Emulation of the SUMMIT Heart Failure Trial in Healthcare Claims Data

Plain English Summary

Emulation of the SUMMIT Heart Failure Trial in Healthcare Claims Data is a Not Applicable clinical trial sponsored by Brigham and Women's Hospital studying Diabetes Mellitus, Type 2, Heart Failure With Preserved Ejection Fraction (HFPEF). This study analyzes how a diabetes and weight loss medication (tirzepatide) might affect patients with a specific type of heart failure and diabetes, using past health records. It is for adults aged 40 and older who have been diagnosed with chronic heart failure with preserved ejection fraction (HFpEF) and type 2 diabetes. Participation involves analyzing existing, anonymized health claims data; no direct patient involvement is required. This study aims to understand if real-world data can reliably predict outcomes similar to large clinical trials, potentially reducing the need for future patient-involved trials. The trial aims to enroll 11265 participants.

Official 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.

Who Can Participate

Here is what you need to know about eligibility for this trial. You may be included if you are 40 or older, have chronic heart failure (NYHA Class II-IV) for at least 3 months, and have a specific heart function measurement (LVEF ≥50%). You must also have type 2 diabetes, a certain kidney function level (eGFR <70 mL/min/1.73m2) or recent heart failure worsening, and a BMI of 27.0 kg/m2 or higher. You cannot be included if you've had recent major heart events, have severe lung disease, certain other medical conditions, or specific types of diabetes complications or treatments. This trial is studying Diabetes Mellitus, Type 2, Heart Failure With Preserved Ejection Fraction (HFPEF), so participants generally need a confirmed diagnosis.

What They're Measuring

The primary outcome measures whether the treatment reduces the risk of death from any cause or hospitalization due to heart failure, indicating its potential to improve survival and reduce serious hea The specific primary outcome measures are: Composite of all-cause mortality or heart failure hospitalisation. (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. (Through study completion (1 day after cohort entry date until the first of outcome or censoring)). These endpoints are how researchers determine whether the treatment is effective and will form the basis of any future regulatory submissions.

About This Phase

This study does not have a traditional clinical phase designation. It may be an observational study that follows patients without intervening in their care, an expanded access or compassionate use program, or other non-interventional research. These studies contribute valuable data about disease progression, treatment patterns, and patient outcomes.

Why This Trial Matters

This trial matters because it seeks to validate the use of existing health data to understand treatment effectiveness, potentially offering a faster and more cost-effective way to evaluate new therapi This research targets Diabetes Mellitus, Type 2, Heart Failure With Preserved Ejection Fraction (HFPEF), where improved treatment options are needed.

Investor Insight

This study's approach of emulating a trial using claims data could signal a shift towards more efficient real-world evidence generation, potentially impacting the market for diabetes and heart failure The large enrollment target of 11265 participants suggests significant investment in this program.

Is This Trial Right for Me?

Ask your doctor if your current heart failure and diabetes medications are stable, as this is a key requirement for the data being analyzed. Understand that this study uses your past health records; you will not be directly involved in any treatments or visits for this specific trial. The study looks at data collected between May 2022 and December 2023, depending on the specific health claims database used. The trial is being conducted at 1 site. Always discuss clinical trial participation with your healthcare provider before making any decisions. This information is for educational purposes only and is not medical advice.

AI-generated analysis for educational purposes only. This is not medical advice. Discuss clinical trial participation with your doctor. Data sourced from ClinicalTrials.gov.

Study Design

• Study Type: OBSERVATIONAL
• Enrollment: 11,265 participants

Interventions

• DRUG: Tirzepatide — New use of tirzepatide dispensing claim is used as the exposure.
• DRUG: Placebo — New use of sitagliptin dispensing claim is used as the reference (active-comparator proxy for placebo).

Primary Outcomes

• Composite of all-cause mortality or heart failure hospitalisation. (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. (Through study completion (1 day after cohort entry date until the first of outcome or censoring))

Secondary Outcomes

• 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))

Full 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

FOLLOWING ELIGIBILITY OF THE SUMMIT TRIAL

Inclusion Criteria:

* ≥ 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

Exclusion Criteria:

* 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
* Have acute or chronic hepatitis, signs and symptoms of any other liver disease other than nonalcoholic fatty liver disease, or any of the following, as determined by the central laboratory during Visit 1: ALT or AST levels \>2.5X the ULN for the reference range.
* Have a family or personal history of medullary thyroid carcinoma (MTC) or Multiple Endocrine Neoplasia (MEN) Syndrome type 2
* Have a history of an active or untreated malignancy or are in remission from a clinically significant malignancy (other than basal- or squamous-cell 

Trial Locations

• Brigham and Women's Hospital, Boston, Massachusetts, United States

Frequently Asked Questions

Related Conditions

• Heart Failure with Preserved Ejection Fraction (HFpEF)
• Type 2 Diabetes Mellitus
• Obesity
• Cardiovascular Disease
• Hypertension
• Chronic Kidney Disease
• Metabolic Syndrome
• Diabetic Retinopathy
• Coronary Artery Disease
• Atrial Fibrillation

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