Prediction of the SURPASS-CVOT Cardiovascular Outcome Trial in Healthcare Claims Data

NCT ID: NCT07088718

Last Updated: 2025-10-15

Basic Information

• Recruitment Status: COMPLETED
• Total Enrollment: 44671 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2024-10-01
• Study Completion Date: 2025-07-30

Brief 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 SURPASS-CVOT 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. 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 and does not provide information on the validity of the original RCT finding.

The SURPASS-CVOT trial is a non-inferiority trial that aims to evaluate the effect of tirzepatide, a dual glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 receptor agonist (GLP-1-RA), vs dulaglutide, a GLP-1-RA, on time to first occurrence of any major adverse cardiovascular event (MACE), defined as cardiovascular death, myocardial infarction, or stroke among patients with type 2 diabetes mellitus (T2DM) and an established cardiovascular disease (CVD). In addition, the trial aims to determine noninferiority with a magnitude of difference that also supports superiority against putative placebo and for superiority to dulaglutide will be performed. With estimated study completion in summer 2025, results of the trial are yet to be announced. Therefore, we aim to predict the results of the SURPASS-CVOT trial by emulating its design with protocol registration and statistical analysis conducted before the results of the trial are made public.

The database study designed to emulate the SURPASS-CVOT trial will be a new-user active-comparative study, conducted using 2 national United States claims databases, where we compare the effect of tirzepatide vs dulaglutide on the composite end point of all-cause mortality, myocardial infarction, or stroke. Clinical guidelines during the study period recommended both agents under investigation as second-line options for glucose lowering and were similarly costly.

Conditions

Type 2 Diabetes; Major Adverse Cardiac Events; Cardiovascular (CV) Risk

Study Design

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

Study Groups

Tirzepatide

Exposure group

Tirzepatide

Intervention Type: DRUG

New use of tirzepatide dispensing claim is used as the exposure.

Dulaglutide

Reference group

Dulaglutide

Intervention Type: DRUG

New use of dulaglutide dispensing claim is used as the reference.

Interventions

Tirzepatide

New use of tirzepatide dispensing claim is used as the exposure.

Intervention Type: DRUG

Dulaglutide

New use of dulaglutide dispensing claim is used as the reference.

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• History of MI, surgical or percutaneous coronary/carotid peripheral artery revascularization
• BMI ≥25.0kg/m2
• Type 2 diabetes, diagnosis of coronary/carotid/peripheral artery disease
• Age ≥40 years
• Male or female sex

Exclusion Criteria

• Medullary thyroid carcinoma, MEN syndrome type 2, malignancy
• Treatment for diabetic retinopathy//macular edema, pancreatitis, gastric emptying abnormality/bariatric surgery, liver disease, end-stage renal disease or dialysis, pregnancy
• Prior use of pramlintide or any GLP-1-RA except tirzepatide or dulaglutide
• Cardiovascular event, hospitalization for heart failure
• Concurrent use of both drugs i.e. tirzepatide and dulaglutide

• Minimum Eligible Age: 40 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

Nils Krüger, MD

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 and Statistical Analysis Plan: Amendment 1 to Study Protocol and Statistical Analysis Plan

View Document

Document Type: Study Protocol and Informed Consent Form: Study Protocol and Statistical Analysis Plan

View Document

Document Type: Study Protocol and Statistical Analysis Plan: Amendment 2 to Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

2018P002966-DUP-SURPASSCVOT

Identifier Type: -

Identifier Source: org_study_id