Evaluation of Hemorrhagic and Thrombotic Risks in Cold Snare Polypectomy of Subcentimeter Colorectal Polyps in Patients on Edoxaban and Drug Combination

The primary objective of this study is to demonstrate that the risk of **postpolypectomy hemorrhage** (immediate or delayed) in patients with non-pedunculated colorectal polyps smaller than 10mm, removed using a cold snare while under antiplatelet or anticoagulant treatment, is not higher than that of a control group where such treatment has been withdrawn according to current clinical practice guidelines. This is clinically relevant as it addresses the safety of continuing antithrombotic therapy during polypectomy, potentially reducing the risk of thrombotic events without increasing bleeding complications.

Secondary objectives include: - Evaluating the risk of postpolypectomy hemorrhage (immediate or delayed) for each drug analyzed, with comparisons between different drugs and strategies. - Assessing the risk of cardiovascular and thrombotic events associated with the withdrawal of these drugs, by comparing the incidence of such events 30 days post-colonoscopy in both groups. Additionally, it will be analyzed whether maintaining the drug during polypectomy is associated with a reduction in these events.

The clinical trial involves **participants** aged between 18 and 80 years, encompassing both male and female subjects. The study population consists of individuals who have been requested to undergo a colonoscopy for any indication and are under chronic antiplatelet therapy (excluding ASA) or anticoagulant treatment. The trial does not include a vulnerable population. The sponsor has not provided the total number of participants. Selection criteria focus on those under specific medical treatments, with no additional lifestyle considerations such as diet or physical activity explicitly mentioned. The trial aims to assess the risk of postpolypectomy hemorrhage in non-pedunculated polyps smaller than 10mm, comparing patients under antiplatelet or anticoagulant treatment with a control group following current clinical practice guidelines.

The clinical trial is designed to evaluate the **risk of postpolypectomy hemorrhage** in patients undergoing cold snare polypectomy of subcentimeter non-pedunculated colorectal polyps while on antiplatelet or anticoagulant therapy. This study is a randomized, double-blind, controlled trial with an estimated duration from June 2024 to October 2026. Participants will be randomly assigned to either continue their antiplatelet or anticoagulant treatment or to have it withdrawn according to current clinical guidelines. The primary endpoint is the occurrence of significant post-polypectomy hemorrhage.

Study visits will follow a structured sequence, beginning with an inclusion (screening) visit to assess eligibility based on criteria such as age (18-80 years) and current chronic antiplatelet or anticoagulant therapy. Follow-up visits will be scheduled to monitor the participants' health status and adherence to the treatment protocol. The end-of-study visit will evaluate the primary endpoint and collect final data. The expected length of participant involvement is up to 8 weeks, corresponding to the maximum treatment period for the investigational products, which include **edoxaban**, **dabigatran etexilate**, **clopidogrel**, **rivaroxaban**, **apixaban**, and **acenocoumarol**. All medications will be administered orally, and the trial is classified as low-intervention, as the investigational products will be used according to their marketing authorizations without altering dosage or treatment duration.

Participants may be subject to early termination from the study if they experience adverse events that compromise their safety or if they fail to comply with the study protocol. The trial aims to ensure that the risk of hemorrhage in the treatment group is not higher than in the control group, thereby providing valuable insights into the management of patients requiring colonoscopy while on antiplatelet or anticoagulant therapy.

The clinical trial involves the administration of several **anticoagulant** and **antiplatelet** medications to evaluate their effects on postpolypectomy hemorrhage in patients undergoing cold snare polypectomy of subcentimeter non-pedunculated colorectal polyps. The experimental medication **Edoxaban** is administered orally in a pharmaceutical form identified as PHF00082MIG. The maximum daily dose is 60 mg, with a total maximum dose of 3360 mg over a treatment period of 8 weeks. Edoxaban is a chemical substance classified under the ATC code B01AF03.

**Dabigatran Etexilate** is another anticoagulant used in the study, administered orally in the form PHF00006MIG. The maximum daily dose is 300 mg, with a total maximum dose of 16800 mg over the same 8-week period. It is classified under the ATC code B01AE07.

The study also includes the administration of **Clopidogrel**, an antiplatelet agent, in the pharmaceutical form PHF00245MIG. The oral administration of Clopidogrel is limited to a maximum daily dose of 75 mg, with a total maximum dose of 4200 mg over 8 weeks. It is classified under the ATC code B01AC04.

**Rivaroxaban** is administered orally in the form PHF00082MIG, with a maximum daily dose of 20 mg and a total maximum dose of 1120 mg over the 8-week treatment period. Rivaroxaban is classified under the ATC code B01AF01 and is a chemical substance.

**Apixaban** is another anticoagulant used in the trial, administered orally in the form PHF00009MIG. The maximum daily dose is 10 mg, with a total maximum dose of 560 mg over 8 weeks. It is classified under the ATC code B01AF02.

Lastly, **Acenocoumarol** is administered orally in the form PHF00245MIG, with a maximum daily dose of 4 mg and a total maximum dose of 224 mg over the 8-week period. Acenocoumarol is classified under the ATC code B01AA07 and is a chemical substance.

All medications are administered orally, and participant compliance is monitored throughout the study. The trial aims to assess the safety and efficacy of these treatments in reducing the risk of postpolypectomy hemorrhage without increasing thrombotic risks. The study does not include any placebo or comparator treatment, as the focus is on the effects of maintaining or withdrawing these medications according to current clinical practice guidelines.

Efficacy in this clinical trial will be assessed by evaluating the primary endpoint of significant post-polypectomy hemorrhage. This endpoint is crucial in determining the safety and effectiveness of maintaining or withdrawing antiplatelet and anticoagulant treatments in patients undergoing cold snare polypectomy for subcentimeter non-pedunculated colorectal polyps. The trial aims to demonstrate that the risk of postpolypectomy hemorrhage in patients under such treatments is not higher than in the control group, where the treatment will have been withdrawn according to current clinical practice guidelines.