A Randomized Controlled Trial of Aliskiren in the Prevention of Major Cardiovascular Events in Elderly People (APOLLO)

February 27, 2014 updated by: Novartis Pharmaceuticals
This study was planned to provide new information regarding the role of aliskiren (with or without additional therapy with a diuretic or a Calcium channel blockers (CCB)) in elderly individuals (≥ 65 years) with systolic blood pressure (SBP) 130 to 159 mmHg, in preventing major cardiovascular (CV) events and on global measures of physical, executive and cognitive function.

Study Overview

Status

Terminated

Conditions

Intervention / Treatment

Detailed Description

This was 2x2 factorial design study with 2 strata. As per protocol, the first co- Primary analysis as well as secondary analysis were aliskiren based regimen vs non-aliskiren based regimen. All aliskiren based arm were combined into the aliskiren based regimen and all non-aliskiren based arms were combined into non-aliskiren based regimen.

Study Type

Interventional

Enrollment (Actual)

2336

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Argentina
      • Buenos Aires, Argentina
        • Novartis Investigative Site
      • Buenos Aires, Argentina, 2800
        • Novartis Investigative Site
      • Buenos Aires, Argentina, 8000
        • Novartis Investigative Site
      • Buenos Aires, Argentina, C1425AWC
        • Novartis Investigative Site
      • Cordoba, Argentina, X5000AAW
        • Novartis Investigative Site
      • Salta, Argentina, A4406CLA
        • Novartis Investigative Site
      • Santa Fe, Argentina, S3000FWO
        • Novartis Investigative Site
    • Buenos Aires
      • Ciudad Autonoma de Bs As, Buenos Aires, Argentina, C1119ACN
        • Novartis Investigative Site
      • Coronel Suarez, Buenos Aires, Argentina, B7540GHD
        • Novartis Investigative Site
      • Jenin, Buenos Aires, Argentina, 6000
        • Novartis Investigative Site
      • Mar del Plata, Buenos Aires, Argentina, B7600FZN
        • Novartis Investigative Site
      • Merlo, Buenos Aires, Argentina, 1722
        • Novartis Investigative Site
      • Quilmes, Buenos Aires, Argentina, B1878GEG
        • Novartis Investigative Site
      • San Nicolas, Buenos Aires, Argentina, 2900
        • Novartis Investigative Site
    • Rio Negro
      • Cipolletti, Rio Negro, Argentina, 8324
        • Novartis Investigative Site
    • San Miguel de Tucuman
      • Tucuman, San Miguel de Tucuman, Argentina, T4000ICL
        • Novartis Investigative Site
    • Santa Fe
      • Rosario, Santa Fe, Argentina, S2000AGE
        • Novartis Investigative Site
      • Venado Tuerto, Santa Fe, Argentina, 2600
        • Novartis Investigative Site
  • Brazil
    • MG
      • Belo Horizonte, MG, Brazil, 30150-221
        • Novartis Investigative Site
      • Uberaba, MG, Brazil, 38010-160
        • Novartis Investigative Site
    • PR
      • Campina Grande do Sul, PR, Brazil, 83430-000
        • Novartis Investigative Site
    • RS
      • Porto Alegre, RS, Brazil, 90880-480
        • Novartis Investigative Site
    • SP
      • Campinas, SP, Brazil, 13060-904
        • Novartis Investigative Site
      • Marilia, SP, Brazil, 17515-000
        • Novartis Investigative Site
      • Sao Jose do Rio Preto, SP, Brazil, 15150-210
        • Novartis Investigative Site
      • São Paulo, SP, Brazil, 04023-900
        • Novartis Investigative Site
      • Votuporanga, SP, Brazil, 15500-003
        • Novartis Investigative Site
  • Canada
      • Quebec, Canada, G1L 3L5
        • Novartis Investigative Site
    • Alberta
      • Calgary, Alberta, Canada, T2N 4N1
        • Novartis Investigative Site
      • Edmonton, Alberta, Canada, T5A 4L8
        • Novartis Investigative Site
    • British Columbia
      • Coquitlam, British Columbia, Canada, V3K 3P4
        • Novartis Investigative Site
    • Manitoba
      • Winnipeg, Manitoba, Canada, R2H0R8
        • Novartis Investigative Site
    • Newfoundland and Labrador
      • St. John's, Newfoundland and Labrador, Canada, A1B 3V6
        • Novartis Investigative Site
    • Ontario
      • Brampton, Ontario, Canada, L6Z 4N5
        • Novartis Investigative Site
      • Hamilton, Ontario, Canada, L8L 2X2
        • Novartis Investigative Site
      • Hamilton, Ontario, Canada, L8M 1K7
        • Novartis Investigative Site
      • Hamilton, Ontario, Canada, L8N 1T8
        • Novartis Investigative Site
      • London, Ontario, Canada, N6C 5J1
        • Novartis Investigative Site
      • Markham, Ontario, Canada, L6B 0P9
        • Novartis Investigative Site
      • Missisauga, Ontario, Canada, L4Y 1A6
        • Novartis Investigative Site
      • Newmarket, Ontario, Canada, L3Y 8C3
        • Novartis Investigative Site
      • Niagara Falls, Ontario, Canada, L2G 6A8
        • Novartis Investigative Site
      • North York, Ontario, Canada, M2N 7J5
        • Novartis Investigative Site
      • Ottawa, Ontario, Canada, K2A 3Z3
        • Novartis Investigative Site
      • Ottawa, Ontario, Canada, K2B 7K2
        • Novartis Investigative Site
      • St Catherines, Ontario, Canada, L2T 3Y4
        • Novartis Investigative Site
      • Toronto, Ontario, Canada, M4N 3M5
        • Novartis Investigative Site
      • Toronto, Ontario, Canada, M4C5T2
        • Novartis Investigative Site
      • Toronto, Ontario, Canada, M4K 1N2
        • Novartis Investigative Site
    • Quebec
      • Lévis, Quebec, Canada, G6V 4Z5
        • Novartis Investigative Site
      • Montreal, Quebec, Canada, H2W 1T8
        • Novartis Investigative Site
      • Montreal, Quebec, Canada, H3T 1E2
        • Novartis Investigative Site
      • Sainte Foy, Quebec, Canada, G1V 4G2
        • Novartis Investigative Site
      • Sainte-Foy, Quebec, Canada, G1V 4G5
        • Novartis Investigative Site
      • St.Gorges de Beauce, Quebec, Canada, G5Y 4TB
        • Novartis Investigative Site
      • Terrebonne, Quebec, Canada, J6V 2H2
        • Novartis Investigative Site
    • Saskatchewan
      • Saskatoon, Saskatchewan, Canada, S7H 5M3
        • Novartis Investigative Site
  • Chile
      • Osorno, Chile, 5290000
        • Novartis Investigative Site
      • Santiago, Chile
        • Novartis Investigative Site
    • Cautin
      • Temuco, Cautin, Chile
        • Novartis Investigative Site
    • I Region
      • Vista Del Mar, I Region, Chile, 2570017
        • Novartis Investigative Site
    • TX
      • Temuca, TX, Chile, 4790869
        • Novartis Investigative Site
  • Colombia
      • Armenia, Colombia
        • Novartis Investigative Site
      • Baranquilla, Colombia
        • Novartis Investigative Site
      • Barranquilla, Colombia
        • Novartis Investigative Site
      • Bogota, Colombia
        • Novartis Investigative Site
      • Bogotá, Colombia, 00000
        • Novartis Investigative Site
      • Cali, Colombia
        • Novartis Investigative Site
      • Cartegena, Colombia
        • Novartis Investigative Site
      • Espinal, Colombia, 11001
        • Novartis Investigative Site
      • Monteria, Colombia
        • Novartis Investigative Site
      • Pasto, Colombia, 745
        • Novartis Investigative Site
    • Atlantico
      • Barranquilla, Atlantico, Colombia
        • Novartis Investigative Site
    • Bolivar
      • Cartagena, Bolivar, Colombia
        • Novartis Investigative Site
    • Caldas
      • Manizoles, Caldas, Colombia, 1700
        • Novartis Investigative Site
    • Cundinamarca
      • Bogota, Cundinamarca, Colombia
        • Novartis Investigative Site
    • Risaralda
      • Pereira, Risaralda, Colombia
        • Novartis Investigative Site
    • Santander
      • Floridablanca, Santander, Colombia, 57-7
        • Novartis Investigative Site
  • Czech Republic
      • Beroun, Czech Republic, 266 01
        • Novartis Investigative Site
      • Brandys nad Labem, Czech Republic, 250 01
        • Novartis Investigative Site
      • Novy Jicin, Czech Republic, 741 01
        • Novartis Investigative Site
      • Prague 4, Czech Republic, 146 24
        • Novartis Investigative Site
      • Prague 6, Czech Republic, 160 00
        • Novartis Investigative Site
      • Praha 9, Czech Republic
        • Novartis Investigative Site
      • Uherske Hradiste, Czech Republic, 68601
        • Novartis Investigative Site
      • Usti nad Orlici, Czech Republic, 562 18
        • Novartis Investigative Site
  • Germany
      • Berlin, Germany, 10117
        • Novartis Investigative Site
      • Frankfurt, Germany, 60594
        • Novartis Investigative Site
      • Melsungen, Germany, 34212
        • Novartis Investigative Site
      • Nuernberg, Germany, 90471
        • Novartis Investigative Site
      • Wiesbaden, Germany, 65191
        • Novartis Investigative Site
      • Witten, Germany, 58455
        • Novartis Investigative Site
  • Hungary
      • Budapest, Hungary, 1125
        • Novartis Investigative Site
      • Budapest, Hungary, 1145
        • Novartis Investigative Site
      • Gyongyos, Hungary, 3200
        • Novartis Investigative Site
      • Kaposvar, Hungary, 7400
        • Novartis Investigative Site
      • Komarom, Hungary, 2900
        • Novartis Investigative Site
      • Mosonmagyarovar, Hungary, 9200
        • Novartis Investigative Site
      • Pecs, Hungary, 7624
        • Novartis Investigative Site
      • Sopron, Hungary, 9400
        • Novartis Investigative Site
      • Szentes, Hungary, 6600
        • Novartis Investigative Site
      • Veszprem, Hungary, 8200
        • Novartis Investigative Site
  • India
      • Chennai, India, 600086
        • Novartis Investigative Site
      • Hyderabad, India, 500 063
        • Novartis Investigative Site
      • Mumbai, India, 400064
        • Novartis Investigative Site
      • Nagpur, India, 440033
        • Novartis Investigative Site
      • Trichy, India, 620 018
        • Novartis Investigative Site
    • Andhra Pradesh
      • Adoni, Andhra Pradesh, India, 518301
        • Novartis Investigative Site
      • Adoni, Andhra Pradesh, India, 518302
        • Novartis Investigative Site
      • Hyderabad, Andhra Pradesh, India, 500004
        • Novartis Investigative Site
      • Visakhapatnam, Andhra Pradesh, India, 530002
        • Novartis Investigative Site
    • Gujarat
      • Ahmedabad, Gujarat, India, 380006
        • Novartis Investigative Site
      • Ahmedabad, Gujarat, India, 380014
        • Novartis Investigative Site
    • Karnataka
      • Bangalore, Karnataka, India, 560052
        • Novartis Investigative Site
      • Bangalore, Karnataka, India, 560034
        • Novartis Investigative Site
      • Belgaum, Karnataka, India, 590001
        • Novartis Investigative Site
      • Bengaluru, Karnataka, India, 560034
        • Novartis Investigative Site
    • Maharashtra
      • Nagpur, Maharashtra, India, 400 012
        • Novartis Investigative Site
      • Nagpur, Maharashtra, India, 440012
        • Novartis Investigative Site
      • Nagpur, Maharashtra, India, 44017
        • Novartis Investigative Site
      • Pune, Maharashtra, India, 411004
        • Novartis Investigative Site
      • Wardha, Maharashtra, India, 442102
        • Novartis Investigative Site
    • Punjab
      • Jalandhar, Punjab, India, 144008
        • Novartis Investigative Site
      • Ludhiana, Punjab, India, 141421
        • Novartis Investigative Site
    • Rajasthan
      • Bikaner, Rajasthan, India, 334003
        • Novartis Investigative Site
    • Tamil Nadu
      • Tiruvannamalai, Tamil Nadu, India, 606603
        • Novartis Investigative Site
      • Trichy, Tamil Nadu, India, 620018
        • Novartis Investigative Site
    • Uttar Pradesh
      • Lucknow, Uttar Pradesh, India, 226003
        • Novartis Investigative Site
  • Ireland
      • Galway, Ireland
        • Novartis Investigative Site
    • Co. Wexford
      • Gorey, Co. Wexford, Ireland
        • Novartis Investigative Site
    • Galway
      • Ballinsloe, Galway, Ireland
        • Novartis Investigative Site
  • Israel
      • Givatayim, Israel, 53583
        • Novartis Investigative Site
      • Haifa, Israel, 34616
        • Novartis Investigative Site
      • Safed, Israel, 13100
        • Novartis Investigative Site
  • Malaysia
      • Kuala Lumpur, Malaysia, 50400
        • Novartis Investigative Site
      • Kuala Lumpur, Malaysia, 56000
        • Novartis Investigative Site
    • Kedah
      • Alor Setar, Kedah, Malaysia, 05460
        • Novartis Investigative Site
    • Kelantan
      • Kota Bahru, Kelantan, Malaysia, 16150
        • Novartis Investigative Site
      • Kota Bharu, Kelantan, Malaysia, 15586
        • Novartis Investigative Site
    • Pahang
      • Kuantan, Pahang, Malaysia, 25100
        • Novartis Investigative Site
    • Selangor
      • Batu Caves, Selangor, Malaysia, 68100
        • Novartis Investigative Site
  • Netherlands
      • Breda, Netherlands, 4811SW
        • Novartis Investigative Site
      • Eindhoven, Netherlands, 5611NJ
        • Novartis Investigative Site
      • Groningen, Netherlands, NL-9711 SG
        • Novartis Investigative Site
      • Leiderdorp, Netherlands, 2352 RA
        • Novartis Investigative Site
      • Rotterdam, Netherlands, 3001 HG
        • Novartis Investigative Site
      • Velp, Netherlands, 6883ES
        • Novartis Investigative Site
      • Zoetermeer, Netherlands, 2722 EP
        • Novartis Investigative Site
  • Philippines
      • Binan City, Philippines, 4024
        • Novartis Investigative Site
      • Manila, Philippines
        • Novartis Investigative Site
      • Manila, Philippines, 1000
        • Novartis Investigative Site
      • Pasig City, Philippines
        • Novartis Investigative Site
      • Quezon City, Philippines, 1100
        • Novartis Investigative Site
    • Cavite
      • Dasmarinas, Cavite, Philippines
        • Novartis Investigative Site
    • Ilocos Norte
      • Laoag City, Ilocos Norte, Philippines, 2900
        • Novartis Investigative Site
    • Metro Manila
      • Quezon City, Metro Manila, Philippines, 1109
        • Novartis Investigative Site
  • South Africa
      • Bloemfontein, South Africa, 9317
        • Novartis Investigative Site
      • Durban, South Africa, 4001
        • Novartis Investigative Site
      • Pretoria, South Africa, 0002
        • Novartis Investigative Site
    • Western Province
      • Paarl, Western Province, South Africa, 7646
        • Novartis Investigative Site
  • Spain
      • Madrid, Spain, 28041
        • Novartis Investigative Site
      • Puerto de Sagunto, Spain, 46520
        • Novartis Investigative Site
    • Comunidad Valenciana
      • Valencia, Comunidad Valenciana, Spain, 46010
        • Novartis Investigative Site
    • Galicia
      • Ferrol, Galicia, Spain, 15405
        • Novartis Investigative Site
  • Sweden
      • Dalby, Sweden, 247 52
        • Novartis Investigative Site
      • Goteborg, Sweden, 412 55
        • Novartis Investigative Site
      • Göteborg, Sweden, 416 85
        • Novartis Investigative Site
      • Malmö, Sweden, 21152
        • Novartis Investigative Site
      • Rättvik, Sweden, 795 30
        • Novartis Investigative Site
      • Stockholm, Sweden, 111 57
        • Novartis Investigative Site
  • United States
    • Alabama
      • Birmingham, Alabama, United States, 35205
        • Novartis Investigative Site
    • California
      • Los Angeles, California, United States, 90033
        • Novartis Investigative Site
      • Northridge, California, United States, 91325
        • Novartis Investigative Site
      • Sylmar, California, United States, 91342
        • Novartis Investigative Site
    • Georgia
      • Tucker, Georgia, United States, 30084
        • Novartis Investigative Site
    • Idaho
      • Pocatello, Idaho, United States, 83209
        • Novartis Investigative Site
    • Massachusetts
      • Haverhill, Massachusetts, United States, 01830
        • Novartis Investigative Site
    • Missouri
      • St. Louis, Missouri, United States, 63125-4181
        • Novartis Investigative Site
    • New York
      • Westfiled, New York, United States, 14787
        • Novartis Investigative Site
    • North Carolina
      • Winston-Salem, North Carolina, United States, 27157
        • Novartis Investigative Site
    • Oregon
      • Portland, Oregon, United States, 97239
        • Novartis Investigative Site
    • Virginia
      • Falls Church, Virginia, United States, 22042
        • Novartis Investigative Site
    • Wisconsin
      • Marshfield, Wisconsin, United States, 54449
        • Novartis Investigative Site
      • Milwaukee, Wisconsin, United States, 53295
        • Novartis Investigative Site

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

65 years and older (Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

Systolic blood pressure 130 - 159 mmHg with any one of the following (1, 2 or 3):

  1. Men and women aged ≥ 65 years if they have at least one of the following: (secondary prevention) Coronary heart disease

    • Previous myocardial infarction or
    • Stable angina or unstable angina with documented multi-vessel coronary artery disease, > 50% stenosis in at least 2 major coronary arteries on coronary angiography, or positive stress test (ECG or nuclear perfusion scintogram), or
    • Multi-vessel PCI, or
    • Multi-vessel CABG surgery > 4 years prior to informed consent, or with recurrent angina or ischemia following surgery Stroke/TIA Previous documented stroke or documented TIA < 1 year before informed consent Peripheral artery disease
    • Previous limb bypass surgery or percutaneous transluminal angioplasty, or
    • Previous limb or foot amputation, or
    • History of intermittent claudication, with an ankle:arm BP ratio ≤ 0.80 on at least one side, or significant peripheral artery stenosis (> 50%) documented by angiography or non-invasive testing
    • Diabetes mellitus: High-risk diabetics with evidence of end-organ damage

  2. Men and women aged ≥ 65 years with no history of CVD, and with at least 1 CV risk factor (primary prevention):

    • History of dyslipidemia, defined as LDL cholesterol > 3.5 mmol/L (135 mg/dL) or HDL< 1.3 mmol/L (50 mg/dL) in women or < 1.0 mmol/L (39 mg/dL) in men or total cholesterol/HDL ratio > 5
    • History of current or recent smoking (regular tobacco use within 5 years)
    • Abdominal adiposity defined as waist/hip ratio ≥ 0.90 in women and ≥ 0.95 in men
    • History of dysglycemia defined as impaired fasting glucose (IFG - fasting plasma glucose 5.6 to 6.9 mmol/L [101 to 124 mg/dL]), or impaired glucose tolerance (IGT - fasting plasma glucose < 7 mmol/L [126 mg/dL] but 2 hour glucose 7.8 to 11.0 mmol/L [140 to 198 mg/dL]) or type 2 diabetes
    • Renal dysfunction: eGFR< 60 ml/min/1.73m2 but > 30 ml/min/1.73m2 (MDRD formula) and/or microalbuminurea/macroalbuminurea
    • Clinical evidence of left ventricular hypertrophy
  3. Men and women aged ≥ 70 years if they do not have any of the above (primary prevention)

Exclusion Criteria:

  1. Current treatment with aliskiren, an ACE-inhibitor, an ARB or an aldosterone antagonist and unable to discontinue this therapy in those without clinical vascular disease. Individuals with CVD or type 2 diabetes and/or renal dysfunction may receive an ACE-inhibitor or an ARB, but not both, contraindications to Aliskiren, Amlodipine or Hydrochlorothiazide.
  2. Use of both thiazide diuretic and amlodipine or another calcium channel blocker. Patients on only one of these two classes of drugs are eligible
  3. Uncontrolled hypertension (systolic blood pressure ≥ 160 mmHg and/or diastolic blood pressure ≥ 100 mmHg)
  4. Symptomatic heart failure, requiring the use of loop diuretics
  5. Hemodynamically significant primary valvular or outflow tract obstruction (e.g. aortic or mitral valve stenosis, asymmetric septal hypertrophy, malfunctioning prosthetic valve). Constrictive pericarditis. Complex congenital heart disease.
  6. Acute stroke < 3 months or TIA ≤ 7 days before informed consent, acute coronary syndrome < 1 months before informed consent
  7. Planned cardiac surgery or angioplasty < 3 months after informed consent or having had the procedure < 3 months before informed consent
  8. Severe renal impairment eGFR ≤ 30 ml/min/1.73m2 (MDRD formula); known renal artery stenosis ; serum potassium ≥ 5.3 mmol/L
  9. Chronic liver disease (i.e. cirrhosis, esophageal varices, portocaval shunt or persistent hepatitis) or abnormal liver function, i.e., alanine transaminase (ALT) or AST > 3x upper limit of normal (ULN)
  10. Concurrent treatment with cyclosporine or quinidine; chronic use of non-steroidal anti-inflammatory drug (NSAIDs) or cyclooxygenase-2 (COX 2) inhibitors in patients with eGFR < 60 ml/min/1.73m2 (MDRD formula)
  11. History of malignancy of any organ system (other than localized basal cell carcinoma of the skin), treated or untreated, within the past 5 years regardless of whether there is evidence of local recurrence or metastases
  12. Other serious condition(s) likely to interfere with study participation or with the ability to complete the study. Significant psychiatric illness, senility, dementia, alcohol or substance abuse, which could impair the ability to provide informed consent and to adhere to the study procedures

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Factorial Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Aliskiren + Amlodipine

In run-in period (4-5 weeks) , patients on thiazide background therapy and approximately 50% of patients on neither CCB nor thiazide background therapy received Amlodipine 5 mg and Aliskiren 150/300 mg daily in a titrated manner as per protocol.

In double blind period, patients who successfully completed run-in with Amlodipine plus Aliskiren were randomized equally to the 4 arms of the Amlodipine add-on stratum.

Patients randomized to this arm received Aliskiren 300 mg + Amlodipine 5 mg once daily during the double blind period.
Drug: Aliskiren
Aliskiren 150/300 mg once daily
Drug: Amlodipine
Amlodipine 5 mg
Experimental: Aliskiren + Hydrochlorothiazide (HCTZ)

In run-in period (4-5 weeks) , patients on CCB background therapy and approximately 50% of patients on neither thiazide nor CCB background therapy: received Hydrochlorothiazide 12.5/25 mg and Aliskiren 150/300 mg daily in a titrated manner as per protocol.

In double blind period, all patients who successfully completed run-in with HCTZ plus Aliskiren were randomized equally to the 4 arms of the HCTZ add-on stratum.

Patients randomized to this arm received Aliskiren 300 mg + HCTZ 25 mg once daily.
Drug: Aliskiren
Aliskiren 150/300 mg once daily
Drug: Hydrochlorothiazide (HCTZ)
HCTZ 12.5/25 mg
Experimental: Aliskiren + Placebo for Amlodipine

In double blind period, all patients who successfully completed run-in with Amlodipine plus Aliskiren were randomized equally to the 4 arms of the Amlodipine add-on stratum.

In double blind period, randomized patients to this arm received Aliskiren 300 mg + Placebo for Amlodipine 5 mg
Drug: Aliskiren
Aliskiren 150/300 mg once daily
Drug: Placebo for Amlodipine
Placebo for Amlodipine
Experimental: Aliskiren + Placebo for HCTZ

In double blind period, all patients who successfully completed run-in with HCTZ plus Aliskiren were randomized equally to the 4 arms of the HCTZ add-on stratum.

In double blind period, randomized patients to this arm received Aliskiren 300 mg + Placebo for HCTZ 25 mg once daily
Drug: Aliskiren
Aliskiren 150/300 mg once daily
Drug: Placebo for Hydrochlorothiazide (HCTZ)
Placebo for HCTZ 12.5/25 mg
Experimental: Amlodipine + Placebo for Aliskiren

In double blind period, all patients who successfully completed run-in with Amlodipine plus Aliskiren were randomized equally to the 4 arms of the Amlodipine add-on stratum.

In double blind period, randomized patients to this arm received Amlodipine 5 mg + placebo for Aliskiren 300 mg once daily
Drug: Amlodipine
Amlodipine 5 mg
Drug: Placebo for Aliskiren
Placebo for Aliskiren 300 mg
Experimental: HCTZ + Placebo for Aliskiren

In double blind period, all patients who successfully completed run-in with HCTZ plus Aliskiren were randomized equally to the 4 arms of the HCTZ add-on stratum.

In double blind period, randomized patients to this arm received HCTZ 25 mg + placebo for Aliskiren 300 mg once daily
Drug: Hydrochlorothiazide (HCTZ)
HCTZ 12.5/25 mg
Drug: Placebo for Aliskiren
Placebo for Aliskiren 300 mg
Placebo Comparator: Placebo for Aliskiren + Placebo for Amlodipine

In double blind period, all patients who successfully completed run-in with Amlodipine plus Aliskiren were randomized equally to the 4 arms of the Amlodipine add-on stratum.

In double blind period, randomized patients to this arm received placebo for Aliskiren 300 mg + placebo for Amlodipine 5 mg once daily
Drug: Placebo for Amlodipine
Placebo for Amlodipine
Drug: Placebo for Aliskiren
Placebo for Aliskiren 300 mg
Placebo Comparator: Placebo for Aliskiren + Placebo for HCTZ

In double blind period, all patients who successfully completed run-in with HCTZ plus Aliskiren were randomized equally to the 4 arms of the HCTZ add-on stratum.

In double blind period, randomized patients to this arm received placebo for Aliskiren 300 mg + placebo for HCTZ 25 mg once daily
Drug: Placebo for Hydrochlorothiazide (HCTZ)
Placebo for HCTZ 12.5/25 mg
Drug: Placebo for Aliskiren
Placebo for Aliskiren 300 mg

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Number of Participants With Composite Cardiovascular Endpoints in Aliskiren Based Regimen Versus Non-Aliskiren Based Regimen
Time Frame: End of study (209 days (median))
The composite CV endpoint is based on the following first adjudicated events: CV death, non-fatal MI,non-fatal stroke, significant heart failure
End of study (209 days (median))
Number of Participants With Composite Cardiovascular Endpoints in Aliskiren+Amlodipine/HCTZ Group Versus All Placebo Group
Time Frame: End of study (209 days (median))
The composite CV endpoint is based on the following first adjudicated events: CV death, non-fatal MI,non-fatal stroke, significant heart failure
End of study (209 days (median))

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change From Baseline to End of Study in Standard Assessment of Global Activities in the Elderly (SAGE) Dimensions (Part I)
Time Frame: Baseline, End of study (209 days [median])

Decline in ability to perform everyday activities independently was measured primarily by using the Standard Assessment of Global Activities in the Elderly (SAGE) scale. The SAGE comprised of 15 questions, each describing an activity. Patient had to indicate how much difficulty he/she had encountered in performing the activity in last month. Each question's score ranges from 0 (No difficulty) to 3 (difficulty levels were mild (score = 1), moderate (score =2) and severe (score=3)). Part I of SAGE included 4 dimensions:

  • Community Cognition (maximum of scores of questions 1 to 6);
  • Instrumental Activities of daily Living (IADL) (maximum of scores of questions 7 to 10);
  • Mobility (maximum of scores of questions 11 and 12);.
  • Basic Activities of daily Living (ADL) (maximum of scores of questions 13 to 15) Each dimension's total score ranged from 0 to 3. 0=best, 3=worst A negative change in value from baseline means improvement in the ability to perform everyday activities.
Baseline, End of study (209 days [median])
Percentage of Participants With Standard Assessment of Global Activities in the Elderly (SAGE) Dimensions (Part II)
Time Frame: End of study (209 days [median])

Decline in ability to perform everyday activities independently was measured primarily by using the Standard Assessment of Global Activities in the Elderly (SAGE) scale. The SAGE was comprised of 15 questions, each describing an activity. Patient had to indicate how much difficulty he/she had encountered in performing the activity in the last month. Each question's score ranges from 0 (No difficulty) to 3 (difficulty levels were mild (score = 1), moderate (score =2) and severe (score=3)).

Part II of SAGE included 2 dimensions:

  • "Normal" if the scores of all SAGE questions is 0 (i.e., No difficulty)
  • "Mobility Only" if scores of both SAGE questions 11 and 12 are 0
End of study (209 days [median])
Number of Participants With Renal Dysfunction in Aliskiren Based Regimen Versus Non-Aliskiren Based Regimen
Time Frame: End of study (209 days (median))

The renal dysfunction (composite endpoint) was defined as the first occurrence of either of the following:

  • End-stage renal disease [ESRD] requiring dialysis or transplantation
  • Doubling of serum creatinine and reaching an eGFR < 45 ml/min/1.73 m^2.
End of study (209 days (median))
Number of Participants With Total Mortality in Aliskiren Based Regimen Versus Non-aliskiren Based Regimen
Time Frame: End of study (209 days (median))
The total mortality endpoint was defined as time to death from any cause. Total mortality analysis used the date of last follow-up including the washout period as the censoring date.
End of study (209 days (median))

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change From Baseline in Mean Sitting Systolic Blood Pressure (msSBP)
Time Frame: Baseline (BL), 6 week, 6 month and 12 month
Mean sitting systolic blood pressure (msSBP) is the average of 2 sitting SBP measurements (2 minutes apart). Since each patient had their final follow-up visit at a different time in the trial, these measurements were classified as falling into the 6 week, 6 month, or 12 month measurement period. All available blood pressures were sorted within these periods and the last value within each time range used for analysis. At each timepoint, a patient must have both baseline and postbaseline values to be included in the analysis.
Baseline (BL), 6 week, 6 month and 12 month
Change From Baseline in Mean Sitting Diastolic Blood Pressure (msDBP)
Time Frame: Baseline (BL), 6 week, 6 month and 12 month
Mean sitting diastolic blood pressure (msDBP) is the average of 2 sitting DBP measurements (2 minutes apart). Since each patient had their final follow-up visit at a different time in the trial, these measurements were classified as falling into the 6 week, 6 month, or 12 month measurement period. All available blood pressures were sorted within these periods and the last value within each time range used for analysis. At each timepoint, a patient must have both baseline and postbaseline values to be included in the analysis.
Baseline (BL), 6 week, 6 month and 12 month

Collaborators and Investigators

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Sponsor

Novartis Pharmaceuticals

Publications and helpful links

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General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

January 1, 2011

Primary Completion (Actual)

November 1, 2012

Study Completion (Actual)

November 1, 2012

Study Registration Dates

First Submitted

December 10, 2010

First Submitted That Met QC Criteria

December 13, 2010

First Posted (Estimate)

December 14, 2010

Study Record Updates

Last Update Posted (Estimate)

April 8, 2014

Last Update Submitted That Met QC Criteria

February 27, 2014

Last Verified

February 1, 2014

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • CSPP100G2301
  • 2009-010170-38 (EudraCT Number)

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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