Effect of High and Low Sodium Diets on Blood Pressure in Hypertensive Patients Treated With Aliskiren

• Sponsor: Novartis (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00441064
• Collaborator: (none)
• Enrollment: 132
• Locations: 19
• Arms: 2
• Duration (Months): 10
• Patients Per Site: 6.9
• Patients Per Site Per Month: 0.7

Study Details

Study Description

Brief Summary

This study will compare the effects of high and low level sodium (salt) diets on blood pressure in patients with hypertension (high blood pressure) who are taking aliskiren 300 mg.

Condition or Disease	Intervention/Treatment	Phase
Hypertension	Drug: Aliskiren	Phase 4

Study Design

• Study Type: Interventional
• Actual Enrollment: 132 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Randomized, Open-label, Blinded Endpoint, Multi-center, Cross-over Study to Evaluate the Effect of High and Low Sodium Diets on Reduction in Mean 24-hour Ambulatory Blood Pressure in Systolic Hypertensive Patients Treated With Aliskiren (300 mg)
• Study Start Date: Jan 1, 2007
• Actual Primary Completion Date: Nov 1, 2007
• Actual Study Completion Date: Nov 1, 2007

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Diet Sequence Low/High Sodium Patients on low sodium diet ( <= 100 mmol/day) for the first 4 weeks and high sodium (>= 200 mmol/day) diet for the next 4 weeks. [with Aliskiren 300 mg]	Drug: Aliskiren
Experimental: Diet Sequence High/Low Sodium Patients on high sodium (>= 200 mmol/day) diet for the first 4 weeks and on low sodium diet ( <= 100 mmol/day) for the next 4 weeks. [with Aliskiren 300 mg]	Drug: Aliskiren

Outcome Measures

Primary Outcome Measures

1. Mean 24 Hour Ambulatory Systolic Blood Pressure (MASBP) in Systolic Hypertensive Patients Treated With Aliskiren (300 mg) for 4 Weeks on a High Sodium Diet Versus 4 Weeks on a Low Sodium Diet [Week 4 and week 8 (4 weeks after crossover)]

   The primary objective of the study was to assess mean 24 hour ambulatory systolic blood pressure (MASBP) in systolic hypertensive patients treated with aliskiren (300 mg) for 4 weeks on a high sodium diet versus 4 weeks on a low sodium diet. [At week 4 patients crossed over from low to high sodium diet and vice versa for 4 weeks. MASBP for patients on high sodium diet versus low sodium diet was also analyzed at week 8 (4 weeks after crossover).]

Secondary Outcome Measures

1. Mean 24 Hour Ambulatory Diastolic Blood Pressure (MADBP) in Systolic Hypertensive Patients Treated With Aliskiren (300 mg) for 4 Weeks on a High Sodium Diet Versus 4 Weeks on a Low Sodium Diet [Week 4 and week 8 (4 weeks after crossover)]

   To evaluate the mean 24 hour ambulatory diastolic blood pressure (MADBP) in systolic hypertensive patients treated with aliskiren (300 mg) for 4 weeks on a high sodium diet versus 4 weeks on a low sodium diet. [At week 4 patients crossed over from low to high sodium diet and vice versa for 4 weeks. MADBP for patients on high sodium diet versus low sodium diet was also analyzed at week 8 (4 weeks after crossover).]

2. Percentage of Responders Defined as MASBP <130 mm Hg or a Decrease From Baseline in MASBP of ≥20 mm Hg in Systolic Hypertensive Patients Treated With Aliskiren (300 mg) for 4 Weeks on a High Sodium Diet Versus 4 Weeks on a Low Sodium Diet [Week 4 and Week 8 (4 weeks after crossover)]

   To evaluate the percentage of responders defined as MASBP < 130 mm Hg or a decrease in MASBP from baseline of ≥20 mm Hg in systolic hypertensive patients treated with aliskiren (300 mg) for 4 weeks on a high sodium diet versus 4 weeks on a low sodium diet. [At week 4 patients crossed over from low to high sodium diet and vice versa for 4 weeks. Percent response for patients on high sodium diet versus low sodium diet was also analyzed at week 8 (4 weeks after crossover).]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 60 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Male or female outpatients 18-60 years old

• Patients with systolic hypertension who met the 24 hour Ambulatory Blood Pressure Monitoring (ABPM) criteria (ABPM mean daytime Systolic Blood Pressure (SBP) >= 135 mmHg and < 160 mmHg)

Exclusion Criteria:

• Overt heart failure (HF) or a history of heart failure within preceding 6 months.

• Unstable angina pectoris.

• Type 1 or Type 2 diabetes mellitus or abnormal hemoglobin A1c(HbA1c)

• Body mass index (BMI) > 30 kg/m2

• Subjects taking more than 2 antihypertensive medications.

• Use of other investigational drugs within 30 days of the time of enrollment

• Use of Tamsulosin hydrochloride and other alpha blockers.

• Use of Antiarrhythmic drugs, including digoxin.

• History of MI or cardiovascular attack (CVA) within the preceding 6 months.

• History of malignancy of any organ system, treated or untreated, within the past 5 years with the exception of localized basal cell carcinoma of the skin

• Pregnant or nursing (lactating) women

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Novartis US	Orangevale	California	United States
2	Novartis US	Brooklyn Center	Minnesota	United States
3	Novartis US	Butte	Montana	United States
4	Novartis US	Missoula	Montana	United States
5	Novartis US	Lincoln	Nebraska	United States
6	Novartis US	Johnson City	New York	United States
7	Novartis US	Asheboro	North Carolina	United States
8	Novartis US	Shelby	North Carolina	United States
9	Novartis US	Cincinnati	Ohio	United States
10	Novartis US	Kettering	Ohio	United States
11	Novartis US	Downington	Pennsylvania	United States
12	Novartis US	Erie	Pennsylvania	United States
13	Novartis US	Pittsburg	Pennsylvania	United States
14	Novartis US	Dallas	Texas	United States
15	Novartis US	Kingsport	Texas	United States
16	Novartis US	Bountiful	Utah	United States
17	Novartis US	Salt Lake City	Utah	United States
18	Novartis US	Port Orchard	Washington	United States
19	Novartis US	Madison	Wisconsin	United States

Sponsors and Collaborators

• Novartis

Investigators

• Study Chair: Novartis, Novartis

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• ClinicalTrials.gov Identifier: NCT00441064
• Other Study ID Numbers: CSPP100AUS02
• First Posted: Feb 28, 2007
• Last Update Posted: Mar 25, 2011
• Last Verified: Feb 1, 2011

• Keywords provided by , ,: High blood pressure, hypertension, aliskiren, low sodium diet
• Additional relevant MeSH terms: Hypertension

Study Results

Participant Flow

Recruitment Details	A total of 132 patients were randomly assigned to one of the two diet sequences: 69 in the low/high and 63 in the high/low diet sequence. After 4 wks on the assigned diet, patients were then crossed over to the other diet. Patients who were on a high sodium diet for the first 4 wks started on a low sodium diet for the next 4 wks vice versa.
Pre-assignment Detail	Safety Population (SP) -Included all randomized patients who received at least 1 dose of study medication. Intent-to-treat population (ITT) -All randomized patients who received at least 1 dose of study medication and had at least 1 valid post baseline assessment of primary efficacy variable.

Arm/Group Title	Diet Sequence Low/High Sodium	Diet Sequence High/Low Sodium
Arm/Group Description	Patients on low sodium diet ( <= 100 mmol/day) for the first 4 weeks who crossed over to the high sodium (>= 200 mmol/day) diet for the next 4 weeks. [with Aliskiren 300 mg]	Patients on high sodium (>= 200 mmol/day) diet for the first 4 weeks and crossed over to the low sodium diet ( <= 100 mmol/day) for the next 4 weeks. [with Aliskiren 300 mg]
Period Title: Overall Study
STARTED	69	63
Safety Population (SP)	69	63
Intent-to-treat (ITT) Population	61	57
COMPLETED	59	56
NOT COMPLETED	10	7

Baseline Characteristics

Arm/Group Title	Diet Sequence Low/High Sodium	Diet Sequence High/Low Sodium	Total
Arm/Group Description	Patients on low sodium diet ( <= 100 mmol/day) for the first 4 weeks and high sodium (>= 200 mmol/day) diet for the next 4 weeks. [with Aliskiren 300 mg]	Patients on high sodium (>= 200 mmol/day) diet for the first 4 weeks and on low sodium diet ( <= 100 mmol/day) for the next 4 weeks. [with Aliskiren 300 mg]	Total of all reporting groups
Overall Participants	69	63	132
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	51.0 (7.16)	52.1 (7.75)	51.5 (7.44)
Sex: Female, Male (Count of Participants)
Female	34 49.3%	25 39.7%	59 44.7%
Male	35 50.7%	38 60.3%	73 55.3%
MSSBP (mm Hg) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [mm Hg]	147.6 (9.21)	146.2 (8.94)	146.9 (9.07)
MSDBP (mm Hg) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [mm Hg]	92.7 (9.81)	93.6 (8.33)	93.1 (9.11)
MASBP (mm Hg) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [mm Hg]	138.7 (8.30)	139.1 (8.52)	138.9 (8.38)
MADBP (mm Hg) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [mm Hg]	86.6 (6.73)	87.7 (7.28)	87.1 (6.99)

Outcome Measures

1. Primary Outcome

Title	Mean 24 Hour Ambulatory Systolic Blood Pressure (MASBP) in Systolic Hypertensive Patients Treated With Aliskiren (300 mg) for 4 Weeks on a High Sodium Diet Versus 4 Weeks on a Low Sodium Diet
Description	The primary objective of the study was to assess mean 24 hour ambulatory systolic blood pressure (MASBP) in systolic hypertensive patients treated with aliskiren (300 mg) for 4 weeks on a high sodium diet versus 4 weeks on a low sodium diet. [At week 4 patients crossed over from low to high sodium diet and vice versa for 4 weeks. MASBP for patients on high sodium diet versus low sodium diet was also analyzed at week 8 (4 weeks after crossover).]
Time Frame	Week 4 and week 8 (4 weeks after crossover)

Outcome Measure Data

Analysis Population Description

Completers Population: Included all patients who completed both diet periods - high and low sodium diets

Arm/Group Title	Low Sodium Diet	High Sodium Diet
Arm/Group Description	All patients who were on low sodium (<= 100 mmol/day) diet	All patients who were on high sodium (>= 200 mmol/day) diet
Measure Participants	115	115
Period 1 (4 weeks)	124.8 (9.12)	134.7 (11.13)
Period 2 (next 4 weeks after crossover)	123.6 (11.69)	132.5 (10.07)

2. Secondary Outcome

Title	Mean 24 Hour Ambulatory Diastolic Blood Pressure (MADBP) in Systolic Hypertensive Patients Treated With Aliskiren (300 mg) for 4 Weeks on a High Sodium Diet Versus 4 Weeks on a Low Sodium Diet
Description	To evaluate the mean 24 hour ambulatory diastolic blood pressure (MADBP) in systolic hypertensive patients treated with aliskiren (300 mg) for 4 weeks on a high sodium diet versus 4 weeks on a low sodium diet. [At week 4 patients crossed over from low to high sodium diet and vice versa for 4 weeks. MADBP for patients on high sodium diet versus low sodium diet was also analyzed at week 8 (4 weeks after crossover).]
Time Frame	Week 4 and week 8 (4 weeks after crossover)

Outcome Measure Data

Analysis Population Description

Completers Population: Included all patients who completed both diet periods - high and low sodium diets

Arm/Group Title	Low Sodium Diet	High Sodium Diet
Arm/Group Description	All patients who were on low sodium (<= 100 mmol/day) diet	All patients who were on high sodium (>= 200 mmol/day) diet
Measure Participants	115	115
Period 1 (4 weeks)	78.5 (7.37)	85.0 (9.06)
Period 2 (next 4 weeks after crossover)	78.3 (9.10)	83.2 (8.10)

3. Secondary Outcome

Title	Percentage of Responders Defined as MASBP <130 mm Hg or a Decrease From Baseline in MASBP of ≥20 mm Hg in Systolic Hypertensive Patients Treated With Aliskiren (300 mg) for 4 Weeks on a High Sodium Diet Versus 4 Weeks on a Low Sodium Diet
Description	To evaluate the percentage of responders defined as MASBP < 130 mm Hg or a decrease in MASBP from baseline of ≥20 mm Hg in systolic hypertensive patients treated with aliskiren (300 mg) for 4 weeks on a high sodium diet versus 4 weeks on a low sodium diet. [At week 4 patients crossed over from low to high sodium diet and vice versa for 4 weeks. Percent response for patients on high sodium diet versus low sodium diet was also analyzed at week 8 (4 weeks after crossover).]
Time Frame	Week 4 and Week 8 (4 weeks after crossover)

Outcome Measure Data

Analysis Population Description

Completers Population: Included all patients who completed both diet periods - high and low sodium diets

Arm/Group Title	Low Sodium Diet	High Sodium Diet
Arm/Group Description	All patients who were on low sodium (<= 100 mmol/day) diet	All patients who were on high sodium (>= 200 mmol/day) diet
Measure Participants	115	115
Period 1 (4 weeks) - Response	78.0	41.1
Period 1 (4 weeks) - No response	20.3	58.9
Period 2 (next 4 weeks after crossover) - Response	75.0	44.1
Period 2 (next 4 wks after crossover) -No Response	25.0	55.9

Adverse Events

Time Frame	AE's in overall Safety Population (SP) after 8 weeks
Adverse Event Reporting Description	Numbers in AE table are by overall diet, not diet sequence. AEs included overall Safety Population. Low Sodium Diet: 126=69 starters+57 after crossover (56 Completed + 1 who received medication but did not complete study); High Sodium Diet: 124=63 starters+61 after crossover (59 Completed + 2 who received medication but did not complete study)
Arm/Group Title	Low Sodium Diet		High Sodium Diet
Arm/Group Description	All patients who were on low sodium (<= 100 mmol/day) diet.		All patients who were on high sodium (>= 200 mmol/day) diet.
All Cause Mortality
	Low Sodium Diet		High Sodium Diet
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Low Sodium Diet		High Sodium Diet
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/126 (0%)		0/124 (0%)
Other (Not Including Serious) Adverse Events
	Low Sodium Diet		High Sodium Diet
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	3/126 (2.4%)		8/124 (6.5%)
Nervous system disorders
Headache	3/126 (2.4%)		8/124 (6.5%)

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; or the publication of the trial results in their entirety.