Replication of the PARADIGM-HF Heart Failure Trial in Healthcare Claims Data.
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 入组人数
- 6,066
- 试验地点
- 1
- 主要终点
- Composite outcome of death from cardiovascular causes or hospitalization for heart failure
研究概览
简要总结
Investigators are building an empirical evidence base for real world data through large-scale replication of randomized controlled trials. The investigators' goal is to understand for what types of clinical questions real world data analyses can be conducted with confidence and how to implement such studies.
详细描述
This is a non-randomized, non-interventional study that is part of the RCT DUPLICATE initiative (www.rctduplicate.org) of the Brigham and Women's Hospital, Harvard Medical School. It is intended to replicate, as closely as is possible in healthcare insurance claims data, the trial listed below/above. Although many features of the trial cannot be directly replicated in healthcare claims, key design features, including outcomes, exposures, and inclusion/exclusion criteria, were selected to proxy those features from the trial. Randomization is also not replicable in healthcare claims data but was proxied through a statistical balancing of measured covariates according to standard practice. Investigators assume that the RCT provides the reference standard treatment effect estimate and that failure to replicate RCT findings is indicative of the inadequacy of the healthcare claims data for replication for a range of possible reasons and does not provide information on the validity of the original RCT finding.
研究设计
- 研究类型
- Observational
- 观察模型
- Cohort
- 时间视角
- Retrospective
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Age 18 years or older
- •NYHA functional class II-IV
- •LVEF ≤ 35%
- •AND the following:
- •Hospitalization for heart failure within the last 12 months
- •Treatment with a stable dose of an ACE inhibitor or an ARB equivalent to enalapril 10 mg/day for at least 4 weeks before the screening visit; and treatment with a stable dose of a beta-blocker for at least 4 weeks prior to the screening visit, unless contraindicted or not tolerated
- •Treatment with a stable dose of an ACE inhibitor or an ARB equivalent to enalapril 10 mg/day for at least 4 weeks before the screening visit
- •AND the following:
- •Treatment with a stable dose of a beta-blocker for at least 4 weeks prior to the screening visit, unless contraindicated or not tolerated
排除标准
- •Known history of angioedema
- •Requirement for treatment with both ACEIs and ARBs
- •Current acute decompensated heart failure (exacerbation of chronic heart failure manifested by signs and symptoms that may require intravenous therapy)
- •Symptomatic hypotension and/or a systolic blood pressure <100 mmHg at Visit 1 (screening) or <95 mmHg at Visit 3 or at Visit 5 (randomization)
- •Estimated glomerular filtration rate (eGFR) <30 mL/min/1.73 m2 at Visit 1 (screening), Visit 3 (end of enalapril run-in), or Visit 5 (end of LCZ696 run-in and randomization) or >35% decline in eGFR between Visit 1 and Visit 3 or between Visit 1 and Visit 5
- •Serum potassium >5.2 mmol/L at Visit 1 (screening) or >5.4 mmol/L at Visit 3 or Visit 5 (randomization)
- •Acute coronary syndrome, stroke, transient ischaemic attack, cardiac, carotid, or other major cardiovascular surgery, PCI, or carotid angioplasty within the 3 months prior to Visit
- •Implantation of a cardiac resynchronization therapy (CRT) device within 3 months prior Visit 1 or intent to implant a CRT
- •History of heart transplant or on a transplant list or with LV assistance device
- •History of severe pulmonary disease
- •Diagnosis of peripartum- or chemotherapy-induced cardiomyopathy within the 12 months prior to Visit 1
- •Documented untreated ventricular arrhythmia with syncopal episodes within the 3 months prior to Visit 1
- •Documented ventricular arrhythmia within the 3 months prior to Visit 1
- •AND the following:
- •Syncopal episodes within the 3 months prior to Visit 1
- •AND the following:
- •Untreated ventricular arrhythmia within the 3 months prior to visit 1
- •OR the following:
- •Untreated ventricular arrhythmia within the 3 months prior to visit 1
- •Symptomatic bradycardia or second- or third-degree atrioventricular block without a pacemaker
- •Presence of haemodynamically significant mitral and/or aortic valve disease, except mitral regurgitation secondary to LV dilatation
- •Presence of other haemodynamically significant obstructive lesions of the LV outflow tract, including aortic and subaortic stenosis
- •Any surgical or medical condition which might significantly alter the absorption, distribution, metabolism, or excretion of study drugs, including, but not limited to, any of the following:
- •History of active inflammatory bowel disease during the 12 months before Visit 1
- •OR the following:
- •Active duodenal or gastric ulcers during the 3 months prior to Visit 1
- •OR the following:
- •Evidence of hepatic disease as determined by any one of the following: aspartate aminotransferase or alanine aminotransferase values exceeding 2× upper limit of normal at Visit 1, history of hepatic encephalopathy, history of oesophageal varices, or history of porto-caval shunt
- •OR the following:
- •Current treatment with cholestyramine or colestipol resins
- •Presence of any other disease with a life expectancy of 5 years
- •Any Ivabradine use -- Approved in April 2015 (same year as Entresto)
研究组 & 干预措施
ACE Inhibitors
Reference group
干预措施: ACE inhibitor (Drug)
Sacubitril/Valsartan
Exposure group
干预措施: Sacubitril/Valsartan (Drug)
结局指标
主要结局
Composite outcome of death from cardiovascular causes or hospitalization for heart failure
时间窗: Through study completion (a median of 102-139 days)
次要结局
未报告次要终点
研究者
Shirley Vichy Wang
Associate Professor of Medicine
Brigham and Women's Hospital