Upstream Targeting for the Prevention of Atrial Fibrillation: Targeting Risk Interventions and Metformin for Atrial Fibrillation (TRIM-AF)
试验速览
- 阶段
- 4 期
- 状态
- 进行中（未招募）
- 发起方
- 入组人数
- 175
- 试验地点
- 2
- 主要终点
- Change in AF burden
研究概览
简要总结
Prospective randomized open-label blinded endpoint (PROBE) 2x2 factorial study of metformin extended release up to 750 mg BID and lifestyle and risk factor modification (LRFM) in CIED patients with at least 1 ≥5 minute episode of AF over the prior 3 months. Randomization will be stratified by pacemaker vs. ICD and rhythm at enrollment (sinus rhythm/atrial paced vs. AF).
详细描述
The purpose of this study is to perform a prospective, randomized study for the reduction of atrial fibrillation (AF) burden and progression, targeting metabolic upstream therapies. The study aims to determine if metformin and/or lifestyle/risk factor modifications reduce AF burden and progression. A secondary aim will attempt to determine clinical, genomic, and biomarker predictors of AF progression that can be used to personalize upstream therapies. This is a prospective randomized open-label blinded endpoint (PROBE) 2x2 factorial study of metformin extended release up to 750 mg twice daily and lifestyle and risk factor modification (LRFM) in patients with implanted pacemakers or defibrillators with atrial leads and at least 1 ≥5 minute episode of AF over the prior 3 months.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Factorial
- 主要目的
- Treatment
- 盲法
- Single (Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •TRIM-AF Cohorts
- •Inclusion Criteria:
- •Permanent pacemaker or implantable cardioverter-defibrillator (ICD) (with or without cardiac resynchronization therapy (CRT) with an implanted atrial lead capable of providing AF diagnostics and remote monitoring.
- •Paroxysmal AF, or persistent AF with plans for conversion.
- •AF on cardiac implantable electrical device (CIED) over the past 3 months with at least 1 episode lasting ≥5 minutes.
- •If on an antiarrhythmic drug, then on a stable regimen for the past 3 months.
排除标准
- •Permanent AF with no plans to convert to sinus rhythm.
- •If in persistent AF, current episode >12 months in duration (current long-standing persistent AF)
- •NYHA Functional Class IV heart failure
- •On metformin or other pharmacologic therapy for diabetes mellitus.
- •Use of anti-retroviral protease inhibitors (e.g. ombitasvir, paritaprevir, ritonavir, dasabuvir) or topiramate.
- •Known sensitivity to metformin
- •Moderate renal disease (eGFR <45 ml/min/1.73 m2)
- •Significant alcohol use (average >2 drinks/day)
- •Hepatic dysfunction - bilirubin >1.5x ULN, unless due to Gilbert's syndrome
- •Planned antiarrhythmic (class I or III) drug change, AF ablation/PVI procedure or cardiac surgery over the first 3 mos of the study
- •AF ablation/PVI procedure performed in the past 6 months
- •Device changed or implanted in the past 3 months
- •For patients on dofetilide with a pacemaker, QTc >490 ms if QRS duration is \100 ms, adjusted QTc >490 ms. Adjusted QTc = QTc - (QRS duration - 100 ms).
- •Women who are pregnant, breast-feeding or of child-bearing potential and not willing or able to use an acceptable form of contraception.
- •Participants considered by the investigator to be unsuitable for the study for any of the following reasons: Not agreeable for treatment with metformin or anticipated to have poor compliance on study drug treatment; inability to follow diet or exercise instructions; unwilling to attend study follow-up visits
- •Life expectancy less than 2 years due to concomitant disease.
- •Age <18 years old.
- •TRIM - No AF Cohort
- •Inclusion Criteria:
- •Permanent pacemaker or ICD (with or without CRT) with an implanted atrial lead capable of providing AF diagnostics and remote monitoring.
- •No AF on CIED over the past 6 months.
- •No history of AF.
- •Age >/=18 years old.
- •Exclusion Criteria:
- •History of AF.
- •NYHA Functional Class IV heart failure
- •On metformin or other pharmacologic therapy for diabetes mellitus.
- •Use of anti-retroviral protease inhibitors (e.g. ombitasvir, paritaprevir, ritonavir, dasabuvir) or topiramate.
- •Moderate renal disease (eGFR <45 ml/min/1.73 m2)
- •Significant alcohol use (average >2 drinks/day)
- •Hepatic dysfunction - bilirubin >1.5x ULN, unless due to Gilbert's syndrome
- •Planned antiarrhythmic (class I or III) drug change, cardiac surgery over the first 3 mos of the study
- •Device changed or implanted in the past 3 months
- •For patients on dofetilide with a pacemaker, QTc >490 ms if QRS duration is \100 ms, adjusted QTc >490 ms. Adjusted QTc = QTc - (QRS duration - 100 ms).
- •Women who are pregnant, breast-feeding or of child-bearing potential and not willing or able to use an acceptable form of contraception.
- •Participants considered by the investigator to be unsuitable for the study for any of the following reasons: Not agreeable for treatment with metformin or anticipated to have poor compliance on study drug treatment; inability to follow diet or exercise instructions; unwilling to attend study follow-up visits
- •Life expectancy less than 2 years due to concomitant disease.
- •Age <18 years old.
研究组 & 干预措施
Metformin + LRFM
Metformin ER up to 750 mg twice daily + Lifestyle/Risk Factor Modification (LRFM) diet/nutrition, exercise, and risk factor modification
干预措施: Metformin (Drug)
Metformin
Metformin ER up to 750 mg twice daily
干预措施: Metformin (Drug)
Lifestyle/Risk Factor Modification
Lifestyle/Risk Factor Modification (LRFM): Diet/nutrition, exercise, and risk factor modification
干预措施: Lifestyle/Risk Factor Modification (Behavioral)
Metformin + LRFM
Metformin ER up to 750 mg twice daily + Lifestyle/Risk Factor Modification (LRFM) diet/nutrition, exercise, and risk factor modification
干预措施: Lifestyle/Risk Factor Modification (Behavioral)
Control
Written educational literature on healthy eating and exercise guideline
No Atrial Fibrillation
Written educational literature on healthy eating and exercise guideline
结局指标
主要结局
Change in AF burden
时间窗: 1 year
Composite of change from baseline to 1 year of average daily AF burden % after a 3 month blanking period and survival at 1 year.
次要结局
- Total time of AF/3 mos(3 months, 1 year, 2 years)
- Average %time in AF/day(3 months, 1 year, 2 years)
- %change in average AF time/day(Baseline to 3 months, 1 year, 2 years)
- Number of days of AF(3 months, 1 year, 2 years)
- Number of AF episodes/month(3 months, 1 year, 2 years)
- Longest duration of AF at each 3 mo. period(3 months, 1 year, 2 years)
- Change in AF burden without blanking period(1 year)
- AF density(1 year, 2 years)
- Change in LDL(Baseline, 1 year, 2 years)
- Time to next AF and to persistent AF(Up to 2 years)
- Incidence of Persistent AF(3 months, 1 year, 2 years)
- Cardioversion for AF(3 months, 1 year, 2 years)
- AF ablation/pulmonary vein isolation (PVI) for increase in burden or persistent AF(3 months, 1 year, 2 years)
- Change of antiarrhythmic drug(3 months, 1 year, 2 years)
- Change in Atrial Fibrillation Symptom Score (AFSS)(Baseline, 1 year, 2 years)
- Change in Short Form-36 (SF-36) scores(Baseline, 1 year, 2 years)
- Change in BMI(Baseline, 1 year, 2 years)
- Change in physical assessment questionnaire scores: Rapid Assessment of Physical Activity (RAPA)(Baseline, 1 year, 2 years)
- Change in GPCOG questionnaire score(Baseline, 1 year, 2 years)
- Change in body fat composition(baseline, 1 year, 2 years)
- Change in weight(baseline, 1 year, 2 years)
- Change in waist/hip ratio(Baseline, 1 year, 2 years)
- Change in HbA1c(Baseline, 1 year, 2 years)
- Change in HDL(Baseline, 1 year, 2 years)
- Change in total cholesterol(Baseline, 1 year, 2 years)
- Change in triglycerides(Baseline, 1 year, 2 years)
- Change in Homeostatic Model Assessment - Insulin Resistance (HOMA-IR)(Baseline, 1 year, 2 years)
- Composite Major Adverse Cardiovascular Events (MACE)(1 year, 2 years)
- All-cause mortality(1 year, 2 years)
- Stroke(1 year, 2 years)
- Transient ischemic attack(1 year, 2 years)
- Activity by implanted device(3 months, 1 year, 2 years)
研究者
Mina Chung, MD
Principal Investigator, Professor of Medicine
The Cleveland Clinic