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Safety and Efficacy of Aliskiren in Post Myocardial Infarction Patients (ASPIRE)

Sponsor
Novartis (Industry)
Overall Status
Completed
CT.gov ID
NCT00414609
Collaborator
(none)
820
Enrollment
23
Locations
2
Arms
55
Duration (Months)
35.7
Patients Per Site
0.6
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The core and extension studies assessed the safety and efficacy of aliskiren when added to optimized standard therapy in patients that have had a high risk acute myocardial infarction (heart attack).

Condition or Disease Intervention/Treatment Phase
Phase 3

Study Design

Study Type:
Interventional
Actual Enrollment :
820 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Double (Participant, Investigator)
Primary Purpose:
Treatment
Official Title:
A 36-week, Multicenter, Randomized, Double-blind, Placebo-controlled, Parallel-group Study Including a 2 Year Extension Study to Evaluate Efficacy and Safety of Aliskiren on the Prevention of Left Ventricular Remodeling in High Risk Post-acute Myocardial Infarction Patients When Added to Optimized Standard Therapy
Study Start Date :
Dec 1, 2006
Actual Primary Completion Date :
Sep 1, 2009
Actual Study Completion Date :
Jul 1, 2011

Arms and Interventions

Arm Intervention/Treatment
Experimental: Aliskiren

Core Study: Aliskiren ascending doses: 75 mg tablet for 1st week, 150 mg for 2nd week, 300 mg for next 34 weeks orally once daily in the morning. Extension Study: Patients from both the core arms who completed core study and signed informed consent form were included in this arm of extension study. Patients received 150 mg aliskiren tablet orally once a day for two weeks. Patients were then up-titrated to 300 mg aliskiren orally once a day at the discretion of the principal investigator based on their clinical condition for the duration of the study.

Drug: Aliskiren
Aliskiren was available in 75 mg tablet, 150 mg tablet
Other Names:
  • Tekturna®

    		•
    Placebo Comparator: placebo

    Core study: placebo for 36 weeks once daily in the morning

    Drug: placebo
    Placebo tablets matching aliskiren for 36 weeks once daily in the morning for core period only.

    Outcome Measures

    Primary Outcome Measures

    1. Core Study: Change From Baseline in Left Ventricular End Systolic Volume (LVESV) as Measured by Echocardiography at End of Study. [Baseline and final visit (after 26 to 36 weeks of treatment)]

      Change from baseline to end of study in left ventricular end systolic volume (LVESV) as measured by echocardiography. LVESV is a measurement of the volume of blood in the heart's left ventricular chamber at the end of the heart's contraction. This measurement was made by the echocardiography lab. LVESV values between 22 to 58 mL for men and 19-49 mL for women are considered normal. Baseline LVESV was a covariate.

    2. Extension Study: Percentage of Participants With Deaths, Serious Adverse Events (SAEs), Discontinuation for Adverse Events (AEs) and Discontinuations for Abnormal Lab Values [Extension study (24 weeks)]

      AEs are defined as any unfavorable and unintended diagnosis, symptom, sign (including an abnormal laboratory finding), syndrome or disease which either occurs during study, having been absent at baseline, or, if present at baseline, appears to worsen. Serious adverse events are any untoward medical occurrences that result in death, are life threatening, require (or prolong) hospitalization, cause persistent or significant disability/incapacity, result in congenital anomalies or birth defects, or are other conditions which in judgment of investigators represent significant hazards.

    Secondary Outcome Measures

    1. Core Study: Time to First Occurrence for the Composite Endpoints of Echocardiogram and Adjudicated Outcomes [LVEF was measured at baseline and at final visit (after 26 to 36 weeks of treatment). Other endpoint components were assessed from randomization until the end of the study (week 36).]

      Composite outcome 1 included: Cardiovascular (CV) Death, hospitalization for heart failure (HF), or absolute reduction in Left Ventricular Ejection Fraction (LVEF) greater than 6%. Composite outcome 2 included: CV Death, hospitalization for HF, recurrent Myocardial Infarction, Stroke, or Resuscitated Sudden Death. LVEF was measured at baseline and final visit. All other events were adjudicated by a blinded external committee. Each composite endpoint analysis was based on (a) the percent of patients with that endpoint and (b) days in study to 1st event (or last exposure if no event occurred).

    2. Core Study: Change From Baseline in Left Ventricular End Diastolic Volume (LVEDV) [Baseline and final visit (after 26 to 36 weeks of treatment)]

      Change from baseline to end of study in left ventricular end diastolic volume (LVEDV) as measured by echocardiography. (LVEDV) is a measurement of the volume of blood in the heart's left ventricular chamber at the beginning of the chamber's filling with blood. This measurement was made by the echocardiography lab. LVEDV values between 67 to 155 mL for men and 56 to 104 mL for women are considered normal. Baseline LVEDV was a covariate.

    3. Core Study: Change From Baseline in Left Ventricular Ejection Fraction (LVEF) [Baseline and final visit (after 26 to 36 weeks of treatment )]

      Change from baseline to end of study in left ventricular ejection fraction (LVEF) (%) as measured by echocardiography. LVEF is the fraction of blood (in percent) pumped out of the heart's left ventricular chamber with each heart beat, and is a measure of cardiac output for the heart. This measurement was made by the echocardiography lab. Ejection fraction percentages > 55% are considered normal. Baseline LVEF was a covariate.

    4. Core Study: Change From Baseline to End of Study in Infarction Segment Length (ISL) as Measured by Echocardiography [Baseline and final visit (after 26 to 36 weeks of treatment)]

      Change from baseline to end of study in infarction segment length (ISL) (%) as measured by echocardiography. This is the length of the myocardial infarction segment as a percentage of the total cavity perimeter length as calculated by the echocardiography lab. Baseline ISL was a covariate.

    5. Core Study: Change From Baseline to End of Study in Wall Motion Score (WMS) as Measured by Echocardiography [Baseline and final visit (after 26 to 36 weeks of treatment)]

      Change from baseline to end of study in Wall Motion Score (WMS) as measured by echocardiography. WMS was obtained by examining multiple segments of the left ventricle and assigning each segment a score based on myocardial thickening: 1 for normal, 2 for hypokinetic; 3 for akinetic; and 4 for dyskinetic. The WMS was obtained as the average score for the segments visualized and was calculated by the echocardiography lab. Possible values range from 1 to 5. Higher scores are considered worse. Baseline WMS was a covariate.

    6. Extension Study: Change From Baseline in Left Ventricular End Systolic Volume (LVESV) at Month 12 [Baseline(extension study), Month 12 (extension study)]

      Change from baseline to Month 12 in left ventricular end systolic volume (LVESV) as measured by echocardiography. LVESV is a measurement of the volume of blood in the heart's left ventricular chamber at the end of the heart's contraction. This measurement was made by the echocardiography lab. LVESV values between 22 to 58 mL for men and 19-49 mL for women are considered normal.

    7. Extension Study: Change From Baseline in Left Ventricular End Diastolic Volume (LVEDV) at Month 12 [Baseline (extension study), Month 12 (extension study)]

      Change from baseline to Month 12 in left ventricular end diastolic volume (LVEDV) as measured by echocardiography. LVEDV is a measurement of the volume of blood in the heart's left ventricular chamber at the beginning of the chamber's filling with blood. This measurement was made by the echocardiography lab. LVEDV values between 67 to 155 mL for men and 56 to 104 mL for women are considered normal.

    8. Extension Study: Change From Baseline in Left Ventricular Ejection Fraction (LVEF) at Month 12 [Baseline(extension study), Month 12 (extension study)]

      Change from baseline to Month 12 in left ventricular ejection fraction (LVEF) (%) as measured by echocardiography. LVEF is the fraction of blood (in percent) pumped out of the heart's left ventricular chamber with each heart beat, and is a measure of cardiac output for the heart. This measurement was made by the echocardiography lab. Ejection fraction percentages > 55% are considered normal.

    9. Extension Study: Percentage of Participants With Orthostatic Blood Pressure Change [Baseline (Day 0 Extension study), Week 2, Months 1, 3, 6, 9,16, 20, 24]

      Orthostatic blood pressure change is defined as a decrease of at least 20 mmHg in systolic blood pressure or a decrease of at least 10 mmHg in diastolic blood pressure when a patient moves from a sitting position to a standing position. A patient could show orthostatic blood pressure change at more than one visit. End of study is Month 24 or early discontinuation.

    10. Extension Study: Percentage of Participants With Specified Criteria in Selected Labs by Laboratory Parameter [24 Months]

      Fasting blood samples were collected throughout the study and were analyzed at a central laboratory. Percentage of participants with the following clinically significant laboratory values are reported: Potassium <3.5 mmol/L; Low value (Normal reference range: 3.5- 5.3) Potassium >5.5 mmol/L and Potassium >6.0 mmol/L; High values (Normal reference range: 3.5-5.3) Creatinine >176.8 μmol/L; High value (Normal reference range= Male: 62- 106 and Female 44- 80) Blood Urea Nitrogen (BUN) >14.28; High value (Normal reference range: 2.1- 8.9)

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    Core Study Inclusion Criteria:

    • Male or female patients 18 years and older.

    • Patients within 7-42 days of an acute myocardial infarction associated with left ventricular systolic dysfunction.

    • Documented left ventricular systolic dysfunction associated with the qualifying acute myocardial.

    • Patients must be on stable doses of the following concomitant medications for at least 2 weeks prior to Visit 1 unless contraindicated due to intolerance:

    • A Beta-blocker

    • An Anti-platelet agent

    • A Statin

    • An evidence-based dose of an Angiotensin Converting Enzyme Inhibitor (ACEI) or Angiotensin Receptor Blocker (ARB) but not both.

    • Qualifying Echocardiogram at Visit 1:

    Core Study Exclusion Criteria:

    • Patients requiring both Angiotensin Converting Enzyme Inhibitor (ACEI) and Angiotensin Receptor Blocker (ARB) combination therapy at V1 or any time during the study.

    • Severe refractory hypertension defined as mean sitting systolic blood pressure (MSSBP) ≥ 180 mmHg and/or mean sitting diastolic blood pressure (MSDBP) ≥ 110 mmHg) at Visit

    • Cardiogenic shock or systolic BP < 100 mmHg or diastolic < 60 mmHg within the 24 hours prior to Visits 1 or 2

    • Estimated Glomerular Filtration Rate (eGFR) < 30 ml/min/1.73m2 using the MDRD formula at Visit 1.

    • Stroke or transient ischemic event (TIA) within 6 months of Study Visit 1

    Extension Study Inclusion Criteria:

    • Male or female patients who completed the core study through Visit 10 while on double-blind study drug

    • Patients who were able to participate in the study, and who consented to do so after the purpose and nature of the study had been clearly explained to them (written informed consent)

    Extension Study Exclusion Criteria:

    • New York Heart Association (NYHA) class IV Congestive Heart Failure at Visit 1 (Core study Visit 10)

    • Symptomatic hypotension or reported systolic blood pressure (BP) < 90 mmHg within 24 hours prior to Visit 1 (Core study Visit 10)

    • Known Estimated Glomerular Filtration Rate (eGFR) < 30 mL/min/1.73m^2 using the Modification of Diet in Renal Disease (MDRD) formula at Visit 1 (Core study Visit 10)

    • Pregnant or nursing (lactating) women, where pregnancy was defined as the state of a female after conception and until the termination of gestation, confirmed by a positive hCG laboratory test (> 5 mIU/mL)

    • Women of child-bearing potential, defined as all women physiologically capable of becoming pregnant Unless post-menopausal or using an acceptable method of contraception

    • Any surgical or medical condition that in the opinion of the investigator may place the patient at higher risk from his/her participation in the study or was likely to prevent the patient from complying with the requirements or completing the study

    Other protocol-defined inclusion/exclusion criteria applied

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Novartis US Novartis US New Jersey United States
    2 Novartis Argentina Novartis Argentina Argentina
    3 Novartis Belgium Novartis Belgium Belgium
    4 Novartis Canada Novartis Canada Canada
    5 Novartis de Colombia S.A. Bogota Colombia
    6 Novartis Czech Republic Praha Praha 3 Czech Republic CZ-130 00
    7 Novartis Denmark Novartis Denmark Denmark
    8 Novartis Germany Novartis Germany Germany
    9 Novartis Hungary Budapest Hungary H-1537
    10 Novartis Healthcare Private Limited Worli, Mumbai India 400018
    11 Novartis Pharma Petach Tikva Israel IL-49250
    12 Novartis Italy Novartis Italy Italy
    13 Novartis Korea Ltd. Seoul Korea, Republic of 100-803
    14 Novartis Netherlands Novartis Netherlands Netherlands
    15 Novartis Norway Novartis Norway Norway
    16 Novartis Poland Sp. z o.o. Warszawa Poland PL-00-710-
    17 Novartis Russia Novartis Russia Russian Federation
    18 Novartis Slovakia Bratislava Slovakia SK-821 09
    19 Novartis Spain Novartis Spain Spain
    20 Novartis Sweden Novartis Sweden Sweden
    21 Novartis Turkey Istanbul Turkey TR-34353
    22 Novartis UK Novartis United Kingdom
    23 Novartis de Venezuela, S.A. Caracas Venezuela 1062

    Sponsors and Collaborators

    • Novartis

    Investigators

    • Study Chair: Novartis US, Novartis

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    Novartis
    ClinicalTrials.gov Identifier:
    NCT00414609
    Other Study ID Numbers:
    • CSPP100A2340
    • NCT00699075
    First Posted:
    Dec 21, 2006
    Last Update Posted:
    Jul 13, 2012
    Last Verified:
    Jul 1, 2012
    Keywords provided by Novartis
    myocardial infarction, aliskiren, heart failure
    Post acute myocardial infarction with systolic dysfunction
    Additional relevant MeSH terms:
    Myocardial Infarction
    Infarction

    Study Results

    Participant Flow

    Recruitment Details
    Pre-assignment Detail
    Arm/Group Title Placebo_Core Aliskiren_Core Aliskiren_Extension
    Arm/Group Description Placebo for 36 weeks once daily in the morning Aliskiren ascending doses: 75 mg tablet for 1st week, 150 mg for 2nd week, 300 mg for the next 34 weeks orally once daily in the morning. Patients from both the arms of the core study who completed core study and signed informed consent form were included in this arm of extension study. Patients received 150 mg aliskiren tablet orally once a day for two weeks. Patients were then up-titrated to 300 mg aliskiren orally once a day at the discretion of the principal investigator based on their clinical condition for the duration of the study.
    Period Title: Core Study
    STARTED 397 423 0
    Received Study Drug 397 422 0
    Echocardiogram Evaluable Set 330 343 0
    COMPLETED 363 378 0
    NOT COMPLETED 34 45 0
    Period Title: Core Study
    STARTED 0 0 422
    Echocardiogram (ECHO) Analysis Set 0 0 400
    COMPLETED 0 0 365
    NOT COMPLETED 0 0 57

    Baseline Characteristics

    Arm/Group Title Placebo Aliskiren Total
    Arm/Group Description Placebo for 36 weeks once daily in the morning Aliskiren ascending doses: 75 mg tablet for 1st week, 150 mg for 2nd week, 300 mg for the next 34 weeks orally once daily in the morning. Total of all reporting groups
    Overall Participants 397 423 820
    Age (years) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [years]
    59.4
    (11.67)
    60.7
    (11.63)
    60.0
    (11.66)
    Age, Customized (Number) [Number]
    < 65 years
    261
    65.7%
    254
    60%
    515
    62.8%
    ≥ 65 years and < 75 years
    93
    23.4%
    114
    27%
    207
    25.2%
    ≥ 75 years
    43
    10.8%
    55
    13%
    98
    12%
    Sex: Female, Male (Count of Participants)
    Female
    61
    15.4%
    80
    18.9%
    141
    17.2%
    Male
    336
    84.6%
    343
    81.1%
    679
    82.8%

    Outcome Measures

    1. Primary Outcome
    Title Core Study: Change From Baseline in Left Ventricular End Systolic Volume (LVESV) as Measured by Echocardiography at End of Study.
    Description Change from baseline to end of study in left ventricular end systolic volume (LVESV) as measured by echocardiography. LVESV is a measurement of the volume of blood in the heart's left ventricular chamber at the end of the heart's contraction. This measurement was made by the echocardiography lab. LVESV values between 22 to 58 mL for men and 19-49 mL for women are considered normal. Baseline LVESV was a covariate.
    Time Frame Baseline and final visit (after 26 to 36 weeks of treatment)

    Outcome Measure Data

    Analysis Population Description
    Echocardiogram evaluable set (patients who had acceptable echocardiogram measurements both at baseline and at post-baseline after receiving at least 26 weeks of treatment)
    Arm/Group Title Placebo_Core Aliskiren_Core
    Arm/Group Description Placebo for 36 weeks once daily in the morning Aliskiren ascending doses: 75 mg tablet for 1st week, 150 mg for 2nd week, 300 mg for the next 34 weeks orally once daily in the morning.
    Measure Participants 329 343
    Least Squares Mean (Standard Error) [mL]
    -3.14
    (1.01)
    -4.13
    (0.97)
    2. Secondary Outcome
    Title Core Study: Time to First Occurrence for the Composite Endpoints of Echocardiogram and Adjudicated Outcomes
    Description Composite outcome 1 included: Cardiovascular (CV) Death, hospitalization for heart failure (HF), or absolute reduction in Left Ventricular Ejection Fraction (LVEF) greater than 6%. Composite outcome 2 included: CV Death, hospitalization for HF, recurrent Myocardial Infarction, Stroke, or Resuscitated Sudden Death. LVEF was measured at baseline and final visit. All other events were adjudicated by a blinded external committee. Each composite endpoint analysis was based on (a) the percent of patients with that endpoint and (b) days in study to 1st event (or last exposure if no event occurred).
    Time Frame LVEF was measured at baseline and at final visit (after 26 to 36 weeks of treatment). Other endpoint components were assessed from randomization until the end of the study (week 36).

    Outcome Measure Data

    Analysis Population Description
    Full Analysis Set (FAS) - All randomized patients who either (a) received study drug or (b) did not receive study drug but were not disqualified from randomization.
    Arm/Group Title Placebo_Core Aliskiren_Core
    Arm/Group Description Placebo for 36 weeks once daily in the morning Aliskiren ascending doses: 75 mg tablet for 1st week, 150 mg for 2nd week, 300 mg for the next 34 weeks orally once daily in the morning.
    Measure Participants 397 423
    Composite Outcome 1
    6.0
    1.5%
    6.9
    1.6%
    Composite Outcome 2
    8.6
    2.2%
    9.2
    2.2%
    3. Secondary Outcome
    Title Core Study: Change From Baseline in Left Ventricular End Diastolic Volume (LVEDV)
    Description Change from baseline to end of study in left ventricular end diastolic volume (LVEDV) as measured by echocardiography. (LVEDV) is a measurement of the volume of blood in the heart's left ventricular chamber at the beginning of the chamber's filling with blood. This measurement was made by the echocardiography lab. LVEDV values between 67 to 155 mL for men and 56 to 104 mL for women are considered normal. Baseline LVEDV was a covariate.
    Time Frame Baseline and final visit (after 26 to 36 weeks of treatment)

    Outcome Measure Data

    Analysis Population Description
    Echocardiogram evaluable set: Patients who had acceptable echocardiogram measurements both at baseline and at post-baseline after receiving at least 26 weeks of treatment.
    Arm/Group Title Placebo_Core Aliskiren_Core
    Arm/Group Description Placebo for 36 weeks once daily in the morning Aliskiren ascending doses: 75 mg tablet for 1st week, 150 mg for 2nd week, 300 mg for the next 34 weeks orally once daily in the morning.
    Measure Participants 329 343
    Least Squares Mean (Standard Error) [mL]
    -1.37
    (1.19)
    -3.08
    (1.15)
    4. Secondary Outcome
    Title Core Study: Change From Baseline in Left Ventricular Ejection Fraction (LVEF)
    Description Change from baseline to end of study in left ventricular ejection fraction (LVEF) (%) as measured by echocardiography. LVEF is the fraction of blood (in percent) pumped out of the heart's left ventricular chamber with each heart beat, and is a measure of cardiac output for the heart. This measurement was made by the echocardiography lab. Ejection fraction percentages > 55% are considered normal. Baseline LVEF was a covariate.
    Time Frame Baseline and final visit (after 26 to 36 weeks of treatment )

    Outcome Measure Data

    Analysis Population Description
    Echocardiogram evaluable set: Patients who had acceptable echocardiogram measurements both at baseline and at post-baseline after receiving at least 26 weeks of treatment.
    Arm/Group Title Placebo_Core Aliskiren_Core
    Arm/Group Description Placebo for 36 weeks once daily in the morning Aliskiren ascending doses: 75 mg tablet for 1st week, 150 mg for 2nd week, 300 mg for the next 34 weeks orally once daily in the morning.
    Measure Participants 329 343
    Least Squares Mean (Standard Error) [percent of blood pumped from LV chamber]
    2.12
    (0.27)
    2.24
    (0.26)
    5. Secondary Outcome
    Title Core Study: Change From Baseline to End of Study in Infarction Segment Length (ISL) as Measured by Echocardiography
    Description Change from baseline to end of study in infarction segment length (ISL) (%) as measured by echocardiography. This is the length of the myocardial infarction segment as a percentage of the total cavity perimeter length as calculated by the echocardiography lab. Baseline ISL was a covariate.
    Time Frame Baseline and final visit (after 26 to 36 weeks of treatment)

    Outcome Measure Data

    Analysis Population Description
    Echocardiogram evaluable set: Patients who had acceptable echocardiogram measurements both at baseline and at post-baseline after receiving at least 26 weeks of treatment.
    Arm/Group Title Placebo_Core Aliskiren_Core
    Arm/Group Description Placebo for 36 weeks once daily in the morning Aliskiren ascending doses: 75 mg tablet for 1st week, 150 mg for 2nd week, 300 mg for the next 34 weeks orally once daily in the morning.
    Measure Participants 330 343
    Least Squares Mean (Standard Error) [percent of total cavity perimeter length]
    -4.30
    (0.53)
    -5.04
    (0.51)
    6. Secondary Outcome
    Title Core Study: Change From Baseline to End of Study in Wall Motion Score (WMS) as Measured by Echocardiography
    Description Change from baseline to end of study in Wall Motion Score (WMS) as measured by echocardiography. WMS was obtained by examining multiple segments of the left ventricle and assigning each segment a score based on myocardial thickening: 1 for normal, 2 for hypokinetic; 3 for akinetic; and 4 for dyskinetic. The WMS was obtained as the average score for the segments visualized and was calculated by the echocardiography lab. Possible values range from 1 to 5. Higher scores are considered worse. Baseline WMS was a covariate.
    Time Frame Baseline and final visit (after 26 to 36 weeks of treatment)

    Outcome Measure Data

    Analysis Population Description
    Echocardiogram evaluable set: Patients who had acceptable echocardiogram measurements both at baseline and at post-baseline after receiving at least 26 weeks of treatment.
    Arm/Group Title Placebo_Core Aliskiren_Core
    Arm/Group Description Placebo for 36 weeks once daily in the morning Aliskiren ascending doses: 75 mg tablet for 1st week, 150 mg for 2nd week, 300 mg for the next 34 weeks orally once daily in the morning.
    Measure Participants 327 340
    Least Squares Mean (Standard Error) [Scores on a scale]
    -0.08
    (0.01)
    -0.10
    (0.01)
    7. Primary Outcome
    Title Extension Study: Percentage of Participants With Deaths, Serious Adverse Events (SAEs), Discontinuation for Adverse Events (AEs) and Discontinuations for Abnormal Lab Values
    Description AEs are defined as any unfavorable and unintended diagnosis, symptom, sign (including an abnormal laboratory finding), syndrome or disease which either occurs during study, having been absent at baseline, or, if present at baseline, appears to worsen. Serious adverse events are any untoward medical occurrences that result in death, are life threatening, require (or prolong) hospitalization, cause persistent or significant disability/incapacity, result in congenital anomalies or birth defects, or are other conditions which in judgment of investigators represent significant hazards.
    Time Frame Extension study (24 weeks)

    Outcome Measure Data

    Analysis Population Description
    Extension Population (considered as Safety population) consisting of all enrolled patients who received at least one dose of study medication in the extension study.
    Arm/Group Title Aliskiren_Extension
    Arm/Group Description Patients from both the arms of the core study who completed core study and signed informed consent form were included in this arm of extension study. Patients received 150 mg aliskiren tablet orally once a day for two weeks. Patients were then up-titrated to 300 mg aliskiren orally once a day at the discretion of the principal investigator based on their clinical condition for the duration of the study.
    Measure Participants 422
    Deaths
    4.0
    1%
    SAEs
    29.9
    7.5%
    AE discontinuations
    7.1
    1.8%
    Drug-related AE discontinuations
    2.4
    0.6%
    SAE discontinuations
    5.2
    1.3%
    Discontinuations for abnormal lab values
    0
    0%
    8. Secondary Outcome
    Title Extension Study: Change From Baseline in Left Ventricular End Systolic Volume (LVESV) at Month 12
    Description Change from baseline to Month 12 in left ventricular end systolic volume (LVESV) as measured by echocardiography. LVESV is a measurement of the volume of blood in the heart's left ventricular chamber at the end of the heart's contraction. This measurement was made by the echocardiography lab. LVESV values between 22 to 58 mL for men and 19-49 mL for women are considered normal.
    Time Frame Baseline(extension study), Month 12 (extension study)

    Outcome Measure Data

    Analysis Population Description
    Echocardiogram Analysis Set consisting of all patients in the extension population who had acceptable ECHO measurements at extension baseline and Month 12.
    Arm/Group Title Aliskiren_Extension
    Arm/Group Description Patients from both the arms of the core study who completed core study and signed informed consent form were included in this arm of extension study. Patients received 150 mg aliskiren tablet orally once a day for two weeks. Patients were then up-titrated to 300 mg aliskiren orally once a day at the discretion of the principal investigator based on their clinical condition for the duration of the study.
    Measure Participants 302
    Mean (Standard Deviation) [Milliliter (mL)]
    -6.2
    (14.32)
    9. Secondary Outcome
    Title Extension Study: Change From Baseline in Left Ventricular End Diastolic Volume (LVEDV) at Month 12
    Description Change from baseline to Month 12 in left ventricular end diastolic volume (LVEDV) as measured by echocardiography. LVEDV is a measurement of the volume of blood in the heart's left ventricular chamber at the beginning of the chamber's filling with blood. This measurement was made by the echocardiography lab. LVEDV values between 67 to 155 mL for men and 56 to 104 mL for women are considered normal.
    Time Frame Baseline (extension study), Month 12 (extension study)

    Outcome Measure Data

    Analysis Population Description
    Echocardiogram Analysis Set consisting of all patients in the extension population who had acceptable ECHO measurements at extension baseline and Month 12.
    Arm/Group Title Aliskiren_Extension
    Arm/Group Description 150 mg aliskiren tablet orally once a day for two weeks. Patients were then up-titrated to 300 mg aliskiren orally once a day at the discretion of the principal investigator based on their clinical condition for the duration of the study.
    Measure Participants 302
    Mean (Standard Deviation) [Milliliter (mL)]
    6.0
    (18.34)
    10. Secondary Outcome
    Title Extension Study: Change From Baseline in Left Ventricular Ejection Fraction (LVEF) at Month 12
    Description Change from baseline to Month 12 in left ventricular ejection fraction (LVEF) (%) as measured by echocardiography. LVEF is the fraction of blood (in percent) pumped out of the heart's left ventricular chamber with each heart beat, and is a measure of cardiac output for the heart. This measurement was made by the echocardiography lab. Ejection fraction percentages > 55% are considered normal.
    Time Frame Baseline(extension study), Month 12 (extension study)

    Outcome Measure Data

    Analysis Population Description
    Echocardiogram Analysis Set consisting of all patients in the extension population who had acceptable ECHO measurements at extension baseline and Month 12.
    Arm/Group Title Aliskiren_Extension
    Arm/Group Description Patients from both the arms of the core study who completed core study and signed informed consent form were included in this arm of extension study. Patients received 150 mg aliskiren tablet orally once a day for two weeks. Patients were then up-titrated to 300 mg aliskiren orally once a day at the discretion of the principal investigator based on their clinical condition for the duration of the study.
    Measure Participants 302
    Mean (Standard Deviation) [percent of blood pumped from LV chamber]
    7.4
    (6.46)
    11. Secondary Outcome
    Title Extension Study: Percentage of Participants With Orthostatic Blood Pressure Change
    Description Orthostatic blood pressure change is defined as a decrease of at least 20 mmHg in systolic blood pressure or a decrease of at least 10 mmHg in diastolic blood pressure when a patient moves from a sitting position to a standing position. A patient could show orthostatic blood pressure change at more than one visit. End of study is Month 24 or early discontinuation.
    Time Frame Baseline (Day 0 Extension study), Week 2, Months 1, 3, 6, 9,16, 20, 24

    Outcome Measure Data

    Analysis Population Description
    Extension population (considered as Safety population) consisted of all enrolled patients who received at least one dose of study medication in the extension study. "n" in each of the categories is the number of participants with data available at the given time-point.
    Arm/Group Title Aliskiren_Extension
    Arm/Group Description Patients from both the arms of the core study who completed core study and signed informed consent form were included in this arm of extension study. Patients received 150 mg aliskiren tablet orally once a day for two weeks. Patients were then up-titrated to 300 mg aliskiren orally once a day at the discretion of the principal investigator based on their clinical condition for the duration of the study.
    Measure Participants 422
    Baseline (n=420)
    2.4
    0.6%
    Week 2 (n=416)
    4.6
    1.2%
    Month 1 (n=418)
    4.1
    1%
    Month 3 (n=410)
    4.6
    1.2%
    Month 6 (n=400)
    3.3
    0.8%
    Month 9 (n=397)
    4.3
    1.1%
    Month 12 (n=385)
    3.6
    0.9%
    Month 16 (n=383)
    5.0
    1.3%
    Month 20 (n=350)
    4.3
    1.1%
    Month 24 (n=360)
    3.6
    0.9%
    End of Study (n=422)
    3.8
    1%
    Any post-baseline visit (n=422)
    23.5
    5.9%
    12. Secondary Outcome
    Title Extension Study: Percentage of Participants With Specified Criteria in Selected Labs by Laboratory Parameter
    Description Fasting blood samples were collected throughout the study and were analyzed at a central laboratory. Percentage of participants with the following clinically significant laboratory values are reported: Potassium <3.5 mmol/L; Low value (Normal reference range: 3.5- 5.3) Potassium >5.5 mmol/L and Potassium >6.0 mmol/L; High values (Normal reference range: 3.5-5.3) Creatinine >176.8 μmol/L; High value (Normal reference range= Male: 62- 106 and Female 44- 80) Blood Urea Nitrogen (BUN) >14.28; High value (Normal reference range: 2.1- 8.9)
    Time Frame 24 Months

    Outcome Measure Data

    Analysis Population Description
    Extension population (considered as Safety population) consisted of all enrolled patients who received at least one dose of study medication in the extension study. "n" in each of the categories is the number of participants with data available at the given time-point.
    Arm/Group Title Aliskiren_Extension
    Arm/Group Description Patients from both the arms of the core study who completed core study and signed informed consent form were included in this arm of extension study. Patients received 150 mg aliskiren tablet orally once a day for two weeks. Patients were then up-titrated to 300 mg aliskiren orally once a day at the discretion of the principal investigator based on their clinical condition for the duration of the study.
    Measure Participants 422
    Potassium <3.5 mmol/L (n=409)
    1.5
    0.4%
    Potassium >5.5 mmol/L (n=409)
    11.2
    2.8%
    Potassium ≥6.0 mmol/L (n=409)
    4.6
    1.2%
    Creatinine >176.8 μmol/L (n=412)
    4.4
    1.1%
    BUN >14.28 mmol/L (n=412)
    8.7
    2.2%

    Adverse Events

    Time Frame
    Adverse Event Reporting Description Core Safety population: All patients that received at least one dose of study drug. Extension Safety Population: All enrolled patients who received at least one dose of study medication in the extension study. Extension study enrolled patients from both the arms of core who complete core study and signed an informed consent form.
    Arm/Group Title Placebo_core Aliskiren_core Aliskiren_extension
    Arm/Group Description Placebo for 36 weeks once daily in the morning Aliskiren ascending doses: 75 mg tablet for 1st week, 150 mg for 2nd week, 300 mg for the next 34 weeks orally once daily in the morning. Patients from both the arms of the core study who completed core study and signed informed consent form were included in this arm of extension study. Patients received 150 mg aliskiren tablet orally once a day for two weeks. Patients were then up-titrated to 300 mg aliskiren orally once a day at the discretion of the principal investigator based on their clinical condition for the duration of the study.
    All Cause Mortality
    Placebo_core Aliskiren_core Aliskiren_extension
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total / (NaN) / (NaN) / (NaN)
    Serious Adverse Events
    Placebo_core Aliskiren_core Aliskiren_extension
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 92/397 (23.2%) 107/422 (25.4%) 126/422 (29.9%)
    Blood and lymphatic system disorders
    Anaemia 0/397 (0%) 4/422 (0.9%) 0/422 (0%)
    Haemorrhagic anaemia 0/397 (0%) 0/422 (0%) 1/422 (0.2%)
    Cardiac disorders
    Acute coronary syndrome 2/397 (0.5%) 3/422 (0.7%) 3/422 (0.7%)
    Acute myocardial infarction 4/397 (1%) 6/422 (1.4%) 6/422 (1.4%)
    Angina pectoris 15/397 (3.8%) 13/422 (3.1%) 15/422 (3.6%)
    Angina unstable 8/397 (2%) 9/422 (2.1%) 4/422 (0.9%)
    Arrhythmia 2/397 (0.5%) 0/422 (0%) 0/422 (0%)
    Arteriospasm coronary 0/397 (0%) 0/422 (0%) 1/422 (0.2%)
    Atrial fibrillation 1/397 (0.3%) 4/422 (0.9%) 3/422 (0.7%)
    Atrioventricular block complete 1/397 (0.3%) 0/422 (0%) 0/422 (0%)
    Bradycardia 1/397 (0.3%) 2/422 (0.5%) 0/422 (0%)
    Cardiac arrest 2/397 (0.5%) 2/422 (0.5%) 2/422 (0.5%)
    Cardiac failure 14/397 (3.5%) 18/422 (4.3%) 9/422 (2.1%)
    Cardiac failure acute 2/397 (0.5%) 0/422 (0%) 0/422 (0%)
    Cardiac failure chronic 1/397 (0.3%) 0/422 (0%) 5/422 (1.2%)
    Cardiac failure congestive 4/397 (1%) 3/422 (0.7%) 1/422 (0.2%)
    Cardio-respiratory arrest 1/397 (0.3%) 0/422 (0%) 1/422 (0.2%)
    Cardiopulmonary failure 0/397 (0%) 0/422 (0%) 1/422 (0.2%)
    Coronary artery disease 2/397 (0.5%) 0/422 (0%) 2/422 (0.5%)
    Coronary artery insufficiency 0/397 (0%) 1/422 (0.2%) 0/422 (0%)
    Coronary artery stenosis 4/397 (1%) 1/422 (0.2%) 2/422 (0.5%)
    Ischaemic cardiomyopathy 0/397 (0%) 1/422 (0.2%) 1/422 (0.2%)
    Left ventricular failure 0/397 (0%) 1/422 (0.2%) 0/422 (0%)
    Myocardial infarction 5/397 (1.3%) 7/422 (1.7%) 6/422 (1.4%)
    Myocardial ischaemia 2/397 (0.5%) 1/422 (0.2%) 2/422 (0.5%)
    Pericarditis 1/397 (0.3%) 0/422 (0%) 0/422 (0%)
    Ventricular arrhythmia 0/397 (0%) 1/422 (0.2%) 0/422 (0%)
    Ventricular extrasystoles 1/397 (0.3%) 0/422 (0%) 0/422 (0%)
    Ventricular fibrillation 1/397 (0.3%) 2/422 (0.5%) 0/422 (0%)
    Ventricular tachycardia 2/397 (0.5%) 0/422 (0%) 1/422 (0.2%)
    Ear and labyrinth disorders
    Vertigo 1/397 (0.3%) 0/422 (0%) 0/422 (0%)
    Eye disorders
    Cataract 0/397 (0%) 1/422 (0.2%) 1/422 (0.2%)
    Gastrointestinal disorders
    Abdominal hernia 0/397 (0%) 0/422 (0%) 1/422 (0.2%)
    Abdominal pain 1/397 (0.3%) 1/422 (0.2%) 0/422 (0%)
    Abdominal pain upper 0/397 (0%) 1/422 (0.2%) 0/422 (0%)
    Abdominal tenderness 0/397 (0%) 0/422 (0%) 1/422 (0.2%)
    Chronic gastrointestinal bleeding 0/397 (0%) 0/422 (0%) 1/422 (0.2%)
    Colitis 1/397 (0.3%) 0/422 (0%) 0/422 (0%)
    Dental caries 1/397 (0.3%) 0/422 (0%) 0/422 (0%)
    Diarrhoea 1/397 (0.3%) 1/422 (0.2%) 0/422 (0%)
    Duodenal ulcer perforation 0/397 (0%) 0/422 (0%) 1/422 (0.2%)
    Gastric haemorrhage 0/397 (0%) 1/422 (0.2%) 0/422 (0%)
    Gastric ulcer 0/397 (0%) 1/422 (0.2%) 0/422 (0%)
    Gastrointestinal obstruction 0/397 (0%) 0/422 (0%) 1/422 (0.2%)
    Inguinal hernia, obstructive 0/397 (0%) 0/422 (0%) 1/422 (0.2%)
    Mouth haemorrhage 1/397 (0.3%) 0/422 (0%) 0/422 (0%)
    Nausea 0/397 (0%) 1/422 (0.2%) 1/422 (0.2%)
    Pancreatitis 1/397 (0.3%) 0/422 (0%) 0/422 (0%)
    Pancreatitis acute 0/397 (0%) 1/422 (0.2%) 0/422 (0%)
    Peritonitis 0/397 (0%) 0/422 (0%) 1/422 (0.2%)
    Rectal haemorrhage 0/397 (0%) 0/422 (0%) 1/422 (0.2%)
    Upper gastrointestinal haemorrhage 0/397 (0%) 1/422 (0.2%) 0/422 (0%)
    Vomiting 1/397 (0.3%) 0/422 (0%) 0/422 (0%)
    General disorders
    Apparent death 2/397 (0.5%) 0/422 (0%) 0/422 (0%)
    Asthenia 0/397 (0%) 1/422 (0.2%) 0/422 (0%)
    Chest pain 0/397 (0%) 2/422 (0.5%) 1/422 (0.2%)
    Death 0/397 (0%) 1/422 (0.2%) 0/422 (0%)
    Device failure 0/397 (0%) 0/422 (0%) 1/422 (0.2%)
    Generalised oedema 1/397 (0.3%) 0/422 (0%) 0/422 (0%)
    Impaired healing 0/397 (0%) 1/422 (0.2%) 0/422 (0%)
    Malaise 1/397 (0.3%) 0/422 (0%) 0/422 (0%)
    Multi-organ failure 0/397 (0%) 0/422 (0%) 1/422 (0.2%)
    Non-cardiac chest pain 6/397 (1.5%) 7/422 (1.7%) 7/422 (1.7%)
    Oedema peripheral 0/397 (0%) 1/422 (0.2%) 0/422 (0%)
    Pyrexia 2/397 (0.5%) 0/422 (0%) 1/422 (0.2%)
    Sudden cardiac death 0/397 (0%) 2/422 (0.5%) 0/422 (0%)
    Sudden death 1/397 (0.3%) 2/422 (0.5%) 4/422 (0.9%)
    Thrombosis in device 0/397 (0%) 0/422 (0%) 2/422 (0.5%)
    Vessel puncture site haematoma 1/397 (0.3%) 0/422 (0%) 0/422 (0%)
    Hepatobiliary disorders
    Bile duct stone 1/397 (0.3%) 0/422 (0%) 0/422 (0%)
    Cholangitis 0/397 (0%) 0/422 (0%) 1/422 (0.2%)
    Cholecystitis acute 1/397 (0.3%) 0/422 (0%) 0/422 (0%)
    Cholelithiasis 2/397 (0.5%) 1/422 (0.2%) 0/422 (0%)
    Hepatic function abnormal 1/397 (0.3%) 0/422 (0%) 0/422 (0%)
    Infections and infestations
    Appendicitis 0/397 (0%) 0/422 (0%) 1/422 (0.2%)
    Bronchitis 0/397 (0%) 1/422 (0.2%) 0/422 (0%)
    Cellulitis 2/397 (0.5%) 1/422 (0.2%) 0/422 (0%)
    Enterococcal infection 1/397 (0.3%) 0/422 (0%) 0/422 (0%)
    Febrile infection 0/397 (0%) 1/422 (0.2%) 0/422 (0%)
    Gangrene 1/397 (0.3%) 1/422 (0.2%) 0/422 (0%)
    Gastroenteritis 1/397 (0.3%) 1/422 (0.2%) 1/422 (0.2%)
    Gastroenteritis norovirus 1/397 (0.3%) 0/422 (0%) 0/422 (0%)
    Nasopharyngitis 0/397 (0%) 1/422 (0.2%) 0/422 (0%)
    Peritoneal abscess 0/397 (0%) 0/422 (0%) 1/422 (0.2%)
    Pneumonia 5/397 (1.3%) 7/422 (1.7%) 3/422 (0.7%)
    Pyelonephritis 1/397 (0.3%) 0/422 (0%) 0/422 (0%)
    Respiratory tract infection 1/397 (0.3%) 1/422 (0.2%) 0/422 (0%)
    Scrotal abscess 1/397 (0.3%) 0/422 (0%) 0/422 (0%)
    Sepsis 0/397 (0%) 2/422 (0.5%) 0/422 (0%)
    Urinary tract infection 1/397 (0.3%) 0/422 (0%) 2/422 (0.5%)
    Injury, poisoning and procedural complications
    Accidental overdose 0/397 (0%) 1/422 (0.2%) 0/422 (0%)
    Ankle fracture 0/397 (0%) 0/422 (0%) 1/422 (0.2%)
    Coronary artery restenosis 0/397 (0%) 2/422 (0.5%) 0/422 (0%)
    Face injury 0/397 (0%) 0/422 (0%) 1/422 (0.2%)
    Fall 1/397 (0.3%) 1/422 (0.2%) 0/422 (0%)
    Femoral neck fracture 1/397 (0.3%) 0/422 (0%) 0/422 (0%)
    Graft thrombosis 0/397 (0%) 0/422 (0%) 1/422 (0.2%)
    Hip fracture 0/397 (0%) 0/422 (0%) 1/422 (0.2%)
    Implantable defibrillator malfunction 1/397 (0.3%) 0/422 (0%) 0/422 (0%)
    In-stent coronary artery restenosis 2/397 (0.5%) 2/422 (0.5%) 2/422 (0.5%)
    Joint sprain 0/397 (0%) 1/422 (0.2%) 0/422 (0%)
    Laceration 0/397 (0%) 0/422 (0%) 1/422 (0.2%)
    Lower limb fracture 0/397 (0%) 0/422 (0%) 1/422 (0.2%)
    Medical device complication 0/397 (0%) 1/422 (0.2%) 0/422 (0%)
    Post procedural haemorrhage 1/397 (0.3%) 0/422 (0%) 0/422 (0%)
    Radius fracture 0/397 (0%) 0/422 (0%) 1/422 (0.2%)
    Tendon rupture 0/397 (0%) 0/422 (0%) 1/422 (0.2%)
    Thrombosis in device 0/397 (0%) 1/422 (0.2%) 0/422 (0%)
    Tibia fracture 0/397 (0%) 1/422 (0.2%) 0/422 (0%)
    Upper limb fracture 1/397 (0.3%) 1/422 (0.2%) 0/422 (0%)
    Investigations
    Aspartate aminotransferase increased 0/397 (0%) 0/422 (0%) 1/422 (0.2%)
    Blood creatinine increased 0/397 (0%) 0/422 (0%) 2/422 (0.5%)
    Blood potassium increased 0/397 (0%) 0/422 (0%) 1/422 (0.2%)
    Blood pressure decreased 0/397 (0%) 1/422 (0.2%) 0/422 (0%)
    Ejection fraction decreased 2/397 (0.5%) 0/422 (0%) 0/422 (0%)
    Electrocardiogram QRS complex prolonged 1/397 (0.3%) 0/422 (0%) 0/422 (0%)
    Renal function test abnormal 0/397 (0%) 0/422 (0%) 1/422 (0.2%)
    Venous pressure jugular increased 0/397 (0%) 1/422 (0.2%) 0/422 (0%)
    Weight decreased 0/397 (0%) 1/422 (0.2%) 0/422 (0%)
    Metabolism and nutrition disorders
    Decreased appetite 0/397 (0%) 1/422 (0.2%) 0/422 (0%)
    Dehydration 0/397 (0%) 0/422 (0%) 1/422 (0.2%)
    Diabetes mellitus 0/397 (0%) 0/422 (0%) 1/422 (0.2%)
    Electrolyte imbalance 1/397 (0.3%) 0/422 (0%) 0/422 (0%)
    Hypoglycaemia 2/397 (0.5%) 1/422 (0.2%) 2/422 (0.5%)
    Hypophagia 1/397 (0.3%) 0/422 (0%) 0/422 (0%)
    Musculoskeletal and connective tissue disorders
    Arthralgia 0/397 (0%) 1/422 (0.2%) 0/422 (0%)
    Back pain 0/397 (0%) 0/422 (0%) 2/422 (0.5%)
    Fibromyalgia 1/397 (0.3%) 0/422 (0%) 0/422 (0%)
    Gouty arthritis 0/397 (0%) 0/422 (0%) 1/422 (0.2%)
    Intervertebral disc protrusion 0/397 (0%) 0/422 (0%) 1/422 (0.2%)
    Muscular weakness 0/397 (0%) 0/422 (0%) 1/422 (0.2%)
    Musculoskeletal chest pain 1/397 (0.3%) 0/422 (0%) 2/422 (0.5%)
    Musculoskeletal pain 1/397 (0.3%) 1/422 (0.2%) 1/422 (0.2%)
    Pain in extremity 1/397 (0.3%) 0/422 (0%) 0/422 (0%)
    Rhabdomyolysis 0/397 (0%) 0/422 (0%) 1/422 (0.2%)
    Rheumatoid arthritis 0/397 (0%) 0/422 (0%) 1/422 (0.2%)
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Basal cell carcinoma 0/397 (0%) 1/422 (0.2%) 0/422 (0%)
    Benign neoplasm of skin 0/397 (0%) 0/422 (0%) 1/422 (0.2%)
    Bile duct cancer 1/397 (0.3%) 0/422 (0%) 0/422 (0%)
    Brain cancer metastatic 1/397 (0.3%) 0/422 (0%) 0/422 (0%)
    Brain neoplasm malignant 0/397 (0%) 0/422 (0%) 1/422 (0.2%)
    Bronchial carcinoma 0/397 (0%) 1/422 (0.2%) 0/422 (0%)
    Carcinoid tumour of the pancreas 0/397 (0%) 1/422 (0.2%) 0/422 (0%)
    Colon cancer 0/397 (0%) 0/422 (0%) 1/422 (0.2%)
    Gastric cancer 0/397 (0%) 1/422 (0.2%) 1/422 (0.2%)
    Leukaemia 0/397 (0%) 0/422 (0%) 1/422 (0.2%)
    Lung neoplasm 0/397 (0%) 0/422 (0%) 2/422 (0.5%)
    Lung neoplasm malignant 0/397 (0%) 1/422 (0.2%) 1/422 (0.2%)
    Metastatic neoplasm 0/397 (0%) 0/422 (0%) 1/422 (0.2%)
    Myeloproliferative disorder 0/397 (0%) 0/422 (0%) 1/422 (0.2%)
    Ovarian cancer 0/397 (0%) 0/422 (0%) 1/422 (0.2%)
    Plasmacytoma 0/397 (0%) 0/422 (0%) 1/422 (0.2%)
    Renal cancer 0/397 (0%) 1/422 (0.2%) 0/422 (0%)
    Small cell lung cancer stage unspecified 0/397 (0%) 1/422 (0.2%) 0/422 (0%)
    Nervous system disorders
    Balance disorder 0/397 (0%) 1/422 (0.2%) 0/422 (0%)
    Basilar artery occlusion 0/397 (0%) 0/422 (0%) 1/422 (0.2%)
    Brain stem infarction 0/397 (0%) 0/422 (0%) 1/422 (0.2%)
    Carotid artery stenosis 0/397 (0%) 0/422 (0%) 1/422 (0.2%)
    Cerebral haemorrhage 0/397 (0%) 1/422 (0.2%) 0/422 (0%)
    Cerebral infarction 0/397 (0%) 0/422 (0%) 1/422 (0.2%)
    Cerebral ischaemia 0/397 (0%) 0/422 (0%) 2/422 (0.5%)
    Cerebral microangiopathy 1/397 (0.3%) 0/422 (0%) 0/422 (0%)
    Cerebrovascular accident 0/397 (0%) 5/422 (1.2%) 5/422 (1.2%)
    Dizziness 1/397 (0.3%) 2/422 (0.5%) 1/422 (0.2%)
    Encephalomalacia 0/397 (0%) 0/422 (0%) 1/422 (0.2%)
    Hypoaesthesia 1/397 (0.3%) 0/422 (0%) 0/422 (0%)
    Intercostal neuralgia 0/397 (0%) 1/422 (0.2%) 0/422 (0%)
    Ischaemic stroke 1/397 (0.3%) 2/422 (0.5%) 0/422 (0%)
    Loss of consciousness 0/397 (0%) 1/422 (0.2%) 0/422 (0%)
    Parkinsonism 0/397 (0%) 1/422 (0.2%) 0/422 (0%)
    Presyncope 0/397 (0%) 1/422 (0.2%) 0/422 (0%)
    Sciatica 1/397 (0.3%) 1/422 (0.2%) 0/422 (0%)
    Syncope 2/397 (0.5%) 2/422 (0.5%) 6/422 (1.4%)
    Transient ischaemic attack 0/397 (0%) 1/422 (0.2%) 3/422 (0.7%)
    Psychiatric disorders
    Anxiety 2/397 (0.5%) 0/422 (0%) 0/422 (0%)
    Confusional state 0/397 (0%) 0/422 (0%) 1/422 (0.2%)
    Depression 0/397 (0%) 2/422 (0.5%) 0/422 (0%)
    Renal and urinary disorders
    Calculus urinary 0/397 (0%) 1/422 (0.2%) 0/422 (0%)
    Haematuria 0/397 (0%) 1/422 (0.2%) 1/422 (0.2%)
    Hydronephrosis 0/397 (0%) 1/422 (0.2%) 0/422 (0%)
    Nephrolithiasis 0/397 (0%) 1/422 (0.2%) 0/422 (0%)
    Nephropathy toxic 0/397 (0%) 0/422 (0%) 1/422 (0.2%)
    Nephrotic syndrome 0/397 (0%) 0/422 (0%) 1/422 (0.2%)
    Renal failure 1/397 (0.3%) 2/422 (0.5%) 1/422 (0.2%)
    Renal failure acute 1/397 (0.3%) 1/422 (0.2%) 1/422 (0.2%)
    Reproductive system and breast disorders
    Epididymitis 1/397 (0.3%) 0/422 (0%) 0/422 (0%)
    Metrorrhagia 0/397 (0%) 0/422 (0%) 1/422 (0.2%)
    Respiratory, thoracic and mediastinal disorders
    Acute pulmonary oedema 4/397 (1%) 2/422 (0.5%) 1/422 (0.2%)
    Chronic obstructive pulmonary disease 1/397 (0.3%) 1/422 (0.2%) 2/422 (0.5%)
    Cough 1/397 (0.3%) 0/422 (0%) 0/422 (0%)
    Dyspnoea 4/397 (1%) 4/422 (0.9%) 2/422 (0.5%)
    Dyspnoea exertional 1/397 (0.3%) 0/422 (0%) 0/422 (0%)
    Haemoptysis 1/397 (0.3%) 0/422 (0%) 0/422 (0%)
    Hydrothorax 0/397 (0%) 1/422 (0.2%) 0/422 (0%)
    Hypercapnia 1/397 (0.3%) 0/422 (0%) 0/422 (0%)
    Hyperventilation 1/397 (0.3%) 0/422 (0%) 0/422 (0%)
    Pleural effusion 0/397 (0%) 0/422 (0%) 1/422 (0.2%)
    Pneumonia aspiration 1/397 (0.3%) 0/422 (0%) 0/422 (0%)
    Pneumothorax 0/397 (0%) 0/422 (0%) 1/422 (0.2%)
    Pulmonary congestion 1/397 (0.3%) 0/422 (0%) 0/422 (0%)
    Pulmonary embolism 0/397 (0%) 0/422 (0%) 2/422 (0.5%)
    Pulmonary mass 1/397 (0.3%) 0/422 (0%) 0/422 (0%)
    Pulmonary oedema 2/397 (0.5%) 4/422 (0.9%) 3/422 (0.7%)
    Respiratory failure 1/397 (0.3%) 1/422 (0.2%) 1/422 (0.2%)
    Wegener's granulomatosis 1/397 (0.3%) 0/422 (0%) 0/422 (0%)
    Skin and subcutaneous tissue disorders
    Cold sweat 0/397 (0%) 0/422 (0%) 1/422 (0.2%)
    Hyperhidrosis 1/397 (0.3%) 0/422 (0%) 0/422 (0%)
    Psoriasis 0/397 (0%) 0/422 (0%) 1/422 (0.2%)
    Surgical and medical procedures
    Hospitalisation 0/397 (0%) 0/422 (0%) 1/422 (0.2%)
    Vascular disorders
    Angiopathy 1/397 (0.3%) 0/422 (0%) 0/422 (0%)
    Aortic aneurysm 0/397 (0%) 0/422 (0%) 1/422 (0.2%)
    Arteriovenous fistula 1/397 (0.3%) 0/422 (0%) 0/422 (0%)
    Deep vein thrombosis 0/397 (0%) 1/422 (0.2%) 0/422 (0%)
    Femoral artery occlusion 0/397 (0%) 0/422 (0%) 1/422 (0.2%)
    Haematoma 1/397 (0.3%) 0/422 (0%) 0/422 (0%)
    Hypertension 0/397 (0%) 1/422 (0.2%) 0/422 (0%)
    Hypertensive crisis 1/397 (0.3%) 1/422 (0.2%) 0/422 (0%)
    Hypotension 3/397 (0.8%) 1/422 (0.2%) 3/422 (0.7%)
    Intermittent claudication 1/397 (0.3%) 0/422 (0%) 1/422 (0.2%)
    Peripheral vascular disorder 0/397 (0%) 0/422 (0%) 1/422 (0.2%)
    Other (Not Including Serious) Adverse Events
    Placebo_core Aliskiren_core Aliskiren_extension
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 118/397 (29.7%) 161/422 (38.2%) 123/422 (29.1%)
    Cardiac disorders
    Angina pectoris 23/397 (5.8%) 24/422 (5.7%) 19/422 (4.5%)
    Cardiac failure 21/397 (5.3%) 30/422 (7.1%) 7/422 (1.7%)
    General disorders
    Non-cardiac chest pain 15/397 (3.8%) 22/422 (5.2%) 19/422 (4.5%)
    Infections and infestations
    Nasopharyngitis 24/397 (6%) 23/422 (5.5%) 28/422 (6.6%)
    Metabolism and nutrition disorders
    Hyperkalaemia 5/397 (1.3%) 22/422 (5.2%) 12/422 (2.8%)
    Nervous system disorders
    Dizziness 15/397 (3.8%) 27/422 (6.4%) 24/422 (5.7%)
    Respiratory, thoracic and mediastinal disorders
    Cough 28/397 (7.1%) 27/422 (6.4%) 15/422 (3.6%)
    Vascular disorders
    Hypotension 16/397 (4%) 36/422 (8.5%) 41/422 (9.7%)

    Limitations/Caveats

    [Not Specified]

    More Information

    Certain Agreements

    Principal Investigators are NOT employed by the organization sponsoring the study.

    The terms and conditions of Novartis' agreements with its investigators may vary. However, Novartis does not prohibit any investigator from publishing. Any publications from a single-site are postponed until the publication of the pooled data (i.e., data from all sites) in the clinical trial.

    Results Point of Contact

    Name/Title Study Director
    Organization Novartis Pharmaceuticals
    Phone 862-778-8300
    Email
    Responsible Party:
    Novartis
    ClinicalTrials.gov Identifier:
    NCT00414609
    Other Study ID Numbers:
    • CSPP100A2340
    • NCT00699075
    First Posted:
    Dec 21, 2006
    Last Update Posted:
    Jul 13, 2012
    Last Verified:
    Jul 1, 2012