Clinical trial NCT06914141: Comparative Effectiveness of Tirzepatide Versus Semaglutide in Individuals With Heart Failure With Preserved Ejection Fraction
Official title: Comparative Effectiveness of Tirzepatide Versus Semaglutide in Individuals With Heart Failure With Preserved Ejection Fraction
Study type: OBSERVATIONAL
Overall status: ACTIVE_NOT_RECRUITING
Conditions: Diabetes Mellitus, Type 2
HFpEF - Heart Failure With Preserved Ejection Fraction
Lead sponsor: Brigham and Women's Hospital
Sponsor class: OTHER
First posted: 2025-04-06
Enrollment: 28118
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: RETROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: The study population includes individuals aged 40 years or older with heart failure with preserved ejection fraction.

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 assess the comparative effectiveness of tirzepatide vs semaglutide after emulating the pivotal RCTs of each drug used to support regulatory approval in heart failure with preserved ejection fraction (SUMMIT and STEP-HFpEF DM trials).This comparative effectiveness target trial described below draws from eligibility criteria from the SUMMIT and STEP-HFpEF DM trials. Although many features of the target 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 target trial. Randomization cannot be achieved in healthcare claims data but was proxied through a statistical balancing of measured covariates according to standard practice.

The database study will be a new-user active-comparative study, conducted using 2 national United States claims databases, where we compare the effect of tirzepatide vs semaglutide on the composite end point of all-cause mortality or heart failure hospitalization. Clinical guidelines during the study period recommended both agents for the same indications of glucose lowering and weight reduction. Indication for heart failure with preserved ejection fraction has not been granted for both drugs during the study period.

Eligibility criteria: Eligible cohort entry dates:

Optum: Study period between May 13, 2022 to November 30, 2024. Marketscan: Study period between May 13, 2022 to December 31, 2023.

Inclusion Criteria:

* Heart failure
* BMI \> 27.0 kg/m2
* History of type 2 diabetes mellitus
* LVEF ≥ 45%
* ≥ 18 years old, male or female sex

Exclusion Criteria:

* Prior treatment with any GLP-1-RA
* History of type 1 diabetes mellitus
* End-stage renal disease or chronic or intermittent haemodialysis or peritoneal dialysis
* History of bariatric surgery
* History of nursing home admission
* Pregnant female or breastfeeding
* Uncontrolled and potentially unstable diabetic retinopathy or maculopathy
* Treatment with continuous subcutaneous insulin infusion
* Multiple endocrine neoplasia type 2 or medullary thyroid carcinoma
* Have a history of an active or untreated malignancy or are in remission from a clinically significant malignancy (other than basal- or squamous-cell skin cancer, in situ carcinoma of the cervix, or in situ prostate cancer) for less than 5 years

Primary outcomes:
measure: Composite of all-cause mortality or heart failure hospitalization
timeFrame: Through study completion (1 day after cohort entry date until the first of outcome or censoring)
Secondary outcomes:
measure: Composite of all-cause mortality or all-cause mortality or a worsening heart failure event (exacerbated symptoms of heart failure resulting in hospitalization, intravenous diuretic therapy in an urgent care setting).
timeFrame: Through study completion (1 day after cohort entry date until the first of outcome or censoring)
measure: Worsening heart failure event (exacerbated symptoms of heart failure resulting in hospitalization or intravenous diuretic therapy in an urgent care setting).
timeFrame: Through study completion (1 day after cohort entry date until the first of outcome or censoring)
measure: Intravenous diuretic therapy in an urgent care setting
timeFrame: Through study completion (1 day after cohort entry date until the first of outcome or censoring)
measure: Hospitalization for heart failure
timeFrame: Through study completion (1 day after cohort entry date until the first of outcome or censoring)
measure: All-cause mortality
timeFrame: Through study completion (1 day after cohort entry date until the first of outcome or censoring)
measure: Urinary tract infection
timeFrame: Through study completion (1 day after cohort entry date until the first of outcome or censoring)
measure: Serious bacterial infection
timeFrame: Through study completion (1 day after cohort entry date until the first of outcome or censoring)
measure: Gastrointestinal adverse events
timeFrame: Through study completion (1 day after cohort entry date until the first of outcome or censoring)
Other outcomes:
measure: Hernia
timeFrame: Through study completion (1 day after cohort entry date until the first of outcome or censoring)
measure: Lumbar radiculopathy
timeFrame: Through study completion (1 day after cohort entry date until the first of outcome or censoring)
Locations:
city: Boston
country: United States
facility: Brigham and Women's Hospital
state: Massachusetts
Study officials:
affiliation: Brigham and Women's Hospital
name: Shirley Wang, PhD, ScM
role: PRINCIPAL_INVESTIGATOR
affiliation: Brigham and Women's Hospital
name: Nils Krüger, MD
role: PRINCIPAL_INVESTIGATOR
References: