Prediction of the SURPASS-CVOT Cardiovascular Outcome Trial in Healthcare Claims Data
- Conditions
- Type 2 DiabetesMajor Adverse Cardiac EventsCardiovascular (CV) Risk
- Interventions
- Registration Number
- NCT07088718
- Lead Sponsor
- Brigham and Women's Hospital
- 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. In addition to closely emulating the trial population, this study also evaluates outcomes in a broader, expanded cohort to enhance generalizability to patients typically encountered in routine clinical practice who are at elevated cardiovascular risk. 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.
Recruitment & Eligibility
- Status
- ACTIVE_NOT_RECRUITING
- Sex
- All
- Target Recruitment
- 60000
- 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
- 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
EXPANDING ELIGIBILITY CRITERIA OF THE SURPASS-CVOT TRIAL
Inclusion Criteria:
- History of MI, surgical or percutaneous coronary/carotid peripheral artery revascularization
- Type 2 diabetes, use of antihypertensive/lipid-lowering drugs, coronary/carotid/peripheral artery disease, hypertension
- Age ≥18 years
- Male or female sex
Exclusion Criteria:
- Medullary thyroid carcinoma, MEN syndrome type 2, Malignancy
- Type 1 diabetes, secondary diabetes, chronic kidney disease or dialysis, uncontrolled diabetic retinopathy or maculopathy, pregnancy
- Prior use of pramlintide or any GLP-1-RA except tirzepatide or dulaglutide
- Concurrent use of both drugs i.e. tirzepatide and dulaglutide
Study & Design
- Study Type
- OBSERVATIONAL
- Study Design
- Not specified
- Arm && Interventions
Group Intervention Description Tirzepatide Tirzepatide Exposure group Dulaglutide Dulaglutide Reference group
- Primary Outcome Measures
Name Time Method First occurence of MACE (all-cause mortailty, myocardial infarction, or death) Through study completion (1 day after cohort entry date until the first of outcome or censoring) To evaluate the comparative effect of tirzepatide vs dulaglutide on time to first occurrence of MACE (all-cause mortailty, myocardial infarction, or death) after expanding the SURPASS-CVOT trial eligibility criteria to include patients with T2DM and elevated cardiovascular risk, reflecting a patient population more representative of routine clinical care : Individuals aged 18 years or older with T2DM and an elevated cardiovascular risk (e.g., including patients indicative of an elevated cardiovascular risk such as use of antihypertensive or lipid-lowering therapy, to reflect a broader patient population from routine care).
- Secondary Outcome Measures
Name Time Method Expanded composite cardiovascular outcome including coronary revascularization and hospitalization for unstable angina Through study completion (1 day after cohort entry date until the first of outcome or censoring) To evaluate the comparative effect of tirzepatide vs dulaglutide on an expanded composite cardiovascular outcome including coronary revascularization and hospitalization for unstable angina in two populations: (1) Patients meeting the eligibility criteria of the SURPASS-CVOT trial and (2) a population after expanding the SURPASS-CVOT trial eligibility criteria to include patients with T2DM and elevated cardiovascular risk, reflecting a patient population more representative of routine clinical care.
All-cause mortality, hospitalization for heart failure, or urgent heart failure visits Through study completion (1 day after cohort entry date until the first of outcome or censoring) To evaluate the comparative effect of tirzepatide vs dulaglutide on all-cause mortality, hospitalization for heart failure, or urgent heart failure visits in two populations: (1) Patients meeting the eligibility criteria of the SURPASS-CVOT trial and (2) a population after expanding the SURPASS-CVOT trial eligibility criteria to include patients with T2DM and elevated cardiovascular risk, reflecting a patient population more representative of routine clinical care.
All-cause mortality or hospitalization for heart failure Through study completion (1 day after cohort entry date until the first of outcome or censoring) To evaluate the comparative effect of tirzepatide vs dulaglutide on all-cause mortality and hospitalization for heart failure in two populations: (1) Patients meeting the eligibility criteria of the SURPASS-CVOT trial and (2) a population after expanding the SURPASS-CVOT trial eligibility criteria to include patients with T2DM and elevated cardiovascular risk, reflecting a patient population more representative of routine clinical care.
Urinary tract infections Through study completion (1 day after cohort entry date until the first of outcome or censoring) To evaluate the comparative effect of tirzepatide vs dulaglutide on the safety outcome of urinary tract infections in two populations: (1) Patients meeting the eligibility criteria of the SURPASS-CVOT trial and (2) a population after expanding the SURPASS-CVOT trial eligibility criteria to include patients with T2DM and elevated cardiovascular risk, reflecting a patient population more representative of routine clinical care.
Serious bacterial infections Through study completion (1 day after cohort entry date until the first of outcome or censoring) To evaluate the comparative effect of tirzepatide vs dulaglutide on the safety outcome of serious bacterial infections in two populations: (1) Patients meeting the eligibility criteria of the SURPASS-CVOT trial and (2) a population after expanding the SURPASS-CVOT trial eligibility criteria to include patients with T2DM and elevated cardiovascular risk, reflecting a patient population more representative of routine clinical care.
Gastrointestinal adverse events Through study completion (1 day after cohort entry date until the first of outcome or censoring) To evaluate the comparative effect of tirzepatide vs dulaglutide on the safety outcome of gastrointestinal adverse events in two populations: (1) Patients meeting the eligibility criteria of the SURPASS-CVOT trial and (2) a population after expanding the SURPASS-CVOT trial eligibility criteria to include patients with T2DM and elevated cardiovascular risk, reflecting a patient population more representative of routine clinical care.
Hernia Through study completion (1 day after cohort entry date until the first of outcome or censoring) To evaluate the effect of tirzepatide vs dulaglutide on a negative control outcome of hernia in two populations: (1) Patients meeting the eligibility criteria of the SURPASS-CVOT trial and (2) a population after expanding the SURPASS-CVOT trial eligibility criteria to include patients with T2DM and elevated cardiovascular risk, reflecting a patient population more representative of routine clinical care.
Lumbar radiculopathy Through study completion (1 day after cohort entry date until the first of outcome or censoring) To evaluate the effect of tirzepatide vs dulaglutide on a negative control outcome of lumbar radiculopathy in two populations: (1) Patients meeting the eligibility criteria of the SURPASS-CVOT trial and (2) a population after expanding the SURPASS-CVOT trial eligibility criteria to include patients with T2DM and elevated cardiovascular risk, reflecting a patient population more representative of routine clinical care..
Trial Locations
- Locations (1)
Brigham and Women's Hospital
🇺🇸Boston, Massachusetts, United States
Brigham and Women's Hospital🇺🇸Boston, Massachusetts, United States