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NCT Number: NCT00923156

Effects of Aliskiren, Ramipril, and the Combination on Levels of Angiotensin II in Patients With Decompensated Systolic Heart Failure

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

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Key information

Conditions

Heart Failure Cardiovascular Diseases Heart Diseases Heart Murmurs Pathological Conditions, Signs and Symptoms Signs and Symptoms Systolic Murmurs

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 2

Primary location

Novartis Investigator Site, Bad Krozingen, Germany

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Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

Aliskiren

Drug

Aliskiren 150 mg once daily up titrated to 300 mg once daily after 1 week of treatment following a clinical safety patient assessment at the study site

Ramipril

Drug

2.5 mg , 5.0 mg or 10 mg once daily

Placebo to Aliskiren

Drug

matching placebo to aliskiren in double blind phase

Placebo to ramipril

Drug

Matching placebo to ramipril capsule in double blind phase

Primary outcomes

  1. Venous Angiotensin II Levels After 12 Weeks of Treatment

    Time frame: Baseline. 12 Weeks (Day 84, period 2)

    Peripheral venous blood was collected after 30 minutes of rest in the sitting position for analysis of biomarkers. Geometric mean ratio to baseline at Week 12 for Venous angiotensin II levels was calculated in patients with decompensated systolic heart failure (SHF) and left ventricular ejection fraction ≤40% at 0 hour pre-dose, 3 hours and 24 hours post-dose.

Secondary outcomes

  1. Biomarker Plasma Renin Concentration (PRC)After 12 Weeks of Treatment

    Time frame: Baseline, 12 weeks (84 days, period 2)

    Peripheral venous blood was collected after 30 minutes of rest in the sitting position for analysis of biomarkers. Geometric Mean Ratio to baseline at 12 weeks for PRC was calculated at 0 hour pre-dose.

  2. Biomarker Trapping Plasma Renin Activity (tPRA) After 12 Weeks of Treatment

    Time frame: Baseline,12 weeks (84 days, Period 2)

    Peripheral venous blood was collected after 30 minutes of rest in the sitting position for analysis of biomarkers. Geometric Mean Ratio to baseline at Week 12 for tPRA was calculated at 0 hour pre-dose, 3 hour and 24 hour post-dose.

  3. Biomarker B-type Natriuretic Peptide (BNP) After 12 Weeks of Treatment

    Time frame: Baseline, 12 weeks (Day 84 period 2)

    Peripheral venous blood was collected after 30 minutes of rest in the sitting position for analysis of biomarkers. Geometric Mean Ratio to baseline at Week 12 for BNP was calculated at 0 hours pre-dose.

  4. Biomarker Urinary Aldosterone After 12 Weeks of Treatment

    Time frame: Baseline,12 weeks (Day 84 period 2)

    24 hour urine collections were performed. Geometric Mean Ratio to baseline at Week 12 for Urinary aldosterone was calculated 24 hours post-dose.

  5. Pharmacokinetic of Aliskiren: Time to Reach the Maximum Concentration (Tmax) After Drug Administration

    Time frame: 12 weeks

    Blood samples (2 mL) for the determination of aliskiren concentration in plasma were collected using an indwelling cannula inserted in a forearm vein. Samples were collected at week 12 (day 84): pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10 and 24 hours post-dose.

  6. Pharmacokinetic of Aliskiren: The Observed Maximum Plasma Concentration (Cmax) Following Drug Administration

    Time frame: 12 weeks

    Blood samples (2 mL) for the determination of aliskiren concentration in plasma were collected using an indwelling cannula inserted in a forearm vein. Samples were collected at week 12 (day 84): pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10 and 24 hours post-dose.

  7. Pharmacokinetic of Aliskiren: The Area Under the Plasma Concentration-time Curve From Time Zero to the End of the Dosing Interval Tau(AUCtau)

    Time frame: 12 weeks

    Blood samples (2 mL) for the determination of aliskiren concentration in plasma were collected using an indwelling cannula inserted in a forearm vein. Samples were collected at week 12 (day 84): pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10 and 24 hours post-dose.

  8. Pharmacokinetic of Aliskiren: The Area Under the Plasma Concentration-time Curve From Time Zero to the Time of the Last Quantifiable Concentration (AUClast)

    Time frame: 12 weeks

    Blood samples (2 mL) for the determination of aliskiren concentration in plasma were collected using an indwelling cannula inserted in a forearm vein. Samples were collected at week 12 (day 84): pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10 and 24 hours post-dose.

  9. Pharmacokinetic of Aliskiren: The Area Under the Plasma Concentration-time Curve From Time Zero to Infinity (AUCinf)

    Time frame: 12 weeks

    Blood samples (2 mL) for the determination of aliskiren concentration in plasma were collected using an indwelling cannula inserted in a forearm vein. Samples were collected at week 12 (day 84): pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10 and 24 hours post-dose.

  10. Pharmacokinetic of Aliskiren: The Terminal Elimination Half-life (T½)

    Time frame: 12 weeks

    Blood samples (2 mL) for the determination of aliskiren concentration in plasma were collected using an indwelling cannula inserted in a forearm vein. Samples were collected at week 12 (day 84): pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10 and 24 hours post-dose.

Sponsors and collaborators

Lead sponsor

Novartis Pharmaceuticals

Industry

Registry information

Official study 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

Acronym: ESCAPE-SHF

Important dates

Study start
2009
Primary completion
2011
Study completion
2011
First posted
Jun 18, 2009
Registry last updated
Jul 26, 2012

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

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This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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