Clinical trial NCT03209180: Immediate Release Versus Slow Release Carvedilol in Heart Failure
Official title: Assessment of Clinical Effect and Treatment Quality of Rapid Release Carvedilol Versus SLOW Release Carvedilol-SR in HEART FAILURE Patient (SLOW-HF): A Prospective Randomized, Open-label, Multicenter Study
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE4
Conditions: Heart Failure With Reduced Ejection Fraction
Keywords: HFrEF
Carvedilol
Slow Release
NT-proBNP
Lead sponsor: Seoul National University Bundang Hospital
Sponsor class: OTHER
Collaborators: name: Chong Kun Dang Pharmaceutical Corp.
First posted: 2017-07-06
Enrollment: 320
Sex: ALL
Minimum age (years): 20
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: PROBE and NON-INFERIORITY DESIGN for Slow Release CarVeDilol-SR to Rapid Release Carvedilol-IR
Primary purpose: TREATMENT

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

Detailed 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.

Eligibility criteria: 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

Primary outcomes:
measure: NT-proBNP
timeFrame: 6 months
Secondary outcomes:
measure: All-cause Death
timeFrame: 6 months
measure: Hospitalization
timeFrame: 6 months
measure: Blood Pressure
timeFrame: 6 months
measure: Dyspnea
timeFrame: 6 months
measure: Drug compliance
timeFrame: 6 months
Other outcomes:
Locations:
city: Gyeonggi-do
country: Korea, Republic of
facility: Sejong Hospital
state: Bucheon
city: Seoul
country: Korea, Republic of
facility: Gangdong Sacred Heart Hospital
state: Gangdong
city: Seoul
country: Korea, Republic of
facility: Korea Univ. Guro Hospital
state: Guro
city: Seoul
country: Korea, Republic of
facility: Samsung Medical Center
state: Il-won
city: Seoul
country: Korea, Republic of
facility: Seoul Medical Center
state: Jungnang
city: Seoul
country: Korea, Republic of
facility: Korea Univ. Anam Hospital
state: Seongbuk
city: Seoul
country: Korea, Republic of
facility: Asan Medical Center
state: Songpa
city: Suwon-si
country: Korea, Republic of
facility: Ajou Univ. Medical Center
state: Yeong-tong
city: Seongnam
country: Korea, Republic of
facility: Seoul National University Bundang Hospital
city: Seoul
country: Korea, Republic of
facility: Severance Hospital
city: Seoul
country: Korea, Republic of
facility: Seoul Metropolitan Government Seoul National University Boramae Medical Center
city: Seoul
country: Korea, Republic of
facility: Seoul National University Hospital
city: Wonju
country: Korea, Republic of
facility: Wonju Severance Christian Hospital
Study officials:
References:
citation: Choi DJ, Park CS, Park JJ, Lee HY, Kang SM, Yoo BS, Jeon ES, Hong SK, Shin JH, Kim MA, Park DG, Kim EJ, Hong SJ, Kim SY, Kim JJ. Assessment of clinical effect and treatment quality of immediate-release carvedilol-IR versus SLOW release carvedilol-SR in Heart Failure patients (SLOW-HF): study protocol for a randomized controlled trial. Trials. 2018 Feb 13;19(1):103. doi: 10.1186/s13063-018-2470-5.