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

Phase 4

• Conditions: Acute Heart Failure
• Interventions: Drug: Warfarin + LMWH; Drug: Rivaroxaban

• Registration Number: NCT03490994
• Lead Sponsor: Yonsei University

Brief Summary

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

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2018-03-11
• Study First Submitted QC: 2018-04-01
• Study First Posted: 2018-04-06
• Study Start: 2018-04-10
• Status Verified: 2019-01
• Last Update Submitted: 2019-01-09
• Last Update Posted: 2019-01-10
• Primary Completion: 2019-09
• Study Completion: 2020-01

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 150

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Warfarin	Warfarin + LMWH	warfarin + enoxaparin
Rivaroxaban	Rivaroxaban	Rivaroxaban

Primary Outcome Measures

Name	Time	Method
the change of high sensitive troponin	Baseline to 72 hours	The maximum hsTn value change from baseline to during hospitalization

Secondary Outcome Measures

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

Trial Locations

Locations (1)

Division of Cardiology, Severance Cardiovascular Hospital, Yonsei University College of Medicine; 🇰🇷 Seoul, Korea, Republic of