APOLLO: A Randomized Controlled Trial of Aliskiren in the Prevention of Major Cardiovascular Events in Elderly People
Sponsor
Novartis Pharmaceuticals (Industry)
Overall Status
Terminated
CT.gov ID
NCT01259297
Collaborator
(none)
2,336
184
8
22
12.7
0.6
Study Details
Study Description
Brief Summary
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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 3 |
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 Design
Study Type:
Interventional
Actual Enrollment
:
2336 participants
Allocation:
Randomized
Intervention Model:
Factorial Assignment
Masking:
Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose:
Treatment
Official Title:
A Randomized Controlled Trial of Aliskiren in the Prevention of Major Cardiovascular Events in Elderly People
Study Start Date
:
Jan 1, 2011
Actual Primary Completion Date
:
Nov 1, 2012
Actual Study Completion Date
:
Nov 1, 2012
Arms and Interventions
| 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 Aliskiren
Placebo for Aliskiren 300 mg
Drug: Placebo for Amlodipine
Placebo for Amlodipine
|
| 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 Aliskiren
Placebo for Aliskiren 300 mg
Drug: Placebo for Hydrochlorothiazide (HCTZ)
Placebo for HCTZ 12.5/25 mg
|
Outcome Measures
Primary Outcome Measures
- Number of Participants With Composite Cardiovascular Endpoints in Aliskiren Based Regimen Versus Non-Aliskiren Based Regimen [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
- Number of Participants With Composite Cardiovascular Endpoints in Aliskiren+Amlodipine/HCTZ Group Versus All Placebo Group [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
Secondary Outcome Measures
- Change From Baseline to End of Study in Standard Assessment of Global Activities in the Elderly (SAGE) Dimensions (Part I) [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.
- Percentage of Participants With Standard Assessment of Global Activities in the Elderly (SAGE) Dimensions (Part II) [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
- Number of Participants With Renal Dysfunction in Aliskiren Based Regimen Versus Non-Aliskiren Based Regimen [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.
- Number of Participants With Total Mortality in Aliskiren Based Regimen Versus Non-aliskiren Based Regimen [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.
Other Outcome Measures
- Change From Baseline in Mean Sitting Systolic Blood Pressure (msSBP) [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.
- Change From Baseline in Mean Sitting Diastolic Blood Pressure (msDBP) [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.
Eligibility Criteria
Criteria
Ages Eligible for Study:
65 Years
and Older
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
Inclusion Criteria:
Systolic blood pressure 130 - 159 mmHg with any one of the following (1, 2 or 3):
- 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
- 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
- Men and women aged ≥ 70 years if they do not have any of the above (primary prevention)
Exclusion Criteria:
-
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.
-
Use of both thiazide diuretic and amlodipine or another calcium channel blocker. Patients on only one of these two classes of drugs are eligible
-
Uncontrolled hypertension (systolic blood pressure ≥ 160 mmHg and/or diastolic blood pressure ≥ 100 mmHg)
-
Symptomatic heart failure, requiring the use of loop diuretics
-
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.
-
Acute stroke < 3 months or TIA ≤ 7 days before informed consent, acute coronary syndrome < 1 months before informed consent
-
Planned cardiac surgery or angioplasty < 3 months after informed consent or having had the procedure < 3 months before informed consent
-
Severe renal impairment eGFR ≤ 30 ml/min/1.73m2 (MDRD formula); known renal artery stenosis ; serum potassium ≥ 5.3 mmol/L
-
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)
-
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)
-
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
-
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
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Novartis Investigative Site | Birmingham | Alabama | United States | 35205 |
| 2 | Novartis Investigative Site | Los Angeles | California | United States | 90033 |
| 3 | Novartis Investigative Site | Northridge | California | United States | 91325 |
| 4 | Novartis Investigative Site | Sylmar | California | United States | 91342 |
| 5 | Novartis Investigative Site | Tucker | Georgia | United States | 30084 |
| 6 | Novartis Investigative Site | Pocatello | Idaho | United States | 83209 |
| 7 | Novartis Investigative Site | Haverhill | Massachusetts | United States | 01830 |
| 8 | Novartis Investigative Site | St. Louis | Missouri | United States | 63125-4181 |
| 9 | Novartis Investigative Site | Westfiled | New York | United States | 14787 |
| 10 | Novartis Investigative Site | Winston-Salem | North Carolina | United States | 27157 |
| 11 | Novartis Investigative Site | Portland | Oregon | United States | 97239 |
| 12 | Novartis Investigative Site | Falls Church | Virginia | United States | 22042 |
| 13 | Novartis Investigative Site | Marshfield | Wisconsin | United States | 54449 |
| 14 | Novartis Investigative Site | Milwaukee | Wisconsin | United States | 53295 |
| 15 | Novartis Investigative Site | Ciudad Autonoma de Bs As | Buenos Aires | Argentina | C1119ACN |
| 16 | Novartis Investigative Site | Coronel Suarez | Buenos Aires | Argentina | B7540GHD |
| 17 | Novartis Investigative Site | Jenin | Buenos Aires | Argentina | 6000 |
| 18 | Novartis Investigative Site | Mar del Plata | Buenos Aires | Argentina | B7600FZN |
| 19 | Novartis Investigative Site | Merlo | Buenos Aires | Argentina | 1722 |
| 20 | Novartis Investigative Site | Quilmes | Buenos Aires | Argentina | B1878GEG |
| 21 | Novartis Investigative Site | San Nicolas | Buenos Aires | Argentina | 2900 |
| 22 | Novartis Investigative Site | Cipolletti | Rio Negro | Argentina | 8324 |
| 23 | Novartis Investigative Site | Tucuman | San Miguel de Tucuman | Argentina | T4000ICL |
| 24 | Novartis Investigative Site | Rosario | Santa Fe | Argentina | S2000AGE |
| 25 | Novartis Investigative Site | Venado Tuerto | Santa Fe | Argentina | 2600 |
| 26 | Novartis Investigative Site | Buenos Aires | Argentina | 2800 | |
| 27 | Novartis Investigative Site | Buenos Aires | Argentina | 8000 | |
| 28 | Novartis Investigative Site | Buenos Aires | Argentina | C1425AWC | |
| 29 | Novartis Investigative Site | Buenos Aires | Argentina | ||
| 30 | Novartis Investigative Site | Cordoba | Argentina | X5000AAW | |
| 31 | Novartis Investigative Site | Salta | Argentina | A4406CLA | |
| 32 | Novartis Investigative Site | Santa Fe | Argentina | S3000FWO | |
| 33 | Novartis Investigative Site | Belo Horizonte | MG | Brazil | 30150-221 |
| 34 | Novartis Investigative Site | Uberaba | MG | Brazil | 38010-160 |
| 35 | Novartis Investigative Site | Campina Grande do Sul | PR | Brazil | 83430-000 |
| 36 | Novartis Investigative Site | Porto Alegre | RS | Brazil | 90880-480 |
| 37 | Novartis Investigative Site | Campinas | SP | Brazil | 13060-904 |
| 38 | Novartis Investigative Site | Marilia | SP | Brazil | 17515-000 |
| 39 | Novartis Investigative Site | Sao Jose do Rio Preto | SP | Brazil | 15150-210 |
| 40 | Novartis Investigative Site | São Paulo | SP | Brazil | 04023-900 |
| 41 | Novartis Investigative Site | Votuporanga | SP | Brazil | 15500-003 |
| 42 | Novartis Investigative Site | Calgary | Alberta | Canada | T2N 4N1 |
| 43 | Novartis Investigative Site | Edmonton | Alberta | Canada | T5A 4L8 |
| 44 | Novartis Investigative Site | Coquitlam | British Columbia | Canada | V3K 3P4 |
| 45 | Novartis Investigative Site | Winnipeg | Manitoba | Canada | R2H0R8 |
| 46 | Novartis Investigative Site | St. John's | Newfoundland and Labrador | Canada | A1B 3V6 |
| 47 | Novartis Investigative Site | Brampton | Ontario | Canada | L6Z 4N5 |
| 48 | Novartis Investigative Site | Hamilton | Ontario | Canada | L8L 2X2 |
| 49 | Novartis Investigative Site | Hamilton | Ontario | Canada | L8M 1K7 |
| 50 | Novartis Investigative Site | Hamilton | Ontario | Canada | L8N 1T8 |
| 51 | Novartis Investigative Site | London | Ontario | Canada | N6C 5J1 |
| 52 | Novartis Investigative Site | Markham | Ontario | Canada | L6B 0P9 |
| 53 | Novartis Investigative Site | Missisauga | Ontario | Canada | L4Y 1A6 |
| 54 | Novartis Investigative Site | Newmarket | Ontario | Canada | L3Y 8C3 |
| 55 | Novartis Investigative Site | Niagara Falls | Ontario | Canada | L2G 6A8 |
| 56 | Novartis Investigative Site | North York | Ontario | Canada | M2N 7J5 |
| 57 | Novartis Investigative Site | Ottawa | Ontario | Canada | K2A 3Z3 |
| 58 | Novartis Investigative Site | Ottawa | Ontario | Canada | K2B 7K2 |
| 59 | Novartis Investigative Site | St Catherines | Ontario | Canada | L2T 3Y4 |
| 60 | Novartis Investigative Site | Toronto | Ontario | Canada | M4C5T2 |
| 61 | Novartis Investigative Site | Toronto | Ontario | Canada | M4K 1N2 |
| 62 | Novartis Investigative Site | Toronto | Ontario | Canada | M4N 3M5 |
| 63 | Novartis Investigative Site | Lévis | Quebec | Canada | G6V 4Z5 |
| 64 | Novartis Investigative Site | Montreal | Quebec | Canada | H2W 1T8 |
| 65 | Novartis Investigative Site | Montreal | Quebec | Canada | H3T 1E2 |
| 66 | Novartis Investigative Site | Sainte Foy | Quebec | Canada | G1V 4G2 |
| 67 | Novartis Investigative Site | Sainte-Foy | Quebec | Canada | G1V 4G5 |
| 68 | Novartis Investigative Site | St.Gorges de Beauce | Quebec | Canada | G5Y 4TB |
| 69 | Novartis Investigative Site | Terrebonne | Quebec | Canada | J6V 2H2 |
| 70 | Novartis Investigative Site | Saskatoon | Saskatchewan | Canada | S7H 5M3 |
| 71 | Novartis Investigative Site | Quebec | Canada | G1L 3L5 | |
| 72 | Novartis Investigative Site | Temuco | Cautin | Chile | |
| 73 | Novartis Investigative Site | Vista Del Mar | I Region | Chile | 2570017 |
| 74 | Novartis Investigative Site | Temuca | TX | Chile | 4790869 |
| 75 | Novartis Investigative Site | Osorno | Chile | 5290000 | |
| 76 | Novartis Investigative Site | Santiago | Chile | ||
| 77 | Novartis Investigative Site | Barranquilla | Atlantico | Colombia | |
| 78 | Novartis Investigative Site | Cartagena | Bolivar | Colombia | |
| 79 | Novartis Investigative Site | Manizoles | Caldas | Colombia | 1700 |
| 80 | Novartis Investigative Site | Bogota | Cundinamarca | Colombia | |
| 81 | Novartis Investigative Site | Pereira | Risaralda | Colombia | |
| 82 | Novartis Investigative Site | Floridablanca | Santander | Colombia | 57-7 |
| 83 | Novartis Investigative Site | Armenia | Colombia | ||
| 84 | Novartis Investigative Site | Baranquilla | Colombia | ||
| 85 | Novartis Investigative Site | Barranquilla | Colombia | ||
| 86 | Novartis Investigative Site | Bogota | Colombia | ||
| 87 | Novartis Investigative Site | Bogotá | Colombia | 00000 | |
| 88 | Novartis Investigative Site | Cali | Colombia | ||
| 89 | Novartis Investigative Site | Cartegena | Colombia | ||
| 90 | Novartis Investigative Site | Espinal | Colombia | 11001 | |
| 91 | Novartis Investigative Site | Monteria | Colombia | ||
| 92 | Novartis Investigative Site | Pasto | Colombia | 745 | |
| 93 | Novartis Investigative Site | Beroun | Czech Republic | 266 01 | |
| 94 | Novartis Investigative Site | Brandys nad Labem | Czech Republic | 250 01 | |
| 95 | Novartis Investigative Site | Novy Jicin | Czech Republic | 741 01 | |
| 96 | Novartis Investigative Site | Prague 4 | Czech Republic | 146 24 | |
| 97 | Novartis Investigative Site | Prague 6 | Czech Republic | 160 00 | |
| 98 | Novartis Investigative Site | Praha 9 | Czech Republic | ||
| 99 | Novartis Investigative Site | Uherske Hradiste | Czech Republic | 68601 | |
| 100 | Novartis Investigative Site | Usti nad Orlici | Czech Republic | 562 18 | |
| 101 | Novartis Investigative Site | Berlin | Germany | 10117 | |
| 102 | Novartis Investigative Site | Frankfurt | Germany | 60594 | |
| 103 | Novartis Investigative Site | Melsungen | Germany | 34212 | |
| 104 | Novartis Investigative Site | Nuernberg | Germany | 90471 | |
| 105 | Novartis Investigative Site | Wiesbaden | Germany | 65191 | |
| 106 | Novartis Investigative Site | Witten | Germany | 58455 | |
| 107 | Novartis Investigative Site | Budapest | Hungary | 1125 | |
| 108 | Novartis Investigative Site | Budapest | Hungary | 1145 | |
| 109 | Novartis Investigative Site | Gyongyos | Hungary | 3200 | |
| 110 | Novartis Investigative Site | Kaposvar | Hungary | 7400 | |
| 111 | Novartis Investigative Site | Komarom | Hungary | 2900 | |
| 112 | Novartis Investigative Site | Mosonmagyarovar | Hungary | 9200 | |
| 113 | Novartis Investigative Site | Pecs | Hungary | 7624 | |
| 114 | Novartis Investigative Site | Sopron | Hungary | 9400 | |
| 115 | Novartis Investigative Site | Szentes | Hungary | 6600 | |
| 116 | Novartis Investigative Site | Veszprem | Hungary | 8200 | |
| 117 | Novartis Investigative Site | Adoni | Andhra Pradesh | India | 518301 |
| 118 | Novartis Investigative Site | Adoni | Andhra Pradesh | India | 518302 |
| 119 | Novartis Investigative Site | Hyderabad | Andhra Pradesh | India | 500004 |
| 120 | Novartis Investigative Site | Visakhapatnam | Andhra Pradesh | India | 530002 |
| 121 | Novartis Investigative Site | Ahmedabad | Gujarat | India | 380006 |
| 122 | Novartis Investigative Site | Ahmedabad | Gujarat | India | 380014 |
| 123 | Novartis Investigative Site | Bangalore | Karnataka | India | 560034 |
| 124 | Novartis Investigative Site | Bangalore | Karnataka | India | 560052 |
| 125 | Novartis Investigative Site | Belgaum | Karnataka | India | 590001 |
| 126 | Novartis Investigative Site | Bengaluru | Karnataka | India | 560034 |
| 127 | Novartis Investigative Site | Nagpur | Maharashtra | India | 400 012 |
| 128 | Novartis Investigative Site | Nagpur | Maharashtra | India | 440012 |
| 129 | Novartis Investigative Site | Nagpur | Maharashtra | India | 44017 |
| 130 | Novartis Investigative Site | Pune | Maharashtra | India | 411004 |
| 131 | Novartis Investigative Site | Wardha | Maharashtra | India | 442102 |
| 132 | Novartis Investigative Site | Jalandhar | Punjab | India | 144008 |
| 133 | Novartis Investigative Site | Ludhiana | Punjab | India | 141421 |
| 134 | Novartis Investigative Site | Bikaner | Rajasthan | India | 334003 |
| 135 | Novartis Investigative Site | Tiruvannamalai | Tamil Nadu | India | 606603 |
| 136 | Novartis Investigative Site | Trichy | Tamil Nadu | India | 620018 |
| 137 | Novartis Investigative Site | Lucknow | Uttar Pradesh | India | 226003 |
| 138 | Novartis Investigative Site | Chennai | India | 600086 | |
| 139 | Novartis Investigative Site | Hyderabad | India | 500 063 | |
| 140 | Novartis Investigative Site | Mumbai | India | 400064 | |
| 141 | Novartis Investigative Site | Nagpur | India | 440033 | |
| 142 | Novartis Investigative Site | Trichy | India | 620 018 | |
| 143 | Novartis Investigative Site | Gorey | Co. Wexford | Ireland | |
| 144 | Novartis Investigative Site | Ballinsloe | Galway | Ireland | |
| 145 | Novartis Investigative Site | Galway | Ireland | ||
| 146 | Novartis Investigative Site | Givatayim | Israel | 53583 | |
| 147 | Novartis Investigative Site | Haifa | Israel | 34616 | |
| 148 | Novartis Investigative Site | Safed | Israel | 13100 | |
| 149 | Novartis Investigative Site | Alor Setar | Kedah | Malaysia | 05460 |
| 150 | Novartis Investigative Site | Kota Bahru | Kelantan | Malaysia | 16150 |
| 151 | Novartis Investigative Site | Kota Bharu | Kelantan | Malaysia | 15586 |
| 152 | Novartis Investigative Site | Kuantan | Pahang | Malaysia | 25100 |
| 153 | Novartis Investigative Site | Batu Caves | Selangor | Malaysia | 68100 |
| 154 | Novartis Investigative Site | Kuala Lumpur | Malaysia | 50400 | |
| 155 | Novartis Investigative Site | Kuala Lumpur | Malaysia | 56000 | |
| 156 | Novartis Investigative Site | Breda | Netherlands | 4811SW | |
| 157 | Novartis Investigative Site | Eindhoven | Netherlands | 5611NJ | |
| 158 | Novartis Investigative Site | Groningen | Netherlands | NL-9711 SG | |
| 159 | Novartis Investigative Site | Leiderdorp | Netherlands | 2352 RA | |
| 160 | Novartis Investigative Site | Rotterdam | Netherlands | 3001 HG | |
| 161 | Novartis Investigative Site | Velp | Netherlands | 6883ES | |
| 162 | Novartis Investigative Site | Zoetermeer | Netherlands | 2722 EP | |
| 163 | Novartis Investigative Site | Dasmarinas | Cavite | Philippines | |
| 164 | Novartis Investigative Site | Laoag City | Ilocos Norte | Philippines | 2900 |
| 165 | Novartis Investigative Site | Quezon City | Metro Manila | Philippines | 1109 |
| 166 | Novartis Investigative Site | Binan City | Philippines | 4024 | |
| 167 | Novartis Investigative Site | Manila | Philippines | 1000 | |
| 168 | Novartis Investigative Site | Manila | Philippines | ||
| 169 | Novartis Investigative Site | Pasig City | Philippines | ||
| 170 | Novartis Investigative Site | Quezon City | Philippines | 1100 | |
| 171 | Novartis Investigative Site | Paarl | Western Province | South Africa | 7646 |
| 172 | Novartis Investigative Site | Bloemfontein | South Africa | 9317 | |
| 173 | Novartis Investigative Site | Durban | South Africa | 4001 | |
| 174 | Novartis Investigative Site | Pretoria | South Africa | 0002 | |
| 175 | Novartis Investigative Site | Valencia | Comunidad Valenciana | Spain | 46010 |
| 176 | Novartis Investigative Site | Ferrol | Galicia | Spain | 15405 |
| 177 | Novartis Investigative Site | Madrid | Spain | 28041 | |
| 178 | Novartis Investigative Site | Puerto de Sagunto | Spain | 46520 | |
| 179 | Novartis Investigative Site | Dalby | Sweden | 247 52 | |
| 180 | Novartis Investigative Site | Goteborg | Sweden | 412 55 | |
| 181 | Novartis Investigative Site | Göteborg | Sweden | 416 85 | |
| 182 | Novartis Investigative Site | Malmö | Sweden | 21152 | |
| 183 | Novartis Investigative Site | Rättvik | Sweden | 795 30 | |
| 184 | Novartis Investigative Site | Stockholm | Sweden | 111 57 |
Sponsors and Collaborators
- Novartis Pharmaceuticals
Investigators
- Study Director: Novartis Pharmaceuticals, Novartis Pharmaceuticals
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.Responsible Party:
Novartis Pharmaceuticals
ClinicalTrials.gov Identifier:
NCT01259297
Other Study ID Numbers:
- CSPP100G2301
- 2009-010170-38
First Posted:
Dec 14, 2010
Last Update Posted:
Apr 8, 2014
Last Verified:
Feb 1, 2014
Keywords provided by Novartis Pharmaceuticals
Additional relevant MeSH terms:
Study Results
Participant Flow
| Recruitment Details | |
|---|---|
| Pre-assignment Detail |
| Arm/Group Title | Aliskiren + Hydrochlorothiazide (HCTZ) | Aliskiren + Placebo for HCTZ | Aliskiren + Amlodipine | Aliskiren + Placebo for Amlodipine | HCTZ + Placebo for Aliskiren | Placebo for Aliskiren + Placebo for HCTZ | Amlodipine + Placebo for Aliskiren | Placebo for Aliskiren + Placebo for Amlodipine |
|---|---|---|---|---|---|---|---|---|
| Arm/Group Description | 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. | 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 | 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. | 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 | 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 | 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 | 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 | 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 |
| Period Title: Run-in Open Label Period (4-5 Weeks) | ||||||||
| STARTED | 1335 | 0 | 1001 | 0 | 0 | 0 | 0 | 0 |
| COMPLETED | 980 | 0 | 779 | 0 | 0 | 0 | 0 | 0 |
| NOT COMPLETED | 355 | 0 | 222 | 0 | 0 | 0 | 0 | 0 |
| Period Title: Run-in Open Label Period (4-5 Weeks) | ||||||||
| STARTED | 244 | 232 | 189 | 195 | 251 | 253 | 196 | 199 |
| COMPLETED | 242 | 229 | 188 | 191 | 247 | 245 | 190 | 196 |
| NOT COMPLETED | 2 | 3 | 1 | 4 | 4 | 8 | 6 | 3 |
Baseline Characteristics
| Arm/Group Title | Aliskiren + Hydrochlorothiazide (HCTZ) | Aliskiren + Placebo for HCTZ | Aliskiren + Amlodipine | Aliskiren + Placebo for Amlodipine | HCTZ + Placebo for Aliskiren | Placebo for Aliskiren + Placebo for HCTZ | Amlodipine + Placebo for Aliskiren | Placebo for Aliskiren + Placebo for Amlodipine | Total |
|---|---|---|---|---|---|---|---|---|---|
| Arm/Group Description | 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. | 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 | 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. Patients randomized to this arm received Aliskiren 300 mg + Amlodipine 5 mg once daily during the double blind period. | 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 | 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 | 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 | In double blind period, all patients who successfully completed run-in with Amlodipine plus Aliskiren were run-in stratum 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 | 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 | Total of all reporting groups |
| Overall Participants | 244 | 232 | 189 | 195 | 251 | 253 | 196 | 199 | 1759 |
| Age, Customized (participants) [Number] | |||||||||
| >=65 to <75 years |
165
67.6%
|
174
75%
|
127
67.2%
|
125
64.1%
|
180
71.7%
|
189
74.7%
|
135
68.9%
|
134
67.3%
|
1229
69.9%
|
| >=75 years |
79
32.4%
|
58
25%
|
62
32.8%
|
70
35.9%
|
71
28.3%
|
64
25.3%
|
61
31.1%
|
65
32.7%
|
530
30.1%
|
| Sex: Female, Male (Count of Participants) | |||||||||
| Female |
119
48.8%
|
109
47%
|
91
48.1%
|
89
45.6%
|
122
48.6%
|
108
42.7%
|
87
44.4%
|
88
44.2%
|
813
46.2%
|
| Male |
125
51.2%
|
123
53%
|
98
51.9%
|
106
54.4%
|
129
51.4%
|
145
57.3%
|
109
55.6%
|
111
55.8%
|
946
53.8%
|
Outcome Measures
| Title | Number of Participants With Composite Cardiovascular Endpoints in Aliskiren Based Regimen Versus Non-Aliskiren Based Regimen |
|---|---|
| Description | The composite CV endpoint is based on the following first adjudicated events: CV death, non-fatal MI,non-fatal stroke, significant heart failure |
| Time Frame | End of study (209 days (median)) |
Outcome Measure Data
| Analysis Population Description |
|---|
| Full Analysis set. 1759 patients were randomized as against the originally planned 11,000. A total of 25 primary CV composite endpoints had accrued during median follow-up of 209 days versus planned 2000 primary endpoints during planned follow-up of average 5 years. These low numbers significantly limit interpretation of the results. |
| Arm/Group Title | Aliskiren Based Regimen | Non-Aliskiren Based Regimen |
|---|---|---|
| Arm/Group Description | This regimen includes all the patients who were randomized to the treatment arms that included Aliskiren such as Aliskiren + hydrochlorothiazide (HCTZ), Aliskiren + placebo for HCTZ, Aliskiren + Amlodipine, Aliskiren + placebo for Amlodipine. | This regimen includes all the patients who were randomized to the treatment arms that did not include Aliskiren such as HCTZ + Placebo for Aliskiren, Placebo for Aliskiren + Placebo for HCTZ, Amlodipine + Placebo for Aliskiren, Placebo for Aliskiren + Placebo for Amlodipine |
| Measure Participants | 860 | 899 |
| Number [participants] |
11
4.5%
|
14
6%
|
| Title | Change From Baseline to End of Study in Standard Assessment of Global Activities in the Elderly (SAGE) Dimensions (Part I) |
|---|---|
| Description | 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. |
| Time Frame | Baseline, End of study (209 days [median]) |
Outcome Measure Data
| Analysis Population Description |
|---|
| Full Analysis Set: Due to the sparse post-baseline data following early termination of the study, this analysis was not performed as planned in protocol.Hence, no meaningful conclusion could be drawn. Patients who completed both baseline and post-baseline SAGE questionnaires (Part II) were included in this analysis. |
| Arm/Group Title | Aliskiren Based Regimen | Non-Aliskiren Based Regimen |
|---|---|---|
| Arm/Group Description | This regimen includes all the patients who were randomized to the treatment arms that included Aliskiren such as Aliskiren + Hydrochlorothiazide (HCTZ), Aliskiren + placebo for HCTZ, Aliskiren + Amlodipine, Aliskiren + placebo for Amlodipine. | This regimen includes all the patients who were randomized to the treatment arms that did not include Aliskiren such as HCTZ + Placebo for Aliskiren, Placebo for Aliskiren + Placebo for HCTZ, Amlodipine + Placebo for Aliskiren, Placebo for Aliskiren + Placebo for Amlodipine |
| Measure Participants | 592 | 618 |
| Community Cognition |
-0.04
(0.768)
|
-0.05
(0.741)
|
| Instrumental Activities of daily Living (IADL) |
-0.06
(0.562)
|
-0.04
(0.505)
|
| Mobility |
0.01
(0.791)
|
0.00
(0.779)
|
| ADL |
-0.09
(0.525)
|
-0.08
(0.520)
|
| Title | Change From Baseline in Mean Sitting Systolic Blood Pressure (msSBP) |
|---|---|
| Description | 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. |
| Time Frame | Baseline (BL), 6 week, 6 month and 12 month |
Outcome Measure Data
| Analysis Population Description |
|---|
| Full analysis Set : All randomized patients, regardless of receiving study medication. n=number of patients with non-missing assessments at baseline and each post-baseline visit. |
| Arm/Group Title | Aliskiren Based Regimen | Non-Aliskiren Based Regimen |
|---|---|---|
| Arm/Group Description | This regimen includes all the patients who were randomized to the treatment arms that included Aliskiren such as Aliskiren + Hydrochlorothiazide (HCTZ), Aliskiren + placebo for HCTZ, Aliskiren + Amlodipine, Aliskiren + placebo for Amlodipine. | This regimen includes all the patients who were randomized to the treatment arms that did not include Aliskiren such as HCTZ + Placebo for Aliskiren, Placebo for Aliskiren + Placebo for HCTZ, Amlodipine + Placebo for Aliskiren, Placebo for Aliskiren + Placebo for Amlodipine |
| Measure Participants | 860 | 899 |
| change from Baseline to 6 week (n=821,867) |
-11.9
(0.50)
|
-8.02
(0.48)
|
| change from baseline to 6 month (n=730,775) |
-10.1
(0.52)
|
-6.8
(0.50)
|
| change from baseline to 12 month (n=397,399) |
-7.7
(0.68)
|
-5.8
(0.68)
|
| Title | Number of Participants With Composite Cardiovascular Endpoints in Aliskiren+Amlodipine/HCTZ Group Versus All Placebo Group |
|---|---|
| Description | The composite CV endpoint is based on the following first adjudicated events: CV death, non-fatal MI,non-fatal stroke, significant heart failure |
| Time Frame | End of study (209 days (median)) |
Outcome Measure Data
| Analysis Population Description |
|---|
| Full Analysis set. 1759 patients were randomized as against the originally planned 11,000. A total of 25 primary CV composite endpoints had accrued during median follow-up of 209 days versus planned 2000 primary endpoints during planned follow-up of average 5 years. These low numbers significantly limit interpretation of the results. |
| Arm/Group Title | Aliskiren+Amlodipine/HCTZ Group | Placebo |
|---|---|---|
| Arm/Group Description | This reporting group includes all the patients who has received Aliskiren plus an additional BP lowering drug (Amlodipine or Hydrochlorothiazide). This reporting group includes patients from arms such as Aliskiren + Hydrochlorothiazide (HCTZ) and Aliskiren + Amlodipine. | This reporting group includes all the patients who has received placebo of aliskiren plus placebo of an additional BP lowering drug (amlodipine or hydrochlorothiazide). This reporting group includes patients from arms such as Placebo for Aliskiren + Placebo for HCTZ and Placebo for aliskiren + Placebo for Amlodipine . |
| Measure Participants | 433 | 452 |
| Number [participants] |
2
0.8%
|
8
3.4%
|
| Title | Percentage of Participants With Standard Assessment of Global Activities in the Elderly (SAGE) Dimensions (Part II) |
|---|---|
| Description | 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 |
| Time Frame | End of study (209 days [median]) |
Outcome Measure Data
| Analysis Population Description |
|---|
| Full Analysis Set. Number of patients with all SAGE questions non-missing for the specific visit are included in this population. Due to the sparse post-baseline data following early termination of the study, this analysis was not performed as planned in protocol.Hence, no meaningful conclusion could be drawn. |
| Arm/Group Title | Aliskiren Based Regimen | Non-Aliskiren Based Regimen |
|---|---|---|
| Arm/Group Description | This regimen includes all the patients who were randomized to the treatment arms that included Aliskiren such as Aliskiren + hydrochlorothiazide (HCTZ), Aliskiren + placebo for HCTZ, Aliskiren + Amlodipine, Aliskiren + placebo for Amlodipine. | This regimen includes all the patients who were randomized to the treatment arms that did not include Aliskiren such as HCTZ + Placebo for Aliskiren, Placebo for Aliskiren + Placebo for HCTZ, Amlodipine + Placebo for Aliskiren, Placebo for Aliskiren + Placebo for Amlodipine |
| Measure Participants | 608 | 641 |
| Normal |
44.2
18.1%
|
46.5
20%
|
| Mobility Only |
66.8
27.4%
|
68.6
29.6%
|
| Title | Number of Participants With Renal Dysfunction in Aliskiren Based Regimen Versus Non-Aliskiren Based Regimen |
|---|---|
| Description | 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. |
| Time Frame | End of study (209 days (median)) |
Outcome Measure Data
| Analysis Population Description |
|---|
| Full Analysis set. 1759 patients were randomized as against the originally planned 11,000. The duration of study follow-up was 209 days (median) as against the planned follow-up of average 5 years. These low numbers significantly limit interpretation of the results. |
| Arm/Group Title | Aliskiren Based Regimen | Non-Aliskiren Based Regimen |
|---|---|---|
| Arm/Group Description | This regimen includes all the patients who were randomized to the treatment arms that included Aliskiren such as Aliskiren + Hydrochlorothiazide (HCTZ), Aliskiren + placebo for HCTZ, Aliskiren + Amlodipine, Aliskiren + placebo for Amlodipine. | This regimen includes all the patients who were randomized to the treatment arms that did not include Aliskiren such as HCTZ + Placebo for Aliskiren, Placebo for Aliskiren + Placebo for HCTZ, Amlodipine + Placebo for Aliskiren, Placebo for Aliskiren + Placebo for Amlodipine |
| Measure Participants | 860 | 899 |
| ESRD requiring dialysis or transplantation |
0
0%
|
0
0%
|
| Doubling of creatinine & eGFR<45 ml/min/1.73 m^2 |
7
2.9%
|
1
0.4%
|
| Title | Change From Baseline in Mean Sitting Diastolic Blood Pressure (msDBP) |
|---|---|
| Description | 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. |
| Time Frame | Baseline (BL), 6 week, 6 month and 12 month |
Outcome Measure Data
| Analysis Population Description |
|---|
| Full analysis Set : All randomized patients, regardless of receiving study medication. n=number of patients with non-missing assessments at baseline and each post-baseline visit. |
| Arm/Group Title | Aliskiren Based Regimen | Non-Aliskiren Based Regimen |
|---|---|---|
| Arm/Group Description | This regimen includes all the patients who were randomized to the treatment arms that included Aliskiren such as Aliskiren + Hydrochlorothiazide (HCTZ), Aliskiren + placebo for HCTZ, Aliskiren + Amlodipine, Aliskiren + placebo for Amlodipine. | This regimen includes all the patients who were randomized to the treatment arms that did not include Aliskiren such as HCTZ + Placebo for Aliskiren, Placebo for Aliskiren + Placebo for HCTZ, Amlodipine + Placebo for Aliskiren, Placebo for Aliskiren + Placebo for Amlodipine |
| Measure Participants | 860 | 899 |
| change from Baseline to 6 week (n=821,867) |
-5.6
(0.31)
|
-3.6
(0.30)
|
| change from baseline to 6 month (n=730,775) |
-4.9
(0.33)
|
-3.5
(0.32)
|
| change from baseline to 12 month (n=397,399) |
-4.3
(0.43)
|
-3.9
(0.43)
|
| Title | Number of Participants With Total Mortality in Aliskiren Based Regimen Versus Non-aliskiren Based Regimen |
|---|---|
| Description | 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. |
| Time Frame | End of study (209 days (median)) |
Outcome Measure Data
| Analysis Population Description |
|---|
| Full Analysis set. 1759 patients were randomized as against the originally planned 11,000. The duration of study follow-up was 209 days (median) as against the planned follow-up of average 5 years. These low numbers significantly limit interpretation of the results. |
| Arm/Group Title | Aliskiren Based Regimen | Non-Aliskiren Based Regimen |
|---|---|---|
| Arm/Group Description | This regimen includes all the patients who were randomized to the treatment arms that included Aliskiren such as Aliskiren + Hydrochlorothiazide (HCTZ), Aliskiren + placebo for HCTZ, Aliskiren + Amlodipine, Aliskiren + placebo for Amlodipine. | This regimen includes all the patients who were randomized to the treatment arms that did not include Aliskiren such as HCTZ + Placebo for Aliskiren, Placebo for Aliskiren + Placebo for HCTZ, Amlodipine + Placebo for Aliskiren, Placebo for Aliskiren + Placebo for Amlodipine |
| Measure Participants | 860 | 899 |
| Number [Participants] |
5
2%
|
9
3.9%
|
Adverse Events
| Time Frame | ||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Adverse Event Reporting Description | Safety Set (SAF): The safety set consists of all randomized patients who took at least one dose of study medication. Patients were analyzed according to treatment received. | |||||||||||||||||||
| Arm/Group Title | Run-in Period: Aliskiren + Hydrochlorothiazide (HCTZ) | Run-in Period: Aliskiren + Amlodipine | Double Blind Period: Aliskiren + Hydrochlorothiazide (HCTZ) | Double Blind Period: Aliskiren + Placebo for HCTZ | Double Blind Period: Aliskiren + Amlodipine | Double Blind Period: Aliskiren + Placebo for Amlodipine | Double Blind Period: HCTZ + Placebo for Aliskiren | Double Blind Period: Placebo for Aliskiren + Placebo for HCTZ | Double Blind Period: Amlodipine + Placebo for Aliskiren | Double Blind Period: Placebo for Aliskiren + Placebo for Amlod | ||||||||||
| Arm/Group Description | 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. Patients randomized to this arm received Aliskiren 300 mg + HCTZ 25 mg once daily. | 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. Patients randomized to this arm received Aliskiren 300 mg + Amlodipine 5 mg once daily during the double blind period. | 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. | 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 | 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. | 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 | 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 | 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 | 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 | 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 | ||||||||||
All Cause Mortality |
||||||||||||||||||||
| Run-in Period: Aliskiren + Hydrochlorothiazide (HCTZ) | Run-in Period: Aliskiren + Amlodipine | Double Blind Period: Aliskiren + Hydrochlorothiazide (HCTZ) | Double Blind Period: Aliskiren + Placebo for HCTZ | Double Blind Period: Aliskiren + Amlodipine | Double Blind Period: Aliskiren + Placebo for Amlodipine | Double Blind Period: HCTZ + Placebo for Aliskiren | Double Blind Period: Placebo for Aliskiren + Placebo for HCTZ | Double Blind Period: Amlodipine + Placebo for Aliskiren | Double Blind Period: Placebo for Aliskiren + Placebo for Amlod | |||||||||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | / (NaN) | / (NaN) | / (NaN) | / (NaN) | / (NaN) | / (NaN) | / (NaN) | / (NaN) | / (NaN) | / (NaN) | ||||||||||
Serious Adverse Events |
||||||||||||||||||||
| Run-in Period: Aliskiren + Hydrochlorothiazide (HCTZ) | Run-in Period: Aliskiren + Amlodipine | Double Blind Period: Aliskiren + Hydrochlorothiazide (HCTZ) | Double Blind Period: Aliskiren + Placebo for HCTZ | Double Blind Period: Aliskiren + Amlodipine | Double Blind Period: Aliskiren + Placebo for Amlodipine | Double Blind Period: HCTZ + Placebo for Aliskiren | Double Blind Period: Placebo for Aliskiren + Placebo for HCTZ | Double Blind Period: Amlodipine + Placebo for Aliskiren | Double Blind Period: Placebo for Aliskiren + Placebo for Amlod | |||||||||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 10/1335 (0.7%) | 10/1001 (1%) | 8/244 (3.3%) | 5/232 (2.2%) | 7/189 (3.7%) | 8/195 (4.1%) | 4/251 (1.6%) | 6/253 (2.4%) | 3/196 (1.5%) | 7/199 (3.5%) | ||||||||||
| Blood and lymphatic system disorders | ||||||||||||||||||||
| Anaemia | 0/1335 (0%) | 1/1001 (0.1%) | 1/244 (0.4%) | 0/232 (0%) | 0/189 (0%) | 0/195 (0%) | 0/251 (0%) | 0/253 (0%) | 0/196 (0%) | 0/199 (0%) | ||||||||||
| Cardiac disorders | ||||||||||||||||||||
| Angina pectoris | 0/1335 (0%) | 0/1001 (0%) | 1/244 (0.4%) | 0/232 (0%) | 0/189 (0%) | 0/195 (0%) | 0/251 (0%) | 0/253 (0%) | 0/196 (0%) | 0/199 (0%) | ||||||||||
| Atrial fibrillation | 0/1335 (0%) | 0/1001 (0%) | 0/244 (0%) | 0/232 (0%) | 0/189 (0%) | 0/195 (0%) | 0/251 (0%) | 1/253 (0.4%) | 1/196 (0.5%) | 0/199 (0%) | ||||||||||
| Cardiac arrest | 0/1335 (0%) | 0/1001 (0%) | 0/244 (0%) | 0/232 (0%) | 0/189 (0%) | 0/195 (0%) | 0/251 (0%) | 1/253 (0.4%) | 0/196 (0%) | 0/199 (0%) | ||||||||||
| Ventricular fibrillation | 0/1335 (0%) | 0/1001 (0%) | 0/244 (0%) | 0/232 (0%) | 0/189 (0%) | 0/195 (0%) | 1/251 (0.4%) | 0/253 (0%) | 0/196 (0%) | 0/199 (0%) | ||||||||||
| Gastrointestinal disorders | ||||||||||||||||||||
| Abdominal hernia | 0/1335 (0%) | 0/1001 (0%) | 0/244 (0%) | 0/232 (0%) | 0/189 (0%) | 0/195 (0%) | 0/251 (0%) | 1/253 (0.4%) | 0/196 (0%) | 0/199 (0%) | ||||||||||
| Diarrhoea | 1/1335 (0.1%) | 0/1001 (0%) | 0/244 (0%) | 0/232 (0%) | 0/189 (0%) | 0/195 (0%) | 1/251 (0.4%) | 0/253 (0%) | 0/196 (0%) | 1/199 (0.5%) | ||||||||||
| Gastrointestinal haemorrhage | 0/1335 (0%) | 1/1001 (0.1%) | 0/244 (0%) | 0/232 (0%) | 0/189 (0%) | 0/195 (0%) | 0/251 (0%) | 0/253 (0%) | 0/196 (0%) | 0/199 (0%) | ||||||||||
| Haematochezia | 0/1335 (0%) | 0/1001 (0%) | 0/244 (0%) | 0/232 (0%) | 0/189 (0%) | 0/195 (0%) | 0/251 (0%) | 0/253 (0%) | 0/196 (0%) | 1/199 (0.5%) | ||||||||||
| Intestinal perforation | 0/1335 (0%) | 0/1001 (0%) | 0/244 (0%) | 0/232 (0%) | 0/189 (0%) | 0/195 (0%) | 0/251 (0%) | 0/253 (0%) | 0/196 (0%) | 1/199 (0.5%) | ||||||||||
| Pancreatitis acute | 0/1335 (0%) | 0/1001 (0%) | 0/244 (0%) | 0/232 (0%) | 0/189 (0%) | 0/195 (0%) | 0/251 (0%) | 0/253 (0%) | 1/196 (0.5%) | 0/199 (0%) | ||||||||||
| General disorders | ||||||||||||||||||||
| Chest pain | 0/1335 (0%) | 1/1001 (0.1%) | 0/244 (0%) | 0/232 (0%) | 0/189 (0%) | 0/195 (0%) | 0/251 (0%) | 0/253 (0%) | 0/196 (0%) | 0/199 (0%) | ||||||||||
| Drug interaction | 1/1335 (0.1%) | 0/1001 (0%) | 0/244 (0%) | 0/232 (0%) | 0/189 (0%) | 0/195 (0%) | 0/251 (0%) | 0/253 (0%) | 0/196 (0%) | 0/199 (0%) | ||||||||||
| Drug intolerance | 1/1335 (0.1%) | 0/1001 (0%) | 0/244 (0%) | 0/232 (0%) | 0/189 (0%) | 0/195 (0%) | 0/251 (0%) | 0/253 (0%) | 0/196 (0%) | 0/199 (0%) | ||||||||||
| Hepatobiliary disorders | ||||||||||||||||||||
| Cholecystitis | 0/1335 (0%) | 0/1001 (0%) | 0/244 (0%) | 0/232 (0%) | 0/189 (0%) | 1/195 (0.5%) | 0/251 (0%) | 0/253 (0%) | 0/196 (0%) | 0/199 (0%) | ||||||||||
| Cholecystitis acute | 0/1335 (0%) | 0/1001 (0%) | 0/244 (0%) | 0/232 (0%) | 0/189 (0%) | 0/195 (0%) | 0/251 (0%) | 1/253 (0.4%) | 0/196 (0%) | 0/199 (0%) | ||||||||||
| Infections and infestations | ||||||||||||||||||||
| Bronchitis | 0/1335 (0%) | 1/1001 (0.1%) | 0/244 (0%) | 0/232 (0%) | 0/189 (0%) | 0/195 (0%) | 0/251 (0%) | 0/253 (0%) | 0/196 (0%) | 0/199 (0%) | ||||||||||
| Cellulitis | 0/1335 (0%) | 0/1001 (0%) | 0/244 (0%) | 0/232 (0%) | 0/189 (0%) | 1/195 (0.5%) | 1/251 (0.4%) | 0/253 (0%) | 0/196 (0%) | 0/199 (0%) | ||||||||||
| Gastroenteritis | 0/1335 (0%) | 0/1001 (0%) | 0/244 (0%) | 1/232 (0.4%) | 0/189 (0%) | 0/195 (0%) | 0/251 (0%) | 0/253 (0%) | 0/196 (0%) | 0/199 (0%) | ||||||||||
| Herpes zoster | 0/1335 (0%) | 0/1001 (0%) | 0/244 (0%) | 0/232 (0%) | 0/189 (0%) | 0/195 (0%) | 1/251 (0.4%) | 0/253 (0%) | 0/196 (0%) | 0/199 (0%) | ||||||||||
| Pneumonia | 1/1335 (0.1%) | 0/1001 (0%) | 0/244 (0%) | 0/232 (0%) | 0/189 (0%) | 0/195 (0%) | 0/251 (0%) | 1/253 (0.4%) | 0/196 (0%) | 0/199 (0%) | ||||||||||
| Urinary tract infection | 0/1335 (0%) | 0/1001 (0%) | 0/244 (0%) | 0/232 (0%) | 0/189 (0%) | 1/195 (0.5%) | 1/251 (0.4%) | 0/253 (0%) | 0/196 (0%) | 0/199 (0%) | ||||||||||
| Viral infection | 0/1335 (0%) | 0/1001 (0%) | 1/244 (0.4%) | 0/232 (0%) | 0/189 (0%) | 0/195 (0%) | 0/251 (0%) | 0/253 (0%) | 0/196 (0%) | 0/199 (0%) | ||||||||||
| Injury, poisoning and procedural complications | ||||||||||||||||||||
| Femur fracture | 0/1335 (0%) | 0/1001 (0%) | 0/244 (0%) | 1/232 (0.4%) | 0/189 (0%) | 0/195 (0%) | 0/251 (0%) | 0/253 (0%) | 0/196 (0%) | 0/199 (0%) | ||||||||||
| Subdural haematoma | 0/1335 (0%) | 0/1001 (0%) | 0/244 (0%) | 0/232 (0%) | 0/189 (0%) | 0/195 (0%) | 0/251 (0%) | 0/253 (0%) | 0/196 (0%) | 1/199 (0.5%) | ||||||||||
| Investigations | ||||||||||||||||||||
| Blood creatinine increased | 1/1335 (0.1%) | 0/1001 (0%) | 0/244 (0%) | 0/232 (0%) | 0/189 (0%) | 0/195 (0%) | 0/251 (0%) | 0/253 (0%) | 0/196 (0%) | 0/199 (0%) | ||||||||||
| Blood urea increased | 1/1335 (0.1%) | 0/1001 (0%) | 0/244 (0%) | 0/232 (0%) | 0/189 (0%) | 0/195 (0%) | 0/251 (0%) | 0/253 (0%) | 0/196 (0%) | 0/199 (0%) | ||||||||||
| Metabolism and nutrition disorders | ||||||||||||||||||||
| Diabetes mellitus | 0/1335 (0%) | 0/1001 (0%) | 0/244 (0%) | 0/232 (0%) | 0/189 (0%) | 0/195 (0%) | 1/251 (0.4%) | 0/253 (0%) | 0/196 (0%) | 0/199 (0%) | ||||||||||
| Electrolyte imbalance | 0/1335 (0%) | 0/1001 (0%) | 0/244 (0%) | 0/232 (0%) | 1/189 (0.5%) | 0/195 (0%) | 0/251 (0%) | 0/253 (0%) | 0/196 (0%) | 0/199 (0%) | ||||||||||
| Hyperkalaemia | 2/1335 (0.1%) | 1/1001 (0.1%) | 1/244 (0.4%) | 0/232 (0%) | 3/189 (1.6%) | 1/195 (0.5%) | 0/251 (0%) | 0/253 (0%) | 1/196 (0.5%) | 0/199 (0%) | ||||||||||
| Hypokalaemia | 2/1335 (0.1%) | 0/1001 (0%) | 0/244 (0%) | 0/232 (0%) | 0/189 (0%) | 0/195 (0%) | 0/251 (0%) | 0/253 (0%) | 0/196 (0%) | 0/199 (0%) | ||||||||||
| Hyponatraemia | 1/1335 (0.1%) | 0/1001 (0%) | 0/244 (0%) | 0/232 (0%) | 0/189 (0%) | 0/195 (0%) | 0/251 (0%) | 0/253 (0%) | 0/196 (0%) | 0/199 (0%) | ||||||||||
| Neoplasms benign, malignant and unspecified (incl cysts and polyps) | ||||||||||||||||||||
| Basal cell carcinoma | 0/1335 (0%) | 0/1001 (0%) | 1/244 (0.4%) | 0/232 (0%) | 0/189 (0%) | 0/195 (0%) | 0/251 (0%) | 0/253 (0%) | 0/196 (0%) | 0/199 (0%) | ||||||||||
| Colon cancer | 0/1335 (0%) | 1/1001 (0.1%) | 0/244 (0%) | 0/232 (0%) | 1/189 (0.5%) | 0/195 (0%) | 0/251 (0%) | 0/253 (0%) | 0/196 (0%) | 1/199 (0.5%) | ||||||||||
| Colon cancer metastatic | 0/1335 (0%) | 1/1001 (0.1%) | 0/244 (0%) | 0/232 (0%) | 0/189 (0%) | 0/195 (0%) | 0/251 (0%) | 0/253 (0%) | 0/196 (0%) | 0/199 (0%) | ||||||||||
| Small intestine carcinoma | 0/1335 (0%) | 0/1001 (0%) | 0/244 (0%) | 1/232 (0.4%) | 0/189 (0%) | 0/195 (0%) | 0/251 (0%) | 0/253 (0%) | 0/196 (0%) | 0/199 (0%) | ||||||||||
| Nervous system disorders | ||||||||||||||||||||
| Cerebral hypoperfusion | 0/1335 (0%) | 0/1001 (0%) | 0/244 (0%) | 0/232 (0%) | 0/189 (0%) | 0/195 (0%) | 0/251 (0%) | 0/253 (0%) | 0/196 (0%) | 1/199 (0.5%) | ||||||||||
| Cerebrovascular accident | 0/1335 (0%) | 0/1001 (0%) | 0/244 (0%) | 0/232 (0%) | 0/189 (0%) | 0/195 (0%) | 0/251 (0%) | 1/253 (0.4%) | 0/196 (0%) | 0/199 (0%) | ||||||||||
| Coma | 0/1335 (0%) | 0/1001 (0%) | 0/244 (0%) | 0/232 (0%) | 0/189 (0%) | 0/195 (0%) | 0/251 (0%) | 1/253 (0.4%) | 0/196 (0%) | 0/199 (0%) | ||||||||||
| Hemiparesis | 0/1335 (0%) | 0/1001 (0%) | 0/244 (0%) | 0/232 (0%) | 1/189 (0.5%) | 0/195 (0%) | 0/251 (0%) | 0/253 (0%) | 0/196 (0%) | 0/199 (0%) | ||||||||||
| Loss of consciousness | 0/1335 (0%) | 1/1001 (0.1%) | 0/244 (0%) | 0/232 (0%) | 0/189 (0%) | 0/195 (0%) | 0/251 (0%) | 0/253 (0%) | 0/196 (0%) | 0/199 (0%) | ||||||||||
| Paraesthesia | 0/1335 (0%) | 0/1001 (0%) | 0/244 (0%) | 0/232 (0%) | 1/189 (0.5%) | 0/195 (0%) | 0/251 (0%) | 0/253 (0%) | 0/196 (0%) | 0/199 (0%) | ||||||||||
| Syncope | 0/1335 (0%) | 1/1001 (0.1%) | 3/244 (1.2%) | 0/232 (0%) | 1/189 (0.5%) | 0/195 (0%) | 0/251 (0%) | 0/253 (0%) | 0/196 (0%) | 0/199 (0%) | ||||||||||
| Psychiatric disorders | ||||||||||||||||||||
| Psychotic disorder | 0/1335 (0%) | 0/1001 (0%) | 0/244 (0%) | 0/232 (0%) | 1/189 (0.5%) | 0/195 (0%) | 0/251 (0%) | 0/253 (0%) | 0/196 (0%) | 0/199 (0%) | ||||||||||
| Renal and urinary disorders | ||||||||||||||||||||
| Azotaemia | 0/1335 (0%) | 0/1001 (0%) | 0/244 (0%) | 0/232 (0%) | 0/189 (0%) | 1/195 (0.5%) | 0/251 (0%) | 0/253 (0%) | 0/196 (0%) | 0/199 (0%) | ||||||||||
| Renal disorder | 0/1335 (0%) | 0/1001 (0%) | 0/244 (0%) | 0/232 (0%) | 0/189 (0%) | 1/195 (0.5%) | 0/251 (0%) | 0/253 (0%) | 0/196 (0%) | 0/199 (0%) | ||||||||||
| Renal failure | 0/1335 (0%) | 0/1001 (0%) | 2/244 (0.8%) | 1/232 (0.4%) | 0/189 (0%) | 0/195 (0%) | 0/251 (0%) | 0/253 (0%) | 0/196 (0%) | 0/199 (0%) | ||||||||||
| Renal failure acute | 0/1335 (0%) | 0/1001 (0%) | 0/244 (0%) | 1/232 (0.4%) | 0/189 (0%) | 0/195 (0%) | 0/251 (0%) | 0/253 (0%) | 0/196 (0%) | 0/199 (0%) | ||||||||||
| Renal impairment | 0/1335 (0%) | 0/1001 (0%) | 0/244 (0%) | 1/232 (0.4%) | 0/189 (0%) | 0/195 (0%) | 0/251 (0%) | 0/253 (0%) | 0/196 (0%) | 0/199 (0%) | ||||||||||
| Respiratory, thoracic and mediastinal disorders | ||||||||||||||||||||
| Pulmonary oedema | 0/1335 (0%) | 0/1001 (0%) | 0/244 (0%) | 0/232 (0%) | 0/189 (0%) | 1/195 (0.5%) | 0/251 (0%) | 0/253 (0%) | 0/196 (0%) | 0/199 (0%) | ||||||||||
| Skin and subcutaneous tissue disorders | ||||||||||||||||||||
| Angioedema | 0/1335 (0%) | 2/1001 (0.2%) | 0/244 (0%) | 0/232 (0%) | 0/189 (0%) | 1/195 (0.5%) | 0/251 (0%) | 0/253 (0%) | 0/196 (0%) | 1/199 (0.5%) | ||||||||||
| Vascular disorders | ||||||||||||||||||||
| Arterial occlusive disease | 0/1335 (0%) | 0/1001 (0%) | 0/244 (0%) | 0/232 (0%) | 0/189 (0%) | 1/195 (0.5%) | 0/251 (0%) | 0/253 (0%) | 0/196 (0%) | 0/199 (0%) | ||||||||||
| Hypertensive crisis | 0/1335 (0%) | 0/1001 (0%) | 0/244 (0%) | 0/232 (0%) | 0/189 (0%) | 1/195 (0.5%) | 0/251 (0%) | 0/253 (0%) | 0/196 (0%) | 0/199 (0%) | ||||||||||
| Hypotension | 0/1335 (0%) | 2/1001 (0.2%) | 0/244 (0%) | 0/232 (0%) | 0/189 (0%) | 0/195 (0%) | 0/251 (0%) | 0/253 (0%) | 0/196 (0%) | 0/199 (0%) | ||||||||||
Other (Not Including Serious) Adverse Events |
||||||||||||||||||||
| Run-in Period: Aliskiren + Hydrochlorothiazide (HCTZ) | Run-in Period: Aliskiren + Amlodipine | Double Blind Period: Aliskiren + Hydrochlorothiazide (HCTZ) | Double Blind Period: Aliskiren + Placebo for HCTZ | Double Blind Period: Aliskiren + Amlodipine | Double Blind Period: Aliskiren + Placebo for Amlodipine | Double Blind Period: HCTZ + Placebo for Aliskiren | Double Blind Period: Placebo for Aliskiren + Placebo for HCTZ | Double Blind Period: Amlodipine + Placebo for Aliskiren | Double Blind Period: Placebo for Aliskiren + Placebo for Amlod | |||||||||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 7/1335 (0.5%) | 19/1001 (1.9%) | 6/244 (2.5%) | 5/232 (2.2%) | 9/189 (4.8%) | 8/195 (4.1%) | 6/251 (2.4%) | 5/253 (2%) | 14/196 (7.1%) | 3/199 (1.5%) | ||||||||||
| Gastrointestinal disorders | ||||||||||||||||||||
| Gastritis | 0/1335 (0%) | 0/1001 (0%) | 0/244 (0%) | 0/232 (0%) | 0/189 (0%) | 2/195 (1%) | 0/251 (0%) | 0/253 (0%) | 1/196 (0.5%) | 1/199 (0.5%) | ||||||||||
| General disorders | ||||||||||||||||||||
| Oedema peripheral | 0/1335 (0%) | 7/1001 (0.7%) | 0/244 (0%) | 1/232 (0.4%) | 4/189 (2.1%) | 0/195 (0%) | 0/251 (0%) | 2/253 (0.8%) | 7/196 (3.6%) | 1/199 (0.5%) | ||||||||||
| Metabolism and nutrition disorders | ||||||||||||||||||||
| Hyperkalaemia | 1/1335 (0.1%) | 0/1001 (0%) | 1/244 (0.4%) | 1/232 (0.4%) | 0/189 (0%) | 2/195 (1%) | 1/251 (0.4%) | 1/253 (0.4%) | 1/196 (0.5%) | 0/199 (0%) | ||||||||||
| Nervous system disorders | ||||||||||||||||||||
| Dizziness | 3/1335 (0.2%) | 7/1001 (0.7%) | 1/244 (0.4%) | 0/232 (0%) | 0/189 (0%) | 2/195 (1%) | 1/251 (0.4%) | 1/253 (0.4%) | 0/196 (0%) | 0/199 (0%) | ||||||||||
| Vascular disorders | ||||||||||||||||||||
| Hypotension | 3/1335 (0.2%) | 5/1001 (0.5%) | 4/244 (1.6%) | 3/232 (1.3%) | 6/189 (3.2%) | 2/195 (1%) | 4/251 (1.6%) | 1/253 (0.4%) | 5/196 (2.6%) | 1/199 (0.5%) | ||||||||||
Limitations/Caveats
Due to early termination, 1759 patients were randomized as against 11,000. Only 25 primary endpoints had accrued during median follow-up of 209 days as against planned 2000 in 5 years. These low numbers significantly limit interpretation of results.
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 or disclosure of trial results in their entirety.
Results Point of Contact
| Name/Title | Study Director |
|---|---|
| Organization | Novartis Pharmaceuticals |
| Phone | 862-778-8300 |
| trialandresults.registries@novartis.com |
Responsible Party:
Novartis Pharmaceuticals
ClinicalTrials.gov Identifier:
NCT01259297
Other Study ID Numbers:
- CSPP100G2301
- 2009-010170-38
First Posted:
Dec 14, 2010
Last Update Posted:
Apr 8, 2014
Last Verified:
Feb 1, 2014