Coronary Artery Disease (CAD), Coronary Atherosclerosis
Conditions
Keywords
CAD, coronary artery disease, coronary atherosclerosis, coronary angiography, IVUS, intravascular ultrasound, plasma renin activity, renin angiotensin aldosterone system,, direct renin inhibitors, coronary atheroma
Brief summary
The study will assess the change in coronary atherosclerotic disease as determined by intravascular ultrasound (IVUS) for aliskiren compared to placebo when given in addition to standard therapy in patients with coronary artery disease (CAD) and a blood pressure in the pre-hypertensive range.
Interventions
DRUGPlacebo
Placebo
DRUGAliskiren
300 mg
Sponsors
The Cleveland Clinic
Novartis Pharmaceuticals
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
35 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Patients with CAD who have blood pressure in the pre-hypertensive range defined as a msSBP ≥ 125 and ≤ 139mmHg and a msDBP \< 90mmHg. * Patients with or without current treatment for hypertension * Angiographic evidence of coronary artery disease * At least 2 qualifying Cardiovascular risk factors at Visit 1
Exclusion criteria
* Baseline IVUS determined unacceptable * Patients requiring treatment with disallowed study medications * Patients with clinically significant heart disease * Previous or current diagnosis of heart failure (NYHA Class IV) or a documented left ventricular ejection fraction of \< 25% * Patients requiring treatment with any 2 of the following classes of medication at Visit 1 or Visit 2: * Angiotensin converting enzyme inhibitors * Angiotensin receptor blockers * aldosterone receptor blockers or a direct renin inhibitor. * Other conditions may apply
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Percent Atheroma Volume(PAV) After 104 Weeks of Treatment | Baseline, 104 weeks | Change from baseline in PAV for all matched slices of anatomically comparable segments of the target coronary artery were assessed by intravascular ultrasound (IVUS) evaluation after 104 weeks of treatment . calculation for change is the value at the later time point minus the value at the earlier time point, with positive numbers to represent increases and negative numbers to represent decreases |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in Normalized Total Atheroma Volume (TAV) as Assessed by IVUS | Baseline, 104 weeks | Change from baseline in normalized total atheroma volume (TAV) (mm\^3) for all matched slices of anatomically comparable segments of the target coronary artery were assess by IVUS after 104 weeks of treatment. calculation for change is the value at the later time point minus the value at the earlier time point, with positive numbers to represent increases and negative numbers to represent decreases |
| Patients That Demonstrated Evidence of Atheroma Regression | Baseline to endpoint (104 weeks) | Atheroma regression is defined as change from baseline to endpoint in PAV \<0 . |
| Number of Patients With Adverse Events, Serious Adverse Events, and Death | 104 weeks | overall safety and tolerability of aliskiren 300 mg compared to placebo in patients with CAD and BP in the pre-hypertensive (high normal) range with or without treatment for hypertension following 104 weeks of treatment. Any Adverse Event was defined as occurrence of any symptom regardless of intensity grade, Serious Adverse Event (SAEs) assessed as medical occurrences that result in death, are life threatening, require hospitalization or prolongation of hospitalization or result in persistent or significant disability/incapacity. |
Countries
Argentina, Australia, Belgium, Canada, France, Germany, Hungary, Italy, Poland, Spain, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Aliskiren Period 1(Screening Period) visit 1(Day -42 to Day -1) eligibility for study participation was assessed. Period 2: Visit 2 to 3, single blind for 1 week: patients received aliskiren 150 mg. Period 3: visit 3 to 15, Double-blind Randomization/Forced Titration and Maintenance Period for 103 weeks: patients received 2 tablets aliskiren 150 mg (force titration) | 305 |
| Placebo Period 1(Screening Period) visit 1(Day -42 to Day -1) eligibility for study participation was assessed. Period 2: visit 2 to 3, single blind for 1 week: patients received 1 tablet aliskiren 150 mg, 1 tablet placebo 150 mg. Period 3: visit 3 to 15, Double-blind Randomization/Forced Titration and Maintenance Period for 103 weeks: patients received 2 tablets placebo 150 mg | 308 |
| Total | 613 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Double Blind Period (103 Weeks) | Abnormal laboratory values | 0 | 3 |
| Double Blind Period (103 Weeks) | Administrative problems | 45 | 56 |
| Double Blind Period (103 Weeks) | Adverse Event | 25 | 14 |
| Double Blind Period (103 Weeks) | Death | 1 | 6 |
| Double Blind Period (103 Weeks) | Lack of Efficacy | 1 | 0 |
| Double Blind Period (103 Weeks) | Lost to Follow-up | 8 | 10 |
| Double Blind Period (103 Weeks) | Patient's no longer requires study drug | 3 | 1 |
| Double Blind Period (103 Weeks) | Protocol Violation | 2 | 1 |
| Double Blind Period (103 Weeks) | Withdrawal by Subject | 19 | 18 |
| Single Blind Period (1 Week) | Abnormal laboratory value | 3 | 0 |
| Single Blind Period (1 Week) | Abnormal test procedure result | 1 | 0 |
| Single Blind Period (1 Week) | Adverse Event | 9 | 0 |
| Single Blind Period (1 Week) | Lost to Follow-up | 1 | 0 |
| Single Blind Period (1 Week) | Other | 4 | 0 |
| Single Blind Period (1 Week) | Protocol Violation | 12 | 0 |
| Single Blind Period (1 Week) | Withdrawal by Subject | 9 | 0 |
Baseline characteristics
| Characteristic | Aliskiren | Placebo | Total |
|---|---|---|---|
| Age, Continuous | 60.2 years STANDARD_DEVIATION 9.35 | 59.2 years STANDARD_DEVIATION 8.32 | 59.7 years STANDARD_DEVIATION 8.86 |
| Sex: Female, Male Female | 77 Participants | 69 Participants | 146 Participants |
| Sex: Female, Male Male | 228 Participants | 239 Participants | 467 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 186 / 305 | 175 / 308 |
| serious Total, serious adverse events | 76 / 305 | 97 / 308 |
Outcome results
Primary
Change From Baseline in Percent Atheroma Volume(PAV) After 104 Weeks of Treatment
Change from baseline in PAV for all matched slices of anatomically comparable segments of the target coronary artery were assessed by intravascular ultrasound (IVUS) evaluation after 104 weeks of treatment . calculation for change is the value at the later time point minus the value at the earlier time point, with positive numbers to represent increases and negative numbers to represent decreases
Time frame: Baseline, 104 weeks
Population: Full Analysis Set (FAS) - All randomized patients. Patients were analyzed according to the treatment that they were assigned at randomization. All patients who had a valid baseline and post baseline IVUS measurement and post-baseline IVUS measurement and at least ≥72 weeks of treatment were included in this analysis.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Aliskiren | Change From Baseline in Percent Atheroma Volume(PAV) After 104 Weeks of Treatment | -0.33 percentage of baseline | Standard Error 0.18 |
| Placebo | Change From Baseline in Percent Atheroma Volume(PAV) After 104 Weeks of Treatment | 0.11 percentage of baseline | Standard Error 0.18 |
Secondary
Change in Normalized Total Atheroma Volume (TAV) as Assessed by IVUS
Change from baseline in normalized total atheroma volume (TAV) (mm\^3) for all matched slices of anatomically comparable segments of the target coronary artery were assess by IVUS after 104 weeks of treatment. calculation for change is the value at the later time point minus the value at the earlier time point, with positive numbers to represent increases and negative numbers to represent decreases
Time frame: Baseline, 104 weeks
Population: Full Analysis Set (FAS) - All randomized patients. Patients were analyzed according to the treatment that they were assigned at randomization. All patients who had a valid baseline and post baseline IVUS measurement and post-baseline IVUS measurement and at least ≥72 weeks of treatment were included in this analysis.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Aliskiren | Change in Normalized Total Atheroma Volume (TAV) as Assessed by IVUS | -4.11 mm^3 | Standard Error 1.1 |
| Placebo | Change in Normalized Total Atheroma Volume (TAV) as Assessed by IVUS | -2.07 mm^3 | Standard Error 1.09 |
Secondary
Number of Patients With Adverse Events, Serious Adverse Events, and Death
overall safety and tolerability of aliskiren 300 mg compared to placebo in patients with CAD and BP in the pre-hypertensive (high normal) range with or without treatment for hypertension following 104 weeks of treatment. Any Adverse Event was defined as occurrence of any symptom regardless of intensity grade, Serious Adverse Event (SAEs) assessed as medical occurrences that result in death, are life threatening, require hospitalization or prolongation of hospitalization or result in persistent or significant disability/incapacity.
Time frame: 104 weeks
Population: Safety - All patients who received at least one dose of double-blind trial medication. Patients were analyzed according to the treatment that they received
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Aliskiren | Number of Patients With Adverse Events, Serious Adverse Events, and Death | SAEs | 76 Number of patients |
| Aliskiren | Number of Patients With Adverse Events, Serious Adverse Events, and Death | AE | 228 Number of patients |
| Aliskiren | Number of Patients With Adverse Events, Serious Adverse Events, and Death | Death | 1 Number of patients |
| Placebo | Number of Patients With Adverse Events, Serious Adverse Events, and Death | Death | 6 Number of patients |
| Placebo | Number of Patients With Adverse Events, Serious Adverse Events, and Death | SAEs | 97 Number of patients |
| Placebo | Number of Patients With Adverse Events, Serious Adverse Events, and Death | AE | 227 Number of patients |
Secondary
Patients That Demonstrated Evidence of Atheroma Regression
Atheroma regression is defined as change from baseline to endpoint in PAV \<0 .
Time frame: Baseline to endpoint (104 weeks)
Population: Full Analysis Set (FAS) - All randomized patients. Patients were analyzed according to the treatment that they were assigned at randomization
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Aliskiren | Patients That Demonstrated Evidence of Atheroma Regression | 128 Participants |
| Placebo | Patients That Demonstrated Evidence of Atheroma Regression | 114 Participants |