Carvedilol SR Study for Biomarkers From Blood and Urine and Safety of in Patients With Heart Failure With Preserved Ejection Fraction : a Prospective, Randomized, Double Blind, Placebo-controlled, Multicenter, Pilot Trial (CAYMUS-HFpEF)
Overview
- Phase
- Phase 4
- Intervention
- Carvedilol SR
- Conditions
- Heart Failure With Preserved Ejection Fraction
- Sponsor
- Yonsei University
- Enrollment
- 300
- Locations
- 1
- Primary Endpoint
- The Maximum NT-proBNP value change after Drug(Carvedilol SR or Placebo) administration.
- Last Updated
- 6 years ago
Overview
Brief Summary
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
Investigators
Eligibility Criteria
Inclusion Criteria
- •Provision of informed consent prior to any study specific procedure
- •Male or female, aged ≥ 19 years
- •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
- •Structural heart disease within 6 months prior to Visit 1 using echocardiagraphy
Exclusion Criteria
- •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
- •Contraindication to beta blocker
- •Heart transplant recipient or listed for heart transplant
- •Hospitalization plan for PCI, coronary artery bypass graft surgery, other cardiac invasive interventions (e.g. catheter ablation, pacemaker, CRT, ICD implantation)
- •Acute decompensated HF (Heart Failure)
- •Symptomatic hypotension or systolic blood pressure \< 100 mmHg)
- •Patients with CrCl \< 30 ml/min using creatinine-based CKD-EPI equations
- •Elevated liver enzymes (3 times over upper reference limit) or liver cirrhosis
- •Symptomatic bradycardia or heart rate \< 60/min
- •Allergy, adverse drug reaction, hypersensitivity to carvedilol
Arms & Interventions
Carvedilol SR
Carvedilol SR 8mg, 16mg, 32mg
Intervention: Carvedilol SR
Placebo
Placebo
Intervention: Placebo
Outcomes
Primary Outcomes
The Maximum NT-proBNP value change after Drug(Carvedilol SR or Placebo) administration.
Time Frame: 24 weeks
The maximum NT-proBNP value change from baseline to End of trial(24weeks).
Secondary Outcomes
- The change in degree of dyspnea using VAS questionnaire(24 weeks)
- all-cause hospitalization & mortality(24 weeks)
- 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.(24 weeks)
- the frequency of hypo/hyperkalemia and worsening kidney function(24 weeks)
- the change of body weight(24 weeks)
- the frequency of symptomatic hypotension, symptomatic bradycardia and AV block above 2nd degree(24 weeks)