Congestive heart failure MedDRA version: 9.1 Level: LLT Classification code 10010684 Term: Congestive heart failure
Conditions
Interventions
Trade Name: Carvedilol
Product Name: Carvedilol
Pharmaceutical Form: Tablet
INN or Proposed INN: CARVEDILOL
CAS Number: 72956093
Trade Name: Metoprolol retard
Product Name: Metoprolol succinate
Pharm
Sponsors
Academisch Medisch Centrum
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Patients 1. Between 18 and 80 years of age, competent and willing of giving informed consent; 2. With stable symptoms of chronic heart failure (NYHA II-III); 3. With left ventricular ejection fraction =40%, measured within the previous 6 months; if the ejection fraction is not determined, a left-ventricular end diastolic diameter of greater then 6.0 cm and a fractional shortening of less than 20% as measured by echocardiography; 4. With sinusrhythm; (necessary to perform spectral analysis); 5. On stable medical therapy with ACE-inhibitors for at least three months, unless contraindicated; otherwise angiotensin receptor blockers (ARBs); 6. Already on beta-blocker therapy with maximal tolerated doses; are included in the study. Digitalis or other vasodilatators can be used at the discretion of the treating physicians; Healthy subjects between 18 and 80 years of age serve as controls to compare sympathetic and hypercoagulable activity with heart failure patients. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: Excluded are patients 1. With a history of adverse reaction on beta-blockers; 2. With a contraindication to ß-blocker therapy (Sick-sinussyndrome, second and third AV-block), severe hypotension (systolic blood pressure 200mg per day) or class-I antiarrhythmic drugs, or administration of any investigational drug in the preceding 30 days. 8. Uncontrolled hypertension (blood pressure systolic >170 mmHg or diastolic >105mmHg), 9. Symptomatic and sustained ventricular arrhythmias within the preceding two months not adequately treated with antiarrhythmic drugs or without implantation of an automatic defibrillator; 10. With implanted pacemaker (necessary for spectral analysis); ICD is allowed 11. Pregnancy and women with childbearing potential on inadequate contraception 12. Known drug or alcohol misuse 13. Poor compliance with treatment 14. Any other serious systemic disease that might complicate management and reduce life expectancy. 15. Known with an allergy for iodine Excluded are healthy controls 1. Taking any medication that will affect our outcome measurements for at least 2 weeks before entering the study 2. With a history of adverse reaction on beta-blockers 3. With a contraindication to beta-blocker therapy as described for patients with heart failure 4. With pregnancy and women with childbearing potential on inadequate contraception 5. Known drug or alcohol misuse 6. Known with poor compliance with treatment
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: 1.To analyse whether the hypercoagulable response to sympathetic activation in heart failure patients is reduced more effectively by carvedilol than metoprolol and whether this response differs from that in healthy controls.. 2.To analyse whether the hypercoagulable response to sympathetic activation in heart failure patients and in healthy controls is determined by the beta2-adrenergic genotype. ;Secondary Objective: 1.To investigate the efficacy of non-selective and selective beta-blockers in downregulating the hypercoagulable response in patients with chronic heart failure. 2.To analyse the beta2-adrenergic genotype-specific effect of carvedilol on hypercoagulable activity in patients with chronic heart failure. 3.To analyse if the increase in sympathetic and procoagulant activity after postural change in healthy controls is determined by the beta2-adrenergic genotype and whether this haplotype determines the response to carvedilol. 4.To analyse if patients have a preference for one of the two beta-blockers and whether this correlates with their haplotypes. ;Primary end point(s): We will assess two primary endpoints at rest and during exercise: 1.Hypercoagulable activity by platelet function and thrombin generation; 2.Sympathetic activity as measured by plasma norepinephrine and epinephrine concentration, spectral analysis of heart rate and blood pressure variability. | — |
Countries
Netherlands
Outcome results
None listed