Tsuyuki R T, Yusuf S, Rouleau J L, Maggioni A P, McKelvie R S, Wiecek E M, Wang Y, Pogue J, Teo K K, White M, Avezum A, Latini R, Held P, Lindgren E, Probstfield J
HGH-McMaster Clinic, Hamilton General Hospital, Ontario.
Can J Cardiol. 1997 Dec;13(12):1166-74.
The Randomized Evaluation of Strategies for Left Ventricular Dysfunction (RESOLVD) Pilot Study is a trial of combination neurohormonal blockade using an angiotensin II antagonist (candesartan), an angiotensin-converting enzyme inhibitor (enalapril) and a beta-blocker (metoprolol) in patients with congestive heart failure (CHF).
Primary objectives of stage I are to determine the efficacy (via the 6 min walk test) and safety of candesartan alone, and in combination with enalapril, versus enalapril alone. Secondary objectives are to determine the effect of the above combinations on neurohormones, ventricular function, quality of life and symptoms. Stage II objectives are similar, evaluating the effect of the addition of metoprolol or placebo to the above medication(s).
Randomized, two-stage trial consisting of a three-way comparison (stage I), followed by a 3 x 2 partial factorial design (stage II).
Sixty out-patient clinics in five countries.
Patients with symptoms of CHF (New York Heart Association functional classes II to IV), ejection fraction less than 40% and 6 min walk distance of 500 m or less.
In stage I, 770 patients are randomized to receive candesartan alone, enalapril alone, or candesartan plus enalapril. After five months (end of stage I), patients are assessed for eligibility to be randomized in stage II. Those who are not candidates for randomization to beta-blocker or placebo are followed on their stage I medications until the end of the study. In stage II, patients are randomized to receive metoprolol or placebo for a further six months in addition to their stage I medications. Endpoints are measured at baseline, end of stage I (week 20) and end of stage II (week 46). STUDY STATUS: The study has recently completed follow-up in both stages. The findings from this study will be used to design a large scale mortality study that will help further define the role of neurohormonal blockade in patients with CHF.
左心室功能障碍策略随机评估（RESOLVD）试点研究是一项针对充血性心力衰竭（CHF）患者联合使用血管紧张素II拮抗剂（坎地沙坦）、血管紧张素转换酶抑制剂（依那普利）和β受体阻滞剂（美托洛尔）进行神经激素阻断治疗的试验。
第一阶段的主要目的是确定单独使用坎地沙坦以及坎地沙坦与依那普利联合使用相对于单独使用依那普利的疗效（通过6分钟步行试验）和安全性。次要目的是确定上述联合用药对神经激素、心室功能、生活质量和症状的影响。第二阶段的目的类似，评估在上述药物基础上加用美托洛尔或安慰剂的效果。
随机两阶段试验，包括三向比较（第一阶段），随后是3×2部分析因设计（第二阶段）。
五个国家的60个门诊诊所。
有CHF症状（纽约心脏协会心功能II至IV级）、射血分数低于40%且6分钟步行距离为500米或更短的患者。
在第一阶段，770名患者被随机分配接受单独的坎地沙坦、单独的依那普利或坎地沙坦加依那普利。五个月后（第一阶段结束时），评估患者是否有资格进入第二阶段随机分组。那些不符合随机分配至β受体阻滞剂或安慰剂条件的患者继续使用第一阶段的药物直至研究结束。在第二阶段，患者除继续使用第一阶段的药物外，还被随机分配接受美托洛尔或安慰剂治疗，为期六个月。在基线、第一阶段结束时（第20周）和第二阶段结束时（第46周）测量终点指标。
该研究最近已完成两个阶段的随访。本研究的结果将用于设计一项大规模死亡率研究，以进一步明确神经激素阻断在CHF患者中的作用。
