Rivaroxaban Once Daily Versus Dose-adjusted Vitamin K Antagonist on the Biomarkers in Acute Decompensated Heart Failure and Atrial Fibrillation (ROAD HF-AF)

Vitamin K antagonists (VKAs) are used to reduce the risk of stroke (cerebral vascular dysfunction) in AF patients. However, VKAs interact with drugs/food and the drug level is influenced by worsening of renal function, liver congestion or hemodynamic alterations in acute decompensated heart failure (ADHF). New oral anticoagulants (rivaroxaban, apixaban, dabigatran) are alternatives to VKA, such as warfarin. In post hoc analysis of ROCKET AF trial, 63.7% patients had HF and treatment-related outcomes were similar in patients with and without HF (Circulation HF. 2013; 6:740-7). So rivaroxaban 20 mg daily (or 15 mg daily in patients with creatinine clearance 30-49 mL/min) was safe in nonvalvular AF patients with HF. However, the clinical effect and safety of rivaroxaban were largely unknown in acute decompensated heart failure (ADHF) patients with atrial fibrillation (AF).

ROAD HF-AF is the exploratory study to assess the change of surrogate markers (hsTn, d-dimer) when treated with rivaroxaban vs. warfarin and to strengthen the basis for future biomarker-based therapy in ADHF patients

Study Overview

• Status: Unknown
• Conditions: Acute Heart Failure
• Intervention / Treatment: Drug: Rivaroxaban; Drug: Warfarin + LMWH

• Study Type: Interventional
• Enrollment (Anticipated): 150
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Seok-Min Kang, MD; Phone Number: 82-2-2228-8450; Email: smkang@yuhs.ac

Study Locations

• Korea, Republic of
  • Seoul, Korea, Republic of, 120-752
    • Recruiting
    • Division of Cardiology, Severance Cardiovascular Hospital, Yonsei University College of Medicine
    • Contact: Seok-Min Kang, MD; Phone Number: 82-2-2228-8450; Email: smkang@yuhs.ac

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 19 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:Hospitalized patients with a primary diagnosis of ADHF with AF One of the following criteria and LVEF ≤ 40% (at least 1 year before admission or admission)

1. dyspnea at rest
2. tachypnea; a respiratory rate > 20/min
3. rales
4. pulmonary edema on chest X-ray

Exclusion Criteria:

1. History of increased bleeding risk (like ROCKET AF exclusion criteria)
2. Contraindication to anti-coagulation therapy
3. ACS diagnosis
4. Hospitalization plan for PCI, coronary artery bypass graft surgery, other cardiac invasive interventions (e.g. catheter ablation, pacemaker, CRT, ICD implantation)
5. Currently on dual anti-platelet therapy (aspirin + ADP receptor antagonist) or single antiplatelet therapy with a novel AP (e.g. Ticagrelor, Prasugrel)
6. Cardiogenic shock (systolic blood pressure, SBP, < 80 mmHg)
7. Patients with CrCl < 30 ml/min using creatinine-based CKD-EPI equations
8. Elevated liver enzymes (3 times over upper reference limit) or liver cirrhosis
9. Uncontrolled hypertension (SBP > 180 mmHg)
10. Allergy, adverse drug reaction, hypersensitivity to rivaroxaban or warfarin
11. Life expectancy < 6 months (e.g. metastatic malignancy)
12. Pregnancy, or women of childbearing age

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Rivaroxaban	Drug: Rivaroxaban; Rivaroxaban 20mg qd (15mg qd when CrCl 30-49 ml/min using creatinine-based CKD-EPI equations) for 6 months
Active Comparator: Warfarin; warfarin + enoxaparin	Drug: Warfarin + LMWH; dose-adjusted warfarin (target INR 2-3) for 6 months + LMWH (enoxaparin 1 mg/kg q12h for a few days until INR target achieved) if indicated

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
the change of high sensitive troponin	The maximum hsTn value change from baseline to during hospitalization	Baseline to 72 hours

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
1) the change of hish sensitive troponin	1) The change from baseline in hsTn on Day2, day4, day7 (or discharge), and follow-up visits at 1 month, 6 months	1) On admission, hospital day #2, hospital day #4, hospital day #7 or discharge, 1 month/6month after discharge
2) the change of D-dimer	2) D-dimer change from baseline during hospitalization (day2, day4, day7 or discharge) & follow-up visits at 1, 6 months	2) On admission, hospital day #2, hospital day #4, hospital day #7 or discharge, 1 month/6month after discharge
3) the change of NT-proBNP	3) TAT complex, PAI-1, hsCRP, NT-proBNP, sST2, galectin-3, cystatin C, NGAL, NAG change from baseline to day7 or discharge & 1,6 months after discharge	3) On admission, hospital day #7 or discharge, 1 month/6month after discharge
4) bleeding event	4) Incidence proportion and rate of major/minor bleeding during the study	4) On admission, hospital day #2, hospital day #4, hospital day #7 or discharge, 1 month/3month/6month after discharge
5) hospital stay	5) Length of hospital stay	5) The duration of hospital stay, average 7 days
6) all-cause mortality	6) Incidence proportion of in-hospital all-cause death cases	6) 6 months after hospitalization
7) all-cause hospitalization & mortality	7) Time to the first composite event of all-cause mortality or cardiovascular re-hospitalization	7) 6 months after hospitalization

Collaborators and Investigators

• Sponsor: Yonsei University

Study record dates

Study Major Dates

• Study Start (Actual): April 10, 2018
• Primary Completion (Anticipated): September 1, 2019
• Study Completion (Anticipated): January 1, 2020

Study Registration Dates

• First Submitted: March 11, 2018
• First Submitted That Met QC Criteria: April 1, 2018
• First Posted (Actual): April 6, 2018

Study Record Updates

• Last Update Posted (Actual): January 10, 2019
• Last Update Submitted That Met QC Criteria: January 9, 2019
• Last Verified: January 1, 2019

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Heart Diseases; Cardiovascular Diseases; Arrhythmias, Cardiac; Heart Failure; Atrial Fibrillation; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Protease Inhibitors; Factor Xa Inhibitors; Antithrombins; Serine Proteinase Inhibitors; Anticoagulants; Rivaroxaban; Warfarin
• Other Study ID Numbers: 4-2017-0776

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No