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

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

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.

Study Overview

• Status: Completed
• Conditions: Functional Gastrointestinal Disorders
• Intervention / Treatment: Drug: STW5 (Iberogast®, BAY98-7411); Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 64
• Phase: Phase 2

Contacts and Locations

Study Locations

• Germany
  • Multiple Locations, Germany
    • Many Locations

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 78 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Patients of either sex aged 18-80 years.

2. 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.
3. 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.
4. 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).
5. Patients willing to comply with the study protocol.
6. Patients who were able to understand and provide written informed consent to participate in the trial (signed informed consent).

Exclusion Criteria:

1. 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).
2. Regular intake of nonsteroidal antiphlogistic drugs incl. cyclooxygenase-2 (COX-2)-inhibitors (exception: acetylsalicylic acid for cardiovascular prevention up to 100 mg daily).
3. History of clinically relevant gastrointestinal disease such as gastric-, pancreatic-, colon-, rectal-cancer.
4. History of gastric and/or duodenal ulcer.
5. History of abdominal surgery (cholecystectomy and appendectomy could be tolerated).
6. History and/or presence of coronary heart disease.
7. Known intolerance to azo dyes E 110 and E 151.
8. Food allergies and known lactose intolerance.
9. Evidence of any gastrointestinal infectious diseases.
10. Participation in a clinical trial 30 days prior to this trial.
11. Concurrent participation in another clinical trial.
12. Female patients of childbearing potential with a positive pregnancy test, breast feeding, or female patients of childbearing potential without adequate contraception.
13. History and/or presence of drug or alcohol abuse.
14. Patients with psychiatric illness.
15. Irritable bowel syndrome.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

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

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

Collaborators and Investigators

• Sponsor: Bayer

Publications and helpful links

Helpful Links

• Click here to find information about studies related to Bayer Healthcare products conducted in Europe
• Click here to find results for studies related to Bayer products

Study record dates

Study Major Dates

• Study Start (Actual): June 18, 2009
• Primary Completion (Actual): May 3, 2013
• Study Completion (Actual): May 3, 2013

Study Registration Dates

• First Submitted: July 12, 2019
• First Submitted That Met QC Criteria: August 15, 2019
• First Posted (Actual): August 16, 2019

Study Record Updates

• Last Update Posted (Actual): September 19, 2019
• Last Update Submitted That Met QC Criteria: September 17, 2019
• Last Verified: September 1, 2019

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Gastrointestinal Diseases; Digestive System Diseases
• Other Study ID Numbers: 20985; 2008-002305-40 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Undecided
• IPD Plan Description: Availability of this study's data will be determined according to Bayer's commitment to the EFPIA/PhRMA "Principles for responsible clinical trial data sharing". This pertains to scope, timepoint and process of data access. As such, Bayer commits to sharing upon request from qualified researchers patient-level clinical trial data, study-level clinical trial data, and protocols from clinical trials in patients for medicines and indications approved in the US and EU as necessary for conducting legitimate research. This applies to data on new medicines and indications that have been approved by the EU and US regulatory agencies on or after January 01, 2014. Interested researchers can use www.clinicalstudydatarequest.com to request access to anonymized patient-level data and supporting documents from clinical studies to conduct research. Information on the Bayer criteria for listing studies and other relevant information is provided in the Study sponsors section of the portal.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No