TIRO-AF: TIRzepatide for the Treatment of Obesity in Patients With Atrial Fibrillation
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 入组人数
- 100
- 试验地点
- 1
- 主要终点
- AFib burden
研究概览
简要总结
This is a single center randomized double blind controlled study of patients (BMI ≥ 27 kg/m2) with obesity and Atrial Fibrillation (AFIB) randomized to Tirzepatide vs. placebo. It is expected that the significant weight loss with Tirzepatide will result in improved control, management, symptom severity, and burden of AFIB at 12 months.
详细描述
It is estimated that 12 million people in the United States will have AFIB by 2030. The obesity epidemic and all its comorbidities such as hypertension, diabetes and sleep apnea are potent risk factors for AFIB. Weight loss has emerged as a potent treatment for AFIB. This will be a randomized double blind controlled study of patients (BMI≥ 27 kg/m2) with obesity and AFIB randomized to Tirzepatide vs. placebo in the Cleveland Clinic Health System. It is expected that the weight loss with Tirzepatide will result in improved control, management, symptom severity, and burden of AFIB at 12 months.
Patients who met the initial screening criteria (including presence of at least 1% AF burden during a 2 week monitoring period with an ambulatory cardiac monitor) will be invited for possible enrolment. 100 Patients will then be randomized 1:1 to Tirzepatide group versus placebo and will be followed for 12 months. AFIB burden will be assessed through FDA approved event monitor. All patients will receive standard care for management of risk factors as well as nutrition and life style modification counseling.
Management of AFIB including pharmacotherapy, ablation, and direct current cardioversion (DCC) will be at the discretion of Cleveland Clinic's cardiologists.
Patients and investigators will be blinded to treatment assignment. Assessment of the primary endpoint will be based on the blinded downloads and interpretation of event monitors.
The primary objective of the study is to examine Tirzepetide 10mg once a week vs. placebo on severity and symptom burden of AFIB at 12 months.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Triple (Participant, Care Provider, Investigator)
入排标准
- 年龄范围
- 18 Years 至 80 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Subjects eligible for inclusion in this study must meet all of the following criteria:
- •Sinus rhythm at randomization
- •Sustained normal sinus rhythm (or)
- •Normal sinus rhythm at office visit
- •Age ≥18 to ≤80 years old
- •BMI ≥ 27 and ≤60 kg/m2
- •AFIB criteria:
- •Must be documented by ECG or monitor.
- •Must have symptomatic AFIB (Atrial Fibrillation).
- •In terms of types of AFIB, either paroxysmal AFIB or persistent AFIB.
- •All anti-diabetic medication (including insulin) must be stable for at least 3 months prior to enrollment,
- •HbA1c ≤10% for patients diagnosed with Type 2 Diabetes Mellitus (T2DM).
- •Ability and willingness to give themselves the medication, comply with study requirements and provide written informed consent.
排除标准
- •Subjects meeting any of the following criteria are not eligible for inclusion in this study.
- •AFIB ablation within the last 6 months
- •Planned ablation prior to 3 months post randomization
- •Significant cardiac valvular disease with planned cardiac valve intervention/surgery in the next 12 months
- •Severe uncompensated cardiopulmonary disease
- •New York Heart Association Class III or IV
- •Left ventricular ejection fraction <35% at the time of screening
- •Hospitalization in the past 6 months for myocardial infarction, unstable angina, stroke, transient ischemic attack, or heart surgery
- •History of solid organ transplant
- •Type 1 diabetes mellitus or auto-immune diabetes
- •Estimated Glomerular Filtration Rate (eGFR) < 30 mL/min/1.73 m2 at screening or on dialysis
- •Advanced and decompensated cirrhosis characterized by: presence of fibrosis stage 4 (cirrhosis) in liver biopsy, ascites, hepatic encephalopathy, portal hypertension, or esophageal varices.
- •Hemoglobin less than 9 g/dL
- •Current participation or use of investigational therapy or less than 3 months since participation in any drug or device trial.
- •Liver transaminase level >300 U/L
- •Subject reports alcohol use of on average >2 drinks/day
- •Presence of active malignancy (except non-melanoma skin cancer)
- •Life expectancy less than 3 years due to concomitant diseases
- •Major mental health, psychological disorders, or substance abuse disorders that could disqualify the patient from metabolic surgery
- •Any condition or major illness that, in the investigator's judgment, places the subject at undue risk by participating in the study
- •Plans to move outside the primary location of study (Northeast Ohio) within the next 12 months
- •Any personal or family history of pancreatitis or medullary thyroid cancer or MEN2 (Multiple Endocrine Neoplasia Type 2)
- •Current use or any use within the last 6 months of GLP-1/DPP4i (Glucagon-Like Peptide-1/Dipeptidyl Peptidase-4 inhibitor) or GIP (Gastric Inhibitory Polypeptide)/GLP-1
- •Known hypersensitivity to investigational product due to prior use of GLP-1/DPP4i or GIP/GLP-1
- •Allergy to medical grade tape or adhesive
- •Pregnant, breast-feeding or plans to become pregnant
研究组 & 干预措施
Control
Participants to inject weekly subcutaneous injections of normal saline starting with dose 2.5mg, then increase dose by 2.5mg at week 4 (5mg), week 8 (7.5mg) and at week 12 (10mg).
干预措施: Placebo (Drug)
Tirzepatide
Participants to inject weekly subcutaneous injections of Tirzepatide starting with dose 2.5mg, then increase dose by 2.5mg at week 4 (5mg), week 8 (7.5mg) and at week 12 (10mg) as tolerated.
干预措施: Tirzepatide (Drug)
结局指标
主要结局
AFib burden
时间窗: Up to 4 weeks
Percentage total duration of being in AFIB
次要结局
未报告次要终点