AusPAR: Ivabradine - Therapeutic Goods Administration

AusPAR Coralan Ivabradine Servier Laboratories (Australia) Pty Ltd PM-2010-03269-3-3
Final 31 October 2012
Therapeutic Goods Administration
between the treatment groups. Among protocol deviations before or at inclusion which
could have impacted the efficacy assessment, the highest incidence in both treatment
groups was the deviation involving “no documented hospitalisation for worsening heart
failure within 12 months prior to selection” (1.3% [43/ 3241] and 1.1% [37/ 3264] in the
ivabradine and placebo treatment groups, respectively).
The disposition of protocol deviations occurring during the study, by category and by
treatment group showed that overall, 132 patients presented at least one protocol
deviation during the study: 69 patients (2.1%) in the ivabradine group and 63 patients
(1.9%) in the placebo group. Overall, 149 protocol deviations were detected during the
study, with 147 deviations which could have impacted the safety assessment and 2
deviations which could have impacted the study management. There were no deviations
observed that could have affected the efficacy assessment.
Baseline data
The baseline demographic characteristics were comparable between the 2 treatment
groups. The overall mean age (± SD) was 60.4 (± 11.4) years with a range from 19 to 92
years. Overall, 38.0% (2474/ 6505) were ≥ 65 years of age and 11.1% (722/ 6505) were
≥75 years of age. The majority of patients were male (76.4%) and Caucasian (88.7%). The
overall mean (± SD) heart rate was 79.9 (± 9.6) bpm, with a range of 48 to 142 bpm. The
baseline heart rate was < 80 bpm in 59.9% of patients, between 80 to 89 bpm in 24.4% of
patients and ≥ 90 bpm in 15.6% of patients.
The main baseline CHF disease characteristics were comparable between the 2 treatment
groups. The overall mean (± SD) duration of the CHF from diagnosis was 3.5 (± 4.2) years,
with a median of 2.0 years. Overall, 50.2% of the study population had a duration of CHF of
< 2 years, 25.7% for ≥2 to 25 to
≤0%, 15.3% with LVEF of >20 to ≤ 25%, and 9.5% with LVEF of ≤ 20%. Only 0.1% had an
LVEF of > 35% (protocol violation).
Main background treatments for heart failure were comparable between the 2 treatment
groups. Overall, the majority of patients (89.5%, 5820/6505) were taking a beta blocker at
randomisation. The most frequent reason for the non prescription of a beta blocker at
randomisation was chronic obstructive pulmonary disease (COPD) (34.5% among patients
not on beta blocker at randomisation), followed by hypotension (18.5%) and asthma
(10.9%). Among patients taking a beta blocker at randomisation, 98.2% were taking one
of the ESC recommended drugs or metoprolol tartrate. Overall, 55.7% of these patients
taking a recommended drug or metoprolol tartrate were taking at least half the target
daily dose, and 26.1% were taking the recommended target daily dose. The main reasons
for not being at the target daily dose were hypotension (44.6%) or fatigue (31.9%).
Overall treatment compliance, mean treatment dose and dose titration profiles showed
that overall 97.8% of patients had a global compliance of between 70% and 130% 20 and
this was comparable between the 2 treatment groups (97.5% and 98.1% of patients in the
ivabradine and placebo groups, respectively). The overall mean (± SD) global compliance
was 96.3% ± 10.2% (96.2% ± 11.3% and 96.4% ± 9.0% in the ivabradine and placebo
groups, respectively). In the ivabradine group, 60.3% of patients were up-titrated from the
20 Global compliance (%) was calculated as (Σ number of tablets taken / (duration of treatment x 2)) x 100
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