Emulation of the SUMMIT Heart Failure Trial in Healthcare Claims Data

NCT06914154 | Completed FDA Drug

• 1 other identifier: 2018P002966-DUP-SUMMIT
• Study Type: observational
• Target: 11,265
• Locations: 1 country
• Sites: 1

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.

Conditions

Heart Failure With Preserved Ejection Fraction (HFPEF); Diabetes Mellitus, Type 2

Outcome Measures

Primary Outcomes (2)

• Composite of all-cause mortality or heart failure hospitalisation.

  To evaluate the comparative effect of tirzepatide vs placebo (sitagliptin) on all-cause mortality or heart failure hospitalization in patients with heart failure with preserved ejection fraction when following the eligibility criteria of the SUMMIT trial.

  Through study completion (1 day after cohort entry date until the first of outcome or censoring)

• Composite of all-cause mortality or heart failure hospitalization.

  To evaluate the comparative effect of tirzepatide vs placebo (sitagliptin) on all-cause mortality or heart failure hospitalization in patients with heart failure with preserved ejection fraction when relaxing the eligibility criteria of the SUMMIT trial.

  Through study completion (1 day after cohort entry date until the first of outcome or censoring)

Secondary Outcomes (8)

• Composite of all-cause mortality or all-cause mortality or a worsening heart failure event (exacerbated symptoms of heart failure resulting in hospitalization or intravenous diuretic therapy in an urgent care setting).

  Through study completion (1 day after cohort entry date until the first of outcome or censoring)

• Worsening heart failure event (exacerbated symptoms of heart failure resulting in hospitalization or intravenous diuretic therapy in an urgent care setting).

  Through study completion (1 day after cohort entry date until the first of outcome or censoring)

• Intravenous diuretic therapy in an urgent care setting

  Through study completion (1 day after cohort entry date until the first of outcome or censoring)

• Hospitalization for heart failure

  Through study completion (1 day after cohort entry date until the first of outcome or censoring)

• All-cause mortality

  Through study completion (1 day after cohort entry date until the first of outcome or censoring)

Other Outcomes (2)

• Hernia

  Through study completion (1 day after cohort entry date until the first of outcome or censoring)

• Lumbar radiculopathy

  Through study completion (1 day after cohort entry date until the first of outcome or censoring)

Study Arms (2)

Tirzepatide

Exposure group

Drug: Tirzepatide

Placebo

Reference group

Drug: Placebo

Interventions

Tirzepatide DRUG

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

Tirzepatide

Placebo DRUG

New use of sitagliptin dispensing claim is used as the reference (active-comparator proxy for placebo).

Placebo

Eligibility Criteria

• Age: 40 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

The study population included individuals aged 40 years or older with heart failure with preserved ejection fraction.

You may qualify if:

• ≥ 40 years old, male or female sex
• Chronic heart failure (NYHA Class II-IV) diagnosed for at least 3 months before Visit 1
• LVEF ≥50% demonstrated by echocardiogram performed at Visit 1 or within 6 months of Visit 1
• Structural heart disease
• Either one of: (1) eGFR \<70 mL/min/1.73m2 at Visit 1, (2) HF decompensation within 12 months of Visit 1, defined as hospitalization for HF requiring IV diuretic treatment or urgent HF visit requiring IV diuretic treatment
• Stable dose of all concomitant HF medications (that is, beta blockers, ACEis, ARBs, and MRAs), except for oral diuretics, for at least 4 weeks prior to Visit 1 a
• If treated with oral diuretics, dose must be stable for at least 2 weeks prior to Visit 1 and throughout the screening period; volume control must be optimally achieved in the opinion of the investigator
• BMI ≥27.0 kg/m2 at Visit 1
• Type 2 diabetes mellitus trial subgroup

You may not qualify if:

• Myocardial infarction, coronary artery bypass graft surgery, or other major CV surgery/intervention, stroke or transient ischemic attack in past 90 days, or unstable angina pectoris in past 30 days, prior to Visit 1 or during screening
• Lung disease: pulmonary arterial hypertension, chronic thromboembolic pulmonary hypertension (CTEPH), or severe pulmonary disease including (COPD)
• Other medical conditions: severe anemia (hemoglobin level \<9 g/dL) at Visit 1, untreated thyroid disease or TSH \>4.0 mU/L at Visit 1, or significant musculoskeletal disease
• Orthopedic conditions that limit the ability to walk, such as severe arthritis in the leg, knee, hip injuries, hemiplegia, or amputation with artificial limb without stable prosthesis function
• Any condition that in the opinion of the investigator would interfere with the assessment of 6MWT
• LVEF \<40% by local echocardiography documented any time within 2 years of Visit 1
• Acute decompensated HF (exacerbation of HF) requiring IV diuretics, IV inotropes, or IV vasodilators, or left ventricular assist device (LVAD) within 4 weeks prior to Visit 1, and/or during the screening period until randomization
• Impaired renal function, defined as eGFR \<15 mL/min/1.73 m2 (CKD-EPI) or requiring dialysis at Visit 1
• Any one of the following: (1) Systolic blood pressure (SBP) ≥180 mmHg at Visit 1 (2) SBP \>160 mmHg both at Visit 1 and at Visit 2 (3) Have symptomatic hypotension or SBP \<100 mmHg at Visit 1 or Visit 2
• Atrial fibrillation or atrial flutter with a resting heart rate \>110 bpm documented by ECG at Visit 1
• Cardiac amyloidosis or cardiomyopathy based on accumulation disease (for example, haemochromatosis, Fabry disease), muscular dystrophy, cardiomyopathy with reversible causes (for example, stress cardiomyopathy), hypertrophic obstructive cardiomyopathy or known pericardial constriction, or any severe (obstructive or regurgitant) valvular heart disease likely to lead to surgery during the study period
• Completed prior surgical treatment for obesity or had liposuction or abdominoplasty within 1 year prior to Visit 1. Participants who plan to have surgical treatment for obesity or liposuction or abdominoplasty during the duration of the study are excluded.
• Have type 1 diabetes mellitus
• For type 2 diabetes mellitus (1) Have uncontrolled diabetes requiring immediate therapy (such as diabetic ketoacidosis) at Visit 1 or Visit 2, in the judgement of the physician (2) Have had 1 or more events of severe hypoglycemia and/or 1 or more events of hypoglycemia unawareness within 6 months prior to Visit 1 (see Section 10.5.1.1 for definition of hypoglycemia) (3) Have a history of proliferative diabetic retinopathy, diabetic maculopathy, or severe nonproliferative diabetic retinopathy that requires acute treatment. Patients with T2DM should have had a dilated fundoscopic examination, performed by an ophthalmologist or optometrist, within 12 months of Visit 1 or prior to randomization (4) Treated with premix or prandial insulins or intensified insulin regimens (multiple daily injection with basal and prandial insulins or insulin pump therapy) at Visit 1
• History of acute or chronic pancreatitis or at high risk for acute pancreatitis (for example, serum triglyceride level \>500 mg/dL

Sponsors & Collaborators

• Brigham and Women's Hospital: lead

Study Sites (1)

Brigham and Women's Hospital

Boston, Massachusetts, 02120, United States

Location

Related Publications (1)

• Kruger N, Schneeweiss S, Fuse K, Matseyko S, Sreedhara SK, Hahn G, Schunkert H, Wang SV. Semaglutide and Tirzepatide in Patients With Heart Failure With Preserved Ejection Fraction. JAMA. 2025 Oct 14;334(14):1255-1266. doi: 10.1001/jama.2025.14092.

  PMID: 40886075 DERIVED

MeSH Terms

Conditions

Diabetes Mellitus, Type 2

Interventions

Tirzepatide

Condition Hierarchy (Ancestors)

Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases

Intervention Hierarchy (Ancestors)

Glucagon-Like Peptide-1 Receptor; Glucagon-Like Peptide Receptors; Receptors, G-Protein-Coupled; Receptors, Cell Surface; Membrane Proteins; Proteins; Amino Acids, Peptides, and Proteins; Receptors, Gastrointestinal Hormone; Receptors, Peptide

Study Officials

• Shirley Wang, PhD, ScM

  Brigham and Women's Hospital

  PRINCIPAL INVESTIGATOR

• Nils Krüger, MD

  Brigham and Women's Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: RETROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor of Medicine

Study Record Dates

• First Submitted: March 31, 2025
• First Posted: April 6, 2025
• Study Start: January 14, 2025
• Primary Completion: June 1, 2025
• Study Completion: June 1, 2025
• Last Updated: January 30, 2026

Record last verified: 2025-05

Locations

US (1)