E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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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 |
To assess whether intervention with aspirin results in a decreased all causes of mortality or conversion rate from Barrett’s metaplasia to adenocarcinoma or high grade dysplasia.
To assess whether high dose PPI therapy decreases the all causes of mortality or conversion rate from Barrett’s Metaplasia to adenocarcinoma or high grade dysplasia.
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E.2.2 | Secondary objectives of the trial |
To assess whether intervention with aspirin and/or high dose PPI; -results in decreased cause-specific mortality. -induces change in expression of molecular markers for BA. -influences the timing and severity of acid reflux into the oesophagus and the change in concentrations of bile acids in the oesophageal aspirates. Can clinical and molecular risk factors be identified in BM for the development of BA? To assess the cost effectiveness of the prevention of BA. Can molecular markers be used to monitor disease and identify high risk groups? Which new genes are important in the progression of BA? To investigate host susceptibility genes and environment-gene interactions. What are the biological risk factors for cardiac disease and aspirin resistance? What is aspirin’s role on the development of colorectal adenomas and cancer, intestinal metaplasia of the stomach, and of Barrett’s metaplasia in patients with benign reflux disease. |
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E.2.3 | Trial contains a sub-study | Yes |
E.2.3.1 | Full title, date and version of each sub-study and their related objectives |
CHOPIN (Chemoprevention of Premalignant Intestinal Neoplasia) translational trial, parts A-E. A. Biomarkers Study. Predictive biomarkers. PGE2 and COX-2 levels between tissues from patients with and without aspirin treatment. Mechanisms of aspirin in the pathology of BM will be assessed, the measurement of inhibition of COX activity in patients taking aspirin, the role of COX-1 and COX-2 in BM. Also, the effects of aspirin and NSAIDs on apoptosis and activation of transcription factors. Prognostic biomarkers of disease progression namely p53, -catenin and cdx-2 expression in serial sections in patients that progress. B. Microarray/Pathophysiology Study. Aspirin’s effect on mucosal inflammation, assessing cytokine signatures, in particular TNF, IL-1, IL-10 expression by measuring RNA/protein levels in tissues and white blood cell response, due to reflux. The role of PPI drugs on serum gastrin levels and gastrin receptor levels in tissues. C. IPOD (Inherited Predisposition to Oesophageal Disease) Genetics Study. Assessing the genetic predisposition to oesophageal reflux disease, Barrett’s Metaplasia, and oesophageal adenocarcinoma through the analysis of mutations and polymorphisms. This study will be linked to the EAGLE study (Esophageal Adenocarcinoma Genetic Linkage study) and will assess all samples for SNPs and minichromosomes. D. SIMS (Stomach Intestinal Metaplasia Study). Gastric biopsies will be assessed for changes identical to those in the Barrett’s tissue as outlined in A. above. E. Peripheral blood mononuclear cells (PBMCs) will be isolated from whole blood and stored for potential studies of immune responses to tumour antigens.
Women’s AspECT study (WASP). Comparing cancer prevention in a cohort of 1000 female Barrett’s patients alongside the male cohort.
Physiology Protocol. 200 patients will be assessed for acid and bile changes in the oesophagus by ambulatory oesophageal and gastric pH and combined oesophageal multisite impedence monitoring; Bilitec bilirubin monitoring is an optional addition. Oesophageal bile acid harvesting by endoscopic aspiration on a separate occasion at the time of surveillance follow up endoscopy. These patients will undergo one impedence/pH monitoring during the first 4 years to assess the long-term level of acid suppression. Patients will also have oesophageal aspirates (20mls) collected and stored for subsequent analysis.
PACT ‘Polyp Aspirin Chemoprevention Trial’ will give patients in 3 centres an optional additional flexible sigmoidoscopy or colonoscopy to ensure they don’t have colorectal polyps according to the guidelines of the National Bowel Cancer Screening programme. All patients will be offered an exit flexible sigmoidoscopy or colonoscopy according to the guidelines of the National Bowel Cancer Screening programme.
HIGH ‘HIgh Grade Histology’ study (in development). Everyone with high grade dysplasia will be randomised to intervention with either surgery, endoscopic mucosal resection or photodynamic or laser ablation therapy. If changes persist after 3 months physicians will be able to treat according to local preferences.
HANDEL(Histological Assessment Determining Epithelial Response). Assessing epidermal growth factor receptor (EGFR) as a target for therapy in patients who present with advanced cancer. Identification of relatives of patients with BM or OA for collection of blood for subsequent genetic linkage and association studies.
SIMS (Stomach Intestinal Metaplasia Study) The histological assessment of oesophageal biopsies is reliant on accurate endoscopic diagnosis of Barrett’s oesophagus; i.e. that the biopsies are from a segment of Barrett’s unless otherwise specified. Distinction from intestinal metaplasia of the cardia is within the scope of the SIMS study. |
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E.3 | Principal inclusion criteria |
1. Aged ≥18 years 2. Circumferential Barrett’s Metaplasia of at least 1cm in length (≥C1M1) or a tongue of Barrett’s metaplasia greater than 2cm in length (≥C0M2) (with or without histologically proven intestinal metaplasia in at least one sample from this endoscopy or past history of intestinal metaplasia). 3. Able to give written consent 4. WHO performance status of 0 or 1 i.e. fully active and self-caring
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E.4 | Principal exclusion criteria |
1. High grade dysplasia or carcinoma at enrolment 2. Medical conditions which would make completing endoscopies or completing the trial difficult including a. Previous transient ischaemic attacks or cerebral vascular disease b. Severe respiratory disease c. Severe ischaemic heart disease or myocardial infarction in the previous 6 months d. Inflammatory bowel disease 3. Continuous/frequent non-steroidal anti-inflammatory drug use or COX-2 inhibitors (more than 60 days/year in total) 4. Patients with absolute contraindications to PPIs or their excipients i.e. allergies, ulcers, renal impairment or use of oral anticoagulants 5. Pregnant or lactating women |
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E.5 End points |
E.5.1 | Primary end point(s) |
All causes of mortality Conversion from Barrett’s metaplasia to adenocarcinoma or high grade dysplasia |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | Information not present in EudraCT |
E.6.2 | Prophylaxis | Information not present in EudraCT |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Information not present in EudraCT |
E.6.5 | Efficacy | Information not present in EudraCT |
E.6.6 | Pharmacokinetic | Information not present in EudraCT |
E.6.7 | Pharmacodynamic | Information not present in EudraCT |
E.6.8 | Bioequivalence | Information not present in EudraCT |
E.6.9 | Dose response | Information not present in EudraCT |
E.6.10 | Pharmacogenetic | Yes |
E.6.11 | Pharmacogenomic | Information not present in EudraCT |
E.6.12 | Pharmacoeconomic | Yes |
E.6.13 | Others | Information not present in EudraCT |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | Information not present in EudraCT |
E.7.1.2 | Bioequivalence study | Information not present in EudraCT |
E.7.1.3 | Other | Information not present in EudraCT |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | Yes |
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) | Yes |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | Yes |
E.8.2.3.1 | Comparator description |
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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.8.4.1 | Number of sites anticipated in Member State concerned | 100 |
E.8.5 | The trial involves multiple Member States | No |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
E.8.7 | Trial has a data monitoring committee | Yes |
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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AspECT will end with the last follow-up visit from the last patient ie 8 years after the last patient recruitment. The DSMC could recommend · Early stopping due, amongst other things, to clear benefit or harm of a treatment, safety concerns on secondary outcome, futility, slow recruitment, or external evidence · Stopping recruitment within a subgroup due to safety concerns · Stopping a single arm of a multi-arm trial . Sanctioning and/or proposing protocol changes |
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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 | 12 |
E.8.9.1 | In the Member State concerned months | 3 |
E.8.9.1 | In the Member State concerned days | 30 |