Trial Outcomes & Findings for Aliskiren Effect on Aortic Plaque Progression (NCT NCT01417104)

NCT ID: NCT01417104

Last Updated: 2017-05-11

Results Overview

All patients underwent imaging using a 3T, MRI system. The MRI sequence method used for wall depiction was a 3D, fat suppressed, dark blood, turbo spin echo sequence with variable flip angles (SPACE). Following co-registration of pre and post treatment MR images, and generation of MPR sections, images were magnified, contrast adjusted and patient/exam identifier information was removed and replaced by pre-assigned code to blind images for measurements. An experienced observer performed manual measurements of lumen and lumen plus wall areas by delineating the inner border and the outer border of the vessel wall in each cross-section image of the aorta. Using an approach similar to intravascular atheroma volume calculations, normalized total aortic wall volume (TWV) for thoracic region, abdominal region and total aorta for each patient and each exam was generated.

Recruitment status

TERMINATED

Study phase

PHASE2/PHASE3

Target enrollment

71 participants

Primary outcome timeframe

Baseline and end of treatment ( 17 to 36 weeks)

Results posted on

2017-05-11

Participant Flow

Participants recruited from The Ohio State Medical Center and Columbus surrounding area between April 2009 to December 2011.

187 participants screened; 116 did not meet inclusion criteria or meet exclusion criteria; 71 randomized.

Participant milestones

Participant milestones
Measure
Aliskiren
Aliskiren will be administered for 2 weeks at 150mg/day oral pill, followed by 34 weeks oral therapy with 300mg/day
Placebo
Placebo (sugar pill) built to mimic both the 150mg Aliskiren tablet ( administered for the first 2 weeks) and the 300mg Aliskiren tablet ( administered for the rest of treatment period)
Overall Study
STARTED
34
37
Overall Study
COMPLETED
28
35
Overall Study
NOT COMPLETED
6
2

Reasons for withdrawal

Reasons for withdrawal
Measure
Aliskiren
Aliskiren will be administered for 2 weeks at 150mg/day oral pill, followed by 34 weeks oral therapy with 300mg/day
Placebo
Placebo (sugar pill) built to mimic both the 150mg Aliskiren tablet ( administered for the first 2 weeks) and the 300mg Aliskiren tablet ( administered for the rest of treatment period)
Overall Study
Withdrawal by Subject
5
1
Overall Study
Failure to make contact
0
1
Overall Study
Adverse Event
1
0

Baseline Characteristics

Aliskiren Effect on Aortic Plaque Progression

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure
Aliskiren
n=34 Participants
Aliskiren will be administered for 2 weeks at 150mg/day oral pill, followed by 34 weeks oral therapy with 300mg/day
Placebo
n=37 Participants
Placebo (sugar pill) built to mimic both the 150mg Aliskiren tablet ( administered for the first 2 weeks) and the 300mg Aliskiren tablet ( administered for the rest of treatment period)
Total
n=71 Participants
Total of all reporting groups
Age, Categorical
<=18 years
0 Participants
n=5 Participants
0 Participants
n=7 Participants
0 Participants
n=5 Participants
Age, Categorical
Between 18 and 65 years
17 Participants
n=5 Participants
13 Participants
n=7 Participants
30 Participants
n=5 Participants
Age, Categorical
>=65 years
17 Participants
n=5 Participants
24 Participants
n=7 Participants
41 Participants
n=5 Participants
Age, Continuous
63.9 years
STANDARD_DEVIATION 11.5 • n=5 Participants
64.5 years
STANDARD_DEVIATION 8.9 • n=7 Participants
64.18 years
STANDARD_DEVIATION 10.17 • n=5 Participants
Sex: Female, Male
Female
9 Participants
n=5 Participants
3 Participants
n=7 Participants
12 Participants
n=5 Participants
Sex: Female, Male
Male
25 Participants
n=5 Participants
34 Participants
n=7 Participants
59 Participants
n=5 Participants
Region of Enrollment
United States
34 participants
n=5 Participants
37 participants
n=7 Participants
71 participants
n=5 Participants

PRIMARY outcome

Timeframe: Baseline and end of treatment ( 17 to 36 weeks)

Population: 3 MRI data sets were not analyzable ( low quality images), and 23 post-treatment MRI not obtained ( \<17 weeks on drug when trial terminated owing to ALTITUDE results)

All patients underwent imaging using a 3T, MRI system. The MRI sequence method used for wall depiction was a 3D, fat suppressed, dark blood, turbo spin echo sequence with variable flip angles (SPACE). Following co-registration of pre and post treatment MR images, and generation of MPR sections, images were magnified, contrast adjusted and patient/exam identifier information was removed and replaced by pre-assigned code to blind images for measurements. An experienced observer performed manual measurements of lumen and lumen plus wall areas by delineating the inner border and the outer border of the vessel wall in each cross-section image of the aorta. Using an approach similar to intravascular atheroma volume calculations, normalized total aortic wall volume (TWV) for thoracic region, abdominal region and total aorta for each patient and each exam was generated.

Outcome measures

Outcome measures
Measure
Aliskiren
n=18 Participants
Aliskiren was administered for 2 weeks at 150mg/day oral pill, followed by 34 weeks oral therapy with 300mg/day
Placebo
n=19 Participants
Placebo (sugar pill) built to mimic both the 150mg Aliskiren tablet ( administered for the first 2 weeks) and the 300mg Aliskiren tablet ( administered for the rest of treatment period)
Change in Normalized Total Aortic Wall Volume (TWV) Between the Trial Arms at the End of the Treatment
5.31 mm3
Standard Deviation 6.57
0.15 mm3
Standard Deviation 4.39

SECONDARY outcome

Timeframe: Baseline and end of treatment ( 17 to 36 weeks)

Population: 3 MRI not analyzable, 23 final MRI not obtained due to trial termination

Using an approach similar to intravascular atheroma volume calculations, percentage wall volume (PWV) for thoracic region, abdominal region and total aorta for each patient and each exam was generated. and a difference between baseline and end of treatment was calculated.

Outcome measures

Outcome measures
Measure
Aliskiren
n=18 Participants
Aliskiren was administered for 2 weeks at 150mg/day oral pill, followed by 34 weeks oral therapy with 300mg/day
Placebo
n=19 Participants
Placebo (sugar pill) built to mimic both the 150mg Aliskiren tablet ( administered for the first 2 weeks) and the 300mg Aliskiren tablet ( administered for the rest of treatment period)
Change in the Percentage Wall Volume (PWV) Between Baseline and End of Treatment
3.37 Percentage of the Outer Wall Volume
Standard Deviation 2.96
0.97 Percentage of the Outer Wall Volume
Standard Deviation 2.02

OTHER_PRE_SPECIFIED outcome

Timeframe: baseline to end of treatment ( up to 36 weeks)

Population: Intent to treat analysis including only participants who had at least one post-baseline assesment

Difference between end of treatment and baseline in resting diastolic blood pressure

Outcome measures

Outcome measures
Measure
Aliskiren
n=28 Participants
Aliskiren was administered for 2 weeks at 150mg/day oral pill, followed by 34 weeks oral therapy with 300mg/day
Placebo
n=35 Participants
Placebo (sugar pill) built to mimic both the 150mg Aliskiren tablet ( administered for the first 2 weeks) and the 300mg Aliskiren tablet ( administered for the rest of treatment period)
Change From Baseline in Resting Diastolic Blood Pressure
-3.88 mm Hg
Interval -9.23 to 1.47
-2.32 mm Hg
Interval -6.39 to 1.7

Adverse Events

Aliskiren

Serious events: 0 serious events
Other events: 1 other events
Deaths: 0 deaths

Placebo

Serious events: 0 serious events
Other events: 0 other events
Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Other adverse events
Measure
Aliskiren
n=34 participants at risk
Aliskiren was administered for 2 weeks at 150mg/day oral pill, followed by 34 weeks oral therapy with 300mg/day
Placebo
n=37 participants at risk
Placebo (sugar pill) built to mimic both the 150mg Aliskiren tablet ( administered for the first 2 weeks) and the 300mg Aliskiren tablet ( administered for the rest of treatment period)
Metabolism and nutrition disorders
Hyperkalemia
2.9%
1/34 • Number of events 1 • up to 36 weeks
0.00%
0/37 • up to 36 weeks

Additional Information

Sanjay Rajagopalan, MD

The Ohio State University

Phone: 614-247-7760

Results disclosure agreements

  • Principal investigator is a sponsor employee
  • Publication restrictions are in place