The primary objectives of this study are to test if aliskiren monotherapy is superior or at least non-inferior to enalapril monotherapy (in the entire study population) and/or to test if aliskiren/enalapril combination is superior to enalapril…
ID
Source
Brief title
Condition
- Heart failures
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
The primary objectives of this study are to test if aliskiren monotherapy is
superior or at least non-inferior to enalapril monotherapy (in the entire study
population) and/or to test if aliskiren/enalapril combination is superior to
enalapril monotherapy (in the entire study population and/or in the
non-diabetic population), in delaying time to first occurrence of either
cardiovascular death or heart failure hospitalization in patients with chronic
heart failure (NYHA Class II - IV).
Secondary outcome
To evaluate whether, aliskiren monotherapy and/or the combination of
aliskiren/enalapril is superior to enalapril monotherapy in improving the
clinical summary score (assessed by KCCQ) from baseline to month 12.
Background summary
The purpose of this study is to evaluate the effect of aliskiren monotherapy
(in the entire study population) and aliskiren/enalapril combination therapy
(in the entire study population and/or in the non-diabetic population),
compared to enalapril monotherapy, on top of conventional CHF treatment (except
for ACEi that will be substituted with study treatment), in delaying time to
first occurrence of either cardiovascular (CV) death or heart failure
hospitalization events in patients with stable chronic heart failure (NYHA
Class II - IV). Data from this study is intended to be used to support a
supplemental worldwide registration submission of aliskiren for treatment to
improve CV death and heart failure hospitalization outcomes in patients with
chronic heart failure (NYHA Class II * IV).
Study objective
The primary objectives of this study are to test if aliskiren monotherapy is
superior or at least non-inferior to enalapril monotherapy (in the entire study
population) and/or to test if aliskiren/enalapril combination is superior to
enalapril monotherapy (in the entire study population and/or in the
non-diabetic population), in delaying time to first occurrence of either
cardiovascular death or heart failure hospitalization in patients with chronic
heart failure (NYHA Class II - IV).
Study design
At Visit 1 (screening), patients with chronic heart failure (NYHA Class II *
IV) on stable pharmacological treatment for heart failure for at least four
weeks prior to visit (except for diuretics) and meeting all inclusion criteria,
will enter a stabilization active run-in period (3-12 weeks), during which the
tolerability to enalapril and aliskiren on top of the pre-existing drugs and
all laboratory eligibility criteria will be evaluated.
Patient randomization will occur after completion of the active run-in period
(Visit 4), once the safety monitoring results are available at the site and the
patient has met all inclusion criteria and none of the exclusion criteria.
Patients will be allocated to one of the two stratification groups, according
to the tolerated dose of enalapril, and be randomized in a 1:1:1 ratio to one
of the three treatment arms (aliskiren monotherapy, enalapril monotherapy, or
aliskiren/enalapril combination therapy). After randomization, patients will be
up-titrated to the maximum dose of the corresponding therapies.
The trial will be event driven and all randomized patients will remain in the
trial until the number of primary events have been reached. It is planned that
the total trial duration will be approximately 6,5 years, with a recruitment
period of 4 years and a target double-blind treatment period of 18-74 months.
Intervention
The patients will be equally randomized to one of the following 3 treatment:
* Aliskiren-enalapril combination therapy
* Enalapril monotherapy
* Aliskiren monotherapy
Study burden and risks
There is no garantuee that one will personally benefit from participation in
this study other than free study medication and regular check ups.
Possible burdens of the study may be: coming to the clinic 14-20 times, regular
measurement of pulse and bloodpressure. Furthermore, EKG's will be made en
there will be blood taken several times.
Raapopseweg 1
Arnhem 6824 DP
NL
Raapopseweg 1
Arnhem 6824 DP
NL
Listed location countries
Age
Inclusion criteria
See protocol for complete criteria (page34)
1. Out patients * 18 years of age, male or female.
2. Patients with a diagnosis of chronic heart failure (NYHA Class II * IV):
* LVEF * 35% at visit 1 (local measurement, within the past 6 months).
* Elevated BNP at visit 1: BNP * 150 pg/ml (according to local measurement).
OR BNP * 100 pg/ml (according to local measurement) and unplanned
hospitalization with HF within the last 12 months prior visit 1.
OR
Elevated NT-proBNP at visit 1: BNP * 600 pg/ml (according to local measurement).
OR NT-proBNP * 400 pg/ml (according to local measurement) and unplanned
hospitalization with HF within the last 12 months prior visit 1.;3. Patients must be treated with an ACE inhibitor at a stable dose (enalapril 10 mg
daily at least or any other ACE inhibitor based on equivalent doses described in
Table 4-1: Dose equivalence guidance table of ACEi's) for at least 4 weeks prior
to visit 1.
4. Patients must be treated with a beta blocker, unless contraindicated or not
tolerated, at a stable dose for at least 4 weeks prior to visit 1 (for patients not
on target dose, according to local guidelines, or in absence of that medication,
the reason should be documented).
Exclusion criteria
See protocol for complete criteria (page34-36)
2. Patients treated concomitantly with both ARB and aldosterone antagonist in
addition to study drug at visit 1.
4. Symptomatic hypotension and/or less than 95 mmHg SBP at Visit 1 and/ or less
than 90 mmHg SBP at Visits 4.
5. Acute coronary syndrome, stroke, transient ischemic attack, cardiac, carotid or
major vascular surgery, percutaneous coronary intervention (PCI) or carotid
angioplasty, within the past 3 months prior to visit 1.
6. Coronary or carotid artery disease likely to require surgical or percutaneous
intervention within the 6 months after visit 1.
18. Serum potassium * 5.0 mmol/L at Visit 1 or * 5.2 mmol/L at Visit 4.
29. Patients with diabetes mellitus
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| EudraCT | EUCTR2008-004104-31-NL |
| ClinicalTrials.gov | NCT00853658 |
| CCMO | NL26299.042.09 |