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

Heart Failure With Preserved Ejection Fraction Clinical Trial

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)

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT03948685
• Other study ID #: 4-2018-1061
• Status: Not yet recruiting
• Phase: Phase 4
• Start date: May 2019
• Est. completion date: January 2021

Study information

• Verified date: May 2019
• Source: Yonsei University
• Contact: Seok-Min Kang, MD, Ph.D
• Phone: 82-2-2228-8450
• Email: smkang[@]yuhs.ac
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 300
• Est. completion date: January 2021
• Est. primary completion date: December 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 19 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Heart Failure
• Heart Failure With Preserved Ejection Fraction

Intervention

Drug:
• Carvedilol SR
blood pressure, heart rate based titrated carvedilol SR for 24 weeks
• Placebo
Placebo

Locations

Country	Name	City	State
Korea, Republic of	Division of Cardiology, Severance Cardiovascular Hospital, Yonsei University College of Medicine	Seoul

Sponsors (1)

Lead Sponsor	Collaborator
Yonsei University

Country where clinical trial is conducted

Korea, Republic of, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	The Maximum NT-proBNP value change after Drug(Carvedilol SR or Placebo) administration.	The maximum NT-proBNP value change at baseline.	Baseline
Primary	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
Primary	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	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
Secondary	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
Secondary	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
Secondary	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
Secondary	The change in degree of dyspnea using VAS questionnaire	the change of dyspnea at baseline.	Baseline
Secondary	The change in degree of dyspnea using VAS questionnaire	the change of dyspnea after 8 weeks.	8 weeks
Secondary	The change in degree of dyspnea using VAS questionnaire	the change of dyspnea after 16 weeks.	16 weeks
Secondary	The change in degree of dyspnea using VAS questionnaire	the change of dyspnea from baseline to end of trial(24 weeks)	24 weeks
Secondary	the change of body weight	the change of body weight at baseline.	Baseline
Secondary	the change of body weight	the change of body weight after 8 weeks.	8 weeks
Secondary	the change of body weight	the change of body weight after 16 weeks.	16 weeks
Secondary	the change of body weight	the change of body weight from baseline to end of trial(24 weeks)	24 weeks
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	the frequency of hypo/hyperkalemia and worsening kidney function	the frequency of hypo/hyperkalemia and worsening kidney function during the trial	Baseline
Secondary	the frequency of hypo/hyperkalemia and worsening kidney function	the frequency of hypo/hyperkalemia and worsening kidney function during the trial	8 weeks
Secondary	the frequency of hypo/hyperkalemia and worsening kidney function	the frequency of hypo/hyperkalemia and worsening kidney function during the trial	16 weeks
Secondary	the frequency of hypo/hyperkalemia and worsening kidney function	the frequency of hypo/hyperkalemia and worsening kidney function during the trial	24 weeks
Secondary	all-cause hospitalization & mortality	all-cause hospitalization & mortality during the trial	Baseline
Secondary	all-cause hospitalization & mortality	all-cause hospitalization & mortality during the trial	8 weeks
Secondary	all-cause hospitalization & mortality	all-cause hospitalization & mortality during the trial	16 weeks
Secondary	all-cause hospitalization & mortality	all-cause hospitalization & mortality during the trial	24 weeks