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

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)

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 Overview

• Status: Unknown
• Conditions: Heart Failure With Preserved Ejection Fraction
• Intervention / Treatment: Drug: Placebo; Drug: Carvedilol SR

• Study Type: Interventional
• Enrollment (Anticipated): 300
• Phase: Phase 4

Contacts and Locations

Study Locations

• Korea, Republic of
  • Seoul, Korea, Republic of, 120-752
    • Division of Cardiology, Severance Cardiovascular Hospital, Yonsei University College of Medicine

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 19 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: NONE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
PLACEBO_COMPARATOR: Placebo	Drug: Placebo; Placebo
EXPERIMENTAL: Carvedilol SR; Carvedilol SR 8mg, 16mg, 32mg	Drug: Carvedilol SR; blood pressure, heart rate based titrated carvedilol SR for 24 weeks

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The Maximum NT-proBNP value change after Drug(Carvedilol SR or Placebo) administration.	The maximum NT-proBNP value change at baseline.	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.	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).	24 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	Baseline
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) after 8 weeks.	8 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.	the change of surrogate markers(hsTn, hsCRP etc) after 16 weeks.	16 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.	the change of surrogate markers(hsTn, hsCRP etc) from baseline to end of trial(24 weeks)	24 weeks
The change in degree of dyspnea using VAS questionnaire	the change of dyspnea at baseline.	Baseline
The change in degree of dyspnea using VAS questionnaire	the change of dyspnea after 8 weeks.	8 weeks
The change in degree of dyspnea using VAS questionnaire	the change of dyspnea after 16 weeks.	16 weeks
The change in degree of dyspnea using VAS questionnaire	the change of dyspnea from baseline to end of trial(24 weeks)	24 weeks
the change of body weight	the change of body weight at baseline.	Baseline
the change of body weight	the change of body weight after 8 weeks.	8 weeks
the change of body weight	the change of body weight after 16 weeks.	16 weeks
the change of body weight	the change of body weight from baseline to end of trial(24 weeks)	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	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	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	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	24 weeks
the frequency of hypo/hyperkalemia and worsening kidney function	the frequency of hypo/hyperkalemia and worsening kidney function during the trial	Baseline
the frequency of hypo/hyperkalemia and worsening kidney function	the frequency of hypo/hyperkalemia and worsening kidney function during the trial	8 weeks
the frequency of hypo/hyperkalemia and worsening kidney function	the frequency of hypo/hyperkalemia and worsening kidney function during the trial	16 weeks
the frequency of hypo/hyperkalemia and worsening kidney function	the frequency of hypo/hyperkalemia and worsening kidney function during the trial	24 weeks
all-cause hospitalization & mortality	all-cause hospitalization & mortality during the trial	Baseline
all-cause hospitalization & mortality	all-cause hospitalization & mortality during the trial	8 weeks
all-cause hospitalization & mortality	all-cause hospitalization & mortality during the trial	16 weeks
all-cause hospitalization & mortality	all-cause hospitalization & mortality during the trial	24 weeks

Collaborators and Investigators

• Sponsor: Yonsei University

Study record dates

Study Major Dates

• Study Start (ANTICIPATED): May 1, 2019
• Primary Completion (ANTICIPATED): December 1, 2020
• Study Completion (ANTICIPATED): January 1, 2021

Study Registration Dates

• First Submitted: May 3, 2019
• First Submitted That Met QC Criteria: May 9, 2019
• First Posted (ACTUAL): May 14, 2019

Study Record Updates

• Last Update Posted (ACTUAL): May 21, 2019
• Last Update Submitted That Met QC Criteria: May 19, 2019
• Last Verified: May 1, 2019

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Heart Diseases; Cardiovascular Diseases; Heart Failure; Physiological Effects of Drugs; Adrenergic beta-Antagonists; Adrenergic Antagonists; Adrenergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Antihypertensive Agents; Vasodilator Agents; Protective Agents; Membrane Transport Modulators; Calcium-Regulating Hormones and Agents; Calcium Channel Blockers; Antioxidants; Adrenergic alpha-1 Receptor Antagonists; Adrenergic alpha-Antagonists; Carvedilol
• Other Study ID Numbers: 4-2018-1061

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No