Clinical trial NCT06285942: EdOxaban in fRagIle Patients With Percutaneous Endoscopic GAstrostoMy and atrIal fIbrIllation
Official title: EdOxaban in fRagIle Patients With Percutaneous Endoscopic GAstrostoMy and atrIal fIbrIllation: the ORIGAMI II Study
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Atrial Fibrillation
Fragility
Keywords: Edoxaban
Fragile Patient
Atrial Fibrillation
Lead sponsor: Azienda Ospedaliero Universitaria Maggiore della Carita
Sponsor class: OTHER
First posted: 2024-02-29
Enrollment: 168
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The goal of this interventional study is to describe the use of Edoxaban via PEG in patients with an indication to anticoagulation therapy. One arm will receive Edoxaban through PEG and the other arm will receive other Direct oral anticoagulants through PEG or subcutaneous heparin or LMWH.

Once enrolled, patients will be treated with a single daily dose of Edoxaban (60 or 30 mg according to specific indications). At day 4 after enrollment (steady state), evaluation of anti-FXa activity and thrombin generation assay will be performed on peripheral whole blood samples. At months 6 and 12 patients will be asked to complete the ACTS (Anti-Clot treatment scale) questionnaire specific for anticoagulation.

The main endpoint will be: the difference in the results of the Anti-Clot treatment scale questionnaire between the two groups evaluated at 12 months.

Detailed description: Direct oral anticoagulants (DOAC) have a remarkable efficacy/safety ratio, a predictable anticoagulant effect and are recommended by ESC guidelines to be preferred over vitamin K antagonist (VKA) wherever possible in the prevention of stroke and systemic embolism in adult patients with non-valvular atrial fibrillation. Enteral access feeding devices are placed in patients who have a functional and accessible gastrointestinal tract but are not able to maintain an adequate oral intake. Among these devices, percutaneous endoscopic gastrostomy (PEG) represents a valid option, especially for long-term feeding, and PEG positioning has shown a steadily increasing trend in fragile patients with several comorbidities.

A significant subgroup of subjects with PEG tube has an indication to long-term anticoagulant therapy, mainly represented by atrial fibrillation. Among the several pharmacodynamic pathway mediating anticoagulation, direct FXa inhibitors block both free FXa and FXa bound to form the prothrombinase complex, whereas the indirect FXa inhibitors, such as LMHW, only inhibit free FXa. It was recently described a safe and effective anticoagulation through the administration of edoxaban 30 mg daily (crushed and diluted in 10 mL of saline solution) through a PEG in a patient with advanced amyotrophic lateral sclerosis, tracheostomy, atrial fibrillation, and a recent acute heart failure. On these premises, the investigators designed the ORal anti-coagulants In fraGile patients with percutAneous endoscopic gastrostoMy and atrIal fibrillation (ORIGAMI) pilot investigation, evaluating the feasibility, anticoagulant effectiveness and preliminary safety and efficacy of edoxaban administration via PEG in fragile patients with NVAF requiring long-term anticoagulation treatment.

The ORIGAMI II study will be a prospective, multi-centre, double arm, open label, clinical trial, aiming to describe the use of Edoxaban via PEG in patients with an indication to anticoagulation therapy according to current guidelines. One arm will receive Edoxaban through PEG and the other arm will receive other DOACs through PEG or subcutaneous heparin or LMWH.

The study will enroll 168 patients, who will be followed-up for 12 months. The Centers that will participate in this study will be: the AOU Maggiore della Carità of Novara (as coordinating center); Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Roma; Ospedale Policlinico San Martino, Genova.

The primary endpoint of this study is the difference in Anti-Clot treatment scale questionnaire results among the two groups assessed at 12 months.

Eligibility criteria: Inclusion Criteria:

* PEG (recent implantation or already present)
* Indication for long-term oral anticoagulation

Exclusion Criteria:

* Under 18 years of age
* Life expectancy \<30 days
* Lack of informed consent
* Contraindication to DOACs

Primary outcomes:
measure: Difference in Anti-Clot treatment scale (ACTS) questionnaire results among the two groups assessed at 6 and 12 months.
timeFrame: at 6 and 12 months
Secondary outcomes:
measure: Number of cardio-embolic events at 6 and12 months
timeFrame: at 6 and 12 months
measure: Number of bleeding events
timeFrame: at 6 and 12 months
measure: Assessment of drugs efficacy by measuring the anti-factor Xa activity
timeFrame: at 6 and 12 months
measure: Assessment of drugs efficacy by measuring the thrombin generation
timeFrame: at 6 and 12 months
measure: Assess the quality of life
timeFrame: at 6 and 12 months
measure: Cost-effectiveness analysis
timeFrame: at 6 and 12 months
Other outcomes:
Locations:
city: Genova
country: Italy
facility: Ospedale Policlinico San Martino
city: Novara
country: Italy
facility: AOU Maggiore della Carità
city: Roma
country: Italy
facility: Fondazione Policlinico Universitario Agostino Gemelli IRCCS
Study officials:
References:
citation: Galli M, Andreotti F, Porto I, Crea F. Intracranial haemorrhages vs. stent thromboses with direct oral anticoagulant plus single antiplatelet agent or triple antithrombotic therapy: a meta-analysis of randomized trials in atrial fibrillation and percutaneous coronary intervention/acute coronary syndrome patients. Europace. 2020 Apr 1;22(4):538-546. doi: 10.1093/europace/euz345.
citation: Galli M, Porto I, Andreotti F, D'Amario D, Vergallo R, Della Bona R, Crea F. Early anticoagulation in the current management of NSTE-ACS: Evidence, guidelines, practice and perspectives. Int J Cardiol. 2019 Jan 15;275:39-45. doi: 10.1016/j.ijcard.2018.10.087. Epub 2018 Oct 27.
citation: Galli M, D'Amario D, Andreotti F, Porto I, Vergallo R, Sabatelli M, Lancellotti S, Meleo E, De Cristofaro R, Crea F. Sustained safe and effective anticoagulation using Edoxaban via percutaneous endoscopic gastrostomy. ESC Heart Fail. 2019 Aug;6(4):884-888. doi: 10.1002/ehf2.12434. Epub 2019 Jun 11.
citation: D'Amario D, Galli M, Canonico F, Restivo A, Arcudi A, Scacciavillani R, Cappannoli L, Riccioni ME, Annetta MG, Di Stefano G, Piccinni C, Vergallo R, Montone RA, Leone AM, Niccoli G, Sabatelli M, Antonelli M, Andreotti F, De Cristofaro R, Crea F. ORal anticoagulants In fraGile patients with percutAneous endoscopic gastrostoMy and atrIal fibrillation: the (ORIGAMI) study. J Cardiovasc Med (Hagerstown). 2021 Mar 1;22(3):175-179. doi: 10.2459/JCM.0000000000001142.
citation: D'Amario D, Galli M, Cappannoli L, Canonico F, Restivo A, Arcudi A, Scacciavillani R, Riccioni ME, Vergallo R, Montone RA, Conte A, Meleo E, Lancellotti S, Sacco M, Antonelli M, Andreotti F, DE Cristofaro R, Crea F. Oral anticoagulants in fragile patients with percutaneous endoscopic gastrostomy and atrial fibrillation: the ORIGAMI pilot investigation. Minerva Cardiol Angiol. 2023 Feb;71(1):109-116. doi: 10.23736/S2724-5683.21.05903-2. Epub 2022 Feb 15.