Effects of APIXaban on BRAIN Protection in Patients With Sinus Rhythm and Heart Failure: APIXBRAIN-HF Trial

Phase 2

• Conditions: Sinus Rhythm; Cerebrovascular Disease; Heart Failure
• Interventions: Drug: Placebo; Drug: Apixaban

• Registration Number: NCT04696120
• Lead Sponsor: Korea University Guro Hospital

Brief Summary

objectives: The primary aim of APIXBRAIN-HF Trial is to explore the effects of apixaban on brain protection in patients with sinus rhythm and heart failure

Primary / Secondary Endpoint

1. New occurrence of brain pathology 1) Cortical cerebral microinfarcts 2) Silent lacunar infarction 3)Progression of white matter hyperintensities

2. Secondary endpoint 1) The change of cognitive function evaluated by MMSE-2 2) Individual variable of primary endpoint

3. Safety Endpoint Evaluation 1) Cerebral microbleeds on imaging

Detailed Description

This study is a double-blind, parallel-group, and randomization study. The investigators will enroll the patients with heart failure who demonstrated LV systolic dysfunction (LVEF ≤ 40%) and sinus rhythm with a CHA2DS2-VASc score ≥ 3. All patients would be randomly assigned to either the apixaban group or placebo group. Patients assigned to the apixaban group will receive 5mg bid or 2.5mg bid (patients with at least 2 of the following characteristics: aged≥80-year, bodyweight ≤60kg, serum creatinine 1.5 ml/dL) and patients in the placebo group will receive a placebo of apixaban. Both drugs will be maintained for 6 months. During the study period, all patients will be carefully monitored for thromboembolic events, including stroke. At the beginning of the study and 6 months after randomization, 3T Brain MRI and MMSE-2 test will be performed to identify changes in brain structure and cognitive function.

Study Timeline

• Status Verified: 2021-01
• Study First Submitted: 2021-01-03
• Study First Submitted QC: 2021-01-03
• Study First Posted: 2021-01-06
• Last Update Submitted: 2021-01-15
• Last Update Posted: 2021-01-20
• Study Start: 2021-03-02
• Primary Completion: 2022-08-30
• Study Completion: 2023-02-28

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 200

Inclusion Criteria

• Patients aged over 19 years old

• Patients with sinus rhythm

• Newly diagnosed of heart failure or aggravated heart failure symptom

  1. Dyspnea (≥ NYHA II)
  2. plasma BNP ≥ 200 pg/ml or NT-proBNP ≥ 800 pg/ml

• LV systolic dysfunction on echocardiography within 3 month of enrollment

  1. LVEF ≤ 40%

• Those with CHA2DS2-VASc ≥ 3

• Modified Rankin Score ≤ 4

Exclusion Criteria

• Patients already subscribed warfarin or antiplatelet therapy or have clear indication for warfarin or antiplatelet therapy
• At high risk for bleeding
• Patients with atrial fibrillation
• Estimated glomerular filtration rate (CKD-EPI formula) < 15 ml/min/1.73 m2)
• Recent stroke or brain hemorrhage (within 3 months)
• Patients who was diagnosed of myocardial infarction or who has plan to PCI/CABG at enrollment
• End stage heart failure with life expectancy ≤ 6 months
• Patients with bed ridden status (Modified Rankin Score ≥ 5)
• Patients with liver dysfunction (AST, ALT > 2 times of upper normal limits or total bilirubin > 1.5 of upper normal limits)
• At of pregnancy or breastfeeding
• Patients who disagree with the use of medically acceptable contraception during the clinical trial period
• Patients with contraindication of apixaban

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Control group: placebo	Placebo	placebo bid
Study group: apixaban	Apixaban	apixaban 2.5mg or 5mg bid

Primary Outcome Measures

Name	Time	Method
New occurrence of brain pathology	24 weeks	1) Cortical cerebral microinfarcts 2) Silent lacunar infarction 3)Progression of white matter hyperintensities

Secondary Outcome Measures

Name	Time	Method
New occurrence of silent lacunar infarction	24 weeks	New occurrence of silent lacunar infarction compared to baseline
The change of Mini-Mental State Examination-2 (MMSE-2) score	24 weeks	The change of Mini-Mental State Examination-2 (MMSE-2) score compared to baseline. Higher scores mean a better outcome.
New occurrence of cortical cerebral microinfarcts	24 weeks	New occurrence of cortical cerebral microinfarcts compared to baseline
Progression of white matter hyperintensities (more than 10% increase)	24 weeks	Progression of white matter hyperintensities (more than 10% increase) compared to baseline

Trial Locations

Locations (10)

Chungnam National University Hospital; 🇰🇷 Daejeon, Korea, Republic of

Severance Hospital; 🇰🇷 Seoul, Korea, Republic of

Korea University Guro Hospital; 🇰🇷 Seoul, Guro-gu, Korea, Republic of

Wonju Severance Christian Hospital; 🇰🇷 Wonju, Korea, Republic of

Korea University Anam Hospital; 🇰🇷 Seoul, Korea, Republic of

Korea University Ansan Hospital; 🇰🇷 Ansan, Korea, Republic of

Hallym University Dongtan Sacred Heart Hospital; 🇰🇷 Hwaseong-si, Korea, Republic of

Seoul National University Bundang Hospital; 🇰🇷 Seongnam-si, Korea, Republic of

Asan Medical Center; 🇰🇷 Seoul, Korea, Republic of

Samsung Medical Center; 🇰🇷 Seoul, Korea, Republic of