Clinical trial NCT03948685: 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
Overall status: UNKNOWN
Phase: PHASE4
Conditions: Heart Failure With Preserved Ejection Fraction
Lead sponsor: Yonsei University
Sponsor class: OTHER
First posted: 2019-05-14
Enrollment: 300
Sex: ALL
Minimum age (years): 19
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Carvedilol SR vs. Placebo
Primary purpose: TREATMENT

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


Eligibility criteria: 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

Primary outcomes:
measure: The Maximum NT-proBNP value change after Drug(Carvedilol SR or Placebo) administration.
timeFrame: Baseline
measure: The Maximum NT-proBNP value change after Drug(Carvedilol SR or Placebo) administration.
timeFrame: 8 weeks
measure: The Maximum NT-proBNP value change after Drug(Carvedilol SR or Placebo) administration.
timeFrame: 24 weeks
Secondary outcomes:
measure: 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.
timeFrame: Baseline
measure: 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.
timeFrame: 8 weeks
measure: 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.
timeFrame: 16 weeks
measure: 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.
timeFrame: 24 weeks
measure: The change in degree of dyspnea using VAS questionnaire
timeFrame: Baseline
measure: The change in degree of dyspnea using VAS questionnaire
timeFrame: 8 weeks
measure: The change in degree of dyspnea using VAS questionnaire
timeFrame: 16 weeks
measure: The change in degree of dyspnea using VAS questionnaire
timeFrame: 24 weeks
measure: the change of body weight
timeFrame: Baseline
measure: the change of body weight
timeFrame: 8 weeks
measure: the change of body weight
timeFrame: 16 weeks
measure: the change of body weight
timeFrame: 24 weeks
measure: the frequency of symptomatic hypotension, symptomatic bradycardia and AV block above 2nd degree
timeFrame: Baseline
measure: the frequency of symptomatic hypotension, symptomatic bradycardia and AV block above 2nd degree
timeFrame: 8 weeks
measure: the frequency of symptomatic hypotension, symptomatic bradycardia and AV block above 2nd degree
timeFrame: 16 weeks
measure: the frequency of symptomatic hypotension, symptomatic bradycardia and AV block above 2nd degree
timeFrame: 24 weeks
measure: the frequency of hypo/hyperkalemia and worsening kidney function
timeFrame: Baseline
measure: the frequency of hypo/hyperkalemia and worsening kidney function
timeFrame: 8 weeks
measure: the frequency of hypo/hyperkalemia and worsening kidney function
timeFrame: 16 weeks
measure: the frequency of hypo/hyperkalemia and worsening kidney function
timeFrame: 24 weeks
measure: all-cause hospitalization & mortality
timeFrame: Baseline
measure: all-cause hospitalization & mortality
timeFrame: 8 weeks
measure: all-cause hospitalization & mortality
timeFrame: 16 weeks
measure: all-cause hospitalization & mortality
timeFrame: 24 weeks
Other outcomes:
Locations:
city: Seoul
country: Korea, Republic of
facility: Division of Cardiology, Severance Cardiovascular Hospital, Yonsei University College of Medicine
Study officials:
References: