NCT06659718

Emulation of the SOUL Diabetes Trial in Healthcare Claims

Emulation of the Effects of Oral Semaglutide on Cardiovascular Outcomes in Individuals With Type 2 Diabetes and Established Atherosclerotic Cardiovascular Disease and/or Chronic Kidney Disease: SOUL Trial

• Status: Completed
• Phase: —
• Study type: Observational
• Enrollment: 43,650 (actual)
• Sponsor: Brigham and Women's Hospital · Academic / Other
• Sex: All
• Age: 50 Years
• Healthy volunteers: —

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 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 trial listed below/above. Although many features of the trial cannot be directly emulated 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 emulable 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 emulation for a range of possible reasons and does not provide information on the validity of the original RCT finding. The SOUL trial, which is a superiority trial to evaluate the effect of oral semaglutide versus placebo on MACE outcomes (CV death, nonfatal MI, or nonfatal stroke) among individuals with type 2 diabetes (T2DM) and established atherosclerotic cardiovascular disease (ASCVD) and/or chronic kidney disease (CKD). The database study designed to emulate SOUL will be a new-user active comparative study, where we compare the effect of oral semaglutide versus sitagliptin on MACE outcome among patients with T2DM and with established ASCVD and/or CKD. Sitagliptin was selected to act as an active-comparator proxy for placebo. Sitagliptin and the class of dipeptidyl peptidase-4 (DPP-4) inhibitors have been demonstrated not to have an effect on MACE in a series of RCTs, and they are used in similar stages of disease/line of therapy as semaglutide, as well as being similarly costly.

Conditions

• Diabetes Mellitus, Type 2

Interventions

Type	Name	Description
DRUG	Oral semaglutide	New use of oral semaglutide dispensing claim is used as the exposure.
DRUG	Sitagliptin	New initiation of sitagliptin dispensing claim is used as the reference.

Timeline

• Start date: 2024-10-24
• Primary completion: 2025-02-13
• Completion: 2025-02-13
• First posted: 2024-10-26
• Last updated: 2025-05-25

Locations

1 site across 1 country: United States

Regulatory

• FDA-regulated drug study