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)
2026年7月30日 更新者：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
調査の概要
詳細な説明
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.
研究の種類
介入
入学 (推定)
60
段階
- フェーズ 3
連絡先と場所
このセクションには、調査を実施する担当者の連絡先の詳細と、この調査が実施されている場所に関する情報が記載されています。
研究連絡先
- 名前：Shadi Shafaghi, MD-MPH-PhD
- 電話番号：989125901135
- メール：shafaghishadi@yahoo.com
参加基準
研究者は、適格基準と呼ばれる特定の説明に適合する人を探します。これらの基準のいくつかの例は、人の一般的な健康状態または以前の治療です。
適格基準
就学可能な年齢
- 大人
- 高齢者
健康ボランティアの受け入れ
いいえ
説明
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
研究計画
このセクションでは、研究がどのように設計され、研究が何を測定しているかなど、研究計画の詳細を提供します。
研究はどのように設計されていますか？
デザインの詳細
- 主な目的：処理
- 割り当て：ランダム化
- 介入モデル：並列代入
- マスキング：4倍
武器と介入
参加者グループ / アーム |
介入・治療 |
|---|---|
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実験的：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.
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dual GLP-1/GIP receptor agonist administered subcutaneously; brief dosing summary
他の名前：
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プラセボコンパレーター：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.
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Matching placebo pen containing all inactive ingredients except tirzepatide
他の名前：
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この研究は何を測定していますか？
主要な結果の測定
結果測定 |
メジャーの説明 |
時間枠 |
|---|---|---|
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Change in 6-Minute Walk Distance
時間枠：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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二次結果の測定
結果測定 |
メジャーの説明 |
時間枠 |
|---|---|---|
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NYHA Functional Class
時間枠：Baseline and 6 months after intervention start
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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)
時間枠：Baseline, end of month 2, end of month 4, and end of month 6
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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
時間枠：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)
時間枠：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)
時間枠：Baseline and 6 months after intervention start
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Assessed using the Kansas City Cardiomyopathy Questionnaire (KCCQ) score.
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Baseline and 6 months after intervention start
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Systolic Blood Pressure
時間枠：Baseline, end of month 2, end of month 4, and end of month 6
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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 Amylase
時間枠：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)
時間枠：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)
時間枠：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
時間枠：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
時間枠：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
時間枠：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
時間枠：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
時間枠：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
時間枠：Baseline, end of month 2, end of month 4, and end of month 6
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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
時間枠：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
時間枠：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
時間枠：Baseline, end of month 2, end of month 4, and end of month 6
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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
時間枠：Baseline, end of month 2, end of month 4, and end of month 6
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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)
時間枠：Baseline, end of month 2, end of month 4, and end of month 6
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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
時間枠：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)
時間枠：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; serum LDL 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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High-Density Lipoprotein (HDL)
時間枠：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; serum HDL 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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Triglycerides
時間枠：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; serum triglycerides measured using standard colorimetric enzymatic laboratory kit at the central laboratory.
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Baseline, end of month 2, end of month 4, and end of month 6
|
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Pulmonary Artery Pressure
時間枠：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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その他の成果指標
結果測定 |
メジャーの説明 |
時間枠 |
|---|---|---|
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Change in Gene Expression of Obesity- and Heart Failure-Related Pathways
時間枠：Baseline and 6 months after intervention start
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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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協力者と研究者
ここでは、この調査に関係する人々や組織を見つけることができます。
出版物と役立つリンク
研究に関する情報を入力する責任者は、自発的にこれらの出版物を提供します。これらは、研究に関連するあらゆるものに関するものである可能性があります。
一般刊行物
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研究記録日
これらの日付は、ClinicalTrials.gov への研究記録と要約結果の提出の進捗状況を追跡します。研究記録と報告された結果は、国立医学図書館 (NLM) によって審査され、公開 Web サイトに掲載される前に、特定の品質管理基準を満たしていることが確認されます。
主要日程の研究
研究開始 (推定)
2026年7月18日
一次修了 (推定)
2027年6月11日
研究の完了 (推定)
2027年12月22日
試験登録日
最初に提出
2026年7月27日
QC基準を満たした最初の提出物
2026年7月30日
最初の投稿 (実際)
2026年7月31日
学習記録の更新
投稿された最後の更新 (実際)
2026年8月3日
QC基準を満たした最後の更新が送信されました
2026年7月30日
最終確認日
2026年7月1日
詳しくは
本研究に関する用語
追加の関連 MeSH 用語
その他の研究ID番号
- IRCT20200209046427N3
医薬品およびデバイス情報、研究文書
米国FDA規制医薬品の研究
はい
米国FDA規制機器製品の研究
いいえ
米国で製造され、米国から輸出された製品。
はい
この情報は、Web サイト clinicaltrials.gov から変更なしで直接取得したものです。研究の詳細を変更、削除、または更新するリクエストがある場合は、register@clinicaltrials.gov。 までご連絡ください。 clinicaltrials.gov に変更が加えられるとすぐに、ウェブサイトでも自動的に更新されます。