SAALT: Subtracting Salt and Adding Losartan Trial (0954A-335)

Study Overview
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Brief Summary
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To evaluate the effectiveness of diet management with a losartan based titration regimen versus losartan based titration regimen alone on blood pressure reduction in hypertensive patients.

Official Title
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Randomized Open-label Trial to Evaluate the Effectiveness of Diet Management With a Losartan Titration Regimen Versus Losartan Titration Regimen Alone on Blood Pressure Reduction in Hypertensives.

Conditions
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Hypertension

Intervention / Treatment
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* Drug: losartan potassium (+ hydrochlorothiazide [HCTZ] + calcium channel blocker [CCB])
* Behavioral: Low Salt Diet


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Non Diabetic, Newly Diagnosed And Untreated For Mild To Moderate Hypertension (blood pressure > 161; < 221; 140/90 mm Hg But < 180/110 mm Hg) Non diabetic, newly diagnosed and untreated for severe hypertension (blood pressure > 180/110 mm Hg but < 200/120 mm Hg); Patients who are asymptomatic with no evidence of significant end organ damage including direct pressure effects can be included. Patients in an urgency/emergency state are to be excluded Or Diabetic, Newly Diagnosed With Hypertension And Untreated With Mild To Moderate Hypertension (blood pressure > 161;< 221; 130/80 mm Hg But < 160/100 mm Hg); Or Patient Receiving One Antihypertensive Agent (Monotherapy Only) Used To Treat Hypertension For At Least 4 Weeks And Whose Blood Pressure Is Not Controlled: blood pressure > 161;< 221; 140/90 mm Hg But < 160/100 mm Hg Or For Diabetic And/Or Coronary Artery Disease Patients: blood pressure > 161;< 221; 130/80 mm Hg But > 161;< 221; 150/90 mm Hg The Antihypertensive Agent Will Need To Be Discontinued Prior To Starting Study Drug Exclusion Criteria: Known Secondary Hypertension Of Any Aetiology (E.G., Uncorrected Renal Artery Stenosis, Malignant Hypertension, Hypertensive Encephalopathy. Patient With Symptomatic Heart Failure (Classes 3 And 4). Patient With A Prior Myocardial Infarction Or Stroke Within The Last 6 Months Patient Has Undergone Percutaneous Coronary Angioplasty, Has Had Coronary Artery Bypass Within The Last 6 Months Or Has Unstable Angina Patient With Anuria Or Confirmed Clinically Significant Renal Or Hepatic Dysfunction (Taken From Current/Past Medical Records) And/Or Electrolyte Imbalance Laboratory Test Within The Last 3 Months Prior To Visit 1: Serum Creatinine > 130 Ìmol/L Or Creatinine Clearance < 45 Ml/Min, Ast > 3 Times Above The Normal Range, Alt > 3 Times Above The Normal Range, Serum Potassium < 3.5 Or > 5.5 Meq/L Significant Liver Or Respiratory Disease, Cancer Or Other concomitant Disease That Is Likely To Affect Life Expectancy Of The Patient

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Losartan-Based Regimen Alone (L Group)<br>Losartan-based regimen, with sequential titration including HCTZ and CCB as needed to achieve target blood pressure. | Drug: losartan potassium (+ hydrochlorothiazide [HCTZ] + calcium channel blocker [CCB])<br>* Losartan 50 mg or 100 mg once daily for 40 weeks with sequential titration including HCTZ 12.5 mg or 25 mg and CCB only as needed to achieve target blood pressure, as follows: Patients with mild-moderate hypertension, uncontrolled hypertension on monotherapy, or diabetes: Losartan 50 mg Losartan 100 mg Losartan 100 mg/HCTZ 12.5 mg Losartan 100 mg/HCTZ 25 mg Losartan 100 mg/HCTZ 25 mg + CCB Patients with severe hypertension: Losartan 50 mg/HCTZ 12.5 mg Losartan 100 mg/HCTZ 12.5 mg Losartan 100 mg/HCTZ 25 mg Losartan 100 mg/HCTZ 25 mg + CCB Losartan 100 mg/HCTZ 25 mg + increasing CCB<br>|
| Experimental: Diet Management and Losartan-Based Regimen (DML Group)<br>Losartan with sequential titration including HCTZ and CCB as needed to achieve target blood pressure combined with low-salt intake diet. | Drug: losartan potassium (+ hydrochlorothiazide [HCTZ] + calcium channel blocker [CCB])<br>* Losartan 50 mg or 100 mg once daily for 40 weeks with sequential titration including HCTZ 12.5 mg or 25 mg and CCB only as needed to achieve target blood pressure, as follows: Patients with mild-moderate hypertension, uncontrolled hypertension on monotherapy, or diabetes: Losartan 50 mg Losartan 100 mg Losartan 100 mg/HCTZ 12.5 mg Losartan 100 mg/HCTZ 25 mg Losartan 100 mg/HCTZ 25 mg + CCB Patients with severe hypertension: Losartan 50 mg/HCTZ 12.5 mg Losartan 100 mg/HCTZ 12.5 mg Losartan 100 mg/HCTZ 25 mg Losartan 100 mg/HCTZ 25 mg + CCB Losartan 100 mg/HCTZ 25 mg + increasing CCB<br>Behavioral: Low Salt Diet<br>* Low-salt intake diet (Dietary Approaches to Stop Hypertension [DASH]) including: Healthy diet Reduction in sodium intake to less than 2300 mmol/day Low alcohol consumption (less than 2 standard drinks/day)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Patients Achieving Target Blood Pressure at Week 14 From Baseline | Number of Patients Achieving Target Blood Pressure (<140/90 mm Hg and <130/80 mm Hg for diabetics) from baseline after 14 weeks of treatment | 14 Weeks | 
| Change in Systolic Blood Pressure From Baseline to Week 14 |  | 14 Weeks | 
| Change in Diastolic Blood Pressure From Baseline to Week 14 |  | 14 Weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Patients Achieving Target Blood Pressure at Week 6 From Baseline | Number of Patients Achieving Target Blood Pressure (<140/90 mm Hg and <130/80 mm Hg for diabetics) from baseline after 6 weeks of treatment | 6 Weeks | 
| Number of Patients Achieving Target Blood Pressure at Week 10 From Baseline | Number of Patients Achieving Target Blood Pressure (<140/90 mm Hg and <130/80 mm Hg for diabetics) from baseline after 10 weeks of treatment | 10 Weeks | 
| Number of Patients Achieving Target Blood Pressure at Week 40 From Baseline | Number of Patients Achieving Target Blood Pressure (<140/90 mm Hg and <130/80 mm Hg for diabetics) from baseline after 40 weeks of treatment | 40 Weeks | 
| Change in Systolic Blood Pressure From Baseline to Week 6 |  | 6 Weeks | 
| Change in Diastolic Blood Pressure From Baseline to Week 6 |  | 6 Weeks | 
| Change in Systolic Blood Pressure From Baseline to Week 10 |  | 10 Weeks | 
| Change in Diastolic Blood Pressure From Baseline to Week 10 |  | 10 Weeks | 
| Time to Achieve the Target Blood Pressure From Baseline | Time to achieve the target blood pressure (<140/90 mm Hg and <130/80 mm Hg for diabetics). | 14 Weeks |