To demonstrate the efficacy of LCZ696 in patients with chronic heart failure with preserved ejection fraction (HF-PEF) by testing the hypothesis that the reduction in NT-proBNP from baseline to study end with LCZ696 is greater than that with…
ID
Source
Brief title
Condition
- Heart failures
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
To demonstrate the efficacy of LCZ696 in patients with chronic heart failure
with preserved ejection fraction (HF-PEF) by testing the hypothesis that the
reduction in NT-proBNP with LCZ696 is greater that that with valsartan after 12
weeks of treatment.
Secondary outcome
To evaluate LCZ696, compared to valsartan on the following parameters:
- BNP, MR-pro-ANP and cGMP
- echocardiographic parameters of diastolic function
- improvement in signs and symptoms of heart failure, changes in quality of
life assessments (assessed by total score and individual scores of the
sub-domains from the KCCQ) and changes in clinical composite score
- major adverse cardiovasular events
- renal function; eGFR, serum creatinine, proteinuria change
- vascular arterial stiffness, in a subset of patients
- changes in blood pressure
- safety and tolerability
Background summary
In this trial, we want to assess whether the efficacy, safety and tolerability
of LCZ696 as compared to valsartan warrants continuation into the next
development phase for HF-PEF (Heart Failure - Preserved Ejection Fraction).
Study objective
To demonstrate the efficacy of LCZ696 in patients with chronic heart failure
with preserved ejection fraction (HF-PEF) by testing the hypothesis that the
reduction in NT-proBNP from baseline to study end with LCZ696 is greater than
that with valsartan after 12 weeks of treatment.
Study design
At visit 1 (screening) patients with chronic heart failure (NYHA-Class II-IV)
who meet all in- and exclusion criteria will start in the placebo run in period
(1-2 weeks). The patients must discontinue their ACEinhibitors and ARBs 24
hours prior to visit 2.
The patients will be randomised at visit 2 (2 weeks after visit 1), if all in-
and exclusion criteria are met. There are 2 randomisations groups: one group of
patients will receive valsartan as treatment, the other group LCZ696. In 2-3
weeks time the doses will be titrated to the maximum dose of the particular
randomisation group. The total treatment period for a patient is 37-38weeks,
there will be 11 study visits performed.
Intervention
- LCZ696 therapy, starts with 50 mg bid at visit 2 (randomisation). Then
titration at visit 3 (after 1 week) to 100 mg bid. At visit 4 (after 2-3 weeks)
titration to 200 mg bid (maximum dose in this trial). This medication is
ongoing until visit 7 (12 weeks after randomisation).
- valsartan therapy, starts with 40 mg bid at visit 2 (randomisation). Then
titration at visit 3 (after 1 week) to 80 mg bid. At visit 4 *after 2-3 weeks)
titration to 160 mg bid (maximum dose in this trial). This medication is
ongoing until visit 7 (12 weeks after randomisation).
Study burden and risks
There is no garantee 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 11 times, regular
measurements of pulse and bloodpressure, echocardiography 3 times, ECGs made 3
times. There will be blood taken every visit and patient is asked to fill out
quality of life questionnaires 3 times.
Raapopseweg 1
6824 DP Arnhem
NL
Raapopseweg 1
6824 DP Arnhem
NL
Listed location countries
Age
Inclusion criteria
See protocol for complete criteria (page 21 -22)
2) Male or female outpatients, * 40 years of age
3) Patients with documented stable chronic heart failure (NYHA II - IV) and:
- LVEF * 45% (local measurement, within the past 6 months or after any event that would effect ejection fraction)
- Plasma NT-proBNP > 400 pg/ml at Visit 1
- Patients must be on diuretic therapy prior to Visit 1 (flexible dose permitted)
4) Patients with at least one of the following symptoms at visit 1:
- Dyspnea on exertion
- Orthopnea
- Paroxysmal nocturnal dyspnea
- Peripheral edema
Exclusion criteria
See protocol for complete criteria pages 22-24
1) Patients with a prior LVEF reading <45%, at any time
2) Patient who require treatment with both an ACE inhibitor and an ARB
3) Isolated right heart failure due to pulmonary disease
4) Dyspnea and/ore edema from non-cardiac causes, such as lung disease, anemia, or severe obesity
7) Presence of hypertrophic obstructive cardiomyopathy
8) Secondary forms of cardiomyopathy such as restrictive cardiomyopathy or infiltrative cardiomyopathy
12) History of MI, unstable angina, coronary bypass surgery or any PCI, stroke or TIA during the past 3 months prior to visit 1
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 | EUCTR2009-010208-27-NL |
| CCMO | NL27808.042.09 |