Trial Outcomes & Findings for Effects of Losartan Versus Atenolol on Aortic and Cardiac Muscle Stiffness in Adults With Marfan Syndrome (NCT NCT00723801)

Results Overview

Aortic stiffness was assessed using applanation tonometry (SphygmoCor®, AtCor Medical, West Ryde, NSW, Sydney, Australia) to measure carotid to femoral artery pulse wave velocity (PWV). With the patient lying supine in a quiet environment, a handheld micromanometer-tipped probe was applied to the skin surface over the carotid and femoral arteries, compressing the vessel wall so that transmural forces within the vessel wall were perpendicular to the arterial surface. The distance from the sternal notch to the sites of carotid and femoral pulse acquisition were measured and inputted into the device to represent the relative distance from the carotid to femoral artery. The calculation of distance divided by time of pulse upstroke relative to the upstroke of the QRS on a 3 lead surface EKG was used by the device to calculate velocity. All recorded measurements met the manufacturer's quality control standards integrated into the software package.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

40 participants

Primary outcome timeframe

Baseline and 6 months

Results posted on

2014-09-09

Participant Flow

Participant milestones

Participant milestones
Measure	Subjects Randomized to Atenolol Atenolol: Atenolol 50mg PO QD	Subjects Randomized to Losartan Losartan: Losartan 100mg PO QD
Overall Study STARTED	20	20
Overall Study COMPLETED	17	17
Overall Study NOT COMPLETED	3	3

Reasons for withdrawal

Reasons for withdrawal
Measure	Subjects Randomized to Atenolol Atenolol: Atenolol 50mg PO QD	Subjects Randomized to Losartan Losartan: Losartan 100mg PO QD
Overall Study Lost to Follow-up	1	2
Overall Study Protocol Violation	2	1

Baseline Characteristics

Effects of Losartan Versus Atenolol on Aortic and Cardiac Muscle Stiffness in Adults With Marfan Syndrome

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Subjects Randomized to Atenolol n=17 Participants Atenolol: Atenolol 50mg PO QD	Subjects Randomized to Losartan n=17 Participants Losartan: Losartan 100mg PO QD	Total n=34 Participants Total of all reporting groups
Age, Continuous	34 years n=5 Participants	36 years n=7 Participants	35 years n=5 Participants
Sex: Female, Male Female	10 Participants n=5 Participants	8 Participants n=7 Participants	18 Participants n=5 Participants
Sex: Female, Male Male	7 Participants n=5 Participants	9 Participants n=7 Participants	16 Participants n=5 Participants
Pulse wave velocity	7.5 meters/second STANDARD_DEVIATION 1.6 • n=5 Participants	7.6 meters/second STANDARD_DEVIATION 2.4 • n=7 Participants	7.55 meters/second STANDARD_DEVIATION 2.0 • n=5 Participants
Ejection Fraction	60 % STANDARD_DEVIATION 4 • n=5 Participants	62 % STANDARD_DEVIATION 6 • n=7 Participants	61 % STANDARD_DEVIATION 5 • n=5 Participants

PRIMARY outcome

Timeframe: Baseline and 6 months

Aortic stiffness was assessed using applanation tonometry (SphygmoCor®, AtCor Medical, West Ryde, NSW, Sydney, Australia) to measure carotid to femoral artery pulse wave velocity (PWV). With the patient lying supine in a quiet environment, a handheld micromanometer-tipped probe was applied to the skin surface over the carotid and femoral arteries, compressing the vessel wall so that transmural forces within the vessel wall were perpendicular to the arterial surface. The distance from the sternal notch to the sites of carotid and femoral pulse acquisition were measured and inputted into the device to represent the relative distance from the carotid to femoral artery. The calculation of distance divided by time of pulse upstroke relative to the upstroke of the QRS on a 3 lead surface EKG was used by the device to calculate velocity. All recorded measurements met the manufacturer's quality control standards integrated into the software package.

Outcome measures

Outcome measures
Measure	Subjects Randomized to Atenolol n=17 Participants Atenolol: Atenolol 50mg PO QD	Subjects Randomized to Losartan n=17 Participants Losartan: Losartan 100mg PO QD
Aortic Biophysical Properties - Pulse Wave Velocity	-1.15 change in meters/second Standard Deviation 1.68	-0.22 change in meters/second Standard Deviation .59

SECONDARY outcome

Timeframe: Baseline and 6 months

Two-dimensional echocardiography was performed using a 3.0 MHz transducer (General Electric VIVID 7). Left ventricular and left atrial dimensions were determined in parasternal long axis views. Left ventricular ejection fraction was calculated using the modified Simpsons calculation in the apical two and four chamber views.

Outcome measures

Outcome measures
Measure	Subjects Randomized to Atenolol n=17 Participants Atenolol: Atenolol 50mg PO QD	Subjects Randomized to Losartan n=17 Participants Losartan: Losartan 100mg PO QD
Diastolic Function - Ejection Fraction	1.31 Change in % ejection fraction Standard Deviation 4.07	1.57 Change in % ejection fraction Standard Deviation 8.29

Adverse Events

Subjects Randomized to Atenolol

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Subjects Randomized to Losartan

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Adverse event data not reported

Additional Information

Mark Creager

Brigham and Women's Hospital

Phone: 617-732-5267

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place