Heart FailurePhase 2ESCAPE-SHFNCT00923156
Effects of Aliskiren, Ramipril, and the Combination on Levels of Angiotensin II in Patients With Decompensated Systolic Heart Failure
A Phase 2 study testing aliskiren and ramipril in people with Heart Failure, run by Novartis Pharmaceuticals at 16 sites in 3 countries.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Heart Failure
- What is being tested?
- aliskiren and ramipril
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 123 participants
- Where
- 16 sitesin 3 countries
- Study dates
- May 2009to Feb 2011
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Decompensated systolic heart failure, left ventricular ejection fraction ≤40%
- Brain natriuretic peptide (BNP) level ≥ 100 pg/mL
Who cannot join
- 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
Trial locations and contacts
16 sites in 3 countries.
16 sites in 3 countries
Germany6 sites
Novartis Investigator Site
Bad Krozingen, 79189
Novartis Investigator Site
Berlin, 12207
Novartis Investigator Site
Berlin, 13353
Novartis Investigator Site
Göttingen, 37057
Novartis Investigator Site
Jena, 07747
Novartis Investigator Site
München, 80336
Poland5 sites
Novartis Investigator Site
Krakow, 31-501
Novartis Investigator Site
Lublin, 20-090
Novartis Investigator Site
Poznan, 61-848
Novartis Investigator Site
Warsaw, 02-507
Novartis Investigator Site
Wroclaw, 50-981
Russia5 sites
Novartis Investigator Site
Moscow, 117292
Novartis Investigator Site
Moscow, 119620
Novartis Investigator Site
Moscow, 121309
Novartis Investigator Site
Moscow, 121552
Novartis Investigative Site
Moscow
About this study
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
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
- Conditions
- Heart Failure
- Being tested
- aliskiren, ramipril, Placebo to aliskiren, Placebo to ramipril
- 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
- Medical subject headings
- Heart Failure, Systolic Murmurs
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
aliskirenDrug
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
ramiprilDrug
2.5 mg , 5.0 mg or 10 mg once daily
Placebo to aliskirenDrug
matching placebo to aliskiren in double blind phase
Placebo to ramiprilDrug
Matching placebo to ramipril capsule in double blind phase
| Study group | Role | What they receive |
|---|---|---|
| Aliskiren | Experimental | In open label run-in phase (period 1), patients started with ramipril 2.5 mg or 5.0 mg capsule once daily (o.d) depending on previous treatment with RAAS blockers and up-titrated to ramipril 10 mg capsule o.d by end of period 1. In double blind phase (Period 2), patients received 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 and matching placebo of ramipril capsules. Receives: Drug: aliskiren; Drug: ramipril; Drug: Placebo to ramipril |
| Ramipril | Experimental | In open label run-in phase (period 1), patients started with ramipril 2.5 mg or 5.0 mg capsule once daily (o.d) depending on previous treatment with RAAS blockers and up-titrated to ramipril 10 mg capsule o.d by end of period 1.
In double blind phase (Period 2), patients received ramipril 10 mg capsule o.d and matching placebo of aliskiren tablet. Receives: Drug: ramipril; Drug: Placebo to aliskiren |
| Aliskiren plus Ramipril | Experimental | In open label run-in phase (period 1), patients started with ramipril 2.5 mg or 5.0 mg capsule once daily (o.d) depending on previous treatment with RAAS blockers and up-titrated to ramipril 10 mg capsule o.d by end of period 1.
In double blind phase (period 2), patients received ramipril (10 mg once daily capsule) and aliskiren (150 mg once daily tablet) up titrated to 300 mg once daily after 1 week of treatment following a clinical safety patient assessment at the study site Receives: Drug: aliskiren; Drug: ramipril |
What is being measured
The primary outcome is the main question the study is designed to answer.
Venous Angiotensin II Levels After 12 Weeks of Treatment
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.
Measured: Baseline. 12 Weeks (Day 84, period 2)
Secondary outcomes (10)
Biomarker Plasma Renin Concentration (PRC)After 12 Weeks of Treatment
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.
Measured: Baseline, 12 weeks (84 days, period 2)
Biomarker Trapping Plasma Renin Activity (tPRA) After 12 Weeks of Treatment
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.
Measured: Baseline,12 weeks (84 days, Period 2)
Biomarker B-type Natriuretic Peptide (BNP) After 12 Weeks of Treatment
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.
Measured: Baseline, 12 weeks (Day 84 period 2)
Biomarker Urinary Aldosterone After 12 Weeks of Treatment
24 hour urine collections were performed. Geometric Mean Ratio to baseline at Week 12 for Urinary aldosterone was calculated 24 hours post-dose.
Measured: Baseline,12 weeks (Day 84 period 2)
Pharmacokinetic of Aliskiren: Time to Reach the Maximum Concentration (Tmax) After Drug Administration
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.
Measured: 12 weeks
Pharmacokinetic of Aliskiren: The Observed Maximum Plasma Concentration (Cmax) Following Drug Administration
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.
Measured: 12 weeks
Pharmacokinetic of Aliskiren: The Area Under the Plasma Concentration-time Curve From Time Zero to the End of the Dosing Interval Tau(AUCtau)
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.
Measured: 12 weeks
Pharmacokinetic of Aliskiren: The Area Under the Plasma Concentration-time Curve From Time Zero to the Time of the Last Quantifiable Concentration (AUClast)
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.
Measured: 12 weeks
Pharmacokinetic of Aliskiren: The Area Under the Plasma Concentration-time Curve From Time Zero to Infinity (AUCinf)
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.
Measured: 12 weeks
Pharmacokinetic of Aliskiren: The Terminal Elimination Half-life (T½)
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.
Measured: 12 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 Jun 2009 (estimated)
- Study startMay 2009
- Primary completionFeb 2011
- Study completionFeb 2011
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Heart FailureStudies of the same condition, open and under way.
- More trials run by Novartis PharmaceuticalsThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 123 participants (actual)
Sponsor and investigators
- Lead sponsor
- Novartis Pharmaceuticals
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Novartis Pharmaceuticals, Study director, Novartis Pharmaceuticals
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00923156
- Sponsor's protocol ID
- CSPP100A2252
- Other IDs
- EudraCT 2008-001035-35
- Acronym
- ESCAPE-SHF
- Status last verified
- Jul 2012
- First submitted
- 17 Jun 2009
- Last updated
- 26 Jul 2012
- Results posted
- Yes, on ClinicalTrials.gov
Publications
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.
PubMed 33089502
Study at a glance
From the registry record, last updated by the sponsor on 26 Jul 2012. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT00923156
- Acronym / sponsor ID
- ESCAPE-SHF / CSPP100A2252
- Conditions
- Heart Failure
- Keywords
- Heart failure, Systolic, Aliskiren, Ramipril, Angiotensin II, Ang II, Plasma Renin Activity, PRA
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 123 participants (actual)
- Lead sponsor
- Novartis PharmaceuticalsIndustry (pharma, biotech, devices)
- Study start
- May 2009
- Primary completion
- Feb 2011 (actual)
- Study completion
- Feb 2011 (actual)
- First posted
- 18 Jun 2009 (estimated)
- Results
- Posted 5 Mar 2012
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Aliskiren | Experimental | Drug: aliskiren, Drug: ramipril, Drug: Placebo to ramiprilIn open label run-in phase (period 1), patients started with ramipril 2.5 mg or 5.0 mg capsule once daily (o.d) depending on previous treatment with RAAS blockers and up-titrated to ramipril 10 mg capsule o.d by end of period 1. In double blind phase (Period 2), patients received 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 and matching placebo of ramipril capsules. |
| Ramipril | Experimental | Drug: ramipril, Drug: Placebo to aliskirenIn open label run-in phase (period 1), patients started with ramipril 2.5 mg or 5.0 mg capsule once daily (o.d) depending on previous treatment with RAAS blockers and up-titrated to ramipril 10 mg capsule o.d by end of period 1. In double blind phase (Period 2), patients received ramipril 10 mg capsule o.d and matching placebo of aliskiren tablet. |
| Aliskiren plus Ramipril | Experimental | Drug: aliskiren, Drug: ramiprilIn open label run-in phase (period 1), patients started with ramipril 2.5 mg or 5.0 mg capsule once daily (o.d) depending on previous treatment with RAAS blockers and up-titrated to ramipril 10 mg capsule o.d by end of period 1. In double blind phase (period 2), patients received ramipril (10 mg once daily capsule) and aliskiren (150 mg once daily tablet) up titrated to 300 mg once daily after 1 week of treatment following a clinical safety patient assessment at the study site |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (2 listed)
- Decompensated systolic heart failure, left ventricular ejection fraction ≤40%
- Brain natriuretic peptide (BNP) level ≥ 100 pg/mL
Key exclusion criteria (7 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| aliskirenAliskiren 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 | Drug | Aliskiren, Aliskiren plus Ramipril |
| ramipril2.5 mg , 5.0 mg or 10 mg once daily | Drug | Aliskiren, Aliskiren plus Ramipril, Ramipril |
| Placebo to aliskirenmatching placebo to aliskiren in double blind phase | Drug | Ramipril |
| Placebo to ramiprilMatching placebo to ramipril capsule in double blind phase | Drug | Aliskiren |
Primary outcome
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.
10 secondary outcomes
Biomarker Plasma Renin Concentration (PRC)After 12 Weeks of Treatment
Time frame: Baseline, 12 weeks (84 days, period 2)
Biomarker Trapping Plasma Renin Activity (tPRA) After 12 Weeks of Treatment
Time frame: Baseline,12 weeks (84 days, Period 2)
Biomarker B-type Natriuretic Peptide (BNP) After 12 Weeks of Treatment
Time frame: Baseline, 12 weeks (Day 84 period 2)
Biomarker Urinary Aldosterone After 12 Weeks of Treatment
Time frame: Baseline,12 weeks (Day 84 period 2)
Pharmacokinetic of Aliskiren: Time to Reach the Maximum Concentration (Tmax) After Drug Administration
Time frame: 12 weeks
Pharmacokinetic of Aliskiren: The Observed Maximum Plasma Concentration (Cmax) Following Drug Administration
Time frame: 12 weeks
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
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
Pharmacokinetic of Aliskiren: The Area Under the Plasma Concentration-time Curve From Time Zero to Infinity (AUCinf)
Time frame: 12 weeks
Pharmacokinetic of Aliskiren: The Terminal Elimination Half-life (T½)
Time frame: 12 weeks
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 26 Jul 2012.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 33089502Wang 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Novartis Pharmaceuticals study director
Novartis Pharmaceuticals
16 sites in 3 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing aliskiren and ramipril in people with Heart Failure, run by Novartis Pharmaceuticals at 16 sites in 3 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 2 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 26 Jul 2012. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 16 sites in Germany, Poland, Russia. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 5 Mar 2012). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Venous Angiotensin II Levels After 12 Weeks of Treatment (time frame: Baseline. 12 Weeks (Day 84, period 2)). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00923156, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 26 Jul 2012.