TerminatedNCT01259297APOLLOUpdated Apr 8, 2014Results posted

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

A Phase 3 interventional study of Aliskiren and Amlodipine in Cardiovascular Events, sponsored by Novartis Pharmaceuticals. Terminated at 185 sites in 18 countries. Open to participants aged 65 Years and older. Per ClinicalTrials.gov, last updated 2014-04-08.

Sponsored by Novartis Pharmaceuticals (part of Novartis) · Phase 3, Interventional, and Treatment

Why this study was terminated

Terminated early in agreement with Health Authorities for feasibility reasons

Phase: Phase 3
Study type: Interventional
Enrollment: 2,336
Allocation: Randomized
Ages: 65 Years and older
Sex: All

Study 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.

Read the 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.

Conditions studied

Cardiovascular Events

Keywords

Aliskiren
Elderly
Major Cardiovascular Events
Effect of aliskiren-based regimen on major CV events (composite of CV death, non-fatal MI, non-fatal stroke and significant heart failure) in the elderly

In context

Lead sponsor

Novartis Pharmaceuticals is the lead sponsor of 2,711 studies on the registry; 218 are open to participants now.

Of its 582 completed or terminated interventional studies of FDA-regulated products, 435 (75%) have results posted.

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Counted across the registry records on this site, refreshed daily.

Who can participate

Ages eligible: 65 Years and older
Sexes eligible: All
Accepts healthy volunteers: No

Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.

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

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

Study design

Phase: Phase 3
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Factorial assignment
Masking: Quadruple (Participant, Care provider, Investigator, Outcomes assessor)
Enrollment: 2,336 participants (actual)

Study arms

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 · Drug: Amlodipine
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 · Drug: Hydrochlorothiazide (HCTZ)
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 · Drug: 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 · Drug: Placebo for Hydrochlorothiazide (HCTZ)
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 · Drug: Placebo for Aliskiren
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) · Drug: Placebo for Aliskiren
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 · Drug: 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 · Drug: Placebo for Hydrochlorothiazide (HCTZ)

Interventions

DrugAliskiren
Aliskiren 150/300 mg once daily
DrugAmlodipine
Amlodipine 5 mg
DrugHydrochlorothiazide (HCTZ)
HCTZ 12.5/25 mg
DrugPlacebo for Aliskiren
Placebo for Aliskiren 300 mg
DrugPlacebo for Amlodipine
Placebo for Amlodipine
DrugPlacebo for Hydrochlorothiazide (HCTZ)
Placebo for HCTZ 12.5/25 mg

What researchers measure

Primary outcomes

Number of Participants With Composite Cardiovascular Endpoints in Aliskiren Based Regimen Versus Non-Aliskiren Based Regimen
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))
Number of Participants With Composite Cardiovascular Endpoints in Aliskiren+Amlodipine/HCTZ Group Versus All Placebo Group
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))

Secondary outcomes

Change From Baseline to End of Study in Standard Assessment of Global Activities in the Elderly (SAGE) Dimensions (Part I)
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])
Percentage of Participants With Standard Assessment of Global Activities in the Elderly (SAGE) Dimensions (Part II)
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])
Number of Participants With Renal Dysfunction in Aliskiren Based Regimen Versus Non-Aliskiren Based Regimen
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))
Number of Participants With Total Mortality in Aliskiren Based Regimen Versus Non-aliskiren Based Regimen
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))

Other outcomes

Change From Baseline in Mean Sitting Systolic Blood Pressure (msSBP)
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
Change From Baseline in Mean Sitting Diastolic Blood Pressure (msDBP)
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

Results

Posted Apr 8, 2014

Limitations and 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.

Participant flow

Run-in Open Label Period (4-5 Weeks)

Participant flow — Run-in Open Label Period (4-5 Weeks)
Milestone	Aliskiren + Hydrochlorothiazide (HCTZ)	Aliskiren + Amlodipine
Started	1335	1001
Completed	980	779
Not completed	355	222

Double Blind Randomized Period

Participant flow — Double Blind Randomized Period
Milestone	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
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
Withdrew: Death	1	1	1	2	1	5	2	1
Withdrew: Withdrew informed consent/ refused visit	1	1	0	2	2	1	1	1
Withdrew: Other reasons	0	1	0	0	1	2	3	1

Outcome measures

PrimaryNumber of Participants With Composite Cardiovascular Endpoints in Aliskiren Based Regimen Versus Non-Aliskiren Based Regimen

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))
Reported as:: Number · participants

Number of Participants With Composite Cardiovascular Endpoints in Aliskiren Based Regimen Versus Non-Aliskiren Based Regimen
participants	Aliskiren Based Regimen	Non-Aliskiren Based Regimen
Number of Participants With Composite Cardiovascular Endpoints in Aliskiren Based Regimen Versus Non-Aliskiren Based Regimen	11	14

SecondaryChange From Baseline to End of Study in Standard Assessment of Global Activities in the Elderly (SAGE) Dimensions (Part I)

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])
Reported as:: Mean · units on a scale

Change From Baseline to End of Study in Standard Assessment of Global Activities in the Elderly (SAGE) Dimensions (Part I)
units on a scale	Aliskiren Based Regimen	Non-Aliskiren Based Regimen
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

Other pre-specifiedChange From Baseline in Mean Sitting Systolic Blood Pressure (msSBP)

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
Reported as:: Least squares mean · mmHg

Change From Baseline in Mean Sitting Systolic Blood Pressure (msSBP)
mmHg	Aliskiren Based Regimen	Non-Aliskiren Based Regimen
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

PrimaryNumber of Participants With Composite Cardiovascular Endpoints in Aliskiren+Amlodipine/HCTZ Group Versus All Placebo Group

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))
Reported as:: Number · participants

Number of Participants With Composite Cardiovascular Endpoints in Aliskiren+Amlodipine/HCTZ Group Versus All Placebo Group
participants	Aliskiren+Amlodipine/HCTZ Group	Placebo
Number of Participants With Composite Cardiovascular Endpoints in Aliskiren+Amlodipine/HCTZ Group Versus All Placebo Group	2	8

SecondaryPercentage of Participants With Standard Assessment of Global Activities in the Elderly (SAGE) Dimensions (Part II)

Time frame:: End of study (209 days [median])
Reported as:: Number · percentage of participants

Percentage of Participants With Standard Assessment of Global Activities in the Elderly (SAGE) Dimensions (Part II)
percentage of participants	Aliskiren Based Regimen	Non-Aliskiren Based Regimen
Normal	44.2	46.5
Mobility Only	66.8	68.6

SecondaryNumber of Participants With Renal Dysfunction in Aliskiren Based Regimen Versus Non-Aliskiren Based Regimen

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))
Reported as:: Number · participants

Number of Participants With Renal Dysfunction in Aliskiren Based Regimen Versus Non-Aliskiren Based Regimen
participants	Aliskiren Based Regimen	Non-Aliskiren Based Regimen
ESRD requiring dialysis or transplantation	0	0
Doubling of creatinine & eGFR<45 ml/min/1.73 m^2	7	1

Other pre-specifiedChange From Baseline in Mean Sitting Diastolic Blood Pressure (msDBP)

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
Reported as:: Least squares mean · mmHg

Change From Baseline in Mean Sitting Diastolic Blood Pressure (msDBP)
mmHg	Aliskiren Based Regimen	Non-Aliskiren Based Regimen
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

SecondaryNumber of Participants With Total Mortality in Aliskiren Based Regimen Versus Non-aliskiren Based Regimen

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))
Reported as:: Number · Participants

Number of Participants With Total Mortality in Aliskiren Based Regimen Versus Non-aliskiren Based Regimen
Participants	Aliskiren Based Regimen	Non-Aliskiren Based Regimen
Number of Participants With Total Mortality in Aliskiren Based Regimen Versus Non-aliskiren Based Regimen	5	9

Adverse events

Non-serious events are listed at a 1% frequency threshold.

Adverse event summary by group
Group	Deaths	Serious	Other
Run-in Period: Aliskiren + Hydrochlorothiazide (HCTZ)	—	10/1,335 (0.7%)	7/1,335 (0.5%)
Run-in Period: Aliskiren + Amlodipine	—	10/1,001 (1%)	19/1,001 (1.9%)
Double Blind Period: Aliskiren + Hydrochlorothiazide (HCTZ)	—	8/244 (3.3%)	6/244 (2.5%)
Double Blind Period: Aliskiren + Placebo for HCTZ	—	5/232 (2.2%)	5/232 (2.2%)
Double Blind Period: Aliskiren + Amlodipine	—	7/189 (3.7%)	9/189 (4.8%)
Double Blind Period: Aliskiren + Placebo for Amlodipine	—	8/195 (4.1%)	8/195 (4.1%)
Double Blind Period: HCTZ + Placebo for Aliskiren	—	4/251 (1.6%)	6/251 (2.4%)
Double Blind Period: Placebo for Aliskiren + Placebo for HCTZ	—	6/253 (2.4%)	5/253 (2%)
Double Blind Period: Amlodipine + Placebo for Aliskiren	—	3/196 (1.5%)	14/196 (7.1%)
Double Blind Period: Placebo for Aliskiren + Placebo for Amlod	—	7/199 (3.5%)	3/199 (1.5%)

Most frequent serious events

Showing 10 of 54

Most frequent serious events
Event	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
HyperkalaemiaMetabolism and nutrition disorders	2/1335	1/1001	1/244	0/232	3/189	1/195	0/251	0/253	1/196	0/199
SyncopeNervous system disorders	0/1335	1/1001	3/244	0/232	1/189	0/195	0/251	0/253	0/196	0/199
Renal failureRenal and urinary disorders	0/1335	0/1001	2/244	1/232	0/189	0/195	0/251	0/253	0/196	0/199
Electrolyte imbalanceMetabolism and nutrition disorders	0/1335	0/1001	0/244	0/232	1/189	0/195	0/251	0/253	0/196	0/199
Colon cancerNeoplasms benign, malignant and unspecified (incl cysts and polyps)	0/1335	1/1001	0/244	0/232	1/189	0/195	0/251	0/253	0/196	1/199
HemiparesisNervous system disorders	0/1335	0/1001	0/244	0/232	1/189	0/195	0/251	0/253	0/196	0/199
ParaesthesiaNervous system disorders	0/1335	0/1001	0/244	0/232	1/189	0/195	0/251	0/253	0/196	0/199
Psychotic disorderPsychiatric disorders	0/1335	0/1001	0/244	0/232	1/189	0/195	0/251	0/253	0/196	0/199
CholecystitisHepatobiliary disorders	0/1335	0/1001	0/244	0/232	0/189	1/195	0/251	0/253	0/196	0/199
CellulitisInfections and infestations	0/1335	0/1001	0/244	0/232	0/189	1/195	1/251	0/253	0/196	0/199

Most frequent other events

Most frequent other events
Event	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
Oedema peripheralGeneral disorders	0/1335	7/1001	0/244	1/232	4/189	0/195	0/251	2/253	7/196	1/199
HypotensionVascular disorders	3/1335	5/1001	4/244	3/232	6/189	2/195	4/251	1/253	5/196	1/199
GastritisGastrointestinal disorders	0/1335	0/1001	0/244	0/232	0/189	2/195	0/251	0/253	1/196	1/199
HyperkalaemiaMetabolism and nutrition disorders	1/1335	0/1001	1/244	1/232	0/189	2/195	1/251	1/253	1/196	0/199
DizzinessNervous system disorders	3/1335	7/1001	1/244	0/232	0/189	2/195	1/251	1/253	0/196	0/199

Baseline characteristics

Full analysis Set (FAS): All randomized patients, regardless of receiving study medication.

Age, Customized
Age, Customized(participants)	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
>=65 to <75 years	165	174	127	125	180	189	135	134	1229
>=75 years	79	58	62	70	71	64	61	65	530

Sex: Female, Male
Sex: Female, Male(Participants)	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
Female	119	109	91	89	122	108	87	88	813
Male	125	123	98	106	129	145	109	111	946

Study locations

185 sites

Novartis Investigative Site
Birmingham, Alabama 35205, United States
Novartis Investigative Site
Los Angeles, California 90033, United States
Novartis Investigative Site
Northridge, California 91325, United States
Novartis Investigative Site
Sylmar, California 91342, United States
Novartis Investigative Site
Tucker, Georgia 30084, United States
Novartis Investigative Site
Pocatello, Idaho 83209, United States
Novartis Investigative Site
Haverhill, Massachusetts 01830, United States
Novartis Investigative Site
St Louis, Missouri 63125-4181, United States
Novartis Investigative Site
Westfiled, New York 14787, United States
Novartis Investigative Site
Winston-Salem, North Carolina 27157, United States
Novartis Investigative Site
Portland, Oregon 97239, United States
Novartis Investigative Site
Falls Church, Virginia 22042, United States
Novartis Investigative Site
Marshfield, Wisconsin 54449, United States
Novartis Investigative Site
Milwaukee, Wisconsin 53295, United States
Novartis Investigative Site
Buenos Aires, Buenos Aires 2800, Argentina
Novartis Investigative Site
Buenos Aires, Buenos Aires 8000, Argentina
Novartis Investigative Site
Buenos Aires, Buenos Aires C1425AWC, Argentina
Novartis Investigative Site
Buenos Aires, Buenos Aires, Argentina
Novartis Investigative Site
Ciudad Autonoma de Bs As, Buenos Aires C1119ACN, Argentina
Novartis Investigative Site
Coronel Suárez, Buenos Aires B7540GHD, Argentina
Novartis Investigative Site
Jenin, Buenos Aires 6000, Argentina
Novartis Investigative Site
Mar del Plata, Buenos Aires B7600FZN, Argentina
Novartis Investigative Site
Merlo, Buenos Aires 1722, Argentina
Novartis Investigative Site
Quilmes, Buenos Aires B1878GEG, Argentina
Novartis Investigative Site
San Nicolás de los Arroyos, Buenos Aires 2900, Argentina
Novartis Investigative Site
Córdoba, Córdoba Province X5000AAW, Argentina
Novartis Investigative Site
Cipolletti, Río Negro Province 8324, Argentina
Novartis Investigative Site
Salta, Salta Province A4406CLA, Argentina
Novartis Investigative Site
San Miguel de Tucumán, San Miguel de Tucuman T4000ICL, Argentina
Novartis Investigative Site
Rosario, Santa Fe Province S2000AGE, Argentina
Novartis Investigative Site
Santa Fe, Santa Fe Province S3000FWO, Argentina
Novartis Investigative Site
Venado Tuerto, Santa Fe Province 2600, Argentina
Novartis Investigative Site
Belo Horizonte, Minas Gerais 30150-221, Brazil
Novartis Investigative Site
Uberaba, Minas Gerais 38010-160, Brazil
Novartis Investigative Site
Campina Grande do Sul, Paraná 83430-000, Brazil
Novartis Investigative Site
Porto Alegre, Rio Grande do Sul 90880-480, Brazil
Novartis Investigative Site
Campinas, São Paulo 13060-904, Brazil
Novartis Investigative Site
Marília, São Paulo 17515-000, Brazil
Novartis Investigative Site
São José do Rio Preto, São Paulo 15150-210, Brazil
Novartis Investigative Site
São Paulo, São Paulo 04023-900, Brazil
Novartis Investigative Site
Votuporanga, São Paulo 15500-003, Brazil
Novartis Investigative Site
Calgary, Alberta T2N 4N1, Canada
Novartis Investigative Site
Edmonton, Alberta T5A 4L8, Canada
Novartis Investigative Site
Coquitlam, British Columbia V3K 3P4, Canada
Novartis Investigative Site
Winnipeg, Manitoba R2H0R8, Canada
Novartis Investigative Site
St. John's, Newfoundland and Labrador A1B 3V6, Canada
Novartis Investigative Site
Brampton, Ontario L6Z 4N5, Canada
Novartis Investigative Site
Hamilton, Ontario L8L 2X2, Canada
Novartis Investigative Site
Hamilton, Ontario L8M 1K7, Canada
Novartis Investigative Site
Hamilton, Ontario L8N 1T8, Canada
Novartis Investigative Site
London, Ontario N6C 5J1, Canada
Novartis Investigative Site
Markham, Ontario L6B 0P9, Canada
Novartis Investigative Site
Missisauga, Ontario L4Y 1A6, Canada
Novartis Investigative Site
Newmarket, Ontario L3Y 8C3, Canada
Novartis Investigative Site
Niagara Falls, Ontario L2G 6A8, Canada
Novartis Investigative Site
North York, Ontario M2N 7J5, Canada
Novartis Investigative Site
Ottawa, Ontario K2A 3Z3, Canada
Novartis Investigative Site
Ottawa, Ontario K2B 7K2, Canada
Novartis Investigative Site
Saint Catherines, Ontario L2T 3Y4, Canada
Novartis Investigative Site
Toronto, Ontario M4C5T2, Canada
Novartis Investigative Site
Toronto, Ontario M4K 1N2, Canada
Novartis Investigative Site
Toronto, Ontario M4N 3M5, Canada
Novartis Investigative Site
Lévis, Quebec G6V 4Z5, Canada
Novartis Investigative Site
Montreal, Quebec H2W 1T8, Canada
Novartis Investigative Site
Montreal, Quebec H3T 1E2, Canada
Novartis Investigative Site
Québec, Quebec G1L 3L5, Canada
Novartis Investigative Site
Sainte-Foy, Quebec G1V 4G2, Canada
Novartis Investigative Site
Sainte-Foy, Quebec G1V 4G5, Canada
Novartis Investigative Site
St.Gorges de Beauce, Quebec G5Y 4TB, Canada
Novartis Investigative Site
Terrebonne, Quebec J6V 2H2, Canada
Novartis Investigative Site
Saskatoon, Saskatchewan S7H 5M3, Canada
Novartis Investigative Site
Temuco, Cautin, Chile
Novartis Investigative Site
Osorno, Osorno 5290000, Chile
Novartis Investigative Site
Vista Del Mar, Tarapacá 2570017, Chile
Novartis Investigative Site
Temuca, TX 4790869, Chile
Novartis Investigative Site
Santiago, Chile
Novartis Investigative Site
Barranquilla, Atlántico, Colombia
Novartis Investigative Site
Manizoles, Caldas Department 1700, Colombia
Novartis Investigative Site
Barranquilla, Colombia, Colombia
Novartis Investigative Site
Cali, Colombia, Colombia
Novartis Investigative Site
Cartegena, Colombia, Colombia
Novartis Investigative Site
Pasto, Colombia 745, Colombia
Novartis Investigative Site
Bogota, Cundinamarca, Colombia
Novartis Investigative Site
Cartagena, Departamento de Bolívar, Colombia
Novartis Investigative Site
Pereira, Risaralda Department, Colombia
Novartis Investigative Site
Floridablanca, Santander Department 57-7, Colombia
Novartis Investigative Site
Armenia, Colombia
Novartis Investigative Site
Baranquilla, Colombia
Novartis Investigative Site
Barranquilla, Colombia
Novartis Investigative Site
Bogotá, 00000, Colombia
Novartis Investigative Site
Bogotá, Colombia
Novartis Investigative Site
Espinal, 11001, Colombia
Novartis Investigative Site
Montería, Colombia
Novartis Investigative Site
Beroun, Czech Republic 266 01, Czechia
Novartis Investigative Site
Brandýs nad Labem, Czech Republic 250 01, Czechia
Novartis Investigative Site
Prague, Czech Republic 160 00, Czechia
Novartis Investigative Site
Prague, Czech Republic, Czechia
Novartis Investigative Site
Ústí nad Orlicí, Czech Republic 562 18, Czechia
Novartis Investigative Site
Nový Jičín, 741 01, Czechia
Novartis Investigative Site
Prague, 146 24, Czechia

Showing the first 100 of 185 sites across 18 countries.

References and documents

Publications

Teo KK, Pfeffer M, Mancia G, O'Donnell M, Dagenais G, Diaz R, Dans A, Liu L, Bosch J, Joseph P, Copland I, Jung H, Pogue J, Yusuf S; Aliskiren Prevention of Later Life Outcomes trial Investigators. Aliskiren alone or with other antihypertensives in the elderly with borderline and stage 1 hypertension: the APOLLO trial. Eur Heart J. 2014 Jul;35(26):1743-51. doi: 10.1093/eurheartj/ehu079. Epub 2014 Mar 9. PubMed 24616335 ↗

Updates

Tracking since Sep 25, 2026

No changes since tracking began. The registry record was last updated on Apr 8, 2014, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗

Registry details

Key details

Study ID: NCT01259297
Lead sponsor: Novartis Pharmaceuticals
Responsible party: Sponsor
First posted: Dec 14, 2010
Start date: Jan 2011
Primary completion: Nov 2012
Completion: Nov 2012
Results posted: Apr 8, 2014
Last update: Apr 8, 2014

Study contacts

Novartis Pharmaceuticals

study director · Novartis Pharmaceuticals

View the source record on ClinicalTrials.gov ↗

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This study is terminated, as verified in Feb 2014. You cannot join it, but the record below documents what was studied.

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Studies of the drugs tested here: Aliskiren · Amlodipine · Hydrochlorothiazide

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