EdOxaban in fRagIle Patients With Percutaneous Endoscopic GAstrostoMy and atrIal fIbrIllation

Atrial Fibrillation Clinical Trial

— ORIGAMI II  

Official title:

EdOxaban in fRagIle Patients With Percutaneous Endoscopic GAstrostoMy and atrIal fIbrIllation: the ORIGAMI II Study

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06285942
• Other study ID #: 277.535
• Secondary ID: CE366/2023
• Status: Recruiting
• Phase: N/A
• Start date: February 1, 2024
• Est. completion date: January 31, 2025

Study information

• Verified date: February 2024
• Source: Azienda Ospedaliero Universitaria Maggiore della Carita
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 168
• Est. completion date: January 31, 2025
• Est. primary completion date: January 31, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Atrial Fibrillation
• Fragility

Intervention

Drug:
• Edoxaban
To use of Edoxaban via PEG in patients with an indication to anticoagulation therapy according to current guidelines
• No Edoxaban
Other DOACs through PEG or subcutaneous heparin or LMWH

Locations

Country	Name	City	State
Italy	Ospedale Policlinico San Martino	Genova
Italy	AOU Maggiore della Carità	Novara
Italy	Fondazione Policlinico Universitario Agostino Gemelli IRCCS	Roma

Sponsors (1)

Lead Sponsor	Collaborator
Azienda Ospedaliero Universitaria Maggiore della Carita

Country where clinical trial is conducted

Italy, 

References & Publications (5)

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. — View 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. — View 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. — View 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. — View 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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Difference in Anti-Clot treatment scale (ACTS) questionnaire results among the two groups assessed at 6 and 12 months.	The Anti-Clot treatment scale (ACTS) is a 15-item patient-reported instrument of satisfaction with anticoagulant treatment. It includes a 12-item ACTS Burdens scale and a 3-item ACTS Benefits scale. The rate of experience of anticoagulant treatment during the past 4 weeks on a 5-point scale of intensity: 1 = not at all, 2 = a little, 3 = moderately, 4 = quite a bit, 5 = extremely.	at 6 and 12 months
Secondary	Number of cardio-embolic events at 6 and12 months	The number of cardio-embolic events consisting of stroke, systemic embolism or symptomatic relapse of deep vein thrombosis/pulmonary embolism.	at 6 and 12 months
Secondary	Number of bleeding events	The Bleeding Academic Research Consortium (BARC) scale and the Thrombolysis in Myocardial Infarction (TIMI) bleeding criteria will be considered.; BARC scale from Type 1 (bleeding that is not actionable) to Type 5b (Fatal bleeding); TIMI bleeding criteria range from Minimal to Major, such as any intracranial bleeding, clinically evident signs of hemorrhage associated with a drop in hemoglobin = 5 g/dl or fatal bleeding.	at 6 and 12 months
Secondary	Assessment of drugs efficacy by measuring the anti-factor Xa activity	Mean DOACs plasma concentration-time profile will be measured at steady state as anti-FXa activity using the STA®-Liquid Anti-Xa assays on a STA Compact Max® instrument. The evaluation of the anti-FXa activity will be performed on peripheral whole blood samples.	at 6 and 12 months
Secondary	Assessment of drugs efficacy by measuring the thrombin generation	At steady state will be measured the thrombin generation assay, both in patients receiving DOACs and in those receiving parenteral anticoagulation. The evaluation of the thrombin generation assay will be performed on peripheral whole blood samples.	at 6 and 12 months
Secondary	Assess the quality of life	The Zarit Burden Interview (ZBI) will be used to assess quality of life. The ZBI is an interview to evaluate the consequences that the care burden of a family member with chronic or degenerative pathologies has on the caregiver, with a scale ranging from 0 with zero care load, to 88 with a maximum level of care load.	at 6 and 12 months
Secondary	Cost-effectiveness analysis	A cost-effectiveness analysis will be carried out to compare the costs (direct and indirect) of treatment with Edoxaban compared to other subcutaneous anticoagulants.	at 6 and 12 months