluated before and after treatment according to H pylori status.

Results: The proportions of patients considered to be in remission (intention to treat) at the end of treatment with placebo, ranitidine 150 mg, omeprazole 10 mg, and omeprazole 20 mg were, respectively, 42%, 50%, 48%, and 59% in the H pylori positive group and 66%, 73%, 64%, and 71% in the H pylori negative group. In H pylori positive patients, the therapeutic gain over placebo was significant for omeprazole 20 mg (17.6%, 95% confidence intervals (CI) 4.2-31.0; p<0.014 using the Bonferroni-adjusted p level of 0.017) but not for omeprazole 10 mg (6.8%, 95% CI -6.7-20.4) or ranitidine 150 mg (8.9%, 95% CI -4.2-21. 9). There was no significant therapeutic gain from active treatment over placebo in H pylori negative patients. Complete disappearance of symptoms and improvement in quality of life also occurred most frequently with omeprazole 20 mg and was significant in both H pylori positive and H pylori negative groups. The six month relapse rate of symptoms requiring treatment was low (<20%) in all groups.

Conclusions: Omeprazole 20 mg per day had a small but significant favourable effect on outcome in H pylori positive patients. The differential response in these patients may be explained by an enhanced antisecretory response in the presence of H pylori. The effect of weaker acid inhibition was unsatisfactory.

Figure 1

Flow chart of the 974 dyspeptic patients who entered the run in week with low dose antacid treatment. A=not randomized after run in period for reasons other than response to antacid treatment (n=52). B=H pylori positive responders not entering follow up (n=17). C=H pylori negative responders not entering follow up (n=19). Responder=no dyspeptic symptoms requiring further management after the two week double blind treatment (main outcome criterion). Hp, Helicobacter pylori; recur.,recurrence of dyspeptic symptoms requiring management

Figure 2

Effect of two week treatment with placebo, ranitidine, omeprazole 10 mg (OM10), or omeprazole 20 mg (OM20) on dyspeptic symptoms according to percentage of patients who became completely symptom free (no symptoms) and those with no need for further management (main outcome criterion) (means and 95% two sided confidence intervals; exact test). For assessment of significance levels, see text. The number of patients per group is given in table 1. Hp, Helicobacter pylori.

Figure 3

Effect of treatment with placebo, ranitidine, omeprazole 10 mg (OM10), or omeprazole 20 mg (OM20) on individual dyspeptic symptoms. The horizontal bars show the percentages of patients with each individual symptom before and after each two week double blind treatment. *p<0.05; **p<0.025, ***p<0.001 compared with placebo in the same Helicobacter pylori (HP) group.

Figure 4

Life table analysis of patients without sufficient symptoms to require specific active management after successful treatment in the four treatment groups (placebo, ranitidine, omeprazole 10 mg (OM10), or omeprazole 20 mg (OM20)). At time 0 the proportion of patients with successful two week treatment is given; these patients entered follow up. The number of patients per group is given in the text. Hp, Helicobacter pylori.