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

Heart Failure Clinical Trial

Official title:

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

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT04696120
• Other study ID #: 2020GR0592
• Status: Not yet recruiting
• Phase: Phase 2
• Start date: March 2, 2021
• Est. completion date: February 28, 2023

Study information

• Verified date: January 2021
• Source: Korea University Guro Hospital
• Contact: Eung Ju Kim, MD, PhD
• Phone: 82-02-2626-3022
• Email: withnoel[@]empas.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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

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.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 200
• Est. completion date: February 28, 2023
• Est. primary completion date: August 30, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 19 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Cerebrovascular Disease
• Cerebrovascular Disorders
• Heart Failure
• Sinus Rhythm

Intervention

Drug:
• Apixaban
Patients who are randomly assigned to apixaban group will receive apixaban 5mg or 2.5mg bid
• Placebo
All patients who are assigned to placebo group will receive placebo

Locations

Country	Name	City	State
Korea, Republic of	Korea University Ansan Hospital	Ansan
Korea, Republic of	Chungnam National University Hospital	Daejeon
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	Korea University Anam Hospital	Seoul
Korea, Republic of	Korea University Guro Hospital	Seoul	Guro-gu
Korea, Republic of	Samsung Medical Center	Seoul
Korea, Republic of	Severance Hospital	Seoul
Korea, Republic of	Wonju Severance Christian Hospital	Wonju

Sponsors (2)

Lead Sponsor	Collaborator
Korea University Guro Hospital	Dt&Sanomedics

Country where clinical trial is conducted

Korea, Republic of, 

References & Publications (40)

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* Note: There are 40 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	New occurrence of brain pathology	1) Cortical cerebral microinfarcts 2) Silent lacunar infarction 3)Progression of white matter hyperintensities	24 weeks
Secondary	The change of Mini-Mental State Examination-2 (MMSE-2) score	The change of Mini-Mental State Examination-2 (MMSE-2) score compared to baseline. Higher scores mean a better outcome.	24 weeks
Secondary	New occurrence of cortical cerebral microinfarcts	New occurrence of cortical cerebral microinfarcts compared to baseline	24 weeks
Secondary	New occurrence of silent lacunar infarction	New occurrence of silent lacunar infarction compared to baseline	24 weeks
Secondary	Progression of white matter hyperintensities (more than 10% increase)	Progression of white matter hyperintensities (more than 10% increase) compared to baseline	24 weeks