DOAC Versus VKA After Cardiac Surgery

Phase 2

Withdrawn

• Conditions: Anticoagulant-induced Bleeding
• Interventions: Drug: Warfarin; Drug: Dabigatran; Drug: Rivaroxaban; Drug: Apixaban; Drug: Edoxaban

• Registration Number: NCT04002011
• Lead Sponsor: Laval University

Brief Summary

Postoperative management of oral anticoagulation is a frequent preoccupation in cardiac surgery, concerning about half of patients. Vitamin K antagonists are often recommended but their management is not easy due to the high dose-response patient variability. Pharmacologically more stable, direct oral anticoagulants have similar efficiency in preventing thromboembolic complications while they decrease the risk of bleeding in certain patient populations. The objective of study is to assess the safety and efficacy of direct oral anticoagulants in the postoperative period of cardiac surgical procedures.

Detailed Description

This study will be composed by 2 groups of 103 participants, patients undergoing cardiac surgery and needing oral anticoagulation in the early postoperative period.

The control group will receive vitamin K antagonist and the study group will receive direct oral anticoagulant. The investigators will call back each participants at 3 months to report the ischemic and bleeding complications during this period and evaluated the quality of life of the oral anticoagulation.

Study Timeline

• Study First Submitted: 2019-06-10
• Study First Submitted QC: 2019-06-26
• Study First Posted: 2019-06-28
• Study Start: 2022-03-09
• Primary Completion: 2023-01-01
• Status Verified: 2023-03
• Study Completion: 2023-03-09
• Last Update Submitted: 2023-03-09
• Last Update Posted: 2023-03-13

Recruitment & Eligibility

• Status: WITHDRAWN
• Sex: All
• Target Recruitment: Not specified

Inclusion Criteria

• Cardiac surgery, with or without cardiopulmonary bypass
• Indication of postoperative oral anticoagulation: preoperative (atrial fibrillation/flutter of idiopathic venous thromboembolism disease), intraoperative (bioprosthetic mitral valve replacement/mitral valve repair or bioprosthetic tricuspid valve repair), postoperative (de novo persistent more than 24 hours or recurrent atrial fibrillation/flutter, venous thromboembolism)

Exclusion Criteria

• mechanical valvular prostheses or ventricular assist devices
• morbidly obesity (body mass index ≥ 40 kg/m²), prior biliopancreatic diversion or sleeve gastrectomy
• perioperative dysphagia needing naso-enteric tube or jejunostomy
• antiretroviral of antifungal oral therapy
• perioperative recent (less than 2 weeks) stroke
• perioperative severe renal failure (clearance of creatinine under 30 mL/min or dialysis)
• perioperative severe hepatic failure (elevated alanine aminotransferase more than 3 times the superior limit of normal range or cirrhosis)
• perioperative recent (less than 3 months) heparin-induced thrombocytopenia

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Group VKA	Warfarin	103 patients. First intake at postoperative day 1 or later when anticoagulation is secondary indicated. Dosage adapted to INR = \[2.0-3.0\], parenteral (subcoutaneous low-weight molecular or intravenous unfractionated heparin) until INR \> or = 2.0. Daily INR during hospital stay, then management by familial doctor. Duration: 3 months
Group DOAC	Apixaban	103 patients - One drug among the 4 DOAC according the morbidity of each patient (preoperative DOAC, oral nutrition recovery). First intake at hospital discharge - parenteral (subcoutaneous low-weight molecular or intravenous unfractionated heparin) during hospital stay. Regular daily dosages according the drug, its indication (atrial fibrillation/flutter or biological mitral replacement/repair or biological tricuspid replacement versus venous thromboembolism) and the morbidity of each patient (age, weight, creatinine ou its clearance). Validation by one referent pharmacist. No biological monitoring. Duration: 3 months
Group DOAC	Dabigatran	103 patients - One drug among the 4 DOAC according the morbidity of each patient (preoperative DOAC, oral nutrition recovery). First intake at hospital discharge - parenteral (subcoutaneous low-weight molecular or intravenous unfractionated heparin) during hospital stay. Regular daily dosages according the drug, its indication (atrial fibrillation/flutter or biological mitral replacement/repair or biological tricuspid replacement versus venous thromboembolism) and the morbidity of each patient (age, weight, creatinine ou its clearance). Validation by one referent pharmacist. No biological monitoring. Duration: 3 months
Group DOAC	Rivaroxaban	103 patients - One drug among the 4 DOAC according the morbidity of each patient (preoperative DOAC, oral nutrition recovery). First intake at hospital discharge - parenteral (subcoutaneous low-weight molecular or intravenous unfractionated heparin) during hospital stay. Regular daily dosages according the drug, its indication (atrial fibrillation/flutter or biological mitral replacement/repair or biological tricuspid replacement versus venous thromboembolism) and the morbidity of each patient (age, weight, creatinine ou its clearance). Validation by one referent pharmacist. No biological monitoring. Duration: 3 months
Group DOAC	Edoxaban	103 patients - One drug among the 4 DOAC according the morbidity of each patient (preoperative DOAC, oral nutrition recovery). First intake at hospital discharge - parenteral (subcoutaneous low-weight molecular or intravenous unfractionated heparin) during hospital stay. Regular daily dosages according the drug, its indication (atrial fibrillation/flutter or biological mitral replacement/repair or biological tricuspid replacement versus venous thromboembolism) and the morbidity of each patient (age, weight, creatinine ou its clearance). Validation by one referent pharmacist. No biological monitoring. Duration: 3 months

Primary Outcome Measures

Name	Time	Method
Statisfaction of the anticoagulant treatment	Evaluation at month 3 after hospital discharge for the last month	The investigators will call back all the participants by phone and use the anti-clot treatment scale (ACTS) to evaluate the feelings of "burdens" (score between 12-60) and "benefits" (score between 3-15) of the anticoagulant treatment
Hemorrhagic events with anticoagulant treatment	Evaluation at month 3 after hospital discharge for all the postoperative period	The investigators will use the regional computerized medical record of each participants to report all the hemorrhagic event during all the postoperative period, and define them according the "Bleeding Academic Research Consortium" (BARC) criteria. Hemorrhage-free survival will be studied.
Death with anticoagulant treatment	Evaluation at month 3 after hospital discharge for all the postoperative period	The investigators will use the regional computerized medical record of each patients to report all the ischemic event during all the postoperative period. Global survival will be studied. Ischemic or hemorrhagic death will be precised.
Ischemic events with anticoagulant treatment	Evaluation at month 3 after hospital discharge for all the postoperative period	The investigators will use the regional computerized medical record of each patients to report all the ischemic event during all the postoperative period. Ischemia-free survival will be studied.
Quality of life with anticoagulant treatment	Evaluation at month 3 after hospital discharge for the last month	The investigators will call back all the participants by phone and use the SF-12 questionnaire (score between 12 and 56) to evaluate the quality of life about several dimensions (global, physic, mental, pain, society).