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

Primary Purpose

Heart Failure With Preserved Ejection Fraction

Status
Unknown status
Phase
Phase 4
Locations
Korea, Republic of
Study Type
Interventional
Intervention
Carvedilol SR
Placebo
Sponsored by
Yonsei University
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Heart Failure With Preserved Ejection Fraction

Eligibility Criteria

19 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Division of Cardiology, Severance Cardiovascular Hospital, Yonsei University College of Medicine

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

Carvedilol SR

Placebo

Arm Description

Carvedilol SR 8mg, 16mg, 32mg

Placebo

Outcomes

Primary Outcome Measures

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

Secondary Outcome Measures

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.
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.
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.
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)
The change in degree of dyspnea using VAS questionnaire
the change of dyspnea at baseline.
The change in degree of dyspnea using VAS questionnaire
the change of dyspnea after 8 weeks.
The change in degree of dyspnea using VAS questionnaire
the change of dyspnea after 16 weeks.
The change in degree of dyspnea using VAS questionnaire
the change of dyspnea from baseline to end of trial(24 weeks)
the change of body weight
the change of body weight at baseline.
the change of body weight
the change of body weight after 8 weeks.
the change of body weight
the change of body weight after 16 weeks.
the change of body weight
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
the frequency of symptomatic hypotension, symptomatic bradycardia and AV block above 2nd degree during the tiral
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
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
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
the frequency of hypo/hyperkalemia and worsening kidney function
the frequency of hypo/hyperkalemia and worsening kidney function during the trial
the frequency of hypo/hyperkalemia and worsening kidney function
the frequency of hypo/hyperkalemia and worsening kidney function during the trial
the frequency of hypo/hyperkalemia and worsening kidney function
the frequency of hypo/hyperkalemia and worsening kidney function during the trial
the frequency of hypo/hyperkalemia and worsening kidney function
the frequency of hypo/hyperkalemia and worsening kidney function during the trial
all-cause hospitalization & mortality
all-cause hospitalization & mortality during the trial
all-cause hospitalization & mortality
all-cause hospitalization & mortality during the trial
all-cause hospitalization & mortality
all-cause hospitalization & mortality during the trial
all-cause hospitalization & mortality
all-cause hospitalization & mortality during the trial

Full Information

First Posted
May 3, 2019
Last Updated
May 19, 2019
Sponsor
Yonsei University
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1. Study Identification

Unique Protocol Identification Number
NCT03948685
Brief Title
Carvedilol SR Study for Biomarkers From Blood and Urine and Safety of in Patients With Heart Failure With Preserved Ejection Fraction
Official Title
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)
Study Type
Interventional

2. Study Status

Record Verification Date
May 2019
Overall Recruitment Status
Unknown status
Study Start Date
May 2019 (Anticipated)
Primary Completion Date
December 2020 (Anticipated)
Study Completion Date
January 2021 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Yonsei University

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

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

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Heart Failure With Preserved Ejection Fraction

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 4
Interventional Study Model
Parallel Assignment
Model Description
Carvedilol SR vs. Placebo
Masking
None (Open Label)
Allocation
Randomized
Enrollment
300 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Carvedilol SR
Arm Type
Experimental
Arm Description
Carvedilol SR 8mg, 16mg, 32mg
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
Placebo
Intervention Type
Drug
Intervention Name(s)
Carvedilol SR
Intervention Description
blood pressure, heart rate based titrated carvedilol SR for 24 weeks
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
Placebo
Primary Outcome Measure Information:
Title
The Maximum NT-proBNP value change after Drug(Carvedilol SR or Placebo) administration.
Description
The maximum NT-proBNP value change at baseline.
Time Frame
Baseline
Title
The Maximum NT-proBNP value change after Drug(Carvedilol SR or Placebo) administration.
Description
The maximum NT-proBNP value change from baseline to 8 weeks.
Time Frame
8 weeks
Title
The Maximum NT-proBNP value change after Drug(Carvedilol SR or Placebo) administration.
Description
The maximum NT-proBNP value change from baseline to End of trial(24weeks).
Time Frame
24 weeks
Secondary Outcome Measure Information:
Title
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.
Description
the change of surrogate markers(hsTn, hsCRP etc) at baseline.
Time Frame
Baseline
Title
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.
Description
the change of surrogate markers(hsTn, hsCRP etc) after 8 weeks.
Time Frame
8 weeks
Title
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.
Description
the change of surrogate markers(hsTn, hsCRP etc) after 16 weeks.
Time Frame
16 weeks
Title
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.
Description
the change of surrogate markers(hsTn, hsCRP etc) from baseline to end of trial(24 weeks)
Time Frame
24 weeks
Title
The change in degree of dyspnea using VAS questionnaire
Description
the change of dyspnea at baseline.
Time Frame
Baseline
Title
The change in degree of dyspnea using VAS questionnaire
Description
the change of dyspnea after 8 weeks.
Time Frame
8 weeks
Title
The change in degree of dyspnea using VAS questionnaire
Description
the change of dyspnea after 16 weeks.
Time Frame
16 weeks
Title
The change in degree of dyspnea using VAS questionnaire
Description
the change of dyspnea from baseline to end of trial(24 weeks)
Time Frame
24 weeks
Title
the change of body weight
Description
the change of body weight at baseline.
Time Frame
Baseline
Title
the change of body weight
Description
the change of body weight after 8 weeks.
Time Frame
8 weeks
Title
the change of body weight
Description
the change of body weight after 16 weeks.
Time Frame
16 weeks
Title
the change of body weight
Description
the change of body weight from baseline to end of trial(24 weeks)
Time Frame
24 weeks
Title
the frequency of symptomatic hypotension, symptomatic bradycardia and AV block above 2nd degree
Description
the frequency of symptomatic hypotension, symptomatic bradycardia and AV block above 2nd degree during the tiral
Time Frame
Baseline
Title
the frequency of symptomatic hypotension, symptomatic bradycardia and AV block above 2nd degree
Description
the frequency of symptomatic hypotension, symptomatic bradycardia and AV block above 2nd degree during the tiral
Time Frame
8 weeks
Title
the frequency of symptomatic hypotension, symptomatic bradycardia and AV block above 2nd degree
Description
the frequency of symptomatic hypotension, symptomatic bradycardia and AV block above 2nd degree during the tiral
Time Frame
16 weeks
Title
the frequency of symptomatic hypotension, symptomatic bradycardia and AV block above 2nd degree
Description
the frequency of symptomatic hypotension, symptomatic bradycardia and AV block above 2nd degree during the tiral
Time Frame
24 weeks
Title
the frequency of hypo/hyperkalemia and worsening kidney function
Description
the frequency of hypo/hyperkalemia and worsening kidney function during the trial
Time Frame
Baseline
Title
the frequency of hypo/hyperkalemia and worsening kidney function
Description
the frequency of hypo/hyperkalemia and worsening kidney function during the trial
Time Frame
8 weeks
Title
the frequency of hypo/hyperkalemia and worsening kidney function
Description
the frequency of hypo/hyperkalemia and worsening kidney function during the trial
Time Frame
16 weeks
Title
the frequency of hypo/hyperkalemia and worsening kidney function
Description
the frequency of hypo/hyperkalemia and worsening kidney function during the trial
Time Frame
24 weeks
Title
all-cause hospitalization & mortality
Description
all-cause hospitalization & mortality during the trial
Time Frame
Baseline
Title
all-cause hospitalization & mortality
Description
all-cause hospitalization & mortality during the trial
Time Frame
8 weeks
Title
all-cause hospitalization & mortality
Description
all-cause hospitalization & mortality during the trial
Time Frame
16 weeks
Title
all-cause hospitalization & mortality
Description
all-cause hospitalization & mortality during the trial
Time Frame
24 weeks

10. Eligibility

Sex
All
Minimum Age & Unit of Time
19 Years
Accepts Healthy Volunteers
No
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 Life expectancy < 6 months (e.g. metastatic malignancy) Pregnancy, or women of childbearing age
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Seok-Min Kang, MD, Ph.D
Phone
82-2-2228-8450
Email
smkang@yuhs.ac
Facility Information:
Facility Name
Division of Cardiology, Severance Cardiovascular Hospital, Yonsei University College of Medicine
City
Seoul
ZIP/Postal Code
120-752
Country
Korea, Republic of

12. IPD Sharing Statement

Plan to Share IPD
No

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

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