Clinical trial NCT04696120: Effects of APIXaban on BRAIN Protection in Patients With Sinus Rhythm and Heart Failure: APIXBRAIN-HF Trial
Official title: Effects of APIXaban on BRAIN Protection in Patients With Sinus Rhythm and Heart Failure: APIXBRAIN-HF Trial
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE2
Conditions: Heart Failure
Sinus Rhythm
Cerebrovascular Disease
Keywords: Heart failure
Sinus rhythm
NOAC
Brain
Lead sponsor: Korea University Guro Hospital
Sponsor class: OTHER
Collaborators: name: Dt&Sanomedics
First posted: 2021-01-06
Enrollment: 200
Sex: ALL
Minimum age (years): 19
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: New occurrence of brain pathology
timeFrame: 24 weeks
Secondary outcomes:
measure: The change of Mini-Mental State Examination-2 (MMSE-2) score
timeFrame: 24 weeks
measure: New occurrence of cortical cerebral microinfarcts
timeFrame: 24 weeks
measure: New occurrence of silent lacunar infarction
timeFrame: 24 weeks
measure: Progression of white matter hyperintensities (more than 10% increase)
timeFrame: 24 weeks
Other outcomes:
Locations:
city: Seoul
country: Korea, Republic of
facility: Korea University Guro Hospital
state: Guro-gu
city: Ansan
country: Korea, Republic of
facility: Korea University Ansan Hospital
city: Daejeon
country: Korea, Republic of
facility: Chungnam National University Hospital
city: Hwaseong-si
country: Korea, Republic of
facility: Hallym University Dongtan Sacred Heart Hospital
city: Seongnam-si
country: Korea, Republic of
facility: Seoul National University Bundang Hospital
city: Seoul
country: Korea, Republic of
facility: Korea University Anam Hospital
city: Seoul
country: Korea, Republic of
facility: Severance Hospital
city: Seoul
country: Korea, Republic of
facility: Asan Medical Center
city: Seoul
country: Korea, Republic of
facility: Samsung Medical Center
city: Wonju
country: Korea, Republic of
facility: Wonju Severance Christian Hospital
Study officials:
affiliation: Professor
name: Eung Ju Kim, MD, PhD.
role: PRINCIPAL_INVESTIGATOR
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