Table I.
Register of all current and planned randomized trials of angiotensin receptor antagonists in Marfan syndrome
| Study | Sample size | Diagnostic criteria | Aortic size criteria | Age (y) | Treatment | Comparator | Follow-up duration (mo) | Primary end point | Timing of follow-up visits (mo) | Imaging methods | Study end date |
|---|---|---|---|---|---|---|---|---|---|---|---|
| ARB vs β-blocker | |||||||||||
| US (Pediatric Heart Network) | 608 | Ghent | z-score >3.0 and aortic root ≤5.0 cm | 0.5-25 | Losartan 0.4-1.4 mg/kg daily | Atenolol | 36 | Rate of change in aortic root (sinus of Valsalva) BSA-adjusted z-score | 6, 12, 24, 36 | Echo | Nov 14 |
| Italy (ARB vs β-blocker arms) | 156 | Ghent and mutation in FBN1 | z-score ≥2 or aortic root >3.8 cm (F)/>4.0 cm (M) and <5.0 cm | 1-55 | Losartan target dose 100 mg daily | Nebivolol | 48 | Aortic root growth rate | 12, 24, 36, 48 | Echo | Sept 15 |
| Spain | 150 | Ghent | No minimum, aortic root ≤4.5 cm | 5-60 | Losartan 12.5-100 mg daily | Atenolol | 36 | Progression of aortic dilation | 6, 12, 24, 36 | CMR | Sept 14 |
| US (Boston) | 50 | Ghent | Unrestricted | 25+ | Losartan | Atenolol | 6 | Arterial stiffness measures | 6 | Echo | Sept 14 |
| Canada | 17 | Ghent | Unrestricted | 12-25 | Losartan | Atenolol | 12 | Pulse wave velocity | 12 | Echo | Sept 14 |
| ARB vs placebo (or open-label control) | |||||||||||
| UK | 490 | Revised Ghent | z-score >0, aortic root <4.5 cm | ≥6-40 | Irbesartan 150-300 mg daily⁎ | Placebo⁎ | 48-60 | Absolute change in aortic root diameter per year | 12, 24, 36, 48, 60 | Echo | Sept 18 |
| The Netherlands | 233 | Ghent | No minimum size, but aortic root <5 cm | ≥18 | Losartan 50-100 mg daily⁎ | Open-label control⁎ | 36 | Largest change at any aortic level by MRI from baseline to end of study | 12, 24, 36 | CMR (0 and 36) | Nov 13 |
| France | 300 | Ghent | Unrestricted | ≥10 | Losartan 50-100 mg daily⁎ | Placebo⁎ | 36 | Rate of change of normalized aortic root diameter expressed as z-score | 6, 12, 18, 24, 30, 36 | Echo | Sept 14 |
| Italy (ARB + β-blocker vs β-blocker arms) | 156 | Ghent and mutation in FBN1 | z-score ≥2 or aortic root >3.8 cm (F)/>4.0 cm (M) and <5.0 cm | 1-55 | Losartan 100 mg and nebivolol | Nebivolol | 48 | Aortic root growth rate | 12, 24, 36, 48 | Echo | Sept 15 |
| Belgium | 39 | Revised Ghent | z-score ≥2.0 | ≥10 | Losartan 25-100 mg daily⁎ | Placebo⁎ | 36 | Rate of change in the aortic root by linear regression of the z-score | 6, 12, 24, 36 | Echo (primary) and CMR (0 and 36) | Dec 14 |
| Taiwan | 29 | Ghent | Recognized aortic dilation | 1+ | Losartan and either atenolol or propranolol | Atenolol or propranolol | 35 | Aortic root growth rate | 35 | Echo | Mar 13 |
Imaging methods: where >1 imaging method is listed (primary) indicates the method used for the primary outcome. Abbreviations: MRI, magnetic resonance imaging; CMR, cardiovascular magnetic resonance
Trials based in the UK, France, Belgium, and the Netherlands allow enrolled patients to remain on their baseline therapy (usually, but not always β-blockers). The Italian and Taiwanese trials mandate β-blocker in the comparator arm(s). The Italian trial is randomizing 235 subjects in a 3-way, 1:1:1 randomization, to losartan alone, nebivolol alone, or losartan + nebivolol. Sample per arm is estimated as 78 (235/3) and 156 per comparison (78 × 2).