The primary objective of the study is to evaluate the efficacy of aliskiren, valsartan and a combination of both drugs versus placebo in lowering levels of NT-proBNP in stabilized patients post ACS
ID
Source
Brief title
Condition
- Vascular haemorrhagic disorders
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Relative reduction to baseline in NT-proBNP at week 8
Secondary outcome
Relative reduction to baseline in NT-proBNP at week 4
Cardiac events
Safety (AEs, safety laboratory)
Biomarkers (a.m. high sensitivity C-reactive protein; plasma renin activity;
aldosterone; refer to protocol, page 59, Biomarkers, for complete list)
Background summary
The renin-angiotensin-aldosterone system (RAAS) is one of the central hormonal
axes that modulates cardiac function, vascular hemodymamics and renal function.
Inhibition of the RAAS has been shown to be of great clinical significance in
the treatment of congestive heart failure and left ventricular dysfunction.
Valsartan and aliskiren inhibit the RAAS. Valsartan is a registered drug and
belongs to the class of the angiotensin receptor blockers (ARBs). Aliskiren is
new drug, a renin antagonist. Aliskiren blocks the RAAS at the rate limiting
step, the cleavage of angiotensinogen by renin, and thereby prevents the
production of angiotensin 1.
(NT-pro)BNP is released from the ventricular myocardium in response to
increased wall stress and its concentration is often elevated in patients
following acute coronary syndromes (ACS). Elevated (NT-pro)BNP has been shown
to be associated with increased risk of heart failure or death. Decreasing the
(NT-pro)BNP concentration could lower this risk.
Inhibition of the RAAS could - by improving ventricular hemodymics - result in
a decrease in the (NT-pro)BNP concentration, and a decreased risk for heart
failure and death.
This phase II study invesitigates the effect of valsartan, aliskiren, a
combination of both drugs or placebo on NT-proBNP levels in stabilized patients
post ACS.
Study objective
The primary objective of the study is to evaluate the efficacy of aliskiren,
valsartan and a combination of both drugs versus placebo in lowering levels of
NT-proBNP in stabilized patients post ACS
Study design
This is a randomized, multinational, double-blind, placebo-controlled,
parallel-group, phase II study. For every patient the study starts with a
screening visit (visit 1, occurs during index hospitalization), 7 study visits
(visit 2 - 8) and a final telephone interview (visit 9). At visit 2, the
patient will be randomized and will subsequently be treated with valsartan,
aliskiren, valsartan + aliskiren or placebo during 8 weeks. During the
treatment period the patient comes to the clinic on a weekly basis for physical
exams, general health and AE assessments.
Intervention
Patients are treated in 4 treatment groups, during 8 weeks:
Valsartan: week 1, 80 mg; week 2, 160 mg; week 3-8, 320 mg
Aliskiren: week 1, 75 mg; week 2, 150 mg; week 3-8, 300 mg
Valsartan + aliskiren: week 1, 80 mg valsartan; week 2, 160 mg valsartan; week
3 +4, 320 mg valsartan; week 5, valsartan/aliskiren 320/75mg; week 6,
valsartan/aliskiren 320/150 mg; week 7 + 8, valsartan/aliskiren 320/300 mg
Placebo: week 1-8, placebo
Study burden and risks
Burden: 8 visits of about an hour during 8 weeks and a telephone interview at
the end of the study; 8x blood collection
Risks: in general, aliskiren and valsartan are well tolerated. The most common
side effects reported in research studies with aliskiren are headache,
dizziness, fatigue, abdominal pain, nausea and diarrhea.
The most common side effected reported for valsartan are headache, dizziness,
diarrhea, fatigue or back pain. Low blood pressure, kidney problems, kidney
failure or increased levels of blood potassium were rarely reported.
The combination of aliskiren and valsartan has been investigated in one
clinical trial, and side effects reported were headache, dizziness, fatigue and
abdominal pain.
Raapopseweg 1
6824 DP
Nederland
Raapopseweg 1
6824 DP
Nederland
Listed location countries
Age
Inclusion criteria
For complete list, please refer to the protocol;- Stable subjects who are hospitalized for ischemic chest discomfort at rest lasting at least 10 minutes and consistent with cardiac ischemia
- Final diagnosis of acute coronary syndrome, that includes either 1) unstable angina defined as chest discomfort or 2) acute myocardial infarction
- Elevated concentrations of natriuretic peptide 3-10 days after admission for their qualifying ACS event
Exclusion criteria
- Known or suspected contraindications, including history of allergy or hypersensitivity to ARBs, renin antagonists, or to drugs with similar chemical structures
- Presence of clinically overt heart failure
- Known evidence of left ventricular systolic dysfunction
- CABG less than 3 months ago
- PCI less than 24 hours before randomization
- Planned revascularisation within 2 months after randomization
- New ACEI, ARBs, or aldosterone inhibitor treatment given for more than 24 hours as part of the index hospitalization
- An increase in a chronic dose of ACEI, ARBs, or aldosterone inhibitor treatment given for more than 24 hours as part of the index hospitalization
- Patients on chronic ACEI or ARB therapy for whom therapy with an ACEI or ARB is clinically required with no reasonable alternative therapy
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 | EUCTR2006-001763-36-NL |
| CCMO | NL14879.003.06 |