EXALT: Valsartan/Amlodipine As Compared to Losartan Treatment in Stage 2 Systolic Hypertension

• Sponsor: Novartis (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00931710
• Collaborator: (none)
• Enrollment: 488
• Location: 1
• Arms: 2
• Duration (Months): 6
• Patients Per Site Per Month: 80.7

Study Details

Study Description

Brief Summary

This study will compare the antihypertensive efficacy and safety of a valsartan/amlodipine-based treatment with a losartan-based treatment in patients with Stage 2 systolic hypertension (high blood pressure, mean systolic blood pressure greater than 160 and less than 200 mmHg).

Condition or Disease	Intervention/Treatment	Phase
Stage 2 Systolic Hypertension	Drug: valsartan, amlodipine, HCTZ; Drug: Losartan, HCTZ followed by valsartan, amlodipine, HCTZ	Phase 4

Study Design

• Study Type: Interventional
• Actual Enrollment: 488 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• Official Title: A 12-week Multicenter, Randomized, Double-blind, Parallel-group, Active-control Study to Evaluate the Antihypertensive Efficacy and Safety of Valsartan/Amlodipine-based Regimen Versus a Losartan-based Regimen in Patients With Stage 2 Systolic Hypertension
• Study Start Date: Jul 1, 2009
• Actual Primary Completion Date: Jan 1, 2010
• Actual Study Completion Date: Jan 1, 2010

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Valsartan/amlodipine/HCTZ Valsartan/amlodipine-based regimen: at randomization (Visit 3) patients were treated with valsartan/amlodipine 160/5 mg for 3 weeks, followed by a forced titration at Visit 4 (Week 3) to valsartan/amlodipine/HCTZ 160/5/25 mg for 3 weeks, and a second forced titration at Visit 5 (Week 6) to valsartan/amlodipine/HCTZ 320/10/25 mg for the remaining 6 weeks of the study.	Drug: valsartan, amlodipine, HCTZ; combination Valsartan/amlodipine160/5 mg tablet for 3 weeks; Valsartan/amlodipine 160/5mg tablet +HCTZ 25 mg capsule for 3 weeks; valsartan/amlodipine 320/10 mg tablet + HCTZ 25mg capsule for remainder (6 weeks) of the study
Active Comparator: Losartan/HCTZ Losartan-based regimen: at randomization (Visit 3) patients were treated with losartan 100 mg for 3 weeks, followed by a forced titration at Visit 4 (Week 3) to losartan/HCTZ 100/25 mg. At Visit 5 (Week 6) patients were switched to valsartan/amlodipine/HCTZ 160/5/25 mg for 3 weeks and, at Visit 6 (Week 9), patients were force titrated to valsartan/amlodipine/HCTZ 320/10/25 mg for the final 3 weeks of the study.	Drug: Losartan, HCTZ followed by valsartan, amlodipine, HCTZ; losartan 100mg capsule for 3 weeks; losartan 100mg capsule +HCTZ 25 mg capsule for 3 weeks; Valsartan/amlodipine 160/5mg tablet +HCTZ 25 mg capsule for 3 weeks; valsartan/amlodipine 320/10 mg tablet + HCTZ 25mg capsule for remainder (3 weeks) of the study

Outcome Measures

Primary Outcome Measures

1. Change in Mean Sitting Systolic Blood Pressure After 6 Weeks [Baseline to Week 6]

   To compare the change from baseline in mean sitting systolic blood pressure (MSSBP) after 6 weeks of valsartan/amlodipine-based regimen with a losartan-based regimen in patients with Stage 2 systolic hypertension.

Secondary Outcome Measures

1. Change in Mean Sitting Diastolic Blood Pressure After 6 Weeks [Baseline to Week 6]

   To compare the change from baseline in mean sitting diastolic blood pressure (MSDBP) after 6 weeks of valsartan/amlodipine-based regimen with losartan-based regimen in patients with Stage 2 systolic hypertension.

2. Cumulative Percentage of Patients Achieving Blood Pressure Control [3 and 6 weeks]

   To compare the percentage of patients achieving blood pressure control (defined as patients achieving MSSBP < 140 mmHg and MSDBP < 90 mmHg) after 3 and 6 weeks of valsartan/amlodipine-based regimen with losartan-based regimen in patients with Stage 2 systolic hypertension.

3. Cumulative Percentage of Treatment Responders [3 and 6 weeks]

   To compare the percentage of treatment responders (defined as patients with MSSBP < 140 mmHg or demonstrating a decrease from baseline of ≥ 20 mmHg) after 3 and 6 weeks of valsartan/amlodipine-based regimen with losartan-based regimen in patients with Stage 2 systolic hypertension.

4. Change in Mean Sitting Systolic and Diastolic Blood Pressure After 12 Weeks [Baseline to week 12]

   To compare the change from baseline in MSSBP and MSDBP after 12 weeks of valsartan/amlodipine-based regimen with losartan-based regimen in patients with Stage 2 systolic hypertension.

5. Cumulative Percentage of Patients With Incidence of Peripheral Edema Before or at the Corresponding Visit [3, 6, 9 and 12 weeks]

   To assess the incidence of peripheral edema occurring with valsartan/amlodipine-based regimen versus losartan-based regimen in patients with Stage 2 systolic hypertension.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Male or female outpatient of 18 years of age or greater

• Stage 2 systolic hypertension defined as office Mean Sitting Systolic blood pressure (MSSBP) greater than or equal to 160 and < 200 mmHg at randomization

• Patients who were able to participate in the study, and who gave written informed consent before any study assessment was performed.

Exclusion Criteria:

• Office systolic blood pressure >200 and/or mean sitting diastolic blood pressure (MSDBP) greater than or equal to 110 mmHg at Visit 1.

• Use of four (4) or more antihypertensive medications within 30 days of Visit 1.

• Refractory hypertension, defined as blood pressure >140/90 mmHg while taking three (3) drugs at the maximum dose of each drug, one of which must be a diuretic. (Therapy with a fixed-dose combination of two active medications represents two drugs).

• Inability to safely discontinue all antihypertensive medications for 1-2 weeks prior to randomization.

Other protocol-defined inclusion/exclusion criteria may apply

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	sites in USA	East Hanover	New Jersey	United States

Sponsors and Collaborators

• Novartis

Investigators

• Study Director: Novartis Pharmaceuticals, 862-778-8300

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• ClinicalTrials.gov Identifier: NCT00931710
• Other Study ID Numbers: CVEA489AUS01
• First Posted: Jul 2, 2009
• Last Update Posted: Mar 7, 2011
• Last Verified: Mar 1, 2011

• Keywords provided by , ,: Hypertension; combination therapy; valsartan; cardiovascular diseases
• Additional relevant MeSH terms: Hypertension; Systolic Murmurs; Losartan; Amlodipine; Valsartan; Hydrochlorothiazide

Study Results

Participant Flow

Arm/Group Title	Valsartan/Amlodipine/HCTZ	Losartan/HCTZ
Arm/Group Description	Valsartan/amlodipine-based regimen: at randomization (Visit 3) patients were treated with valsartan/amlodipine 160/5 mg for 3 weeks, followed by a forced titration at Visit 4 (Week 3) to valsartan/amlodipine/HCTZ 160/5/25 mg for 3 weeks, and a second forced titration at Visit 5 (Week 6) to valsartan/amlodipine/HCTZ 320/10/25 mg for the remaining 6 weeks of the study.	Losartan-based regimen: at randomization (Visit 3) patients were treated with losartan 100 mg for 3 weeks, followed by a forced titration at Visit 4 (Week 3) to losartan/HCTZ 100/25 mg. At Visit 5 (Week 6) patients were switched to valsartan/amlodipine/HCTZ 160/5/25 mg for 3 weeks and, at Visit 6 (Week 9), patients were force-titrated to valsartan/amlodipine/HCTZ 320/10/25 mg for the final 3 weeks of the study.
Period Title: Overall Study
STARTED	241	247
COMPLETED	207	209
NOT COMPLETED	34	38

Baseline Characteristics

Arm/Group Title	Valsartan/Amlodipine/HCTZ	Losartan/HCTZ	Total
Arm/Group Description	Valsartan/amlodipine-based regimen: at randomization (Visit 3) patients were treated with valsartan/amlodipine 160/5 mg for 3 weeks, followed by a forced titration at Visit 4 (Week 3) to valsartan/amlodipine/HCTZ 160/5/25 mg for 3 weeks, and a second forced titration at Visit 5 (Week 6) to valsartan/amlodipine/HCTZ 320/10/25 mg for the remaining 6 weeks of the study.	Losartan-based regimen: at randomization (Visit 3) patients were treated with losartan 100 mg for 3 weeks, followed by a forced titration at Visit 4 (Week 3) to losartan/HCTZ 100/25 mg. At Visit 5 (Week 6) patients were switched to valsartan/amlodipine/HCTZ 160/5/25 mg for 3 weeks and, at Visit 6 (Week 9), patients were force-titrated to valsartan/amlodipine/HCTZ 320/10/25 mg for the final 3 weeks of the study.	Total of all reporting groups
Overall Participants	241	247	488
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	55.0 (9.83)	57.1 (9.69)	56.1 (9.81)
Sex: Female, Male (Count of Participants)
Female	102 42.3%	111 44.9%	213 43.6%
Male	139 57.7%	136 55.1%	275 56.4%

Outcome Measures

1. Primary Outcome

Title	Change in Mean Sitting Systolic Blood Pressure After 6 Weeks
Description	To compare the change from baseline in mean sitting systolic blood pressure (MSSBP) after 6 weeks of valsartan/amlodipine-based regimen with a losartan-based regimen in patients with Stage 2 systolic hypertension.
Time Frame	Baseline to Week 6

Outcome Measure Data

Analysis Population Description

Full Analysis Set (FAS). Last observation carried forward (LOCF).

Arm/Group Title	Valsartan/Amlodipine/HCTZ	Losartan/HCTZ
Arm/Group Description	Valsartan/amlodipine-based regimen: at randomization (Visit 3) patients were treated with valsartan/amlodipine 160/5 mg for 3 weeks, followed by a forced titration at Visit 4 (Week 3) to valsartan/amlodipine/HCTZ 160/5/25 mg for 3 weeks, and a second forced titration at Visit 5 (Week 6) to valsartan/amlodipine/HCTZ 320/10/25 mg for the remaining 6 weeks of the study.	Losartan-based regimen: at randomization (Visit 3) patients were treated with losartan 100 mg for 3 weeks, followed by a forced titration at Visit 4 (Week 3) to losartan/HCTZ 100/25 mg. At Visit 5 (Week 6) patients were switched to valsartan/amlodipine/HCTZ 160/5/25 mg for 3 weeks and, at Visit 6 (Week 9), patients were force-titrated to valsartan/amlodipine/HCTZ 320/10/25 mg for the final 3 weeks of the study.
Measure Participants	241	247
Baseline	166.8 (7.03)	168.5 (9.03)
Week 6	135.5 (16.26)	142.5 (18.89)
Change from Baseline to Week 6	-31.3 (15.87)	-26.0 (16.62)

2. Secondary Outcome

Title	Change in Mean Sitting Diastolic Blood Pressure After 6 Weeks
Description	To compare the change from baseline in mean sitting diastolic blood pressure (MSDBP) after 6 weeks of valsartan/amlodipine-based regimen with losartan-based regimen in patients with Stage 2 systolic hypertension.
Time Frame	Baseline to Week 6

Outcome Measure Data

Analysis Population Description

Full Analysis Set (FAS). Last observation carried forward (LOCF).

Arm/Group Title	Valsartan/Amlodipine/HCTZ	Losartan/HCTZ
Arm/Group Description	Valsartan/amlodipine-based regimen: at randomization (Visit 3) patients were treated with valsartan/amlodipine 160/5 mg for 3 weeks, followed by a forced titration at Visit 4 (Week 3) to valsartan/amlodipine/HCTZ 160/5/25 mg for 3 weeks, and a second forced titration at Visit 5 (Week 6) to valsartan/amlodipine/HCTZ 320/10/25 mg for the remaining 6 weeks of the study.	Losartan-based regimen: at randomization (Visit 3) patients were treated with losartan 100 mg for 3 weeks, followed by a forced titration at Visit 4 (Week 3) to losartan/HCTZ 100/25 mg. At Visit 5 (Week 6) patients were switched to valsartan/amlodipine/HCTZ 160/5/25 mg for 3 weeks and, at Visit 6 (Week 9), patients were force-titrated to valsartan/amlodipine/HCTZ 320/10/25 mg for the final 3 weeks of the study.
Measure Participants	241	247
Baseline	98.6 (7.71)	97.6 (7.88)
Week 6	85.1 (10.05)	88.5 (11.36)
Change from Baseline to Week 6	-13.6 (9.48)	-9.1 (10.03)

3. Secondary Outcome

Title	Cumulative Percentage of Patients Achieving Blood Pressure Control
Description	To compare the percentage of patients achieving blood pressure control (defined as patients achieving MSSBP < 140 mmHg and MSDBP < 90 mmHg) after 3 and 6 weeks of valsartan/amlodipine-based regimen with losartan-based regimen in patients with Stage 2 systolic hypertension.
Time Frame	3 and 6 weeks

Outcome Measure Data

Analysis Population Description

Full Analysis Set (FAS).

Arm/Group Title	Valsartan/Amlodipine/HCTZ	Losartan/HCTZ
Arm/Group Description	Valsartan/amlodipine-based regimen: at randomization (Visit 3) patients were treated with valsartan/amlodipine 160/5 mg for 3 weeks, followed by a forced titration at Visit 4 (Week 3) to valsartan/amlodipine/HCTZ 160/5/25 mg for 3 weeks, and a second forced titration at Visit 5 (Week 6) to valsartan/amlodipine/HCTZ 320/10/25 mg for the remaining 6 weeks of the study.	Losartan-based regimen: at randomization (Visit 3) patients were treated with losartan 100 mg for 3 weeks, followed by a forced titration at Visit 4 (Week 3) to losartan/HCTZ 100/25 mg. At Visit 5 (Week 6) patients were switched to valsartan/amlodipine/HCTZ 160/5/25 mg for 3 weeks and, at Visit 6 (Week 9), patients were force-titrated to valsartan/amlodipine/HCTZ 320/10/25 mg for the final 3 weeks of the study.
Measure Participants	241	247
Week 3	30.5	15.3
Week 6	61.5	47.1

4. Secondary Outcome

Title	Cumulative Percentage of Treatment Responders
Description	To compare the percentage of treatment responders (defined as patients with MSSBP < 140 mmHg or demonstrating a decrease from baseline of ≥ 20 mmHg) after 3 and 6 weeks of valsartan/amlodipine-based regimen with losartan-based regimen in patients with Stage 2 systolic hypertension.
Time Frame	3 and 6 weeks

Outcome Measure Data

Analysis Population Description

Full Analysis Set (FAS).

Arm/Group Title	Valsartan/Amlodipine/HCTZ	Losartan/HCTZ
Arm/Group Description	Valsartan/amlodipine-based regimen: at randomization (Visit 3) patients were treated with valsartan/amlodipine 160/5 mg for 3 weeks, followed by a forced titration at Visit 4 (Week 3) to valsartan/amlodipine/HCTZ 160/5/25 mg for 3 weeks, and a second forced titration at Visit 5 (Week 6) to valsartan/amlodipine/HCTZ 320/10/25 mg for the remaining 6 weeks of the study.	Losartan-based regimen: at randomization (Visit 3) patients were treated with losartan 100 mg for 3 weeks, followed by a forced titration at Visit 4 (Week 3) to losartan/HCTZ 100/25 mg. At Visit 5 (Week 6) patients were switched to valsartan/amlodipine/HCTZ 160/5/25 mg for 3 weeks and, at Visit 6 (Week 9), patients were force-titrated to valsartan/amlodipine/HCTZ 320/10/25 mg for the final 3 weeks of the study.
Measure Participants	241	247
Week 3	65.3	34.3
Week 6	87.0	71.5

5. Secondary Outcome

Title	Change in Mean Sitting Systolic and Diastolic Blood Pressure After 12 Weeks
Description	To compare the change from baseline in MSSBP and MSDBP after 12 weeks of valsartan/amlodipine-based regimen with losartan-based regimen in patients with Stage 2 systolic hypertension.
Time Frame	Baseline to week 12

Outcome Measure Data

Analysis Population Description

Full Analysis Set (FAS). Last observation carried forward (LOCF).

Arm/Group Title	Valsartan/Amlodipine/HCTZ	Losartan/HCTZ
Arm/Group Description	Valsartan/amlodipine-based regimen: at randomization (Visit 3) patients were treated with valsartan/amlodipine 160/5 mg for 3 weeks, followed by a forced titration at Visit 4 (Week 3) to valsartan/amlodipine/HCTZ 160/5/25 mg for 3 weeks, and a second forced titration at Visit 5 (Week 6) to valsartan/amlodipine/HCTZ 320/10/25 mg for the remaining 6 weeks of the study.	Losartan-based regimen: at randomization (Visit 3) patients were treated with losartan 100 mg for 3 weeks, followed by a forced titration at Visit 4 (Week 3) to losartan/HCTZ 100/25 mg. At Visit 5 (Week 6) patients were switched to valsartan/amlodipine/HCTZ 160/5/25 mg for 3 weeks and, at Visit 6 (Week 9), patients were force-titrated to valsartan/amlodipine/HCTZ 320/10/25 mg for the final 3 weeks of the study.
Measure Participants	241	247
Baseline MSSBP	166.8 (7.03)	168.5 (9.03)
Week 12 MSSBP	130.8 (16.22)	134.3 (19.41)
Change in MSSBP from baseline to Week 12	-36.0 (16.08)	-34.2 (17.69)
Baseline MSDBP	98.6 (7.71)	97.6 (7.88)
Week 12 MSDBP	82.5 (10.18)	82.5 (11.43)
Change in MSDBP from baseline to Week 12	-16.1 (9.91)	-15.1 (10.57)

6. Secondary Outcome

Title	Cumulative Percentage of Patients With Incidence of Peripheral Edema Before or at the Corresponding Visit
Description	To assess the incidence of peripheral edema occurring with valsartan/amlodipine-based regimen versus losartan-based regimen in patients with Stage 2 systolic hypertension.
Time Frame	3, 6, 9 and 12 weeks

Outcome Measure Data

Analysis Population Description

Full Analysis Set (FAS).

Arm/Group Title	Valsartan/Amlodipine/HCTZ	Losartan/HCTZ
Arm/Group Description	Valsartan/amlodipine-based regimen: at randomization (Visit 3) patients were treated with valsartan/amlodipine 160/5 mg for 3 weeks, followed by a forced titration at Visit 4 (Week 3) to valsartan/amlodipine/HCTZ 160/5/25 mg for 3 weeks, and a second forced titration at Visit 5 (Week 6) to valsartan/amlodipine/HCTZ 320/10/25 mg for the remaining 6 weeks of the study.	Losartan-based regimen: at randomization (Visit 3) patients were treated with losartan 100 mg for 3 weeks, followed by a forced titration at Visit 4 (Week 3) to losartan/HCTZ 100/25 mg. At Visit 5 (Week 6) patients were switched to valsartan/amlodipine/HCTZ 160/5/25 mg for 3 weeks and, at Visit 6 (Week 9), patients were force-titrated to valsartan/amlodipine/HCTZ 320/10/25 mg for the final 3 weeks of the study.
Measure Participants	241	247
Week 3	0.8	0.8
Week 6	0.8	0.8
Week 9	1.3	0.8
Week 12	2.9	4.5

Adverse Events

Arm/Group Title	Valsartan / Amlodipine / HCTZ		Losartan / HCTZ
Arm/Group Description	Valsartan / amlodipine / HCTZ		Losartan / HCTZ
All Cause Mortality
	Valsartan / Amlodipine / HCTZ		Losartan / HCTZ
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Valsartan / Amlodipine / HCTZ		Losartan / HCTZ
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/241 (0.4%)		2/247 (0.8%)
General disorders
Non-cardiac chest pain	1/241 (0.4%)		0/247 (0%)
Infections and infestations
Urinary tract infection	0/241 (0%)		1/247 (0.4%)
Nervous system disorders
Dizziness	0/241 (0%)		1/247 (0.4%)
Other (Not Including Serious) Adverse Events
	Valsartan / Amlodipine / HCTZ		Losartan / HCTZ
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	13/241 (5.4%)		8/247 (3.2%)
Nervous system disorders
Dizziness	13/241 (5.4%)		8/247 (3.2%)

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.