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

This study has been completed.
Sponsor:
Collaborator:
Children's Hospital Boston
Information provided by (Responsible Party):
Mark Alan Creager, MD, Brigham and Women's Hospital
ClinicalTrials.gov Identifier:
NCT00723801
First received: July 25, 2008
Last updated: September 8, 2014
Last verified: September 2014

July 25, 2008
September 8, 2014
October 2007
December 2012   (final data collection date for primary outcome measure)
Aortic Biophysical Properties - Pulse Wave Velocity [ Time Frame: Baseline and 6 months ] [ Designated as safety issue: No ]
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.
Aortic biophysical properties [ Time Frame: 6 months ] [ Designated as safety issue: No ]
Complete list of historical versions of study NCT00723801 on ClinicalTrials.gov Archive Site
Diastolic Function - Ejection Fraction [ Time Frame: Baseline and 6 months ] [ Designated as safety issue: No ]
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.
Diastolic Function [ Time Frame: 6 months ] [ Designated as safety issue: No ]
Not Provided
Not Provided
 
Effects of Losartan Versus Atenolol on Aortic and Cardiac Muscle Stiffness in Adults With Marfan Syndrome
Effects of Losartan vs Atenolol on Aortic Stiffness and Diastolic Function in Adults With Marfan Syndrome

Marfan syndrome is an inherited connective tissue disorder with morbidity and mortality from aortic dilation and dissection. The degree of aortic dilation and response to beta-blockade (standard of care) vary in adults with Marfan syndrome. However, aortic stiffness is often present, and can be a predictor of aortic dilation and cardiovascular complications. In addition, adults with Marfan syndrome develop left ventricular diastolic dysfunction, which can progress to heart failure. Aortic stiffness and diastolic dysfunction are important and logical therapeutic targets in adults with Marfan syndrome.

TGF-beta mediates disease pathogenesis in Marfan syndrome and contributes to aortic stiffness. The angiotensin receptor blocker, losartan, inhibits TGF-beta activity and reverses aortic wall pathology in a Marfan mouse model. Losartan also decreases aortic stiffness and improves diastolic function in hypertension, renal disease and hypertrophic cardiomyopathy.

This trial is a randomized, double-blind trial of 50 adults with Marfan syndrome, treated with 6 months of atenolol vs. losartan. Arterial tonometry for aortic stiffness and echocardiography for diastolic function will be performed at the beginning and end of treatment. A blood draw for serum markers of extracellular matrix turnover and inflammation will also be performed at 0 and 6 months. We plan to determine whether losartan decreases aortic stiffness and left ventricular diastolic dysfunction significantly more than atenolol.

Please See Summary.

Interventional
Phase 3
Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Marfan Syndrome
  • Drug: Atenolol
    Atenolol 50mg PO QD
    Other Name: Tenormin
  • Drug: Losartan
    Losartan 100mg PO QD
    Other Name: Cozaar
  • Active Comparator: Subjects Randomized to Losartan
    Losartan: 100 mg PO QD
    Intervention: Drug: Losartan
  • Active Comparator: Subjects Randomized to Atenolol
    Atenolol: 50 mg PO QD
    Intervention: Drug: Atenolol
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
40
December 2012
December 2012   (final data collection date for primary outcome measure)

Inclusion Criteria:

  • Age greater than 25 years
  • Clinical Marfan Syndrome

Exclusion Criteria:

  • Previous aortic or cardiac surgery
  • Pregnancy
  • Renal Insufficiency
  • Medication intolerance
Both
25 Years and older
No
Contact information is only displayed when the study is recruiting subjects
United States
 
NCT00723801
2007p-001762
Yes
Mark Alan Creager, MD, Brigham and Women's Hospital
Brigham and Women's Hospital
Children's Hospital Boston
Principal Investigator: Mark A Creager, MD Brigham and Women;s Hospital
Brigham and Women's Hospital
September 2014

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP