Evaluation of the Efficacy and Safety of Tirzepatide, a Dual GLP-1/GIP Agonist, on Functional Capacity in Reduced Ejection Fraction Heart Failure Patients With Obesity (DUAL-HFrEF)
2026년 7월 30일 업데이트: Shadi Shafaghi, Shahid Beheshti University of Medical Sciences
Evaluation of the Efficacy and Safety of Tirzepatide, a Dual GLP-1/GIP Agonist, on Functional Capacity in Reduced Ejection Fraction Heart Failure Patients With Obesity: A Double-Blinded Randomized Controlled Trial
The goal of this clinical trial is to learn if tirzepatide works to improve physical function in adults with heart failure and obesity. It will also learn about the safety of tirzepatide. The main questions it aims to answer are:
Does tirzepatide improve how far participants can walk in 6 minutes? Does tirzepatide improve heart failure symptoms and quality of life? What side effects do participants have when taking tirzepatide?
Researchers will compare tirzepatide to a placebo (a look-alike substance that contains no drug) to see if tirzepatide improves physical function in people with heart failure and obesity.
Participants will:
Get a weekly injection of tirzepatide or a placebo under the skin for 6 months Start at a low dose, which may be raised slowly based on how well they tolerate it Keep taking their usual heart failure medicines Visit the clinic for checkups, blood tests, heart ultrasounds, and a 6-minute walk test Answer questions about their quality of life and heart failure symptoms
연구 개요
상태
상태
아직 모집하지 않음
정황
정황
개입 / 치료
개입 / 치료
상세 설명
This is a phase 3, randomized, double-blind (participant, care provider, investigator, and outcomes assessor blinded), placebo-controlled, parallel- group clinical trial evaluating the efficacy and safety of tirzepatide, a dual glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) receptor agonist, in participants with heart failure with reduced ejection fraction (HFrEF) and obesity.
Eligible participants are adults aged 18 years or older with HFrEF (left ventricular ejection fraction ≤40% on echocardiography within the prior 3 months), a body mass index ≥27 kg/m² with at least one obesity-related comorbidity (hypertension, diabetes, or dyslipidemia), and stable guideline-directed heart failure therapy for at least 4 weeks prior to enrollment. Key exclusion criteria include recent acute heart failure decompensation or hospitalization, uncontrolled blood pressure, advanced kidney disease (eGFR <30 mL/min/1.73m²), significant hepatic impairment, active pancreatitis, personal or family history of medullary thyroid carcinoma or multiple endocrine neoplasia type 2, and pregnancy or breastfeeding.
A total of 60 participants will be randomized 1:1 using a computer-generated block randomization schedule (block size of 4) to receive either tirzepatide or matching placebo, both administered as weekly subcutaneous injections. Study drug is initiated at 2.5 mg once weekly and titrated every 4 weeks, as tolerated, up to a maximum of 10 mg once weekly, continuing through month 6. The placebo pen is identical in appearance, packaging, and dosing schedule to maintain blinding.
The primary outcome is change in 6-minute walk distance from baseline to 6 months. Secondary outcomes include change in New York Heart Association functional class, Kansas City Cardiomyopathy Questionnaire quality-of-life score, body mass index, ejection fraction, pulmonary artery pressure, and metabolic parameters (fasting glucose, glycated hemoglobin, lipid panel), measured at baseline and at months 2, 4, and 6. Safety outcomes include gastrointestinal adverse events, injection-site reactions, hypoglycemia, pancreatitis, gallbladder events, and changes in liver enzymes, amylase, and lipase. An exploratory outcome evaluates shared molecular and genetic pathways linking obesity and HFrEF using peripheral blood RNA analysis via quantitative PCR or next-generation sequencing.
The study is being conducted at seven sites in Tehran, Iran, including Masih Daneshvari Hospital, Shahid Rajaei Cardiovascular Medical and Research Center, Rasoul Akram Hospital, Tehran Heart Center, Firoozgar Hospital, Ayatollah Taleghani Hospital, and Imam Khomeini Hospital Complex.
연구 유형
연구 유형
중재적
등록 (추정된)
등록
60
단계
단계
- 3단계
연락처 및 위치
이 섹션에서는 연구를 수행하는 사람들의 연락처 정보와 이 연구가 수행되는 장소에 대한 정보를 제공합니다.
연구 연락처
연구 연락처
- 이름: Shadi Shafaghi, MD-MPH-PhD
- 전화번호: 989125901135
- 이메일: shafaghishadi@yahoo.com
참여기준
연구원은 적격성 기준이라는 특정 설명에 맞는 사람을 찾습니다. 이러한 기준의 몇 가지 예는 개인의 일반적인 건강 상태 또는 이전 치료입니다.
자격 기준
자격 기준
공부할 수 있는 나이
- 성인
- 고령자
건강한 자원 봉사자를 받아들입니다
아니
설명
Inclusion Criteria:
- Age 18 years or older
- Heart failure with reduced ejection fraction, defined as left ventricular ejection fraction ≤40% on echocardiography performed within the prior 3 months
- Body mass index ≥27 kg/m², with at least one obesity-related comorbidity (hypertension, diabetes, or dyslipidemia)
- Stable heart failure therapy for at least 4 weeks prior to enrollment, including beta-blockers, renin-angiotensin system inhibitors/angiotensin receptor-neprilysin inhibitors, and sodium-glucose cotransporter-2 inhibitors, if prescribed
- Written informed consent
Exclusion Criteria:
- Acute heart failure decompensation or cardiac hospitalization within the prior 4 weeks
- Uncontrolled blood pressure (systolic blood pressure <90 mmHg or ≥180 mmHg)
- Advanced renal impairment (estimated glomerular filtration rate <30 mL/min/1.73m²)
- Severe hepatic impairment (liver enzymes elevated to 3 times the upper limit of normal)
- Active pancreatitis
- Personal or first-degree family history of medullary thyroid carcinoma or multiple endocrine neoplasia type 2
- Pregnancy or breastfeeding
- Known hypersensitivity to glucagon-like peptide-1 (GLP-1) or glucose-dependent insulinotropic polypeptide (GIP) receptor agonist drugs
- Concurrent use of other weight-loss medications
공부 계획
이 섹션에서는 연구 설계 방법과 연구가 측정하는 내용을 포함하여 연구 계획에 대한 세부 정보를 제공합니다.
연구는 어떻게 설계됩니까?
디자인 세부사항
- 주 목적: 치료
- 할당: 무작위
- 중재 모델: 병렬 할당
- 마스킹: 네 배로
팔의 수
2
무기와 개입
참가자 그룹 / 팔참가자 그룹 / 팔 |
개입 / 치료개입 / 치료 |
|---|---|
|
실험적: Tirzepatide
Participants receive tirzepatide via prefilled subcutaneous injection pen once weekly, in addition to standard heart failure therapy.
Starting dose is 2.5 mg once weekly for 4 weeks, titrated based on tolerability every 4 weeks up to a maximum of 10 mg once weekly, continued through month 6.
|
dual GLP-1/GIP receptor agonist administered subcutaneously; brief dosing summary
다른 이름들:
|
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위약 비교기: Placebo
Participants receive matching placebo via identical prefilled subcutaneous injection pen once weekly, in addition to standard heart failure therapy, with the same dosing schedule and titration pattern as the tirzepatide group, continued through month 6.
|
Matching placebo pen containing all inactive ingredients except tirzepatide
다른 이름들:
|
연구는 무엇을 측정합니까?
주요 결과 측정
주요 결과 측정
결과 측정 |
측정값 설명 |
기간 |
|---|---|---|
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Change in 6-Minute Walk Distance
기간: Baseline and 6 months after intervention start
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The 6-minute walk test will be performed according to the American Thoracic Society standard guidelines in a straight 30-meter corridor.
Participants will be asked to walk as far as possible in 6 minutes at their own pace, with rest breaks permitted if needed.
Total distance walked will be recorded in meters.
This is a standardized, validated, and reproducible tool for assessing functional capacity and exercise tolerance in patients with heart failure.
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Baseline and 6 months after intervention start
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2차 결과 측정
2차 결과 측정
결과 측정 |
측정값 설명 |
기간 |
|---|---|---|
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NYHA Functional Class
기간: Baseline and 6 months after intervention start
|
Heart failure severity classified according to the New York Heart Association (NYHA) functional classification system.
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Baseline and 6 months after intervention start
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Glycated Hemoglobin (HbA1c)
기간: Baseline, end of month 2, end of month 4, and end of month 6
|
Measured using standard biochemical assay kit.
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Baseline, end of month 2, end of month 4, and end of month 6
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Fasting Blood Glucose
기간: Baseline, end of month 2, end of month 4, and end of month 6
|
Venous blood sample collected after at least 8 hours of fasting; fasting glucose measured using standard enzymatic glucose oxidase laboratory kit.
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Baseline, end of month 2, end of month 4, and end of month 6
|
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Body Mass Index (BMI)
기간: Baseline and 6 months after intervention start
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Calculated as weight in kilograms divided by height in meters squared, using standardized stadiometer and scale.
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Baseline and 6 months after intervention start
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Quality of Life (QoL)
기간: Baseline and 6 months after intervention start
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Assessed using the Kansas City Cardiomyopathy Questionnaire (KCCQ) score.
|
Baseline and 6 months after intervention start
|
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Systolic Blood Pressure
기간: Baseline, end of month 2, end of month 4, and end of month 6
|
Measured using a calibrated automatic blood pressure device after at least 5 minutes of rest in a seated position.
|
Baseline, end of month 2, end of month 4, and end of month 6
|
|
Serum Amylase
기간: Baseline, end of month 2, end of month 4, and end of month 6
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Venous blood sample; serum amylase measured using standard colorimetric enzymatic laboratory kit.
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Baseline, end of month 2, end of month 4, and end of month 6
|
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Alanine Aminotransferase (ALT)
기간: Baseline, end of month 2, end of month 4, and end of month 6
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Venous blood sample; serum ALT measured using standard enzymatic spectrophotometric laboratory kit.
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Baseline, end of month 2, end of month 4, and end of month 6
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N-terminal Pro B-type Natriuretic Peptide (NT-proBNP)
기간: Baseline, end of month 2, end of month 4, and end of month 6
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Measured using human NT-proBNP ELISA kit.
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Baseline, end of month 2, end of month 4, and end of month 6
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|
Total Cholesterol
기간: Baseline, end of month 2, end of month 4, and end of month 6
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Venous blood sample collected after at least 8 hours of fasting; total cholesterol measured using standard colorimetric enzymatic laboratory kit.
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Baseline, end of month 2, end of month 4, and end of month 6
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Ejection Fraction
기간: Baseline, end of month 2, end of month 4, and end of month 6
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Assessed by echocardiography.
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Baseline, end of month 2, end of month 4, and end of month 6
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Number of Participants With Gallbladder Problems
기간: Baseline, end of month 2, end of month 4, and end of month 6
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Gallbladder problems (gallstones or cholecystitis) confirmed by abdominal ultrasound.
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Baseline, end of month 2, end of month 4, and end of month 6
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Number of Participants With Hypoglycemia
기간: Baseline, end of month 2, end of month 4, and end of month 6
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Hypoglycemia, defined as blood glucose below 70 mg/dL, measured using standard enzymatic glucose oxidase laboratory kit.
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Baseline, end of month 2, end of month 4, and end of month 6
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Number of Participants With Injection Site Reactions
기간: Baseline, end of month 2, end of month 4, and end of month 6
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Injection site reactions (including redness, swelling, itching, or pain at the injection site) assessed by physical examination.
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Baseline, end of month 2, end of month 4, and end of month 6
|
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Number of Participants With Gastrointestinal Adverse Events
기간: Baseline, end of month 2, end of month 4, and end of month 6
|
Gastrointestinal adverse events (including nausea, vomiting, diarrhea, constipation, or abdominal pain) graded according to the Common Terminology Criteria for Adverse Events (CTCAE) version 5.0, and assessed through participant interview and monitoring form.
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Baseline, end of month 2, end of month 4, and end of month 6
|
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Number of Participants With Pancreatitis
기간: Baseline, end of month 2, end of month 4, and end of month 6
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Pancreatitis diagnosed according to the revised Atlanta classification criteria, requiring at least two of the following: characteristic abdominal pain, serum amylase or lipase greater than three times the upper limit of normal, or characteristic findings on abdominal imaging.
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Baseline, end of month 2, end of month 4, and end of month 6
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Number of Participants With Tachycardia
기간: Baseline, end of month 2, end of month 4, and end of month 6
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Tachycardia, defined as a resting heart rate greater than 100 beats per minute measured by pulse oximetry or ECG monitoring at scheduled study visits.
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Baseline, end of month 2, end of month 4, and end of month 6
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Diastolic Blood Pressure
기간: Baseline, end of month 2, end of month 4, and end of month 6
|
Measured using a calibrated automatic blood pressure device after at least 5 minutes of rest in a seated position.
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Baseline, end of month 2, end of month 4, and end of month 6
|
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Serum Lipase
기간: Baseline, end of month 2, end of month 4, and end of month 6
|
Venous blood sample; serum lipase measured using standard colorimetric enzymatic laboratory kit.
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Baseline, end of month 2, end of month 4, and end of month 6
|
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Aspartate Aminotransferase (AST)
기간: Baseline, end of month 2, end of month 4, and end of month 6
|
Venous blood sample; serum AST measured using standard enzymatic spectrophotometric laboratory kit.
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Baseline, end of month 2, end of month 4, and end of month 6
|
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Alkaline Phosphatase
기간: Baseline, end of month 2, end of month 4, and end of month 6
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Venous blood sample; serum alkaline phosphatase measured using standard enzymatic spectrophotometric laboratory kit.
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Baseline, end of month 2, end of month 4, and end of month 6
|
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Low-Density Lipoprotein (LDL)
기간: Baseline, end of month 2, end of month 4, and end of month 6
|
Venous blood sample collected after at least 8 hours of fasting; serum LDL measured using standard colorimetric enzymatic laboratory kit.
|
Baseline, end of month 2, end of month 4, and end of month 6
|
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High-Density Lipoprotein (HDL)
기간: Baseline, end of month 2, end of month 4, and end of month 6
|
Venous blood sample collected after at least 8 hours of fasting; serum HDL measured using standard colorimetric enzymatic laboratory kit.
|
Baseline, end of month 2, end of month 4, and end of month 6
|
|
Triglycerides
기간: Baseline, end of month 2, end of month 4, and end of month 6
|
Venous blood sample collected after at least 8 hours of fasting; serum triglycerides measured using standard colorimetric enzymatic laboratory kit at the central laboratory.
|
Baseline, end of month 2, end of month 4, and end of month 6
|
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Pulmonary Artery Pressure
기간: Baseline, end of month 2, end of month 4, and end of month 6
|
Assessed by echocardiography.
|
Baseline, end of month 2, end of month 4, and end of month 6
|
기타 결과 측정
기타 결과 측정
결과 측정 |
측정값 설명 |
기간 |
|---|---|---|
|
Change in Gene Expression of Obesity- and Heart Failure-Related Pathways
기간: Baseline and 6 months after intervention start
|
Venous blood sampling before the intervention and at the end of the study, extraction of ribonucleic acid from peripheral blood samples, and assessment of changes in the expression of genes involved in the shared molecular pathways of obesity and Heart Failure with Reduced Ejection Fraction using quantitative real-time polymerase chain reaction (PCR).
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Baseline and 6 months after intervention start
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공동 작업자 및 조사자
여기에서 이 연구와 관련된 사람과 조직을 찾을 수 있습니다.
간행물 및 유용한 링크
연구에 대한 정보 입력을 담당하는 사람이 자발적으로 이러한 간행물을 제공합니다. 이것은 연구와 관련된 모든 것에 관한 것일 수 있습니다.
일반 간행물
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- Wallner M, Biber ME, Stolfo D, Sinagra G, Benson L, Dahlstrom U, Gudbjornsdottir S, Cosentino F, Mol PGM, Rosano GMC, Butler J, Metra M, Lund LH, Ferrannini G, Savarese G. Glucagon-like peptide-1 receptor agonists use and associations with outcomes in heart failure and type 2 diabetes: data from the Swedish Heart Failure and Swedish National Diabetes Registries. Eur Heart J Cardiovasc Pharmacother. 2024 Jul 16;10(4):296-306. doi: 10.1093/ehjcvp/pvae026.
- Hankosky ER, Wang H, Neff LM, Kan H, Wang F, Ahmad NN, Griffin R, Stefanski A, Garvey WT. Tirzepatide reduces the predicted risk of atherosclerotic cardiovascular disease and improves cardiometabolic risk factors in adults with obesity or overweight: SURMOUNT-1 post hoc analysis. Diabetes Obes Metab. 2024 Jan;26(1):319-328. doi: 10.1111/dom.15318. Epub 2023 Nov 6.
- Borlaug BA, Zile MR, Kramer CM, Baum SJ, Hurt K, Litwin SE, Murakami M, Ou Y, Upadhyay N, Packer M. Effects of tirzepatide on circulatory overload and end-organ damage in heart failure with preserved ejection fraction and obesity: a secondary analysis of the SUMMIT trial. Nat Med. 2025 Feb;31(2):544-551. doi: 10.1038/s41591-024-03374-z. Epub 2024 Nov 17.
- Zile MR, Borlaug BA, Kramer CM, Baum SJ, Litwin SE, Menon V, Ou Y, Weerakkody GJ, Hurt KC, Kanu C, Murakami M, Packer M; SUMMIT Trial Study Group. Effects of Tirzepatide on the Clinical Trajectory of Patients With Heart Failure, Preserved Ejection Fraction, and Obesity. Circulation. 2025 Mar 11;151(10):656-668. doi: 10.1161/CIRCULATIONAHA.124.072679. Epub 2024 Nov 18.
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연구 기록 날짜
이 날짜는 ClinicalTrials.gov에 대한 연구 기록 및 요약 결과 제출의 진행 상황을 추적합니다. 연구 기록 및 보고된 결과는 공개 웹사이트에 게시되기 전에 특정 품질 관리 기준을 충족하는지 확인하기 위해 국립 의학 도서관(NLM)에서 검토합니다.
연구 주요 날짜
연구 시작 (추정된)
연구 시작
2026년 7월 18일
기본 완료 (추정된)
기본 완료
2027년 6월 11일
연구 완료 (추정된)
연구 완료
2027년 12월 22일
연구 등록 날짜
최초 제출
최초 제출
2026년 7월 27일
QC 기준을 충족하는 최초 제출
QC 기준을 충족하는 최초 제출
2026년 7월 30일
처음 게시됨 (실제)
처음 게시됨
2026년 7월 31일
연구 기록 업데이트
마지막 업데이트 게시됨 (실제)
마지막 업데이트 게시됨
2026년 8월 3일
QC 기준을 충족하는 마지막 업데이트 제출
QC 기준을 충족하는 마지막 업데이트 제출
2026년 7월 30일
마지막으로 확인됨
마지막으로 확인됨
2026년 7월 1일
추가 정보
이 연구와 관련된 용어
추가 관련 MeSH 약관
기타 연구 ID 번호
기타 연구 ID 번호
- IRCT20200209046427N3
약물 및 장치 정보, 연구 문서
미국 FDA 규제 의약품 연구
예
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아니
미국에서 제조되어 미국에서 수출되는 제품
예
이 정보는 변경 없이 clinicaltrials.gov 웹사이트에서 직접 가져온 것입니다. 귀하의 연구 세부 정보를 변경, 제거 또는 업데이트하도록 요청하는 경우 register@clinicaltrials.gov. 문의하십시오. 변경 사항이 clinicaltrials.gov에 구현되는 즉시 저희 웹사이트에도 자동으로 업데이트됩니다. .