Acetylsalicylic acid for Colorectal adenomas | Lynch syndrome

Inclusion criteria

• {"criterion_text":"- Men and women with Lynch syndrome bearing an alteration of “mismatch repair” genes or,when no characteristic alteration has been found, with a personal or family history of Lynch syndrome according to modified Amsterdam criteria\n- Aged more than 25 years, et aged more than 18 years with an early familial history and any reason to perform a colonoscopy every 2 years\n- Aged less than 75 years\n- A colonoscopy done within 180 days prior to inclusion, with removal of all polyps endoscopically resectable\n- Patients accept that not use aspirin regularly all along the study (during 7 consecutive days during at least 3 weeks per year or during more than 21 days per year)\n- Effective contraception for womens of childbearing age, defined by a hormonal method, an intrauterine device (IUD), or surgical sterilization of the patient or her partner\n- Patients covered by French Social Security (AME not accepted)\n- Patients signed informed consent"}

Exclusion criteria

• {"criterion_text":"- History of total colectomy\n- Gastrointestinal bleeding linked to ulcerative disease in the previous 12 months before inclusion\n- Gastric pathology deemed significant by the investigator and not corrected by appropriate treatment\n- Uncontrolled hypertension\n- Kidney failure (creatinine clearance < 30 ml/mn)\n- Severe hepatic impairment (defined as TP <70%)\n- Severe uncontrolled heart failure\n- G6PD deficiency\n- Recent diagnosis of colorectal cancer implying a specific management\n- Menorrhagia deemed significant by the investigator and not corrected by appropriate treatment\n- Pregnancy or breast feeding\n- Adenomatous polyposis related to a known alteration of the APC gene or the MYH gene\n- Any disease susceptible to interfere with protocol-defined follow-up or to impair the comprehension of the information provided by the protocol and informed consent\n- Patient waiting for or have been signified a justice decision\n- Participation to another clinical trial during the 12 weeks before inclusion\n- Allergy to aspirin (including a history of asthma induced by the administration of salicylates or substances with similar activity, including non-steroidal anti-inflammatory)\n- Allergy to one food coloring potentially used in a chromo-endoscopy (indigo carmine, for example)\n- Need for a prolonged treatment (prevention of cardio-vascular risk) or repeated treatments (recurring migraines) using aspirin or another non-steroidal anti-inflammatory drug (NSAID)\n- Need for a prolonged and high-dose systemic glucocorticoid therapy\n- Known disease affecting primary hemostasis or coagulation (gastrointestinal bleeding, hemorrhagic stroke and thrombocytopenia history)\n- Need for a prolonged anticoagulant, antiplatelet agents, anagrelide, uricosurics, probenecid, ticagrelor, nicorandil, defibrotide, clopidogrel, ticlopidine, ticagrelor, ibrutinib, or cobimetinib\n- History of gastro-duodenal ulcer"}

Primary endpoints

• {"endpoint_text":"- Number of patients with at least 1adenoma on chromoendoscopy 48months after complete withdrawal of polyps and initiation of IMP. Only neoplastic polyps (progress to cancer), defined by the following histological types as determined by ACP result, will be considered: 1) Adenoma not otherwise specified 2) Tubular adenoma 3) Tubulovillous adenoma 4) Mixed or serrated adenoma (sessile serrated adenoma) 5) Villous adenoma. Additionally, cancers will also be considered for primary endpoint analysis","definition_or_measurement_approach":"Assessed by chromoendoscopy at 48 months after complete polyp resection and start of IMP; only neoplastic polyps defined by specified histological types (as determined by ACP result) are counted; colorectal cancers are also included in the primary endpoint analysis."}

Secondary endpoints

• {"endpoint_text":"- Delay between the onset of 1 adenoma after complete resection of polyps and date of start of treatment (aspirin vs placebo)","definition_or_measurement_approach":"Time from complete polyp resection to first adenoma onset; comparison between aspirin and placebo arms."}
• {"endpoint_text":"- Number of patients who presented an adenoma during follow-up based on the gene reached (MLH1, MSH2, MSH6, PMS2, or without other identified anomalies)","definition_or_measurement_approach":"Count of patients with adenoma during follow-up stratified by germline mismatch repair gene (MLH1, MSH2, MSH6, PMS2 or none identified)."}
• {"endpoint_text":"- Load serrated polyps after 24 and 48 months of treatment","definition_or_measurement_approach":"Assessment of number/ burden of serrated polyps at 24 and 48 months by chromoendoscopy."}
• {"endpoint_text":"- Adenomatous polyp burden, measured by chromoendoscopy as the sum of the size of all adenomatous polyps as a function of the dose of ASA (100 or 300 mg)","definition_or_measurement_approach":"Polyp burden quantified by chromoendoscopy as sum of sizes of all adenomatous polyps; analyzed by aspirin dose (100 vs 300 mg)."}
• {"endpoint_text":"- Load measured by polyps chromoendoscopy as the sum of the size of all polyps according to the aspirin dose (100 or 300mg)","definition_or_measurement_approach":"Total polyp burden measured by chromoendoscopy (sum of sizes) compared across aspirin dose groups."}
• {"endpoint_text":"- Colon cancers diagnosed during the scheduled surveillance colonoscopies","definition_or_measurement_approach":"Number of colon cancers detected during scheduled surveillance colonoscopies."}
• {"endpoint_text":"- Time to onset of colon cancer diagnosed during the scheduled surveillance colonoscopies","definition_or_measurement_approach":"Time-to-event analysis for colon cancer diagnosis during scheduled surveillance colonoscopies."}
• {"endpoint_text":"- Cancers of the colon interval (diagnosed between 2 surveillance colonoscopies programmed)","definition_or_measurement_approach":"Count of interval colon cancers (diagnosed between two scheduled surveillance colonoscopies)."}
• {"endpoint_text":"- Time to onset of interval colorectal cancer","definition_or_measurement_approach":"Time from randomization or start of treatment to diagnosis of interval colorectal cancer."}
• {"endpoint_text":"- Number of colonoscopies performed during follow-up in study","definition_or_measurement_approach":"Count of colonoscopies performed per participant during study follow-up."}
• {"endpoint_text":"- Quality of preparation before colonoscopy","definition_or_measurement_approach":"Assessment of colonoscopy bowel preparation quality prior to procedures (as recorded in follow-up)."}
• {"endpoint_text":"- Chromoendoscopy expected execution","definition_or_measurement_approach":"Recording whether chromoendoscopy was performed as expected per protocol."}
• {"endpoint_text":"- Counting of remaining tablets in blisters","definition_or_measurement_approach":"Medication adherence assessed by counting remaining tablets in blister packs."}
• {"endpoint_text":"- Number of events or side effects","definition_or_measurement_approach":"Safety outcomes: count and classification of adverse events and side effects."}
• {"endpoint_text":"- Food frequency","definition_or_measurement_approach":"Dietary assessment via a food frequency questionnaire completed by voluntaries."}
• {"endpoint_text":"- Distribution of the bacterial population based on two groups (treated / untreated) and recidivism","definition_or_measurement_approach":"Microbiota composition analysis comparing treated vs untreated groups and by recurrence status."}
• {"endpoint_text":"- Distribution of polymorphisms based on 2 groups (treated / untreated) and recidivism","definition_or_measurement_approach":"Genetic polymorphism distribution analysis by treatment group and recurrence."}
• {"endpoint_text":"- Proportion of patients with at least one adenoma seen on chromo-endoscopy within 48 months after complete polyp resection and the start of treatment (aspirin vs placebo)","definition_or_measurement_approach":"Proportion (%) of patients with ≥1 adenoma on chromoendoscopy within 48 months post-resection and treatment start; comparison aspirin vs placebo."}

France

Earliest CTIS Part Ii Submission Date

22-07-2024

Latest Decision Or Authorization Date

13-03-2025

Processing Time Days

234

Number Of Sites

29

Number Of Participants

852

Primary sponsor

Full Name

Assistance Publique Hopitaux De Paris

Organisation Type

Hospital/Clinic/Other health care facility

Country Of Registered Address

France