HSC Section 6 Nov2016 Green Book

Reichel et al Double-blind, placebo-controlled trial with . . .

All documented adverse events were considered mild and not treatment-related. The most common ones were bronchitis (n 7), pharyngitis (n 5), and headache (n 5). One patient receiving esomeprazole was lost to fol- low-up after the initial visit. Two female patients com- plained of abdominal pain two and three weeks after receiv- ing the study medication and were withdrawn from treatment. Their treatment was unblinded, and as they were part of the placebo group their complaints could not be caused by esomeprazole. Another female patient developed a skin rash six weeks after the beginning of therapy. Al- though this drop-out patient was not a placebo recipient, allergologic testing excluded drug hypersensitivity to es- omeprazole ( Fig 1 ). DISCUSSION Our study is the second largest to assess the efficacy of a PPI therapy for symptoms and signs associated with LPR compared to placebo and the second one choosing esome- prazole for a controlled trial. The results of this study demonstrate a significant placebo effect in the therapy of LPR-related symptoms as reported by patients especially within the first 6 weeks of PPI treatment. This phenomenon was already observed in former placebo-controlled studies investigating the efficacy of PPI therapy in patients with

Table 1 Baseline characteristics*

Control (n 28)

PPI (n 30)

P value†

Variable

Sex: male Smoker

13 (46.4%) 17 (56.7%) 0.160

5 (17.9 %)

6 (20.0%) 0.871

Total RSI before therapy Total RFS before therapy

21.79 6.69 23.1 7.45 0.503

14.89 2.5 14.9 2.75 0.969

When asked about persisting complaints at the end of the trial, 11 of 26 placebo recipients (42%) felt themselves to be free of symptoms compared to 22 of 28 patients ( 78%) from the esomeprazole group (two patients of each study group could not clearly answer the question with “yes” or “no”). This difference is statistically significant ( P 0.006). Age 47.6 16 49 13.9 0.663 n, number of subjects in each group; PPI, proton pump inhibitor (esomeprazole); RFS, reflux finding score; RSI, re- flux symptom index. *Comparison of baseline characteristics between groups, re- ported as mean standard deviation (SD) or proportion of subjects (%). † P value Mann-Whitney U test or 2 test, all nonsignificant.

Table 2 Change from baseline within each group after six weeks

Visit I vs visit II

Esomeprazole

Placebo

Difference

RSI

Total

9.87 1.61‡ 1.03 0.31† 1.20 0.31† 1.10 0.28† 1.23 0.30† 0.53 0.34 0.50 0.29 0.87 0.39* 1.60 0.32‡ 1.53 0.32‡ 3.47 0.47‡ 0.07 0.07 0.60 0.17† 0.77 0.21† 0.33 0.09† 0.60 0.13‡ 0.80 0.15‡ 0.07 0.07 0.40 0.23

6.93 1.61‡ 1.07 0.35† 1.32 0.32† 0.75 0.22† 0.57 0.27* 0.11 0.32 0.57 0.25* 0.68 0.27* 1.25 0.34† 0.75 0.27† 2.46 0.71† 0.21 0.19 0.36 0.18 0.43 0.26 0.46 0.13† 0.21 0.11 0.54 0.13† 0.00 0.18 0.29 0.25

2.94 2.27 0.04 0.47 0.12 0.45 0.35 0.35 0.66 0.41 0.64 0.47 0.07 0.39 0.19 0.48 0.35 0.46 0.78 0.42* 1.00 0.85 0.28 0.12 0.24 0.25 0.34 0.33 0.13 0.16 0.39 0.16* 0.26 0.20 0.07 0.19

Hoarseness Throat clear Throat mucus

Difficulty swallowing Coughing after meals Breathing difficulties Annoying cough Throat sensations

Heartburn

RFS

Total

Subglottic edema

Ventricular Erythema

Vocal fold edema

Diffuse laryngeal edema

Posterior commissure hypertrophy Granuloma/granulation tissue Thick endolaryngeal mucus

0.11 0.33 Data are given as mean differences standard error of the mean (SEM). The first two data columns show differences from baseline and the third demonstrates the difference between study groups. P values are from Wilcoxon signed rank test and Mann-Whitney U test as appropriate. * P 0.05; † P 0.01; ‡ P 0.001.

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