Roche trials database

Protocol number:

ML17139

Title of Study:

Influence of carvedilol (Dilatrend) on physical fitness and quality of life: assessment by accelerometry (using Physilog) in patients with heart failure (CALL study)

Sponsor:

Roche Pharma (Schweiz) AG

Company division:

Pharmaceutical

Product name:

Dilatrend

Generic name:

carvedilol

Therapeutic area:

• Heart Failure

Clinical study summary:

This open-label, uncontrolled, single arm study was designed to evaluate the efficacy and tolerability of Dilatrend in patients with heart failure. Patients took part in an outpatient cardiovascular rehabilitation program to study the influence of Dilatrend on physical fitness and quality of life.

Study center(s):

1 center in Switzerland

Phase of development:

IV

Objectives:

Primary objective: Effect of Dilatrend treatment on left ventricular function (difference in proBNP concentrations).
Secondary objective: Median change in fitness parameters (as assessed by accelerometry); quality of life (QoL) assessments

Methodology:

For patients who took part in an outpatient cardiovascular rehabilitation program, formal in-/exclusion criteria were checked. After baseline assessments, the patients took the initial dose of 3.125 mg Dilatrend bid. In a bi-weekly rhythm patients were assessed during the next 8 – 12 weeks for further up-titration to 6.25 mg, 12.5 mg and a maximum of 25.0 mg twice daily, respectively, based on the efficacy-tolerability relationship. Depending on the duration of the titration phase, the patients continued with their individual maximally tolerated dose of Dilatrend for the next 16 – 12 weeks, with a maximum of 24 weeks treatment duration. Twelve weeks after start of Dilatrend treatment the patients were assessed for their final evaluation of the efficacy parameters. A total of 7 visits over a time period of 24 weeks were done.

Number of patients (planned/analyzed):

28 planned; 8 dosed

Diagnosis and main criteria for inclusion:

Men and women >18 years with heart failure of any etiology, no established treatment with beta-blockers and with an ability to participate in an outpatient cardiac rehabilitation program.

Test product, dose and mode of administration or test procedure:

Dilatrend (carvedilol) (commercial supply) administered at 3.125 mg (starting dose), 6.25 mg, 12.5 mg or 25.0 mg orally bid for a minimum of 2 weeks during titration phase and a maximum of 24 weeks overall treatment.

Duration of treatment:

24 weeks

Reference therapy, dose and mode of administration or reference procedure:

N/A

Criteria for evaluation (efficacy, safety):

Efficacy: Spiroergemetry: heart rate at ventilatory threshold; heart rate (HR) at 65% Watt; heart rate at 50% VO₂; 60% heart rate reserve; 65% peak heart rate.
proBNP measurements were not done.
Quality of Life: QoL questionnaires were only completed by a few patients, and not consistently throughout the study. QoL analyses were therefore not performed.
Physilog measurements were also done irregularly, therefore no analysis was done.
Safety: Measurement of vital signs (systolic/diastolic blood pressure, heart rate, weight); frequency of adverse events (AEs)

Statistical methods:

Statistical analysis was performed using the SPSS® for Windows® software (version 12.0, SPSS® Inc., Chicago, Illinois, USA). Mean comparisons were effectuated using non-parametric tests (Wilcoxon and Mann-Whitney). All statistical tests were two-tailed and a value of p < 0.05 was considered statistically significant.

Summary (efficacy, safety, other results):

Efficacy: Four weeks after administration of the first beta-blocker dosage (4 patients on 3.125 mg bid, 4 patients on 6.25 mg bid), HR at ventilatory threshold, at 65% of maximal power output, at 50% of peak VO₂, at 60% of heart rate reserve and at 65% of peak HR, had decreased by 9 to 14 beats/minute (p < 0.05). Training heart rates did not significantly change with beta-blocker dosage up-titration, except for HR at 50% of peak VO₂. O₂ uptake at anaerobic threshold and at peak exercise was not affected by beta-blocker dosage and increased throughout the training programme from 16.0 ± 4.2 to 17.9 ± 5.1 mL/kg/minute (p = 0.141) and from 19.6 ± 6.6 to 21.8 ± 6.8 mL/kg/minute (p = 0.176), respectively.

Safety: No SAEs were observed. Four AEs were observed: leg edema and slight dyspnea in 1 patient, with no suspicion of a causal relationship to the study medication. Headache (one patient) and fluid overload in the veins of the legs (one patient) were suspected to be related to the study medication.

Conclusions:

Beta-blocker treatment initiation, but not up-titration necessitates adaptation of training heart rate prescription in heart failure patients except for the training heart rate determination using % of peak VO₂. Beta-blocker up-titration does not impair gain in work capacity and maximal oxygen consumption during exercise training in heart failure patients.

Publications (references, if available):

N/A

Date of report:

16.04.2008

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