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

Acute Heart Failure Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03490994
• Other study ID #: 4-2017-0776
• Status: Recruiting
• Phase: Phase 4
• Start date: April 10, 2018
• Est. completion date: January 2020

Study information

• Verified date: January 2019
• Source: Yonsei University
• Contact: Seok-Min Kang, MD
• Phone: 82-2-2228-8450
• Email: smkang[@]yuhs.ac
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 150
• Est. completion date: January 2020
• Est. primary completion date: September 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 19 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Acute Heart Failure
• Atrial Fibrillation
• Heart Failure

Intervention

Drug:
• Rivaroxaban
Rivaroxaban 20mg qd (15mg qd when CrCl 30-49 ml/min using creatinine-based CKD-EPI equations) for 6 months
• 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

Locations

Country	Name	City	State
Korea, Republic of	Division of Cardiology, Severance Cardiovascular Hospital, Yonsei University College of Medicine	Seoul

Sponsors (1)

Lead Sponsor	Collaborator
Yonsei University

Country where clinical trial is conducted

Korea, Republic of, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	the change of high sensitive troponin	The maximum hsTn value change from baseline to during hospitalization	Baseline to 72 hours
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	5) hospital stay	5) Length of hospital stay	5) The duration of hospital stay, average 7 days
Secondary	6) all-cause mortality	6) Incidence proportion of in-hospital all-cause death cases	6) 6 months after hospitalization
Secondary	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