Diabetes, Hypertension, Stage 2 Hypertension
Conditions
Keywords
High blood pressure, diabetes
Brief summary
This was a study to assess the safety and efficacy of Valturna and amlodipine or Valturna and chlorthalidone when compared to Valturna alone in patients with stage 2 hypertension and diabetes mellitus 2.
Interventions
DRUGValturna
Valturna (aliskiren 150 mg/valsartan 160 mg) tablet
DRUGAmlodipine
Amlodipine 5 mg and 10 mg capsule
DRUGChlorthalidone
Chlorthalidone 15 mg and 25 mg capsule
DRUGPlacebo of Valturna Tablet
Matching placebo of valturna tablet
DRUGPlacebo Capsule
Matching placebo of Amlodipine capsule OR Matching placebo of chlorthalidone capsule
Sponsors
Novartis Pharmaceuticals
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Patients with stage 2 hypertension within protocol limits at randomization * Patients with type 2 diabetes mellitus with HgA1c less than or equal to 9% * Patients with newly diagnosed hypertension or patients who have not received antihypertensive therapy for at least 4 weeks prior to screening
Exclusion criteria
* Patients taking 4 or more antihypertensive medications at screening visit * Patients with uncontrolled BP (\> 140/90 mmHg) while taking 3 or more antihypertensives at their maximum approved doses * Type 2 diabetes mellitus requiring insulin treatment * Patients with HgA1c \> 9% * Patients with known gout * Known history of cancer within the past 5 years * Patients who are pregnant or nursing mothers * Patients who have participated in an investigational clinical trial within the 30 days prior to screening. * Other protocol-defined inclusion/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Mean Sitting Systolic Blood Pressure (MSSBP) After 12 Weeks of Treatment Ending With the Combination of Valturna and Amlodipine Versus Valturna Alone | Baseline, 12 weeks | Sitting BP was measured at trough (24 hours ± 3 hours postdose) and recorded at all study visits. At the first study visit, the patient had his/her BP measured in both arms; the arm in which the highest sitting DBP was found was used for all subsequent readings throughout the study. At each study visit, after the patient had been sitting for 5 minutes, SBP were measured 3 times using a standard mercury sphygmomanometer and appropriate size cuff. The repeat sitting measurements were made at 1- to 2-minute intervals and the mean of those 3 measurements was used as the average sitting office BP for that visit. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in MSSBP After 12 Weeks of Treatment Ending With Between the Valturna + Chlorthalidone Combination and Valturna Alone | Baseline, 12 weeks | Sitting BP was measured at trough (24 hours ± 3 hours postdose) and recorded at all study visits. At the first study visit, the patient had his/her BP measured in both arms; the arm in which the highest sitting DBP was found was used for all subsequent readings throughout the study. At each study visit, after the patient had been sitting for 5 minutes, SBP were measured 3 times using a standard mercury sphygmomanometer and appropriate size cuff. The repeat sitting measurements were made at 1- to 2-minute intervals and the mean of those 3 measurements was used as the average sitting office BP for that visit. |
| Change From Baseline in Mean Sitting Diastolic Blood Pressure (MSDBP) After 12 Weeks of Treatment | Baseline, 12 weeks | Sitting blood pressure (BP) was measured at trough (24 hours ± 3 hours postdose) and recorded at all study visits. At the first study visit, the patient had his/her BP measured in both arms; the arm in which the highest sitting DBP was found was used for all subsequent readings throughout the study. At each study visit, after the patient had been sitting for 5 minutes, DBP were measured 3 times using a standard mercury sphygmomanometer and appropriate size cuff. The repeat sitting measurements were made at 1- to 2-minute intervals and the mean of those 3 measurements was used as the average sitting office BP for that visit. |
| Percentage of Responders After Treatment | Baseline, 12 weeks | Responders are defined as patients with MSSBP \<130 mmHg or a decrease from baseline in MSSBP of ≥20 mmHg |
| Percentage of Patients Achieving Blood Pressure Control After Treatment | 12 weeks | Patient with blood pressure control is defined as patients achieving MSSBP \<130 mmHg and MSDBP \<80 mmHg. |
| Number of Patients With Adverse Events, Serious Adverse Events and Death to Assess Safety and Tolerability of Treatment With Valturna and Chlorthalidone or Valturna and Amlodipine Versus Valturna Alone | 12 weeks | — |
Countries
Puerto Rico, United States
Participant flow
Pre-assignment details
Of the 975 patients screened, 417 were randomized.
Participants by arm
| Arm | Count |
|---|---|
| Valturna At double-blind randomization, all patients received 1 tablet Valturna 150/160 mg + 1 tablet Placebo Valturna+ 1 capsule placebo for 2 weeks. From Week 2, patients received 1 tablet Valturna 150/160 mg, + 1 tablet Valturna 150/160 mg + 1 capsule placebo for 6 weeks. From Week 8, patients received 1 tablet Valturna 150/160 mg + 1 tablet Valturna 150/160 mg + 1 capsule placebo for 4 weeks. | 138 |
| Valturna + Amlodipine At double-blind randomization, all patients received 1 tablet Valturna 150/160 mg + 1 tablet Placebo Valturna+ 1 capsule placebo for 2 weeks. From Week 2, patients received 1 tablet Valturna 150/160 mg, + 1 tablet Valturna 150/160 mg + 1 capsule 5 mg amlodipine for 6 weeks. From Week 8, patients received 1 tablet Valturna 150/160 mg + 1 tablet Valturna 150/160 mg + 1 capsule 10 mg amlodipine for 4 weeks. | 137 |
| Valturna + Chlorthalidone At double-blind randomization, all patients received 1 tablet Valturna 150/160 mg + 1 tablet Placebo Valturna+ 1 capsule placebo for 2 weeks. From Week 2, patients received 1 tablet Valturna 150/160 mg, + 1 tablet Valturna 150/160 mg + 1 capsule 15 mg chlorthalidone for 6 weeks. From Week 8, patients received 1 tablet Valturna 150/160 mg + 1 tablet Valturna 150/160 mg + 1 capsule 25 mg chlorthalidonefor 4 weeks. | 141 |
| Total | 416 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Abnormal laboratory value(s) | 0 | 1 | 2 |
| Overall Study | Abnormal test procedure result(s) | 0 | 0 | 1 |
| Overall Study | Administrative problems | 34 | 39 | 35 |
| Overall Study | Adverse Event | 5 | 6 | 8 |
| Overall Study | Lost to Follow-up | 3 | 3 | 5 |
| Overall Study | No longer required study medication | 0 | 0 | 1 |
| Overall Study | Protocol deviation | 0 | 3 | 1 |
| Overall Study | Unsatisfactory therapeutic effect | 7 | 2 | 2 |
| Overall Study | Withdrawal by Subject | 2 | 5 | 4 |
Baseline characteristics
| Characteristic | Valturna | Valturna + Amlodipine | Valturna + Chlorthalidone | Total |
|---|---|---|---|---|
| Age Continuous | 54.7 Years STANDARD_DEVIATION 8.65 | 56.0 Years STANDARD_DEVIATION 9.56 | 54.6 Years STANDARD_DEVIATION 9.35 | 55.1 Years STANDARD_DEVIATION 9.2 |
| Sex: Female, Male Female | 73 Participants | 73 Participants | 70 Participants | 216 Participants |
| Sex: Female, Male Male | 65 Participants | 64 Participants | 71 Participants | 200 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 23 / 138 | 16 / 137 | 23 / 142 |
| serious Total, serious adverse events | 0 / 138 | 0 / 137 | 0 / 142 |
Outcome results
Primary
Change From Baseline in Mean Sitting Systolic Blood Pressure (MSSBP) After 12 Weeks of Treatment Ending With the Combination of Valturna and Amlodipine Versus Valturna Alone
Sitting BP was measured at trough (24 hours ± 3 hours postdose) and recorded at all study visits. At the first study visit, the patient had his/her BP measured in both arms; the arm in which the highest sitting DBP was found was used for all subsequent readings throughout the study. At each study visit, after the patient had been sitting for 5 minutes, SBP were measured 3 times using a standard mercury sphygmomanometer and appropriate size cuff. The repeat sitting measurements were made at 1- to 2-minute intervals and the mean of those 3 measurements was used as the average sitting office BP for that visit.
Time frame: Baseline, 12 weeks
Population: The study was terminated and consequentially was underpowered for adequate statistical analysis
Secondary
Change From Baseline in Mean Sitting Diastolic Blood Pressure (MSDBP) After 12 Weeks of Treatment
Sitting blood pressure (BP) was measured at trough (24 hours ± 3 hours postdose) and recorded at all study visits. At the first study visit, the patient had his/her BP measured in both arms; the arm in which the highest sitting DBP was found was used for all subsequent readings throughout the study. At each study visit, after the patient had been sitting for 5 minutes, DBP were measured 3 times using a standard mercury sphygmomanometer and appropriate size cuff. The repeat sitting measurements were made at 1- to 2-minute intervals and the mean of those 3 measurements was used as the average sitting office BP for that visit.
Time frame: Baseline, 12 weeks
Population: The study was terminated and consequentially was underpowered for adequate statistical analysis
Secondary
Change From Baseline in MSSBP After 12 Weeks of Treatment Ending With Between the Valturna + Chlorthalidone Combination and Valturna Alone
Sitting BP was measured at trough (24 hours ± 3 hours postdose) and recorded at all study visits. At the first study visit, the patient had his/her BP measured in both arms; the arm in which the highest sitting DBP was found was used for all subsequent readings throughout the study. At each study visit, after the patient had been sitting for 5 minutes, SBP were measured 3 times using a standard mercury sphygmomanometer and appropriate size cuff. The repeat sitting measurements were made at 1- to 2-minute intervals and the mean of those 3 measurements was used as the average sitting office BP for that visit.
Time frame: Baseline, 12 weeks
Population: The study was terminated and consequentially was underpowered for adequate statistical analysis
Secondary
Number of Patients With Adverse Events, Serious Adverse Events and Death to Assess Safety and Tolerability of Treatment With Valturna and Chlorthalidone or Valturna and Amlodipine Versus Valturna Alone
Time frame: 12 weeks
Population: Safety Set - Consists of all patients who received at least one dose of the double-blind study drug. Patients were analyzed according to the treatment that they received.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Valturna | Number of Patients With Adverse Events, Serious Adverse Events and Death to Assess Safety and Tolerability of Treatment With Valturna and Chlorthalidone or Valturna and Amlodipine Versus Valturna Alone | Death | 0 Participants |
| Valturna | Number of Patients With Adverse Events, Serious Adverse Events and Death to Assess Safety and Tolerability of Treatment With Valturna and Chlorthalidone or Valturna and Amlodipine Versus Valturna Alone | Adverse Events | 62 Participants |
| Valturna | Number of Patients With Adverse Events, Serious Adverse Events and Death to Assess Safety and Tolerability of Treatment With Valturna and Chlorthalidone or Valturna and Amlodipine Versus Valturna Alone | Serious Adverse Events | 0 Participants |
| Valturna + Amlodipine | Number of Patients With Adverse Events, Serious Adverse Events and Death to Assess Safety and Tolerability of Treatment With Valturna and Chlorthalidone or Valturna and Amlodipine Versus Valturna Alone | Adverse Events | 54 Participants |
| Valturna + Amlodipine | Number of Patients With Adverse Events, Serious Adverse Events and Death to Assess Safety and Tolerability of Treatment With Valturna and Chlorthalidone or Valturna and Amlodipine Versus Valturna Alone | Serious Adverse Events | 0 Participants |
| Valturna + Amlodipine | Number of Patients With Adverse Events, Serious Adverse Events and Death to Assess Safety and Tolerability of Treatment With Valturna and Chlorthalidone or Valturna and Amlodipine Versus Valturna Alone | Death | 0 Participants |
| Valturna + Chlorthalidone | Number of Patients With Adverse Events, Serious Adverse Events and Death to Assess Safety and Tolerability of Treatment With Valturna and Chlorthalidone or Valturna and Amlodipine Versus Valturna Alone | Serious Adverse Events | 0 Participants |
| Valturna + Chlorthalidone | Number of Patients With Adverse Events, Serious Adverse Events and Death to Assess Safety and Tolerability of Treatment With Valturna and Chlorthalidone or Valturna and Amlodipine Versus Valturna Alone | Death | 0 Participants |
| Valturna + Chlorthalidone | Number of Patients With Adverse Events, Serious Adverse Events and Death to Assess Safety and Tolerability of Treatment With Valturna and Chlorthalidone or Valturna and Amlodipine Versus Valturna Alone | Adverse Events | 58 Participants |
Secondary
Percentage of Patients Achieving Blood Pressure Control After Treatment
Patient with blood pressure control is defined as patients achieving MSSBP \<130 mmHg and MSDBP \<80 mmHg.
Time frame: 12 weeks
Population: The study was terminated and consequentially was underpowered for adequate statistical analysis
Secondary
Percentage of Responders After Treatment
Responders are defined as patients with MSSBP \<130 mmHg or a decrease from baseline in MSSBP of ≥20 mmHg
Time frame: Baseline, 12 weeks
Population: The study was terminated and consequentially was underpowered for adequate statistical analysis