Carvedilol SR Study for Biomarkers From Blood and Urine and Safety of in Patients With Heart Failure With Preserved Ejection Fraction

Yonsei University300 enrolled

Overview

Beta blockers have been used to reduce the mortality and heart failure rehospitalization in heart failure with reduced ejection fraction (HFrEF) patients in addition to ACEI/ARB, MRA, ivabradine and ARNI. However, the effective and safe medical therapy is not well established in heart failure with preserved ejection fraction (HFpEF) yet. Recent meta-analysis showed that beta blockers may also be beneficial for reducing the mortality and heart failure rehospitalization in HFpEF like HFrEF. However, the clinical effect and safety of carvedilol have been largely unknown in HFpEF. Therefore, CAYMUS HFpEF is the exploratory study to assess the change of surrogate markers (NTproBNP, hsTn) when treated with carvedilol SR vs. placebo in HFpEF patients

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

300

Conditions

Heart Failure With Preserved Ejection Fraction

Interventions

Eligibility

Sex: ALLMin age: 19 Years

Medical Language ↔ Plain English

Inclusion Criteria: 1. Provision of informed consent prior to any study specific procedure 2. Male or female, aged ≥ 19 years 3. Patients with chronic HF (Chronic Heart Failure) NYHA (New York Heart Association classification) class II-IV and preserved EF (Ejection Fraction)(LVEF (Left Ventricular Ejection Fraction) \> 40 %) and elevated NT-proBNP (N-terminal of the prohormone brain natriuretic peptide) \> 200 pg/ml for patients without AF, OR \> 600 pg/ml for patients with AF, analysed at the Central laboratory at Visit 1 4. Structural heart disease within 6 months prior to Visit 1 using echocardiagraphy Exclusion Criteria: 1. Myocardial infarction, coronary artery bypass graft surgery or other major cardiovascular surgery, stroke or TIA (Transient Ischaemic Attack) in past 90 days prior to Visit 1 2. Contraindication to beta blocker 3. Heart transplant recipient or listed for heart transplant 4. Hospitalization plan for PCI, coronary artery bypass graft surgery, other cardiac invasive interventions (e.g. catheter ablation, pacemaker, CRT, ICD implantation) 5. Acute decompensated HF (Heart Failure) 6. Symptomatic hypotension or systolic blood pressure \< 100 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. Symptomatic bradycardia or heart rate \< 60/min 10. Allergy, adverse drug reaction, hypersensitivity to carvedilol 11. Life expectancy \< 6 months (e.g. metastatic malignancy) 12. Pregnancy, or women of childbearing age

Outcomes

Primary Outcomes

The Maximum NT-proBNP value change after Drug(Carvedilol SR or Placebo) administration.

The maximum NT-proBNP value change at baseline.

Time frame: Baseline

The Maximum NT-proBNP value change after Drug(Carvedilol SR or Placebo) administration.

The maximum NT-proBNP value change from baseline to 8 weeks.

Time frame: 8 weeks

The Maximum NT-proBNP value change after Drug(Carvedilol SR or Placebo) administration.

The maximum NT-proBNP value change from baseline to End of trial(24weeks).

Time frame: 24 weeks

Secondary Outcomes

The changes of maximum surrogate markers values(hsTn, hsCRP, sST2, Galectine-3, IGFBP7, Neprilysin, D-dimer, MMP-2, Cystatin C, NAG, NGAL, KIM-1, BUN, Creatinine, Chloride, Na, K, PICP and spondin-1) after Drug(Carvedilol SR or Placebo) administration.

the change of surrogate markers(hsTn, hsCRP etc) at baseline.

Time frame: Baseline

the change of surrogate markers(hsTn, hsCRP etc) after 8 weeks.

Time frame: 8 weeks

the change of surrogate markers(hsTn, hsCRP etc) after 16 weeks.

Time frame: 16 weeks

the change of surrogate markers(hsTn, hsCRP etc) from baseline to end of trial(24 weeks)

Time frame: 24 weeks

The change in degree of dyspnea using VAS questionnaire

the change of dyspnea at baseline.

Time frame: Baseline

The change in degree of dyspnea using VAS questionnaire

the change of dyspnea after 8 weeks.

Time frame: 8 weeks

The change in degree of dyspnea using VAS questionnaire

the change of dyspnea after 16 weeks.

Time frame: 16 weeks

The change in degree of dyspnea using VAS questionnaire

the change of dyspnea from baseline to end of trial(24 weeks)

Time frame: 24 weeks

the change of body weight

the change of body weight at baseline.

Time frame: Baseline

the change of body weight

the change of body weight after 8 weeks.

Time frame: 8 weeks

the change of body weight

the change of body weight after 16 weeks.

Time frame: 16 weeks

the change of body weight

the change of body weight from baseline to end of trial(24 weeks)

Time frame: 24 weeks

the frequency of symptomatic hypotension, symptomatic bradycardia and AV block above 2nd degree

the frequency of symptomatic hypotension, symptomatic bradycardia and AV block above 2nd degree during the tiral

Time frame: Baseline

the frequency of symptomatic hypotension, symptomatic bradycardia and AV block above 2nd degree

the frequency of symptomatic hypotension, symptomatic bradycardia and AV block above 2nd degree during the tiral

Time frame: 8 weeks

the frequency of symptomatic hypotension, symptomatic bradycardia and AV block above 2nd degree

the frequency of symptomatic hypotension, symptomatic bradycardia and AV block above 2nd degree during the tiral

Time frame: 16 weeks

the frequency of symptomatic hypotension, symptomatic bradycardia and AV block above 2nd degree

the frequency of symptomatic hypotension, symptomatic bradycardia and AV block above 2nd degree during the tiral

Time frame: 24 weeks

the frequency of hypo/hyperkalemia and worsening kidney function

the frequency of hypo/hyperkalemia and worsening kidney function during the trial

Time frame: Baseline

the frequency of hypo/hyperkalemia and worsening kidney function

the frequency of hypo/hyperkalemia and worsening kidney function during the trial

Time frame: 8 weeks

the frequency of hypo/hyperkalemia and worsening kidney function

the frequency of hypo/hyperkalemia and worsening kidney function during the trial

Time frame: 16 weeks

the frequency of hypo/hyperkalemia and worsening kidney function

the frequency of hypo/hyperkalemia and worsening kidney function during the trial

Time frame: 24 weeks

all-cause hospitalization & mortality

all-cause hospitalization \& mortality during the trial

Time frame: Baseline

all-cause hospitalization & mortality

all-cause hospitalization \& mortality during the trial

Time frame: 8 weeks

all-cause hospitalization & mortality

all-cause hospitalization \& mortality during the trial

Time frame: 16 weeks

all-cause hospitalization & mortality

all-cause hospitalization \& mortality during the trial

Time frame: 24 weeks

Carvedilol SR Study for Biomarkers From Blood and Urine and Safety of in Patients With Heart Failure With Preserved Ejection Fraction

Overview

Conditions

Interventions

Eligibility

Locations (1)

Outcomes

Primary Outcomes

Secondary Outcomes

Central Contacts