Study in Patients Suffering From Heartburn and Backward Flow of Stomach Liquid Into the Esophagus

Study Overview
=================
Brief Summary
-----------------
In this study researchers want to learn more about the effectiveness of Iberogast® in patients with irritable stomach and concomitant chronic or recurrent heartburn and backward flow of stomach liquid into the esophagus. 60 patients in the age range from 18 - 80 year will be treated over 4 weeks with Iberogast® or placebo - an inactive substance which looks identical to Iberogast®. Patients completed diaries will provide researchers with detailed information on the change of stomach and intestinal symptoms during the treatment period. In addition information on the acidity of the esophagus and stomach liquid will be collected.

Official Title
-----------------
A Double-blind, Randomised, Placebo-controlled Study on the Efficacy of Iberogast® (STW 5) in Patients With Functional Dyspepsia and Concomitant Reflux Symptoms Measured With Impedance and Wireless pH Monitoring

Conditions
-----------------
Functional Gastrointestinal Disorders

Intervention / Treatment
-----------------
* Drug: STW5 (Iberogast®, BAY98-7411)
* Drug: Placebo


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Patients of either sex aged 18-80 years. Diagnosis of functional dyspepsia according to Rome III criteria: Pain or burning localized to the epigastrium of at least moderate severity at least once per week with a total duration of at least 6 months. Pain was intermittent. Pain was not generalized or localized to other abdominal or chest regions. Pain was not relieved by defecation or passage of flatus. Pain did not fulfil criteria for gallbladder and sphincter of Oddi disorders. At assessment (visit 1 or 3) three items of GIS had to be judged at least as moderate including reflux symptoms, but reflux symptoms not dominating the clinical picture. Endoscopy of the upper gastrointestinal tract and abdominal sonography without pathological findings that could have explained the symptoms (findings of up to 5 gastric erosions could be tolerated if patient had no concomitant intake of acetylsalicylic acid). Patients willing to comply with the study protocol. Patients who were able to understand and provide written informed consent to participate in the trial (signed informed consent). Exclusion Criteria: Concomitant treatment during the study with any medication that could influence the gastrointestinal function (e.g. prokinetics, antacids, antibiotics, antidepressant, laxatives, calcium antagonists, beta-blocker, antidiarrheics). Regular intake of nonsteroidal antiphlogistic drugs incl. cyclooxygenase-2 (COX-2)-inhibitors (exception: acetylsalicylic acid for cardiovascular prevention up to 100 mg daily). History of clinically relevant gastrointestinal disease such as gastric-, pancreatic-, colon-, rectal-cancer. History of gastric and/or duodenal ulcer. History of abdominal surgery (cholecystectomy and appendectomy could be tolerated). History and/or presence of coronary heart disease. Known intolerance to azo dyes E 110 and E 151. Food allergies and known lactose intolerance. Evidence of any gastrointestinal infectious diseases. Participation in a clinical trial 30 days prior to this trial. Concurrent participation in another clinical trial. Female patients of childbearing potential with a positive pregnancy test, breast feeding, or female patients of childbearing potential without adequate contraception. History and/or presence of drug or alcohol abuse. Patients with psychiatric illness. Irritable bowel syndrome.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Supportive Care
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: STW5 (Iberogast®, BAY98-7411)<br>The medication was applied daily per os (orally, p.o.) from day 0 to day 28. The dosage was 20 drops three times daily before the meals. | Drug: STW5 (Iberogast®, BAY98-7411)<br>* The medication was applied daily per os (orally, p.o.) from day 0 to day 28. The dosage was 20 drops three times daily before the meals.<br>|
| Placebo Comparator: Placebo<br>The medication was applied daily p.o. from day 0 to day 28. The dosage was 20 drops three times daily before the meals | Drug: Placebo<br>* The medication was applied daily p.o. from day 0 to day 28. The dosage was 20 drops three times daily before the meals<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| AUC of Patients' assessment of gastrointestinal symptoms evaluated by a daily measured VAS scale. | Area under the curve (AUC) of patients' assessment of gastrointestinal symptoms evaluated by daily visual analogue scale (VAS) | Up to 28 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Global Subject Outcome Assessment at visit 5 | Assessed by Global Improvement Scale (substantially worsened/moderately worsened/ marginally worsened/not changed/ marginally improved/ moderately improved/ substantially improved). | At day 28 (visit 5) | 
| Change of the Gastrointestinal Symptoms Profile (GIS) from baseline (visit 3) at the end of study (day 28) | The GIS is a symptom related score, validated in German language, which allows the investigator to assess the dyspeptic symptoms by asking the patient for the following 10 items (GIS): epigastric pain / upper abdominal pain, abdominal cramps, fullness, early satiety, loss of appetite, sickness, nausea, vomiting, retrosternal discomfort and acid eructation/heartburn. The total GIS score is 40 points and an increasing summary score therefore represents a higher intensity of dyspeptic symptoms. | At baseline and day 28 | 
| AUC of reflux symptoms assessment measured by daily VAS scale | Area under the curve (AUC) of assessment of reflux symptoms evaluated by daily visual analogue scale (VAS). VAS is an s an unmarked scale on a line 100 mm in length, indicating from 0 mm (no symptoms) to 100 mm (severe symptoms) | Up to 28 days | 
| Quality of Life evaluation as assessed by Functional Dyspepsia Quality of Life (FDDQL) | The FDDQL provided a profile with eight subscores (daily activities, anxiety, diet, sleep, discomfort, health perceptions, coping with disease and impact of stress) as well as a global score. Sub-scale scores and the global score were transformed to a range from 0 = Poor QoL to 100= Good QoL. | At baseline and day 28 | 
| Relative time with an esophageal pH < 4 during 24 hours of measurement by Bravo™ pH system | The Bravo™ pH system is a new, single use, disposable class I catheter free pH monitoring system, which involves the attachment of a miniaturised radiotelemetry pH capsule to the mucosal wall of the esophagus. It simultaneously measures the pH and transmits data to a pager-sized receiver clipped into the subject's belt | At day -7/ -5 (screening phase) and day 29/30 if applicable | 
| Relative time with an esophageal pH < 4 during 24 hours of measurement using intraluminal impedance | pH measured by pH-metry | At day -1 (screening phase) and day 29/30 if applicable | 
| Calculation of the DeMeester Score measured based on Bravo™ pH system | The score is calculated from the following parameters: percentual part of measurement with pH<4, number of reflux periods with a duration of more than 5 minutes, duration of the longest reflux period and total number of reflux periods | At day -7/ -5 (screening phase) and day 29/30 if applicable | 
| System index measurement in parallel to the pH measurement by Bravo™ pH system | The study patients will be instructed to enter concomitant symptoms (heartburn and upper abdominal pain) which might occur during the measurement by pushing pre-programmed buttons on the data logger A positive symptom index is defined with >50% (more than a half of the concomitant symptoms occur within 5 minutes after bolus exposition) | At day -7/ -5 (screening phase) and day 29/30 if applicable | 
| Calculation of the DeMeester Score based on intraluminal impedance | The score is calculated from the following parameters: percentual part of measurement with pH<4, number of reflux periods with a duration of more than 5 minutes, duration of the longest reflux period and total number of reflux periods) | At day -1 (screening phase) and day 29/30 if applicable | 
| Bolus exposition time in minutes and as percentual part of measurement time for acid reflux, non-acid reflux and total (acid and non-acid) reflux using intraluminal impedance | Impedance is a measure of the total resistance to current flow between adjacent electrodes. As reflux contents are characterized by different conductivity, which is the inverse of impedance, a pH-independent accurate and practical qualitative analysis of refluxate is possible | At day -1 (screening phase) and day 29/30 if applicable | 
| Symptom index measurement in parallel to the pH measurement by intraluminal impedance | The study patients will be instructed to enter concomitant symptoms (heartburn, retrosternal discomfort, upper abdominal pain) which might occur during the measurement by pushing pre-programmed buttons on the data logger. A positive symptom index is defined with >50% (more than a half of the concomitant symptoms occur within 5 minutes after bolus exposition). | At day -1 (screening phase) and day 29/30 if applicable | 
| Global assessment of efficacy judged by patient using a five point Likert scale | 1 = very good, 2 = good, 3 = moderate, 4 = poor, 5 = very poor | At day 28 | 
| Global assessment of efficacy judged by physician using a five point Likert scale | 1 = very good, 2 = good, 3 = moderate, 4 = poor, 5 = very poor | At day 28 | 
| Change of Individual symptom score from baseline at the end of study (day 28) | The GIS sub-scores for epigastric pain (item 1) and reflux symptoms (item 10). The sub-scores were assessed and analysed using the following scores: 0 = No problem, 1 = Mild problem, 2 = Moderate problem, 3 = Severe problem, 4 = Very severe | At baseline and day 28 |