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

NCT04736433 | Completed FDA Drug

• 1 other identifier: 2018P002966-DUP-PARADIGM-HF
• Study Type: observational
• Target: 6,066
• Locations: 1 country
• Sites: 1

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.

Conditions

Heart Failure

Outcome Measures

Primary Outcomes (1)

• Composite outcome of death from cardiovascular causes or hospitalization for heart failure

  Through study completion (a median of 102-139 days)

Study Arms (2)

ACE Inhibitors

Reference group

Drug: ACE inhibitor

Sacubitril/Valsartan

Exposure group

Drug: Sacubitril/Valsartan

Interventions

ACE inhibitor DRUG

ACE inhibitor dispensing claim is used as the reference

ACE Inhibitors

Sacubitril/Valsartan DRUG

Sacubitril/Valsartan dispensing claim is used as the reference

Sacubitril/Valsartan

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Probability Sample

Study Population

This study will involve a new user, parallel group retrospective cohort study design comparing sacubitril/valsartan to ACE inhibitors. Although the trial compared sacubitril/valsartan to enalapril, we expanded the definition of the comparator group to include all ACEi therapies to improve power, since all medications within this class of medication are indicated and guideline recommended for use in heart failure with reduced ejection fraction patients and would be expected to have similar effects on the primary outcome of CV death and HF hospitalization. The patients will be required to have continuous enrollment during the baseline period of 180 days before initiation of sacubitril/valsartan or a ACEi (cohort entry).

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Brigham and Women's Hospital: lead

Study Sites (1)

Brigham and Women's Hospital

Boston, Massachusetts, 02120, United States

Location

MeSH Terms

Conditions

Heart Failure

Interventions

Angiotensin-Converting Enzyme Inhibitors; sacubitril and valsartan sodium hydrate drug combination

Condition Hierarchy (Ancestors)

Heart Diseases; Cardiovascular Diseases

Intervention Hierarchy (Ancestors)

Protease Inhibitors; Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action; Pharmacologic Actions; Chemical Actions and Uses

Study Officials

• Shirley Wang, PhD, ScM

  Brigham and Women's Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: RETROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor of Medicine

Study Record Dates

• First Submitted: January 25, 2021
• First Posted: February 3, 2021
• Study Start: September 22, 2020
• Primary Completion: February 18, 2021
• Study Completion: February 18, 2021
• Last Updated: August 1, 2023

Record last verified: 2023-07

Locations

US (1)