Replication of the PARADIGM-HF Heart Failure Trial in Healthcare Claims Data.

NCT ID: NCT04736433

Last Updated: 2023-08-01

Basic Information

• Recruitment Status: COMPLETED
• Total Enrollment: 6066 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2020-09-22
• Study Completion Date: 2021-02-18

Brief Summary

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.

Detailed Description

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.

Conditions

Heart Failure

Study Design

• Observational Model Type: COHORT
• Study Time Perspective: RETROSPECTIVE

Study Groups

ACE Inhibitors

Reference group

ACE inhibitor

Intervention Type: DRUG

ACE inhibitor dispensing claim is used as the reference

Sacubitril/Valsartan

Exposure group

Sacubitril/Valsartan

Intervention Type: DRUG

Sacubitril/Valsartan dispensing claim is used as the reference

Interventions

ACE inhibitor

ACE inhibitor dispensing claim is used as the reference

Intervention Type: DRUG

Sacubitril/Valsartan

Sacubitril/Valsartan dispensing claim is used as the reference

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

Market availability of sacubitril/valsartan in the U.S. started on July 7, 2015.

• For Marketscan: July 7, 2015 - December 31, 2018 (end of data availability)
• For Optum: July 7, 2015 - March 31, 2020 (end of data availability)
• For Medicare: July 7, 2015 - December 31, 2017 (end of data availability)

• 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

Exclusion Criteria

• 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 1.
• 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)

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Brigham and Women's Hospital

OTHER

Sponsor Role: lead

Responsible Party

Shirley Vichy Wang

Associate Professor of Medicine

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Shirley Wang, PhD, ScM

Role: PRINCIPAL_INVESTIGATOR

Brigham and Women's Hospital

Locations

Brigham and Women's Hospital

Boston, Massachusetts, United States

Countries

United States

Provided Documents

Document Type: Study Protocol

View Document

Other Identifiers

2018P002966-DUP-PARADIGM-HF

Identifier Type: -

Identifier Source: org_study_id