Hypertension
Conditions
Keywords
High blood pressure, hypertension, aliskiren, low sodium diet
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.
Interventions
DRUGAliskiren
Sponsors
Novartis
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 60 Years
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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. \[At week 4 patients crossed over from low to high sodium diet and vice versa for 4 weeks. MADBP for patients on high sodium diet versus low sodium diet was also analyzed at week 8 (4 weeks after crossover).\] |
| 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. \[At week 4 patients crossed over from low to high sodium diet and vice versa for 4 weeks. Percent response for patients on high sodium diet versus low sodium diet was also analyzed at week 8 (4 weeks after crossover).\] |
Countries
United States
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 details
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.
Participants by arm
| Arm | Count |
|---|---|
| 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. \[with Aliskiren 300 mg\] | 69 |
| 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. \[with Aliskiren 300 mg\] | 63 |
| Total | 132 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Abnormal laboratory values | 0 | 2 |
| Overall Study | Abnormal test procedure results | 0 | 1 |
| Overall Study | Adverse Event | 1 | 0 |
| Overall Study | Patient withdrew consent | 5 | 2 |
| Overall Study | Protocol Deviation | 3 | 2 |
| Overall Study | Unsatisfactory therapeutic effect | 1 | 0 |
Baseline characteristics
| Characteristic | Diet Sequence Low/High Sodium | Diet Sequence High/Low Sodium | Total |
|---|---|---|---|
| Age Continuous | 51.0 years STANDARD_DEVIATION 7.16 | 52.1 years STANDARD_DEVIATION 7.75 | 51.5 years STANDARD_DEVIATION 7.44 |
| MADBP | 86.6 mm Hg STANDARD_DEVIATION 6.73 | 87.7 mm Hg STANDARD_DEVIATION 7.28 | 87.1 mm Hg STANDARD_DEVIATION 6.99 |
| MASBP | 138.7 mm Hg STANDARD_DEVIATION 8.3 | 139.1 mm Hg STANDARD_DEVIATION 8.52 | 138.9 mm Hg STANDARD_DEVIATION 8.38 |
| MSDBP | 92.7 mm Hg STANDARD_DEVIATION 9.81 | 93.6 mm Hg STANDARD_DEVIATION 8.33 | 93.1 mm Hg STANDARD_DEVIATION 9.11 |
| MSSBP | 147.6 mm Hg STANDARD_DEVIATION 9.21 | 146.2 mm Hg STANDARD_DEVIATION 8.94 | 146.9 mm Hg STANDARD_DEVIATION 9.07 |
| Sex: Female, Male Female | 34 Participants | 25 Participants | 59 Participants |
| Sex: Female, Male Male | 35 Participants | 38 Participants | 73 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 3 / 126 | 8 / 124 |
| serious Total, serious adverse events | 0 / 126 | 0 / 124 |
Outcome results
Primary
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
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)
Population: Completers Population: Included all patients who completed both diet periods - high and low sodium diets
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Low Sodium Diet | 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 | Period 1 (4 weeks) | 124.8 mm Hg | Standard Deviation 9.12 |
| Low Sodium Diet | 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 | Period 2 (next 4 weeks after crossover) | 123.6 mm Hg | Standard Deviation 11.69 |
| High Sodium Diet | 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 | Period 1 (4 weeks) | 134.7 mm Hg | Standard Deviation 11.13 |
| High Sodium Diet | 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 | Period 2 (next 4 weeks after crossover) | 132.5 mm Hg | Standard Deviation 10.07 |
Secondary
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
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)
Population: Completers Population: Included all patients who completed both diet periods - high and low sodium diets
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Low Sodium Diet | 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 | Period 1 (4 weeks) | 78.5 mm Hg | Standard Deviation 7.37 |
| Low Sodium Diet | 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 | Period 2 (next 4 weeks after crossover) | 78.3 mm Hg | Standard Deviation 9.1 |
| High Sodium Diet | 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 | Period 1 (4 weeks) | 85.0 mm Hg | Standard Deviation 9.06 |
| High Sodium Diet | 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 | Period 2 (next 4 weeks after crossover) | 83.2 mm Hg | Standard Deviation 8.1 |
Secondary
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
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)
Population: Completers Population: Included all patients who completed both diet periods - high and low sodium diets
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Low Sodium Diet | 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 | Period 1 (4 weeks) - Response | 78.0 Percentage of responders |
| Low Sodium Diet | 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 | Period 1 (4 weeks) - No response | 20.3 Percentage of responders |
| Low Sodium Diet | 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 | Period 2 (next 4 weeks after crossover) - Response | 75.0 Percentage of responders |
| Low Sodium Diet | 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 | Period 2 (next 4 wks after crossover) -No Response | 25.0 Percentage of responders |
| High Sodium Diet | 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 | Period 2 (next 4 wks after crossover) -No Response | 55.9 Percentage of responders |
| High Sodium Diet | 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 | Period 1 (4 weeks) - Response | 41.1 Percentage of responders |
| High Sodium Diet | 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 | Period 2 (next 4 weeks after crossover) - Response | 44.1 Percentage of responders |
| High Sodium Diet | 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 | Period 1 (4 weeks) - No response | 58.9 Percentage of responders |