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

Phase 4

• Conditions: Heart Failure With Preserved Ejection Fraction
• Interventions: Drug: Carvedilol SR; Drug: Placebo

• Registration Number: NCT03948685
• Lead Sponsor: Yonsei University

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

Detailed Description

Not available

Study Timeline

• Status Verified: 2019-05
• Study Start: 2019-05
• Study First Submitted: 2019-05-03
• Study First Submitted QC: 2019-05-09
• Study First Posted: 2019-05-14
• Last Update Submitted: 2019-05-19
• Last Update Posted: 2019-05-21
• Primary Completion: 2020-12
• Study Completion: 2021-01

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 300

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Carvedilol SR	Carvedilol SR	Carvedilol SR 8mg, 16mg, 32mg
Placebo	Placebo	Placebo

Primary Outcome Measures

Name	Time	Method
The Maximum NT-proBNP value change after Drug(Carvedilol SR or Placebo) administration.	24 weeks	The maximum NT-proBNP value change from baseline to End of trial(24weeks).

Secondary Outcome Measures

Name	Time	Method
The change in degree of dyspnea using VAS questionnaire	24 weeks	the change of dyspnea from baseline to end of trial(24 weeks)
all-cause hospitalization & mortality	24 weeks	all-cause hospitalization \& mortality during the trial
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 change of surrogate markers(hsTn, hsCRP etc) from baseline to end of trial(24 weeks)
the frequency of hypo/hyperkalemia and worsening kidney function	24 weeks	the frequency of hypo/hyperkalemia and worsening kidney function during the trial
the change of body weight	24 weeks	the change of body weight from baseline to end of trial(24 weeks)
the frequency of symptomatic hypotension, symptomatic bradycardia and AV block above 2nd degree	24 weeks	the frequency of symptomatic hypotension, symptomatic bradycardia and AV block above 2nd degree during the tiral

Trial Locations

Locations (1)

Division of Cardiology, Severance Cardiovascular Hospital, Yonsei University College of Medicine; 🇰🇷 Seoul, Korea, Republic of