E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Symptoms from the upper gastrointestinal tract |
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MedDRA Classification |
E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
The primary objective of this study is to determine the accuracy of the RDQ as a diagnostic test for gastroesophageal reflux disease. Symptom evaluation by the RDQ will be compared with other established approaches to the diagnosis of GERD in a primary care patient population with symptoms thought to be of upper gastrointestinal (GI) tract origin. |
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E.2.2 | Secondary objectives of the trial |
1. To estimate the sensitivity and specificity of the selection of RDQ items, endoscopy, esophageal pH monitoring, response to proton pump inhibitors (PPIs) and Symptom Association Probability (SAP) as diagnostic tests for GERD by using Latent Class Analysis (LCA) and Bayesian statistics 2. To estimate the prevalence of GERD with LCA and Bayesian statistics 3. To describe the study population at the initial and last visit with the Gastrointestinal Symptom Rating Scale (GSRS) dimensions in the whole study population and by GERD diagnosis 4. To estimate responsiveness of the RDQ during therapy in subjects categorised as having or not having GERD
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E.2.3 | Trial contains a sub-study | Information not present in EudraCT |
E.3 | Principal inclusion criteria |
For inclusion in the study, subjects must fulfil all of the following criteria: 1. Subjects must have provided informed consent in writing for the participation in this study 2. Subjects aged 18 to 79 years inclusive, male or female 3. Subjects who seek medical advice in primary care for symptoms thought by the PCP to arise from the upper GI tract (any of those symptoms listed in Table 3) 4. The symptoms thought to pertain to the upper GI tract must have been present for at least 4 weeks prior to Visit 1 and to have occurred at least twice a week during that period 5. The symptoms thought to pertain to the upper GI tract must have been of at least mild severity for a minimum of 3 days during the week prior to Visit 1 6. Subjects judged to be capable to understand and to complete diaries and questionnaires reliably.
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E.4 | Principal exclusion criteria |
Any of the following is regarded as a criterion for exclusion from the study: 1. Upper GI endoscopy performed within a year prior to Visit 1 2. Previous anti-reflux surgery, surgery for peptic ulcer or any form of upper gastrointestinal resective surgery 3. Contra-indication to the Bravo™ procedure such as subjects with a history of bleeding diathesis, strictures anywhere along the GI-tract, esophageal varices, obstructions, or subjects equipped with a pacemaker, an implantable cardiac defibrillator or an implantable neurostimulator (NB: subjects with LA Grade D confirmed by endoscopy at Visit 2 can continue the study without performing the Bravo™ procedure) 4. Any use of PPIs within 2 months prior to Visit 1, including those obtained OTC 5. Use of the following drug therapy within 4 weeks prior to Visit 1: - Daily use of acetylsalicylic acid (ASA) at any dose greater than 165 mg - Daily use of non-steroidal anti-inflammatory drugs (NSAIDs) including COX-2 inhibitors at any dose 6. Presence of any alarm features, such as: - Unintentional weight loss >3 kg in the previous 3 months - Haematemesis, melaena or per-rectum blood loss in the previous year - Progressive dysphagia - Anaemia - Any other symptom suggestive of malignancy 7. Any significant past or current disease or disorder (e.g.; cardiovascular, pulmonary, gastrointestinal, hepatic, renal, neurological, musculoskeletal, endocrine, malignant, or psychiatric), as revealed by history, physical examination or laboratory assessments, which, in the opinion of the investigator, may put the subject at risk, alter their performance or influence the subject’s ability to participate in the study 8. Unwillingness to undergo endoscopy, esophageal pH monitoring or to complete any other standard assessments used in the study 9. History of alcohol or drug abuse in the last two years or any condition associated with poor compliance, including expected non-cooperation, as judged by the investigator 10. Pregnancy or lactation. Women of childbearing potential must maintain effective contraception during the study period, as judged by the investigator 11. Treatment with phenytoin, warfarin (or other vitamin K antagonists), ketoconazole, itraconazole and cisapride 12. Planned donation of blood during the study period 13. Planned hospitalisation during the study period 14. Involvement in the planning and conduct of the study (applies to both AstraZeneca staff or staff at the study site) 15. Treatment with any medicinal investigational product within 30 days prior to Visit 1 or within another time-frame according to local requirements, if applicable 16. Previous enrolment in the present study 17. Participation as a subject in any other medical research project during and in the 4 weeks prior to the start of the study In addition to the above, the following criterion excludes the subject from participation into the study at Visit 2: 18. Any findings at endoscopy that make further participation in the study clinically inappropriate as judged by the investigator, such as suspected malignancy or evidence of clinically significant gastrointestinal bleeding (i.e. visible vessel or other stigmata of current bleeding) [NB: Subjects with macroscopic Barrett’s esophagus (defined as subjects with endoscopic indications of any columnar lined epithelium in the esophagus) are not to be excluded; Subjects with LA Grade D confirmed by endoscopy at Visit 2 can continue the study without performing the Bravo™ procedure.].
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E.5 End points |
E.5.1 | Primary end point(s) |
There are no primary end point in this study.
Based on the selection of RDQ items and the various methods of diagnosing GERD, i.e. presence/absence of GERD as assessed by endoscopic Los Angeles (LA) grade, pH monitoring (% time with esophageal pH<4), SAP, outcome of PPI test, the primary variables are the cut-off level(s), sensitivity, specificity and predictive abilities of the RDQ score(s) (ROC curve and c-statistic), as assessed against each other diagnostic tool in use in this study
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | Yes |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | No |
E.6.4 | Safety | No |
E.6.5 | Efficacy | No |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | Information not present in EudraCT |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | Yes |
E.6.13.1 | Other scope of the trial description |
Validation of the Reflux Disease Questionnaire |
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E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | Yes |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | Yes |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | Yes |
E.8.1.7.1 | Other trial design description |
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E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
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E.8.7 | Trial has a data monitoring committee | Information not present in EudraCT |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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End of study is defined as date of database lock, which is the time point after which no subject will be exposed to study related activities. |
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | |
E.8.9.1 | In the Member State concerned months | 10 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial months | 10 |