Trial Outcomes & Findings for Comparison of Aliskiren vs Negative Controls on Aortic Stiffness in Patients With MFS (NCT NCT01715207)

Last Updated: 2017-06-05

Results Overview

Analyses of the MRIs were performed using commercial software (Argus version 4.02, Siemens Medical Systems, Germany) by experienced observers who were blinded to patient information. To measure central aortic distensibility, the systolic and diastolic cross-sectional areas were measured by manual contouring of the aorta through the cardiac cycle on the cine image. Distensibility at the four regions was calculated as the mean of values obtained from the following equation: Distensibility = (Amax - Amin)/\[Amin × (Pmax - Pmin)\](10-3mm/Hg), where Amax is the maximal (systolic) aortic area, Amin is the minimal (diastolic) aortic area, Pmax is the systolic blood pressure (SBP), and Pmin is the diastolic blood pressure (DBP). Central aortic blood pressure measured non-invasively by SphygmoCor was used for systolic and diastolic blood pressure.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

30 participants

Primary outcome timeframe

6 months

Results posted on

2017-06-05

Participant Flow

The study was premature termination due to the stop of supporting medication from company.

Participant milestones

Participant milestones
Measure	Atenolol & Aliskiren Atenolol tablet and Aliskiren 150mg or 300mg tablet by mouth per day for 6month Aliskiren Atenolol	Atenolol Atenolol tablet(Negative controls, Open-label) Atenolol
Overall Study STARTED	15	15
Overall Study COMPLETED	14	14
Overall Study NOT COMPLETED	1	1

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Comparison of Aliskiren vs Negative Controls on Aortic Stiffness in Patients With MFS

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Atenolol & Aliskiren n=14 Participants Atenolol tablet and Aliskiren 150mg or 300mg tablet by mouth per day for 6month Aliskiren Atenolol	Atenolol n=14 Participants Atenolol tablet(Negative controls, Open-label) Atenolol	Total n=28 Participants Total of all reporting groups
Age, Continuous	32.1 yeaars STANDARD_DEVIATION 9.3 • n=5 Participants	33.2 yeaars STANDARD_DEVIATION 12.0 • n=7 Participants	32.6 yeaars STANDARD_DEVIATION 9.0 • n=5 Participants
Sex: Female, Male Female	8 Participants n=5 Participants	5 Participants n=7 Participants	13 Participants n=5 Participants
Sex: Female, Male Male	6 Participants n=5 Participants	9 Participants n=7 Participants	15 Participants n=5 Participants

PRIMARY outcome

Timeframe: 6 months

Population: MFS patients were recruited at Samsung Medical Center from November 2009 to October 2014. All patients were receiving atenolol as standard β-blocker therapy.

Outcome measures

Outcome measures
Measure	Atenolol & Aliskiren n=14 Participants Atenolol tablet and Aliskiren 150mg or 300mg tablet by mouth per day for 6month Aliskiren Atenolol	Atenolol n=14 Participants Atenolol tablet(Negative controls, Open-label) Atenolol
Central Aortic Distensibility by MRI initial ascending aorta	3.7 (mmHg ^ -1) x 10 ^ -3 Standard Deviation 1.3	4.7 (mmHg ^ -1) x 10 ^ -3 Standard Deviation 2.8
Central Aortic Distensibility by MRI initial upper descending aorta	5.7 (mmHg ^ -1) x 10 ^ -3 Standard Deviation 1.8	5.1 (mmHg ^ -1) x 10 ^ -3 Standard Deviation 2.5
Central Aortic Distensibility by MRI initial lower descending aorta	7.5 (mmHg ^ -1) x 10 ^ -3 Standard Deviation 2.7	6.3 (mmHg ^ -1) x 10 ^ -3 Standard Deviation 2.7
Central Aortic Distensibility by MRI initial abdominal aorta	2.4 (mmHg ^ -1) x 10 ^ -3 Standard Deviation 1.7	2.7 (mmHg ^ -1) x 10 ^ -3 Standard Deviation 1.3
Central Aortic Distensibility by MRI follow up ascending aorta	5.2 (mmHg ^ -1) x 10 ^ -3 Standard Deviation 2.7	5.0 (mmHg ^ -1) x 10 ^ -3 Standard Deviation 2.9
Central Aortic Distensibility by MRI follow up upper descending aorta	8.3 (mmHg ^ -1) x 10 ^ -3 Standard Deviation 4.7	6.0 (mmHg ^ -1) x 10 ^ -3 Standard Deviation 2.8
Central Aortic Distensibility by MRI follow up lower descending aorta	9.7 (mmHg ^ -1) x 10 ^ -3 Standard Deviation 4.6	7.1 (mmHg ^ -1) x 10 ^ -3 Standard Deviation 2.9
Central Aortic Distensibility by MRI follow up abdominal aorta	4.5 (mmHg ^ -1) x 10 ^ -3 Standard Deviation 3.4	3.5 (mmHg ^ -1) x 10 ^ -3 Standard Deviation 1.9

SECONDARY outcome

Timeframe: 6 months

Population: MFS patients were recruited at Samsung Medical Center from November 2009 to October 2014. All patients were receiving atenolol as standard β-blocker therapy.

Aortic PWV was measured according to the well-validated method using MRI 19. From the velocity-encoded MRIs, aortic contours were automatically detected and manually adjusted in each slice area throughout the cardiac cycle. The transit time between the flow curves of each region of the aorta was determined from the midpoint of the systolic up-slope on the flow versus time curve 26-28. The up-slopes were identified by drawing a line between the points of 40% and 60% maximum velocity on the waveform. The distance between each aortic level was measured on black blood images using a curved line along the center of the aorta. Based on these data, the regional PWV was calculated as the ratio of the distance between levels and the time differences between the arrival of the pulse wave at each level. The PWV was measured at two regions: the proximal aorta (proximal PWV between level 1 and level 2) and the entire aorta (PWV-total between level 1 and level 4).

Outcome measures

Outcome measures
Measure	Atenolol & Aliskiren n=14 Participants Atenolol tablet and Aliskiren 150mg or 300mg tablet by mouth per day for 6month Aliskiren Atenolol	Atenolol n=14 Participants Atenolol tablet(Negative controls, Open-label) Atenolol
Central Aortic PWV(Pulsed Wave Velocity) baseline regional PWV A	3.3 m/s Standard Deviation 1.03	3.8 m/s Standard Deviation 1.7
Central Aortic PWV(Pulsed Wave Velocity) baseline PWV total	4.5 m/s Standard Deviation 0.77	5.0 m/s Standard Deviation 1.03
Central Aortic PWV(Pulsed Wave Velocity) follow up regional PWV A	3.2 m/s Standard Deviation 0.8	3.6 m/s Standard Deviation 1.23
Central Aortic PWV(Pulsed Wave Velocity) follow up PWV total	4.7 m/s Standard Deviation 1.1	4.9 m/s Standard Deviation 1.24

Adverse Events

Atenolol & Aliskiren

Serious events: 2 serious events

Other events: 8 other events

Deaths: 0 deaths

Atenolol

Serious events: 0 serious events

Other events: 4 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Atenolol & Aliskiren n=14 participants at risk Atenolol tablet and Aliskiren 150mg or 300mg tablet by mouth per day for 6month Treatment (n=14) Overall rate of adverse events 12 (85.7%) moderate to severe cases 0 generalized symptoms 8 (57.1%) gastrointestinal symptoms 4 (28.6%) lung problems 0 cardiovascular symptoms 3 (21.4%) central nervous system symptoms 5 (35.7%) Eye, nose, throat symptoms 4 (28.6%) gynecologic problems 1 (7.1%) problems of extremities 1 (7.1%)	Atenolol n=14 participants at risk Atenolol tablet(Negative controls, Open-label) Control (n=14) Overall rate of adverse events 10 (71.4%) moderate to severe cases 2 (14.3%) generalized symptoms 4 (28.6%) gastrointestinal symptoms 3 (21.4%) lung problems 1 (7.1%) cardiovascular symptoms 0 central nervous system symptoms 1 (7.1%) Eye, nose, throat symptoms 1 (7.1%) gynecologic problems 1 (7.1%) problems of extremities 2 (14.3%)
Respiratory, thoracic and mediastinal disorders pneumothorax	7.1% 1/14 • Number of events 1 • 6months angioedema, GI symptom, rash, gout, hypotension, renal stone K, EKG, creatinine, uric acid, urine analysis Safety information will be collected including all AEs (adverse events) and all SAEs (Serious adverse events). Specially, a serious adverse event form should be completed for all serious adverse events during the study period. The serious adverse event will be checked by investigators. And investigators will report all SAEs to Novartis Safety desk within 24 hours since they know.	0.00% 0/14 • 6months angioedema, GI symptom, rash, gout, hypotension, renal stone K, EKG, creatinine, uric acid, urine analysis Safety information will be collected including all AEs (adverse events) and all SAEs (Serious adverse events). Specially, a serious adverse event form should be completed for all serious adverse events during the study period. The serious adverse event will be checked by investigators. And investigators will report all SAEs to Novartis Safety desk within 24 hours since they know.
Gastrointestinal disorders inguinal hernia	7.1% 1/14 • Number of events 1 • 6months angioedema, GI symptom, rash, gout, hypotension, renal stone K, EKG, creatinine, uric acid, urine analysis Safety information will be collected including all AEs (adverse events) and all SAEs (Serious adverse events). Specially, a serious adverse event form should be completed for all serious adverse events during the study period. The serious adverse event will be checked by investigators. And investigators will report all SAEs to Novartis Safety desk within 24 hours since they know.	0.00% 0/14 • 6months angioedema, GI symptom, rash, gout, hypotension, renal stone K, EKG, creatinine, uric acid, urine analysis Safety information will be collected including all AEs (adverse events) and all SAEs (Serious adverse events). Specially, a serious adverse event form should be completed for all serious adverse events during the study period. The serious adverse event will be checked by investigators. And investigators will report all SAEs to Novartis Safety desk within 24 hours since they know.

Other adverse events

Other adverse events
Measure	Atenolol & Aliskiren n=14 participants at risk Atenolol tablet and Aliskiren 150mg or 300mg tablet by mouth per day for 6month Treatment (n=14) Overall rate of adverse events 12 (85.7%) moderate to severe cases 0 generalized symptoms 8 (57.1%) gastrointestinal symptoms 4 (28.6%) lung problems 0 cardiovascular symptoms 3 (21.4%) central nervous system symptoms 5 (35.7%) Eye, nose, throat symptoms 4 (28.6%) gynecologic problems 1 (7.1%) problems of extremities 1 (7.1%)	Atenolol n=14 participants at risk Atenolol tablet(Negative controls, Open-label) Control (n=14) Overall rate of adverse events 10 (71.4%) moderate to severe cases 2 (14.3%) generalized symptoms 4 (28.6%) gastrointestinal symptoms 3 (21.4%) lung problems 1 (7.1%) cardiovascular symptoms 0 central nervous system symptoms 1 (7.1%) Eye, nose, throat symptoms 1 (7.1%) gynecologic problems 1 (7.1%) problems of extremities 2 (14.3%)
General disorders generalized symptoms	57.1% 8/14 • Number of events 8 • 6months angioedema, GI symptom, rash, gout, hypotension, renal stone K, EKG, creatinine, uric acid, urine analysis Safety information will be collected including all AEs (adverse events) and all SAEs (Serious adverse events). Specially, a serious adverse event form should be completed for all serious adverse events during the study period. The serious adverse event will be checked by investigators. And investigators will report all SAEs to Novartis Safety desk within 24 hours since they know.	28.6% 4/14 • Number of events 4 • 6months angioedema, GI symptom, rash, gout, hypotension, renal stone K, EKG, creatinine, uric acid, urine analysis Safety information will be collected including all AEs (adverse events) and all SAEs (Serious adverse events). Specially, a serious adverse event form should be completed for all serious adverse events during the study period. The serious adverse event will be checked by investigators. And investigators will report all SAEs to Novartis Safety desk within 24 hours since they know.

Additional Information

Prof Duk-Kyung Kim

SamsungMC

Phone: 01099333413

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place