Clinical trial NCT00923156: Effects of Aliskiren, Ramipril, and the Combination on Levels of Angiotensin II in Patients With Decompensated Systolic Heart Failure
Official title: ESCAPE-SHF: A Double-blind, Double-dummy, Randomized, Multicenter, Parallel Group Study to Evaluate the Effects of Aliskiren, Ramipril and Combination Treatment on Plasma Concentration of Angiotensin II in Patients With Decompensated Systolic Heart Failure
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Heart Failure
Keywords: Heart failure
Systolic
Aliskiren
Ramipril
Angiotensin II
Ang II
Plasma Renin Activity
PRA
Plasma Renin Concentration
PR,
brain natriuretic peptide
BNP
urinary aldosterone
Escape
Pharmacokinetic
PK
Lead sponsor: Novartis
Sponsor class: INDUSTRY
First posted: 2009-06-18
Enrollment: 123
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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


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

Primary outcomes:
measure: Venous Angiotensin II Levels After 12 Weeks of Treatment
timeFrame: Baseline. 12 Weeks (Day 84, period 2)
Secondary outcomes:
measure: Biomarker Plasma Renin Concentration (PRC)After 12 Weeks of Treatment
timeFrame: Baseline, 12 weeks (84 days, period 2)
measure: Biomarker Trapping Plasma Renin Activity (tPRA) After 12 Weeks of Treatment
timeFrame: Baseline,12 weeks (84 days, Period 2)
measure: Biomarker B-type Natriuretic Peptide (BNP) After 12 Weeks of Treatment
timeFrame: Baseline, 12 weeks (Day 84 period 2)
measure: Biomarker Urinary Aldosterone After 12 Weeks of Treatment
timeFrame: Baseline,12 weeks (Day 84 period 2)
measure: Pharmacokinetic of Aliskiren: Time to Reach the Maximum Concentration (Tmax) After Drug Administration
timeFrame: 12 weeks
measure: Pharmacokinetic of Aliskiren: The Observed Maximum Plasma Concentration (Cmax) Following Drug Administration
timeFrame: 12 weeks
measure: Pharmacokinetic of Aliskiren: The Area Under the Plasma Concentration-time Curve From Time Zero to the End of the Dosing Interval Tau(AUCtau)
timeFrame: 12 weeks
measure: Pharmacokinetic of Aliskiren: The Area Under the Plasma Concentration-time Curve From Time Zero to the Time of the Last Quantifiable Concentration (AUClast)
timeFrame: 12 weeks
measure: Pharmacokinetic of Aliskiren: The Area Under the Plasma Concentration-time Curve From Time Zero to Infinity (AUCinf)
timeFrame: 12 weeks
measure: Pharmacokinetic of Aliskiren: The Terminal Elimination Half-life (T½)
timeFrame: 12 weeks
Other outcomes:
Locations:
city: Bad Krozingen
country: Germany
facility: Novartis Investigator Site
city: Berlin
country: Germany
facility: Novartis Investigator Site
city: Berlin
country: Germany
facility: Novartis Investigator Site
city: Göttingen
country: Germany
facility: Novartis Investigator Site
city: Jena
country: Germany
facility: Novartis Investigator Site
city: München
country: Germany
facility: Novartis Investigator Site
city: Krakow
country: Poland
facility: Novartis Investigator Site
city: Lublin
country: Poland
facility: Novartis Investigator Site
city: Poznan
country: Poland
facility: Novartis Investigator Site
city: Warszawa
country: Poland
facility: Novartis Investigator Site
city: Wroclaw
country: Poland
facility: Novartis Investigator Site
city: Moscow
country: Russian Federation
facility: Novartis Investigator Site
city: Moscow
country: Russian Federation
facility: Novartis Investigator Site
city: Moscow
country: Russian Federation
facility: Novartis Investigator Site
city: Moscow
country: Russian Federation
facility: Novartis Investigator Site
city: Moscow
country: Russian Federation
facility: Novartis Investigative Site
Study officials:
affiliation: Novartis Pharmaceuticals
name: Novartis Pharmaceuticals
role: STUDY_DIRECTOR
References:
citation: Wang GM, Li LJ, Tang WL, Wright JM. Renin inhibitors versus angiotensin converting enzyme (ACE) inhibitors for primary hypertension. Cochrane Database Syst Rev. 2020 Oct 22;10(10):CD012569. doi: 10.1002/14651858.CD012569.pub2.