A Safety and Efficacy Trial of Aliskiren 150mg , 300 mg Compared to Ramipril 5mg, 10mg in the Elderly

• Sponsor: Novartis Pharmaceuticals (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00368277
• Collaborator: (none)
• Enrollment: 901
• Location: 1
• Arms: 2
• Duration (Months): 17
• Patients Per Site Per Month: 52.9

Study Details

Study Description

Brief Summary

Evaluate the systolic blood pressure lowering effect of aliskiren 150mg and 300mg compared to ramipril 5mg and 10mg in elderly patients with essential systolic hypertension.

Condition or Disease	Intervention/Treatment	Phase
Hypertension	Drug: Aliskiren; Drug: Ramipril; Drug: Hydrochlorothiazide; Drug: Amlodipine	Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 901 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• Official Title: A 36 Week Randomized, Double-blind, Parallel Group, Multi-center, Active-controlled, Optional Titration Study Comparing an Aliskiren-based Regimen to a Ramipril-based Regimen in Patients ≥ 65 Years Old With Systolic Essential Hypertension
• Study Start Date: Sep 1, 2006
• Actual Primary Completion Date: Feb 1, 2008
• Actual Study Completion Date: Feb 1, 2008

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Aliskiren-based regimen Aliskiren 150 mg; aliskiren 300 mg; aliskiren 300mg + hydrochlorothiazide 12.5 mg; aliskiren 300 mg + hydrochlorothiazide 25 mg; aliskiren 300 mg + hydrochlorothiazide 25 mg + amlodipine 5 mg; aliskiren 300 mg + hydrochlorothiazide 25 mg + amlodipine 10 mg	Drug: Aliskiren; Aliskiren 150 mg and 300 mg tablets taken orally, once a day in the morning; Drug: Hydrochlorothiazide; Hydrochlorothiazide 12.5 or 25 mg capsules taken orally, once a day in the morning; Drug: Amlodipine; Amlodipine 5 mg or 10 mg tablets taken orally, once a day in the morning
Active Comparator: Ramipril-based regimen Ramipril 5 mg; Ramipril 10 mg; Ramipril 10 mg + hydrochlorothiazide 12.5 mg; Ramipril 10 mg + hydrochlorothiazide 25 mg; Ramipril 10 mg + hydrochlorothiazide 25 mg + amlodipine 5 mg; Ramipril 10 mg + hydrochlorothiazide 25 mg + amlodipine 10mg	Drug: Ramipril; Ramipril 5 mg and 10 mg capsules taken orally, once a day in the morning; Drug: Hydrochlorothiazide; Hydrochlorothiazide 12.5 or 25 mg capsules taken orally, once a day in the morning; Drug: Amlodipine; Amlodipine 5 mg or 10 mg tablets taken orally, once a day in the morning

Outcome Measures

Primary Outcome Measures

1. Change From Baseline in Mean Sitting Systolic Blood Pressure to Week 12 [Baseline and Week 12]

Secondary Outcome Measures

1. Percentage of Patients With Cough [Weeks 12 and 36]

2. Percentage of Patients Achieving Blood Pressure Control at Weeks 12 and 36 Endpoints [Weeks 12 and 36]

   Blood pressure control is defined as a mean sitting blood pressure < 140/90 mm Hg

3. Change From Baseline in the Mean Sitting Diastolic Blood Pressure to Week 36 [Baseline and week 36]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 65 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Male or female outpatients ≥ 65 years old.

• Patients with essential hypertension with an msSBP ≥ 140 mmHg and < 180 mmHg, and msDBP < 110 mmHg at Visits 2 and 3. (Visit 201 was deleted by the Administrative Changes document.)

• Patients must have had a difference in msSBP of ≤ 20 mmHg between Visit 3 and the visit immediately prior to Visit 3.

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

Exclusion Criteria:

• History of renal artery stenosis.

• Known Keith-Wagener grade III or IV hypertensive retinopathy.

• History of hypertensive encephalopathy.

• Current diagnosis of heart failure (New York Heart Association Class III-IV).

• History of transient ischemic cerebral attack or cerebrovascular accident within 6 months.

• History of myocardial infarction, bypass surgery, or any percutaneous coronary intervention within 6 months.

• Current unstable angina pectoris. Patients on a stable dose of oral or topical nitrates or beta blockers for angina were acceptable.

• Concurrent potentially life threatening arrhythmia or symptomatic arrhythmia.

• Clinically significant valvular heart disease.

• Concurrent use of any antihypersensitive medications except a stable dose 3 months prior to visit 1 of alpha adrenergic blockers for benign prostatic hypertrophy (e.g., Flomax for BPH), beta blockers for angina, or beta blockers ophthalmic preparations.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Novartis Pharmaceuticals	East Hanover	New Jersey	United States	07936

Sponsors and Collaborators

• Novartis Pharmaceuticals

Investigators

• Study Director: Novartis Pharmaceuticals, Novartis Pharmaceuticals

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• ClinicalTrials.gov Identifier: NCT00368277
• Other Study ID Numbers: CSPP100A2344
• First Posted: Aug 24, 2006
• Last Update Posted: Mar 25, 2011
• Last Verified: Feb 1, 2011

• Keywords provided by , ,: Systolic hypertension; hypertension; aliskiren; blood pressure; ramipril; HTN
• Additional relevant MeSH terms: Hypertension; Amlodipine; Hydrochlorothiazide; Ramipril

Study Results

Participant Flow

Arm/Group Title	Aliskiren Based Treatment Regimen	Ramipril Based Treatment Regimen
Arm/Group Description	Aliskiren 150 mg; aliskiren 300 mg; aliskiren 300mg + hydrochlorothiazide 12.5 mg; aliskiren 300 mg + hydrochlorothiazide 25 mg; aliskiren 300 mg + hydrochlorothiazide 25 mg + amlodipine 5 mg; aliskiren 300 mg + hydrochlorothiazide 25 mg + amlodipine 10 mg	Ramipril 5 mg; Ramipril 10 mg; Ramipril 10 mg + hydrochlorothiazide 12.5 mg; Ramipril 10 mg + hydrochlorothiazide 25 mg; Ramipril 10 mg + hydrochlorothiazide 25 mg + amlodipine 5 mg; Ramipril 10 mg + hydrochlorothiazide 25 mg + amlodipine 10mg
Period Title: Overall Study
STARTED	457	444
COMPLETED	344	336
NOT COMPLETED	113	108

Baseline Characteristics

Arm/Group Title	Aliskiren Based Treatment Regimen	Ramipril Based Treatment Regimen	Total
Arm/Group Description	Aliskiren 150 mg; aliskiren 300 mg; aliskiren 300mg + hydrochlorothiazide 12.5 mg; aliskiren 300 mg + hydrochlorothiazide 25 mg; aliskiren 300 mg + hydrochlorothiazide 25 mg + amlodipine 5 mg; aliskiren 300 mg + hydrochlorothiazide 25 mg + amlodipine 10 mg	Ramipril 5 mg; Ramipril 10 mg; Ramipril 10 mg + hydrochlorothiazide 12.5 mg; Ramipril 10 mg + hydrochlorothiazide 25 mg; Ramipril 10 mg + hydrochlorothiazide 25 mg + amlodipine 5 mg; Ramipril 10 mg + hydrochlorothiazide 25 mg + amlodipine 10mg	Total of all reporting groups
Overall Participants	457	444	901
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	72.0 (5.56)	72.2 (5.62)	72.1 (5.58)
Age, Customized (participants) [Number]
65 - 74 years	312 68.3%	296 66.7%	608 67.5%
75 years and older	145 31.7%	148 33.3%	293 32.5%
Sex: Female, Male (Count of Participants)
Female	235 51.4%	237 53.4%	472 52.4%
Male	222 48.6%	207 46.6%	429 47.6%

Outcome Measures

1. Primary Outcome

Title	Change From Baseline in Mean Sitting Systolic Blood Pressure to Week 12
Time Frame	Baseline and Week 12

Outcome Measure Data

Analysis Population Description

Intent to treat (ITT), Last Observation Carried forward (LOCF)

Arm/Group Title	Aliskiren Based Treatment Regimen	Ramipril Based Treatment Regimen
Arm/Group Description	Aliskiren 150 mg; aliskiren 300 mg; aliskiren 300mg + hydrochlorothiazide 12.5 mg; aliskiren 300 mg + hydrochlorothiazide 25 mg; aliskiren 300 mg + hydrochlorothiazide 25 mg + amlodipine 5 mg; aliskiren 300 mg + hydrochlorothiazide 25 mg + amlodipine 10 mg	Ramipril 5 mg; Ramipril 10 mg; Ramipril 10 mg + hydrochlorothiazide 12.5 mg; Ramipril 10 mg + hydrochlorothiazide 25 mg; Ramipril 10 mg + hydrochlorothiazide 25 mg + amlodipine 5 mg; Ramipril 10 mg + hydrochlorothiazide 25 mg + amlodipine 10mg
Measure Participants	451	439
Least Squares Mean (Standard Error) [mm Hg]	-13.96 (0.754)	-11.64 (0.759)

2. Secondary Outcome

Title	Percentage of Patients With Cough
Time Frame	Weeks 12 and 36

Outcome Measure Data

Analysis Population Description

Safety population

Arm/Group Title	Aliskiren Based Treatment Regimen	Ramipril Based Treatment Regimen
Arm/Group Description	Aliskiren 150 mg; aliskiren 300 mg; aliskiren 300mg + hydrochlorothiazide 12.5 mg; aliskiren 300 mg + hydrochlorothiazide 25 mg; aliskiren 300 mg + hydrochlorothiazide 25 mg + amlodipine 5 mg; aliskiren 300 mg + hydrochlorothiazide 25 mg + amlodipine 10 mg	Ramipril 5 mg; Ramipril 10 mg; Ramipril 10 mg + hydrochlorothiazide 12.5 mg; Ramipril 10 mg + hydrochlorothiazide 25 mg; Ramipril 10 mg + hydrochlorothiazide 25 mg + amlodipine 5 mg; Ramipril 10 mg + hydrochlorothiazide 25 mg + amlodipine 10mg
Measure Participants	452	444
Week 12	3.1 (0.788) 0.7%	9.9 (0.794) 2.2%
Week 36	4.4 1%	14.2 3.2%

3. Secondary Outcome

Title	Percentage of Patients Achieving Blood Pressure Control at Weeks 12 and 36 Endpoints
Description	Blood pressure control is defined as a mean sitting blood pressure < 140/90 mm Hg
Time Frame	Weeks 12 and 36

Outcome Measure Data

Analysis Population Description

intent to treat (ITT), last observation carried forward (LOCF)

Arm/Group Title	Aliskiren Based Treatment Regimen	Ramipril Based Treatment Regimen
Arm/Group Description	Aliskiren 150 mg; aliskiren 300 mg; aliskiren 300mg + hydrochlorothiazide 12.5 mg; aliskiren 300 mg + hydrochlorothiazide 25 mg; aliskiren 300 mg + hydrochlorothiazide 25 mg + amlodipine 5 mg; aliskiren 300 mg + hydrochlorothiazide 25 mg + amlodipine 10 mg	Ramipril 5 mg; Ramipril 10 mg; Ramipril 10 mg + hydrochlorothiazide 12.5 mg; Ramipril 10 mg + hydrochlorothiazide 25 mg; Ramipril 10 mg + hydrochlorothiazide 25 mg + amlodipine 5 mg; Ramipril 10 mg + hydrochlorothiazide 25 mg + amlodipine 10mg
Measure Participants	451	440
week 12 endpoint	46.3 10.1%	39.3 8.9%
week 36 endpoint	65.6 14.4%	57.5 13%

4. Secondary Outcome

Title	Change From Baseline in the Mean Sitting Diastolic Blood Pressure to Week 36
Time Frame	Baseline and week 36

Outcome Measure Data

Analysis Population Description

Intent to treat (ITT), Last Observation Carried forward (LOCF)

Arm/Group Title	Aliskiren Based Treatment Regimen	Ramipril Based Treatment Regimen
Arm/Group Description	Aliskiren 150 mg; aliskiren 300 mg; aliskiren 300mg + hydrochlorothiazide 12.5 mg; aliskiren 300 mg + hydrochlorothiazide 25 mg; aliskiren 300 mg + hydrochlorothiazide 25 mg + amlodipine 5 mg; aliskiren 300 mg + hydrochlorothiazide 25 mg + amlodipine 10 mg	Ramipril 5 mg; Ramipril 10 mg; Ramipril 10 mg + hydrochlorothiazide 12.5 mg; Ramipril 10 mg + hydrochlorothiazide 25 mg; Ramipril 10 mg + hydrochlorothiazide 25 mg + amlodipine 5 mg; Ramipril 10 mg + hydrochlorothiazide 25 mg + amlodipine 10mg
Measure Participants	451	439
Least Squares Mean (Standard Error) [mm Hg]	-8.24 (0.409)	-7.02 (0.411)

Adverse Events

Time Frame	36 weeks
Arm/Group Title	Aliskiren		Ramipril
Arm/Group Description	Aliskiren based regimen		Ramipril based regimen
All Cause Mortality
	Aliskiren		Ramipril
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Aliskiren		Ramipril
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	35/452 (7.7%)		27/444 (6.1%)
Blood and lymphatic system disorders
Anaemia	0/452 (0%)		1/444 (0.2%)
Cardiac disorders
Acute myocardial infarction	0/452 (0%)		1/444 (0.2%)
Angina pectoris	0/452 (0%)		1/444 (0.2%)
Atrial fibrillation	3/452 (0.7%)		1/444 (0.2%)
Cardiac arrest	0/452 (0%)		1/444 (0.2%)
Coronary artery disease	1/452 (0.2%)		2/444 (0.5%)
Sinus bradycardia	1/452 (0.2%)		0/444 (0%)
Sinus tachycardia	0/452 (0%)		1/444 (0.2%)
Tachycardia	0/452 (0%)		1/444 (0.2%)
Trifascicular block	0/452 (0%)		1/444 (0.2%)
Ventricular tachycardia	1/452 (0.2%)		0/444 (0%)
Ear and labyrinth disorders
Vertigo	2/452 (0.4%)		0/444 (0%)
Endocrine disorders
Thyroid mass	0/452 (0%)		1/444 (0.2%)
Eye disorders
Diplopia	1/452 (0.2%)		0/444 (0%)
Eye movement disorder	1/452 (0.2%)		0/444 (0%)
Gastrointestinal disorders
Abdominal pain	1/452 (0.2%)		0/444 (0%)
Aphagia	0/452 (0%)		1/444 (0.2%)
Ascites	1/452 (0.2%)		0/444 (0%)
Colitis ischaemic	1/452 (0.2%)		0/444 (0%)
Diarrhoea	1/452 (0.2%)		0/444 (0%)
Diverticulum	0/452 (0%)		1/444 (0.2%)
Gastrointestinal pain	0/452 (0%)		1/444 (0.2%)
Nausea	2/452 (0.4%)		1/444 (0.2%)
Pancreatic mass	1/452 (0.2%)		0/444 (0%)
Pancreatitis acute	1/452 (0.2%)		0/444 (0%)
Vomiting	2/452 (0.4%)		1/444 (0.2%)
General disorders
Malaise	1/452 (0.2%)		0/444 (0%)
Non-cardiac chest pain	3/452 (0.7%)		3/444 (0.7%)
Oedema peripheral	1/452 (0.2%)		0/444 (0%)
Infections and infestations
Abdominal abscess	0/452 (0%)		1/444 (0.2%)
Catheter site infection	1/452 (0.2%)		0/444 (0%)
Diverticulitis	1/452 (0.2%)		1/444 (0.2%)
Myringitis bullous	0/452 (0%)		1/444 (0.2%)
Otitis externa	0/452 (0%)		1/444 (0.2%)
Pneumonia	2/452 (0.4%)		1/444 (0.2%)
Sepsis	0/452 (0%)		1/444 (0.2%)
Urinary tract infection	0/452 (0%)		1/444 (0.2%)
Injury, poisoning and procedural complications
Ankle fracture	0/452 (0%)		1/444 (0.2%)
Fall	1/452 (0.2%)		2/444 (0.5%)
Hip fracture	2/452 (0.4%)		1/444 (0.2%)
Lower limb fracture	0/452 (0%)		1/444 (0.2%)
Skin laceration	0/452 (0%)		1/444 (0.2%)
Metabolism and nutrition disorders
Dehydration	1/452 (0.2%)		3/444 (0.7%)
Hyperglycaemia	1/452 (0.2%)		0/444 (0%)
Hypokalaemia	0/452 (0%)		2/444 (0.5%)
Musculoskeletal and connective tissue disorders
Costochondritis	1/452 (0.2%)		0/444 (0%)
Pain in extremity	1/452 (0.2%)		0/444 (0%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Basal cell carcinoma	1/452 (0.2%)		0/444 (0%)
Bladder cancer	1/452 (0.2%)		0/444 (0%)
Breast cancer	1/452 (0.2%)		0/444 (0%)
Colon cancer stage 0	0/452 (0%)		1/444 (0.2%)
Glioblastoma	0/452 (0%)		1/444 (0.2%)
Head and neck cancer	1/452 (0.2%)		0/444 (0%)
Malignant melanoma	1/452 (0.2%)		0/444 (0%)
Metastatic neoplasm	1/452 (0.2%)		0/444 (0%)
Ovarian cancer	1/452 (0.2%)		0/444 (0%)
Pancreatic carcinoma	1/452 (0.2%)		0/444 (0%)
Prostate cancer	1/452 (0.2%)		0/444 (0%)
Squamous cell carcinoma	1/452 (0.2%)		0/444 (0%)
Squamous cell carcinoma of skin	1/452 (0.2%)		0/444 (0%)
Nervous system disorders
Anoxic encephalopathy	0/452 (0%)		1/444 (0.2%)
Cerebrovascular accident	2/452 (0.4%)		1/444 (0.2%)
Coma	0/452 (0%)		1/444 (0.2%)
Convulsion	0/452 (0%)		1/444 (0.2%)
Hypoaesthesia	0/452 (0%)		1/444 (0.2%)
Syncope	2/452 (0.4%)		4/444 (0.9%)
VIth nerve paralysis	1/452 (0.2%)		0/444 (0%)
Respiratory, thoracic and mediastinal disorders
Asthma	1/452 (0.2%)		0/444 (0%)
Chronic obstructive pulmonary disease	0/452 (0%)		1/444 (0.2%)
Pulmonary embolism	1/452 (0.2%)		0/444 (0%)
Pulmonary oedema	1/452 (0.2%)		0/444 (0%)
Vascular disorders
Deep vein thrombosis	1/452 (0.2%)		0/444 (0%)
Femoral arterial stenosis	1/452 (0.2%)		0/444 (0%)
Haematoma	0/452 (0%)		1/444 (0.2%)
Hypertension	1/452 (0.2%)		1/444 (0.2%)
Hypotension	1/452 (0.2%)		0/444 (0%)
Intermittent claudication	1/452 (0.2%)		0/444 (0%)
Malignant hypertension	0/452 (0%)		1/444 (0.2%)
Other (Not Including Serious) Adverse Events
	Aliskiren		Ramipril
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	170/452 (37.6%)		181/444 (40.8%)
Gastrointestinal disorders
Diarrhoea	29/452 (6.4%)		22/444 (5%)
General disorders
Fatigue	28/452 (6.2%)		20/444 (4.5%)
Infections and infestations
Nasopharyngitis	23/452 (5.1%)		20/444 (4.5%)
Upper respiratory tract infection	35/452 (7.7%)		28/444 (6.3%)
Urinary tract infection	17/452 (3.8%)		24/444 (5.4%)
Nervous system disorders
Dizziness	34/452 (7.5%)		37/444 (8.3%)
Headache	42/452 (9.3%)		40/444 (9%)
Respiratory, thoracic and mediastinal disorders
Cough	19/452 (4.2%)		59/444 (13.3%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

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