Table 3.
Design of VANISH and other clinical trials assessing the effect of Angiotensin II Receptor Blockers in Hypertrophic Cardiomyopathy
| VANISH (N=212)* | INHERIT21 (N=133) | SHIMADA ET AL20 (N=20) | CHANCE19 (N=24) | YAMAZAKI ET AL17 (N=19) | KAWANO ET AL16 (N=23) | ARAUJO ET AL18 (N=30) | |
|---|---|---|---|---|---|---|---|
| YEAR PUBLISHED | -- | 2014 | 2013 | 2009 | 2007 | 2005 | 2005 |
| STUDY DESIGN | |||||||
| Randomized | Yes | Yes | Yes | Yes | Yes | Yes | No |
| Placebo-controlled | Yes | Yes | Yes | Yes | No | No | No |
| Double-blind | Yes | Yes | Yes | Yes | No | No | No |
| INCLUSION CRITERIA | |||||||
| Sarcomeric mutation | Pathogenic or likely pathogenic | -- | -- | -- | -- | -- | -- |
| LV wall thickness | Primary Cohort: 12–25mm or z score 3–18 Exploratory Cohort: <12 mm and Z <3† |
≥15mm or 13–14 mm in first-degree relatives | -- | ≥15 mm | ≥15mm | -- | ≥15 mm |
| Age (years) | Primary 8–45; Preclinical 10–25 | ≥18 | ≥18 | ≥18 | -- | -- | 18–50 |
| NYHA | I-II | -- | -- | -- | -- | -- | I-III |
| Obstruction | Peak gradient ≤30 mmHg at rest or with provocation | No limit for peak gradient | Peak gradient ≤30 mmHg at rest or with provocation | Peak gradient ≤30 mmHg at rest | No obstruction | No obstruction | Peak gradient ≤30 mmHg |
| LVEF | ≥55% | ≥50% | ≥55% | ≥60% | -- | -- | Normal |
| INTERVENTION | Valsartan (adults 320mg/d, children ≥ 35 kg: 160 mg/d; children <35 kg: 80 mg/d) | Losartan (100 mg per day) | Losartan (100 mg per day) | Candesartan (target 32 mg per day) | Losartan (50 mg per day) | Valsartan (80 mg per day) | Losartan (100 mg per day) |
| RECRUITMENT PERIOD | April 2014 - Feb 2017 | Dec 2011 - May 2013 | April 2007 -March 2010 | -- | -- | -- | -- |
| FOLLOW-UP TIME | 24 months | 12 months | 12 months | 12 months | 12 months | 12 months | 6 months |
| PRIMARY ENDPOINT | Composite | LV mass by CMR/CT | LGE by CMR | Not specified | LV mass by CMR | Not specified | Not specified |
| SECONDARY END-POINTS | Safety | LGE by CMR, LV wall thickness, LV mass, diastolic indices, exercise capacity, LA volume, NT-pro-BNP | LV mass by CMR, symptoms, diastolic indices, LA volume, collagen markers | LV wall thickness, LV mass, diastolic indices, exercise time. | -- | LV metrics, collagen markers | LV metrics, diastolic indices, LA diameter, symptoms, NT-pro-BNP |
| COUNTRY | US, Canada, Brazil, Denmark | Denmark | US | Czech republic | Japan | Japan | Brazil |
| SINGLE OR MULTICENTER | Multi | Single | SIngle | Multi | SIngle | Single | SIngle |
178 participants with left ventricular hypertrophy in the primary cohort and 34 participants with preclinical disease in the exploratory cohort.
Not reported.
E’ z score ≤ −1.5 OR electrocardiographic abnormalities other than non-specific ST-T wave changes (Q waves, T wave inversion, repolarization changes) OR LV wall thickness z-score 1.5–2.9 combined with LV thickness to dimension ratio ≥0.19 for preclinical subjects. BP indicates blood pressure; CMR, cardiovascular magnetic resonance imaging; CT, cardiac computed tomography; HCM, hypertrophic cardiomyopathy; LA, left atrial; LGE, late gadolinium enhancement; LV, left ventricular; LVEF, left ventricular ejection fraction; NYHA, New York Heart Association Class.