Immediate Release Versus Slow Release Carvedilol in Heart Failure (SLOW-HF)

Seoul National University

Status and phase: Unknown; Phase 4

Conditions: Heart Failure With Reduced Ejection Fraction

Treatments: Drug: CarVeDilol-SR (Slow Release); Drug: Carvedilol IR (Immediate Release)

Study type: Interventional

Funder types: Other; Industry

Identifiers

NCT03209180

CVDSR

Details and patient eligibility

About

Assessment of clinical effect and treatment quality of immediate release carvedilol (IR) versus slow release carvedilol (SR) in patients with HFrEF

Full description

The SLOW-HF trial is a phase 4, randomized, open label, multicenter study to evaluate the therapeutic efficacy of carvedilol-SR compared to carvedilol-IR in patients with heart failure with reduced ejection fraction. Patients with stable HFrEF will be randomly assigned (1:1) to carvedilol SR group (160 patients) and carvedilol IR group (160 patients).

After randomization, patients will be followed for 6 months. The primary endpoint is the change in NT-proBNP level from baseline to the study end. The secondary endpoints include the frequency of NT-proBNP increment >10% from baseline, composite of all-cause mortality and readmission, mortality rate, readmission rate, changes in blood pressure, quality of life, and drug compliance.

Enrollment: 320 estimated patients

Sex: All

Ages: 20+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

1. At least or more than 20-years-old male and female
2. Confirmed left ventricular ejection fraction ≤40% by echocardiography within pre-analytical 6 months
3. NT-proBNP level ≥ 125 pg/ml or BNP level ≥ 35 pg/ml within pre-analytical 3 months
4. Clinically stable patient without evidence of congestion or extracellular fluid retention; those could be candidate of β-blockers
5. Patients providing written informed consent

Exclusion criteria

1. Systolic blood pressure at sitting position < 90mmHg or resting heart rate < 50 /min at screening

2. Patient has a contraindication to β-blockers

3. Patient who are expected to take another β-blocker after randomization

4. Cardiovascular diseases

   • Ischemic heart disease (unstable angina, myocardial infarction) within 1 month
   • Hypertrophic cardiomyopathy
   • Cor pulmonale
   • Hemodynamically significant stenosis of aorta, aortic valve, or mitral valve
   • any acute myocardial infarction with complication

5. Severe cerebrovascular accident (for example, ischemic stroke or cerebral hemorrhage) pre-analytical within 6 months

6. Glottis edema, allergic rhinitis, respiratory diseases with bronchospasm such as asthma and chronic obstructive lung disease

7. Peripheral vascular disease (for example, Raynaud syndrome, intermittent claudication)

8. Patients who need vasopressor due to prominent volume retention/overload

9. Moderate to Severe retinopathy (for example, retinal hemorrhage, visual disturbance, retinal microaneurysm within 6 months)

10. Impaired renal function (Serum creatinine ≥ 2.5 mg/dL) or hepatic function (AST or ALT ≥ 3 x ULM)

11. Patients in clinical status that can significantly influence on absorption, distribution, metabolism, and secretion of drugs for clinical trial

    • history of major gastrointestinal surgery, such as gastrectomy or gastric bypass surgery
    • inflammatory bowel disease within 12 months
    • current gastric ulcer, pancreatic function abnormality including pancreatitis, gastrointestinal/rectal bleeding which demand treatment
    • current urologic stenosis or obstruction which demand treatment

12. Confirmed or suspected drug/alcohol abuse within 6 months

13. Pregnant or lactating women, suspected pregnant women or lactating women

14. Chronic inflammatory diseases which demand anti-inflammatory treatment

15. Hypersensitivity to carvedilol

16. Malignant disease including lymphoma and leukemia within 5 years

17. Patients who were prescribed other medication for any clinical trials pre-analytical within 28 days

18. Patients who are predicted to have prolonged hospital days due to other medical problems other than chronic heart failure (for example, femur neck fracture)

19. Patients who are considered as inappropriate to participate in the clinical trial by testers

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Triple Blind

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320 participants in 2 patient groups

Carvedilol IR (Immediate Release)

Active Comparator group

Description:

Carvedilol IR 3.125mg, 6.25mg, 12.5mg, 25mg twice daily p.o. for 6 months

Treatment:

Drug: Carvedilol IR (Immediate Release)

CarVeDilol-SR (Slow Release)

Experimental group

Description:

CarVeDilol-SR 8mg, 16mg, 32mg, 64mg once daily p.o. for 6 months

Treatment:

Drug: CarVeDilol-SR (Slow Release)