Phase 2
Completed N=123
Effects of Aliskiren, Ramipril, and the Combination on Levels of Angiotensin II in Patients With Decompensated Systolic Heart Failure
Source: ClinicalTrials.gov NCT00923156 ↗Enrolled (actual)
123
Serious AEs
9.8%
Results posted
Mar 2012
Primary outcomePrimary: Venous Angiotensin II Levels After 12 Weeks of Treatment — 0.91; 1.08; 0.66; 0.38 ratio
Summary
In addition to the blood pressure lowering effects of aliskiren, it may have beneficial effects on blocking the so called RAAS (renin-angiotensin-aldosterone system) at the tissue level. An increase of angiotensin II is associated with progression of heart failure. Although the use of ACE-inhibitors in heart failure shows clinical benefit, an increase in angiotensin II due to an angiotensin II "escape" phenomenon is not desirable. It is not yet known if a direct renin inhibitor can reduce or even prevent the angiotensin II escape phenomenon associated with the use of an ACE-inhibitor. Therefore the study tested the effects of ramipril, aliskiren and the combination of both on levels of angiotensin II in the blood in patients with systolic heart failure
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Venous Angiotensin II Levels After 12 Weeks of Treatment |
0.91; 1.08; 0.66; 0.38; 0.44; 0.38 | — |
| SECONDARY Biomarker Plasma Renin Concentration (PRC)After 12 Weeks of Treatment |
2.48; 0.96; 4.67 | — |
| SECONDARY Biomarker Trapping Plasma Renin Activity (tPRA) After 12 Weeks of Treatment |
0.14; 1.02; 0.25; 0.07; 1.50; 0.15 | — |
| SECONDARY Biomarker B-type Natriuretic Peptide (BNP) After 12 Weeks of Treatment |
0.96; 0.84; 0.78 | — |
| SECONDARY Biomarker Urinary Aldosterone After 12 Weeks of Treatment |
0.83; 0.96; 0.87 | — |
| SECONDARY Pharmacokinetic of Aliskiren: Time to Reach the Maximum Concentration (Tmax) After Drug Administration |
1.50 | — |
| SECONDARY Pharmacokinetic of Aliskiren: The Observed Maximum Plasma Concentration (Cmax) Following Drug Administration |
257.2 | — |
| SECONDARY Pharmacokinetic of Aliskiren: The Area Under the Plasma Concentration-time Curve From Time Zero to the End of the Dosing Interval Tau(AUCtau) |
1707 | — |
| SECONDARY Pharmacokinetic of Aliskiren: The Area Under the Plasma Concentration-time Curve From Time Zero to the Time of the Last Quantifiable Concentration (AUClast) |
3041 | — |
| SECONDARY Pharmacokinetic of Aliskiren: The Area Under the Plasma Concentration-time Curve From Time Zero to Infinity (AUCinf) |
3502 | — |
| SECONDARY Pharmacokinetic of Aliskiren: The Terminal Elimination Half-life (T½) |
31.02 | — |
Eligibility Criteria
Inclusion Criteria
- Decompensated systolic heart failure, left ventricular ejection fraction ≤40%
- Brain natriuretic peptide (BNP) level ≥ 100 pg/mL
Exclusion criteria
- Use of Angiotensin Converting Enzyme(ACE) or Angiotensin Receptor Blocker (ARB) inhibitor treatment following the run-in period or requirement of both treatments
- Acute heart failure secondary to acute myocardial infarction, acute coronary syndrome or new tachyarrhythmia
- Occurrence of unstable angina or myocardial infarction within 12 weeks prior to screening
- History of cardiomyopathy such as postpartum, restrictive, infective, hypertrophic obstructive
- History of right heart failure due to pulmonary disease
- History of untreated second or third degree atrioventricular heart block
Other protocol-defined inclusion/exclusion criteria applied
Data sourced from ClinicalTrials.gov (NCT00923156). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication. Informational only — not medical advice.