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

• Sponsor: Novartis
• Information provided by: Novartis

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 (Clinical Trial)
• 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: July 2009
• Actual Primary Completion Date: January 2010
• Actual Study Completion Date: January 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

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

United States, New Jersey

sites in USA

East Hanover, New Jersey, United States

Sponsors and Collaborators

Novartis

Investigators

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

More Information

• Responsible Party: External Affairs, Novartis Pharmaceuticals
• ClinicalTrials.gov Identifier: NCT00931710 History of Changes
• Other Study ID Numbers: CVEA489AUS01
• First Posted: July 2, 2009
• Results First Posted: February 4, 2011
• Last Update Posted: March 7, 2011
• Last Verified: March 2011

Keywords provided by Novartis:

Hypertension; combination therapy; valsartan; cardiovascular diseases

Additional relevant MeSH terms:

Hypertension; Vascular Diseases; Cardiovascular Diseases; Amlodipine; Valsartan; Losartan; Hydrochlorothiazide; Antihypertensive Agents; Calcium Channel Blockers; Membrane Transport Modulators; Molecular Mechanisms of Pharmacological Action; Calcium-Regulating Hormones and Agents; Physiological Effects of Drugs; Vasodilator Agents; Angiotensin II Type 1 Receptor Blockers; Angiotensin Receptor Antagonists; Anti-Arrhythmia Agents; Diuretics; Natriuretic Agents; Sodium Chloride Symporter Inhibitors