Sirs, In the December 2000 issue of Alimentary Pharmacology and Therapeutics, we reported the results of our double-blind, placebo-controlled, randomized clinical trial proving the efficacy of PCC (marketed in Germany under the trade name Enteroplant by Dr Willmar Schwabe GmbH & Co., Karlsruhe, and Spitzner Arzneimittelfabrik GmbH, Ettlingen), a fixed combination of 90 mg peppermint oil (WS 1340) and 50 mg caraway oil (WS 1520) (WS 1340 and WS 1520 are registered trademarks of Dr Willmar Schwabe GmbH & Co., Karlsruhe, Germany), in the treatment of functional dyspepsia.1 As approximately one-half of patients suffering from functional dyspepsia are infected with Helicobacter pylori,2, 3 we have investigated the influence of H. pylori status (determined during screening using the rapid urease test with biopsy) on the efficacy of functional dyspepsia treatment with PCC in a post hoc sub-group analysis.
The efficacy variables ‘intensity of gastric pain’, ‘sensation of pressure, heaviness and fullness’ and ‘persistence of functional dyspepsia-related pain’ (patients' self-ratings) were assessed for changes between baseline and the end of treatment using continuous visual analogue scales (0, absent/never; 10, extremely severe/constant). Within each treatment group, separate calculations were performed for H. pylori-positive and H. pylori-negative patients. The analyses, based on all 96 randomized patients (PCC, 48; placebo, 48), followed the intention-to-treat principle.
In both sub-groups, which revealed comparable baseline characteristics, patients given PCC showed notably larger improvements in all three outcome measures than those given placebo (Table 1). The treatment group differences were somewhat more pronounced in H. pylori-positive patients, and the decreases in the symptom ratings vs. baseline were notably larger in patients given PCC.
|H. pylori-positive (n = 24; 25%)||H. pylori-negative (n = 72; 75%)|
|PCC (n = 10)||Placebo (n = 14)||PCC (n = 38)||Placebo (n = 34)|
|Intensity of pain|
|Baseline||6.2 ± 1.0||6.4 ± 1.2||6.6 ± 1.5||6.9 ± 1.1|
|End of treatment||2.8 ± 2.1||5.0 ± 1.8||4.2 ± 2.5||5.4 ± 2.2|
|Baseline vs.||3.4 ± 1.7||1.4 ± 1.5||2.4 ± 2.6||1.5 ± 1.9|
|end of treatment||(55%)||(22%)||(36%)||(22%)|
|Sensation of pressure, heaviness and fullness|
|Baseline||6.6 ± 1.5||6.4 ± 1.1||6.4 ± 1.5||6.6 ± 1.2|
|End of treatment||2.3 ± 2.3||4.6 ± 2.0||4.0 ± 2.6||5.3 ± 2.1|
|Baseline vs.||4.3 ± 2.7||1.7 ± 1.9||2.4 ± 2.5||1.4 ± 2.3|
|end of treatment||(65%)||(27%)||(38%)||(21%)|
|Persistence of pain|
|Baseline||6.2 ± 1.3||6.1 ± 1.2||6.3 ± 1.7||6.7 ± 1.6|
|End of treatment||2.5 ± 2.2||4.7 ± 2.1||4.0 ± 2.7||5.2 ± 2.2|
|Baseline vs.||3.7 ± 2.1||1.4 ± 2.0||2.3 ± 2.7||1.5 ± 1.9|
|end of treatment||(60%)||(23%)||(37%)||(22%)|
H. pylori-positive patients given PCC showed a more pronounced symptom alleviation, but score improvements in H. pylori-negative patients given PCC were still larger than those in patients given placebo. In the placebo group, no differences between H. pylori-positive and H. pylori-negative patients were observed, and both sub-groups showed essentially comparable changes vs. baseline.
These results, which were fully confirmed in a per protocol analysis, confirm the proof of efficacy reported previously for the entire study population.1
If it is presumed that H. pylori infection has a role in the aetiology of functional dyspepsia,4–6 we would expect a treatment related to other causes of this disorder to be less effective in H. pylori-positive patients if the bacterium is not eradicated simultaneously. In our trial, however, H. pylori-positive patients given PCC showed a substantially better treatment response, and there were no interpretable differences in treatment outcome between the two sub-groups given placebo. Our results are different from those reported by Madisch et al., who found no systematic efficacy differences between H. pylori-positive and H. pylori-negative patients given PCC.7
Although the sub-groups of H. pylori-positive patients were quite small, and our treatment groups contained fractions of H. pylori-positive patients that were considerably lower than the prevalence of the infection quoted in the literature,2, 3 these findings leave no doubt that the treatment of functional dyspepsia with PCC is justified despite the presence of H. pylori infection. Why PCC was more effective in H. pylori-positive patients has yet to be investigated in further studies.