Phase 3 N=608 Randomized Single-blind Treatment

Comparison of Two Medications Aimed at Slowing Aortic Root Enlargement in Individuals With Marfan Syndrome

Marfan Syndrome

Bottom Line

View on ClinicalTrials.gov: NCT00429364 ↗

Enrolled (actual)

608

Serious AEs

9.9%

Results posted

Apr 2015

Primary outcome: Primary: Annual Rate of Change in Aortic Root (Sinuses of Valsalva) Body-surface-area-adjusted Z-score — -0.139; -0.107 z-score/year — p=0.08

Study Design & Population

Study type: Interventional
Phase: Phase 3
Interventions: Losartan Potassium (Drug); Atenolol (Drug)
Age: Pediatric, Adult · 0+ yrs
Sex: All
Sponsor: Carelon Research
Primary completion: Feb 2014

Outcome Measures

Outcome	Result	p-value
PRIMARY Annual Rate of Change in Aortic Root (Sinuses of Valsalva) Body-surface-area-adjusted Z-score	-0.139; -0.107	0.08
SECONDARY Annual Rate of Change in Aortic Root (Sinuses of Valsalva) Absolute Dimension	0.069; 0.075	0.20
SECONDARY Annual Rate of Change in Ascending-aorta-diameter Z Score, Adjusted by Body-surface-area.	-0.140; -0.114	0.15
SECONDARY Annual Rate of Change in the Absolute Diameter of the Ascending Aorta	0.039; 0.044	0.30
SECONDARY Annual Rate of Change in Aortic-annulus-diameter Z Score, Adjusted by Body-surface Area	-0.279; -0.175	<0.001 sig
SECONDARY Annual Rate of Change in the Absolute Diameter of the Aortic Annulus	0.015; 0.030	0.002 sig
SECONDARY Annual Rate of Change in Total Aortic Proximal Regurgitant Jet Area Indexed to Body-surface-area	0.005; 0.001	0.29
SECONDARY Annual Rate of Change in Weight	0.239; 0.229	0.96
SECONDARY Annual Rate of Change in Weight-for-age Z-score	0.011; 0.019	0.45
SECONDARY Annual Rate of Change in Weight-for-height Z-score	-0.001; -0.157	0.13
SECONDARY Annual Rate of Change in Height	0.822; 0.935	0.65
SECONDARY Annual Rate of Change in Height-for-age Z-score	0.046; 0.019	0.13
SECONDARY Annual Rate of Change in Body Mass Index	0.063; 0.076	0.82
SECONDARY Annual Rate of Change in Body Mass Index for Age Z-score	0.007; 0.021	0.64
SECONDARY Annual Rate of Change in Arm Span to Height Ratio	0.001; 0.001	0.49
SECONDARY Annual Rate of Change in Upper to Lower Segment Ratio	-0.014; -0.015	0.59
SECONDARY Number of Participants With Aortic Dissection.	0; 2	—
SECONDARY Event Rate of Aortic Dissection.	0; 0.7	0.16
SECONDARY Number of Participants With Aortic-root Surgery.	10; 18	—
SECONDARY Event Rate of Aortic-Root Surgery	3.4; 6.0	0.13
SECONDARY Number of Death.	0; 1	—
SECONDARY Event Rate of Death	0; 0.3	0.32
SECONDARY Number of Participants With the Composite Adverse Clinical Outcomes, Including Aortic Dissection, Aortic-root Surgery and Death.	10; 19	—
SECONDARY Event Rate of the Composite Adverse Clinical Outcomes, Including Aortic Dissection, Aortic-root Surgery and Death.	3.4; 6.4	0.10
SECONDARY Adverse Drug Reactions Reported at the Baseline Visit	112; 114; 10; 10; 84; 105	—
SECONDARY Adverse Drug Reactions Reported During Routine Follow-up Surveillance	202; 208; 27; 20; 152; 153	—

Summary

Marfan syndrome is a hereditary connective tissue disorder. Many individuals with this condition die because of the associated heart and blood vessel abnormalities. This study will compare the effectiveness of two medications, losartan and atenolol, at slowing aortic root enlargement in individuals with Marfan syndrome.

Eligibility Criteria

Inclusion Criteria

Diagnosis of Marfan syndrome, according to Ghent criteria (more information can be found in Appendix D of the protocol)
Aortic root Z-score greater than 3.0

Exclusion Criteria

Prior aortic surgery
Aortic root dimension at the sinuses of Valsalva greater than 5 cm
Planned aortic surgery within 6 months of study entry
Aortic dissection
Shprintzen-Goldberg syndrome
Loeys-Dietz syndrome
Therapeutic (i.e., for arrhythmia, ventricular dysfunction, or valve regurgitation) rather than prophylactic use of angiotensin-converting enzyme (ACE) inhibitor, beta-blocker, or calcium channel blocker
History of angioedema while taking an ACE inhibitor or beta-blocker
Intolerance to losartan or other angiotensin II receptor blocker (ARB) that resulted in termination of therapy
Intolerance to atenolol or other beta-blocker that resulted in termination of therapy
Kidney dysfunction (i.e., creatinine greater than the upper limit of age-related normal values)
Asthma of sufficient severity to prohibit the use of a beta-blocker
Chronic use of steroids and/or beta-adrenergic agents with exacerbations of asthma that are frequent (averaging three or more per year) or severe (requiring hospitalization)
Diabetes mellitus
Pregnant or planning to become pregnant within 36 months of study entry
Inability to complete study procedures, including history of poor acoustic windows (i.e., inability to obtain accurate measurement of aortic root)

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Data sourced from ClinicalTrials.gov (NCT00429364). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.