Clinical trial NCT05553314: Carvedilol in HF With Preserved EF
Official title: Slow-release CArvedilol in Patients With REduced Strain and Preserved Ejection Fraction Heart Failure (CARE-preserved HF): A Prospective Randomized, Double-Blinded, Multicenter Study
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE4
Conditions: Heart Failure With Preserved Ejection Fraction
Beta Blocker
Myocardial Strain
Keywords: HFPEF
beta-blocker
reduced strain
BNP
Lead sponsor: Seoul National University Bundang Hospital
Sponsor class: OTHER
Collaborators: name: Samsung Medical Center
name: Wonju Severance Christian Hospital
First posted: 2022-09-23
Enrollment: 100
Sex: ALL
Minimum age (years): 20
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: A prospective, randomized, double-blinded, placebo-controlled study
Primary purpose: TREATMENT

Brief summary: Beta-blockers improve clinical outcomes in heart failure and reduced ejection fraction (HFrEF); but not in those with preserved EF. Global longitudinal strain (GLS) is a prognostic factor independent of left ventricular ejection fraction (LVEF). In a retrospective with 1969 patients with HF and LVEF of ≥40%, beta-blocker was associated with improved survival in those with low GLS (GLS \<14%), but not in those with GLS ≥14%. In this prospective, randomized clinical study, the investigators will assess the effect of slow-release carvedilol in patients with HFpEF and hypertension. The primary endpoint is the time-averaged proportional changes in NT-proBNP level and GLS change from baseline to month 6.


Eligibility criteria: Inclusion Criteria:

* age ≥20 yrs
* symptomatic HFpEF with LVEF≥50%
* NT-proBNP ≥220 pg/ml (sinus rhythm) or ≥660 pg/ml(AF) (BNP ≥80 pg/ml (sinus rhythm) or ≥240 pg/ml(AF) )
* SBP≥140mmHg and/or DBP ≥90mmHg, or if taking anti-hypertensive medication, SBP ≥110mmHg.
* LAVI≥29(sinus rhythm)/34ml/m2 (AF) or LVMI≥115(male)/95(female) g/m2
* meet one the following

  1. Average E/e'≥ 9
  2. Septal e' \< 7 cm/s
  3. Lateral e' \<10 cm/s
  4. TR velocity \> 2.8 m/s
  5. PASP \> 35 mmHg
  6. GLS \< 16%

Exclusion Criteria:

* systolic blood pressure \< 110 mmHg, or heart rate \< 60 beats/min
* contra-indication to beta-blockers
* creatinine\> 2.4mg/dL
* amyloidosis, hypertrophic cardiomyopathy with obstruction, severe aortic or mitral valve disease, acute coronary syndrome, Cerebrovascular event within 6 months, PCI within 3 months before
* AST/ALT \>3 x normal upper range

Primary outcomes:
measure: NT-proBNP change
timeFrame: 6 months
measure: GLS change
timeFrame: 6 months
Secondary outcomes:
measure: off-level NT-proBNP
timeFrame: 6 months
measure: Mortality
timeFrame: 6 months
measure: rehospitalization
timeFrame: 6 months
Other outcomes:
Locations:
city: Seoul
country: Korea, Republic of
facility: Samsung Medical Center
state: Il-won
city: Wonju
country: Korea, Republic of
facility: Wonju Severance Christian Hospital
Study officials:
affiliation: Seoul National Univeristy Bundang Hospital
name: Dong-Ju Choi, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Park JJ, Park JB, Park JH, Cho GY. Global Longitudinal Strain to Predict Mortality in Patients With Acute Heart Failure. J Am Coll Cardiol. 2018 May 8;71(18):1947-1957. doi: 10.1016/j.jacc.2018.02.064.
citation: Yamamoto K, Origasa H, Hori M; J-DHF Investigators. Effects of carvedilol on heart failure with preserved ejection fraction: the Japanese Diastolic Heart Failure Study (J-DHF). Eur J Heart Fail. 2013 Jan;15(1):110-8. doi: 10.1093/eurjhf/hfs141. Epub 2012 Sep 14.
citation: Park JJ, Choi HM, Hwang IC, Park JB, Park JH, Cho GY. Myocardial Strain for Identification of beta-Blocker Responders in Heart Failure with Preserved Ejection Fraction. J Am Soc Echocardiogr. 2019 Nov;32(11):1462-1469.e8. doi: 10.1016/j.echo.2019.06.017. Epub 2019 Sep 17.