NCT06914102

Emulation of the STEP-HFpEF DM Heart Failure Trial in Healthcare Claims Data

• Status: Completed
• Phase: —
• Study type: Observational
• Enrollment: 58,387 (actual)
• Sponsor: Brigham and Women's Hospital · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

Investigators are building an empirical evidence base for real-world data through large-scale emulation 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 Randomized Controlled Trials Duplicated Using Prospective Longitudinal Insurance Claims: Applying Techniques of Epidemiology (RCT DUPLICATE) initiative (www.rctduplicate.org) of the Brigham and Women's Hospital, Harvard Medical School. It is intended to emulate, as closely as is possible in healthcare insurance claims data, the STEP-HFpEF DM trial described below. 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. In addition to closely emulating the trial population, this study also evaluates outcomes in a broader, less restrictive cohort to enhance generalizability to patients typically encountered in routine clinical practice. Randomization cannot be achieved in healthcare claims data but was proxied through a statistical balancing of measured covariates according to standard practice. Investigators assume that the RCT provides guidance on the reference standard treatment effect estimate. However, failure to replicate RCT findings is not necessarily indicative of the inadequacy of the healthcare claims data for emulation for a range of possible reasons, as the end points examined in the database study were only of exploratory nature in the trial. Moreover, divergence from these end points do not provide information on the validity of the original RCT finding. The STEP-HFpEF DM trial is a superiority trial that included an evaluation of the effect of semaglutide, a glucagon-like peptide-1 receptor agonist (GLP-1-RA), vs placebo on all-cause mortality or worsening heart failure events among individuals with heart failure with preserved ejection fraction. The database study designed to emulate STEP-HFpEF DM will be a new-user active-comparative study, conducted using 3 national United States claims databases, where we compare the effect of semaglutide vs sitagliptin, a dipeptidyl peptidase-4 inhibitor (DPP4i) on the composite end point of all-cause mortality or heart failure hospitalization. While the STEP-HFpEF DM trial compared semaglutide vs placebo, we chose to use sitagliptin as an active-comparator proxy for placebo. Sitagliptin was specifically chosen because a major randomized controlled trial on cardiovascular outcomes demonstrated that the drug does not affect the cardiovascular outcomes under investigation. Furthermore, clinical guidelines during the study period recommended both drug classes under investigation as second- or third-line options for glucose lowering and were similarly costly

Conditions

• Diabetes Mellitus, Type 2
• HFpEF - Heart Failure With Preserved Ejection Fraction

Interventions

Type	Name	Description
DRUG	Semaglutide	New use of semaglutide dispensing claim is used as the exposure.
DRUG	Placebo	New use of sitagliptin dispensing claim is used as the reference (active-comparator proxy for placebo).

Timeline

• Start date: 2025-01-14
• Primary completion: 2025-06-01
• Completion: 2025-06-01
• First posted: 2025-04-06
• Last updated: 2026-01-30

Locations

1 site across 1 country: United States

Regulatory

• FDA-regulated drug study