Atrial FibrillationPhase 4METSAFENCT07027969
Metabolic Surgery for Atrial Fibrillation Elimination
A Phase 4 study testing Roux-en-Y Gastric Bypass or Sleeve Gastrectomy and Anti-Obesity Medication (AOM) treatment in people with Atrial Fibrillation and Obesity and Obesity-related Medical Conditions, run by Ali Aminian at 1 site in United States.
Trial summary
Atrial fibrillation (AF) is the most common sustained cardiac arrhythmia. It is estimated that between 3 and 6 million Americans are currently living with AF, while 12 million people in the United States will have AF in 2030. Read more about this study
- Who is it for?
- Ages 18 to 80 yearsHealthy volunteers can take part
- Conditions the study is for
- Atrial Fibrillation, Obesity and Obesity-related Medical Conditions
- What is being tested?
- Roux-en-Y Gastric Bypass or Sleeve Gastrectomy and Anti-Obesity Medication (AOM) treatment
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 100 participants
- Where
- 1 siteUnited States
- Study dates
- 1 Nov 2026to 31 Mar 2030
- Phase
- Phase 4
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 80 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- Entry into the study would require that the patient:
- Is a candidate for general anesthesia
- Is eligible for metabolic surgery (RYGB or SG)
- Is ≥18 and ≤80 years old
- has a BMI ≥35 and ≤65 kg/m2
- has AF criteria, which:
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- Must be documented by EKG or cardiac monitor or Zio XT Patch
- Must have symptomatic AF
- In terms of types of AF, either paroxysmal AF with at least one episode lasting ≥5 minutes in the last 3 months prior to screening, or persistent AF, or longstanding AF.
- Must have a minimum burden of 1% during a 2-week screening time with an ambulatory noninvasive cardiac monitor.
- Must be assessed and confirmed by an expert cardiologist (e.g., cardiac electrophysiologist) to meet eligibility.
- Patients without history of prior AF ablation/PVI procedure or with history of prior failed AF ablation/PVI procedure are eligible for the study.
- Patients with and without T2DM are eligible for the study. Patients with T2DM should have been on a stable dose of anti-diabetic medication (including insulin) for at least 3 months prior to entry, with HbA1c ≤12%.
- Have the ability and willingness to participate in the study and agree to any of the arms involved in the study.
- Able to understand the options and to comply with the requirements of each arm.
- Have a negative urine pregnancy test at screening and randomization visits for women of childbearing potential.
- Women, of childbearing age, must agree to use reliable method of contraception for 2 years.
Who cannot join
- Significant cardiac valvular disease (planned to undergo cardiac valve intervention/surgery in the next 12 months)
- Significant atherosclerotic disease (planned to undergo coronary, carotid, or peripheral artery revascularization procedures in the next 12 months)
- Severe uncompensated cardiopulmonary disease leading to American Society of Anesthesiologists Class IV or V
- Classified as New York Heart Association Class IV
- Left ventricular ejection fraction <20% at the time of screening
- Hospitalization for myocardial infarction, unstable angina, stroke, transient ischemic attack, heart surgery, coronary stent placement in the past 6 months
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- Prior bariatric and metabolic surgery of any kind (patients who had a gastric balloon or gastric band that were removed more than one year prior to enrollment are allowed to participate)
- History of solid organ transplant
- Type 1 diabetes or autoimmune diabetes
- eGFR < 30 mL/min/1.73 m2 at screening or being on dialysis
- Decompensated cirrhosis characterized by ascites, hepatic encephalopathy, portal hypertension, or esophageal varices.
- Anemia defined as hemoglobin less than 9 g/dL
- Use of investigational therapy
- Liver transaminase level >300 U/L
- Significant alcohol use (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 in the opinion of the investigators 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
- Unable to understand the risks, benefits and compliance requirements of study
- Lack capacity to give informed consent
- Plans to move outside the primary location of study (Northeast Ohio) within the next 12 months
- Pregnant, breast-feeding or the intention of becoming pregnant or not using adequate contraceptive measures
- Known adhesive allergies
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
United States1 site
The Cleveland Clinic
Cleveland, Ohio, 44195
Chytaine Hall, (216) 445-3983, hallc1@ccf.org
About this study
Official title: Efficacy of Cardiometabolic Risk Factor Control Through Metabolic Surgery on Management and Severity of Atrial Fibrillation: METSAFE Randomized Clinical Trial
Atrial fibrillation (AF) is the most common sustained cardiac arrhythmia. It is estimated that between 3 and 6 million Americans are currently living with AF, while 12 million people in the United States will have AF in 2030. Obesity and its comorbidities such as type 2 diabetes (T2DM), hypertension, and obstructive sleep apnea (OSA) are major risk factors for development and progression of AF. Metabolic and Bariatric Surgery (MBS) is the most effective currently available treatment for obesity. Patients typically lose 20 to 35 percent of body weight after surgery which is often sustained for many years. MBS can improve all 5 major risk factors of AF including obesity, hypertension, T2DM, OSA, and systemic inflammation.
The purpose of the study is to understand if MBS can affect the severity of AF and the toll AF's symptoms take on patients.
Read the detailed description
This is randomized trial of 100 patients with BMI ≥35 kg/m2 and AF. 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 enrollment. Patients will then be randomized 1:1 to MBS group versus nonsurgical control group and will be followed for 12 months (phase 1) and then for an additional 18 months (phase 2).
Interventions include Roux-en-Y Gastric Bypass or Sleeve Gastrectomy surgical procedures based on the shared medical decision between the bariatric surgeon and patients considering the patient's conditions. In the control group, patients are allowed to take anti-obesity medications (AOMs) that are not contraindicated in patients with AF at the discretion of obesity medicine specialists.
Lifestyle and risk factor modification in both groups will consist of targeted and personalized diet plans, exercise, and risk factor reduction, including optimal therapies for T2DM, hypertension, dyslipidemia, heart failure, coronary artery disease, and OSA.
- Being tested
- Roux-en-Y Gastric Bypass or Sleeve Gastrectomy, Anti-Obesity Medication (AOM) treatment
- Keywords
- Atrial Fibrillation, Bariatric Surgery, Metabolic Syndrome, Weight Loss Surgery, Roux-en-Y gastric bypass, Sleeve Gastrectomy, GLP-1 Receptor Agonist, Tirzepatide, Semaglutide
- Medical subject headings
- Atrial Fibrillation, Obesity, Metabolic Syndrome
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Roux-en-Y Gastric Bypass or Sleeve GastrectomyProcedure or surgery
Also called Roux-en-Y Gastric Bypass (RYGB), Sleeve Gastrectomy (SG), Bariatric Surgery
Patients receive either RYGB or SG. The surgical risk, differential impact of each procedure on body weight and other obesity-related diseases, presence of other medical and mental problems, patient's behavioral factors (e.g., postoperative compliance, active smoking), medications, and goals will be considered when the patient and local medical team make a shared decision about the most appropriate surgical procedure.
Anti-Obesity Medication (AOM) treatmentDrug
Implementation of obesity pharmacotherapy in the nonsurgical group includes initial assessment of side effects and response, followed by achieving a clinically meaningful weight loss (5% weight loss) after three months. Once this goal is reached, AOMs will be continued throughout the study. If a weight plateau is reached within the first AOM, then another AOM may be added in combination in a stepwise fashion. The choice of AOMs considered may include metformin, topiramate, liraglutide, dulaglutide, semaglutide, tirzepatide, and empagliflozin.
| Study group | Role | What they receive |
|---|---|---|
| Metabolic Surgery | Active comparator | Roux-en-Y Gastric Bypass (RYGB) and Sleeve Gastrectomy (SG) Receives: Procedure: Roux-en-Y Gastric Bypass or Sleeve Gastrectomy |
| Control group (nonsurgical standard of care for obesity) | Other | In the Control group, the subjects will be receiving standard of care for nonsurgical management of obesity, including possible AOMs that are not contraindicated in patients with AF at the discretion of obesity medicine specialists. Receives: Drug: Anti-Obesity Medication (AOM) treatment |
What is being measured
The primary outcome is the main question the study is designed to answer.
Relative change in total duration of being in atrial fibrillation (AF)
Relative change from baseline to 52 weeks in the percentage total duration of being in AF during a 2-week monitoring period (i.e., %burden), assessed by the Zio XT Patch (iRhythm).
Measured: First 52 weeks of the study
Secondary outcomes (10)
Presence of at least 1 AF episode
Presence of at least 1 AF episode (present or absent) in a 2-week monitoring time by Zio XT Patch at 52 weeks.
Measured: First 52 weeks of the study
Change in number of AF episodes (≥30 seconds)
Change in Zio XT Patch derived variables from baseline to 52 weeks including number of AF episodes (≥30 seconds) in a 2-week monitoring time.
Measured: First 52 weeks of the study
Change in number of AF espisodes longer than 6 minutes
Change in Zio XT Patch derived variables from baseline to 52 weeks including number of AF episodes longer than 6 minutes in a 2-week monitoring time.
Measured: First 52 weeks of the study
Change in the longest AF duration
Change in Zio XT Patch derived variables from baseline to 52 weeks including the longest AF duration in a 2-week monitoring time.
Measured: First 52 weeks of the study
Change in the second longest AF duration
Change in Zio XT Patch derived variables from baseline to 52 weeks including the second longest AF duration in a 2-week monitoring time.
Measured: First 52 weeks of the study
Change in the AF type
Change in the AF type (e.g. regression from or progression to persistent form of AF)
Measured: First 52 weeks of the study
Change in AF Symptom burden
Change in AF Symptom burden and severity assessed by the Toronto AF Severity Score (AFSS)
Measured: First 52 weeks of the study
Relapse of AF after ablation
Number of relapses of AF after ablation in each group
*Since more ablation is expected in the second phase of study, this end point will be more relevant in the phase 2 of study.
Measured: Throughout the study, 130 weeks
Change in cardiac structure
Change in cardiac structure assessed by transthoracic echocardiography including LA and LV size, morphology, and function
Measured: First 52 weeks of the study
Change in weight
Percent and absolute changes in body weight and BMI
Measured: First 52 weeks of the study
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Jun 2025
- Study start1 Nov 2026 (estimated)
- Primary completion31 Dec 2029 (estimated)
- Study completion31 Mar 2030 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Atrial FibrillationStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- METSAFE is a randomized open-label blinded-endpoint single-center controlled efficacy/safety study with 2 parallel groups of patients with obesity and AF who will either receive metabolic surgery or nonsurgical obesity care for 30 months. The study has 2 phases: the first 12 months and the subsequent 18 months.
- Masking
- None (open label)
- Enrolment
- 100 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Ali Aminian
- Sponsor type
- University, hospital or other
- Collaborators
- Ethicon, Inc., iRhythm Technologies, Inc.
- Responsible party
- Sponsor-investigator, Ali Aminian, The Cleveland Clinic
- Investigators
- Ali Aminani, Principal investigator, Bariatric Research Medical Director
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07027969
- Sponsor's protocol ID
- 23-1039
- Acronym
- METSAFE
- Status last verified
- Apr 2026
- First submitted
- 11 Jun 2025
- Last updated
- 17 Apr 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 17 Apr 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Efficacy of Cardiometabolic Risk Factor Control Through Metabolic Surgery on Management and Severity of Atrial Fibrillation: METSAFE Randomized Clinical Trial
- ClinicalTrials.gov ID
- NCT07027969
- Acronym / sponsor ID
- METSAFE / 23-1039
- Keywords
- Atrial Fibrillation, Bariatric Surgery, Metabolic Syndrome, Weight Loss Surgery, Roux-en-Y gastric bypass, Sleeve Gastrectomy, GLP-1 Receptor Agonist, Tirzepatide
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Not yet recruiting
- Enrolment
- 100 participants (estimated)
- Lead sponsor
- Ali AminianUniversity, hospital or other
- Collaborators
- Ethicon, Inc., iRhythm Technologies, Inc.
- Study start
- 1 Nov 2026 (estimated)
- Primary completion
- 31 Dec 2029 (estimated)
- Study completion
- 31 Mar 2030 (estimated)
- First posted
- 19 Jun 2025 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Atrial fibrillation (AF) is the most common sustained cardiac arrhythmia. It is estimated that between 3 and 6 million Americans are currently living with AF, while 12 million people in the United States will have AF in 2030. Obesity and its comorbidities such as type 2 diabetes (T2DM), hypertension, and obstructive sleep apnea (OSA) are major risk factors for development and progression of AF. Metabolic and Bariatric Surgery (MBS) is the most effective currently available treatment for obesity. Patients typically lose 20 to 35 percent of body weight after surgery which is often sustained for many years. MBS can improve all 5 major risk factors of AF including obesity, hypertension, T2DM, OSA, and systemic inflammation.
The purpose of the study is to understand if MBS can affect the severity of AF and the toll AF's symptoms take on patients.
Detailed description
This is randomized trial of 100 patients with BMI ≥35 kg/m2 and AF. 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 enrollment. Patients will then be randomized 1:1 to MBS group versus nonsurgical control group and will be followed for 12 months (phase 1) and then for an additional 18 months (phase 2).
Interventions include Roux-en-Y Gastric Bypass or Sleeve Gastrectomy surgical procedures based on the shared medical decision between the bariatric surgeon and patients considering the patient's conditions. In the control group, patients are allowed to take anti-obesity medications (AOMs) that are not contraindicated in patients with AF at the discretion of obesity medicine specialists.
Lifestyle and risk factor modification in both groups will consist of targeted and personalized diet plans, exercise, and risk factor reduction, including optimal therapies for T2DM, hypertension, dyslipidemia, heart failure, coronary artery disease, and OSA.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
- Model description
- METSAFE is a randomized open-label blinded-endpoint single-center controlled efficacy/safety study with 2 parallel groups of patients with obesity and AF who will either receive metabolic surgery or nonsurgical obesity care for 30 months. The study has 2 phases: the first 12 months and the subsequent 18 months.
| Arm | Type | Receives |
|---|---|---|
| Metabolic Surgery | Active comparator | Procedure: Roux-en-Y Gastric Bypass or Sleeve GastrectomyRoux-en-Y Gastric Bypass (RYGB) and Sleeve Gastrectomy (SG) |
| Control group (nonsurgical standard of care for obesity) | Other | Drug: Anti-Obesity Medication (AOM) treatmentIn the Control group, the subjects will be receiving standard of care for nonsurgical management of obesity, including possible AOMs that are not contraindicated in patients with AF at the discretion of obesity medicine specialists. |
Who may qualify
- Ages
- 18 to 80 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (17 listed)
- Is a candidate for general anesthesia
- Is eligible for metabolic surgery (RYGB or SG)
- Is ≥18 and ≤80 years old
- has a BMI ≥35 and ≤65 kg/m2
- has AF criteria, which:
Key exclusion criteria (24 listed)
- Significant cardiac valvular disease (planned to undergo cardiac valve intervention/surgery in the next 12 months)
- Significant atherosclerotic disease (planned to undergo coronary, carotid, or peripheral artery revascularization procedures in the next 12 months)
- Severe uncompensated cardiopulmonary disease leading to American Society of Anesthesiologists Class IV or V
- Classified as New York Heart Association Class IV
- Left ventricular ejection fraction <20% at the time of screening
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Roux-en-Y Gastric Bypass or Sleeve GastrectomyAlso: Roux-en-Y Gastric Bypass (RYGB), Sleeve Gastrectomy (SG), Bariatric SurgeryPatients receive either RYGB or SG. The surgical risk, differential impact of each procedure on body weight and other obesity-related diseases, presence of other medical and mental problems, patient's behavioral factors (e.g., postoperative compliance, active smoking), medications, and goals will be considered when the patient and local medical team make a shared decision about the most appropriate surgical procedure. | Procedure or surgery | Metabolic Surgery |
| Anti-Obesity Medication (AOM) treatmentImplementation of obesity pharmacotherapy in the nonsurgical group includes initial assessment of side effects and response, followed by achieving a clinically meaningful weight loss (5% weight loss) after three months. Once this goal is reached, AOMs will be continued throughout the study. If a weight plateau is reached within the first AOM, then another AOM may be added in combination in a stepwise fashion. The choice of AOMs considered may include metformin, topiramate, liraglutide, dulaglutide, semaglutide, tirzepatide, and empagliflozin. | Drug | Control group (nonsurgical standard of care for obesity) |
Primary outcome
Relative change in total duration of being in atrial fibrillation (AF)
Time frame: First 52 weeks of the study
Relative change from baseline to 52 weeks in the percentage total duration of being in AF during a 2-week monitoring period (i.e., %burden), assessed by the Zio XT Patch (iRhythm).
10 secondary outcomes
Presence of at least 1 AF episode
Time frame: First 52 weeks of the study
Change in number of AF episodes (≥30 seconds)
Time frame: First 52 weeks of the study
Change in number of AF espisodes longer than 6 minutes
Time frame: First 52 weeks of the study
Change in the longest AF duration
Time frame: First 52 weeks of the study
Change in the second longest AF duration
Time frame: First 52 weeks of the study
Change in the AF type
Time frame: First 52 weeks of the study
Change in AF Symptom burden
Time frame: First 52 weeks of the study
Relapse of AF after ablation
Time frame: Throughout the study, 130 weeks
Change in cardiac structure
Time frame: First 52 weeks of the study
Change in weight
Time frame: First 52 weeks of the study
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 17 Apr 2026.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Ali Aminani principal investigator
Bariatric Research Medical Director
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Roux-en-Y Gastric Bypass or Sleeve Gastrectomy and Anti-Obesity Medication (AOM) treatment in people with Atrial Fibrillation and Obesity and Obesity-related Medical Conditions, run by Ali Aminian at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 17 inclusion and 24 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: opening soon, as of the sponsor's last update on 17 Apr 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Chytaine Hall (216-445-3983, hallc1@ccf.org), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Relative change in total duration of being in atrial fibrillation (AF) (time frame: First 52 weeks of the study). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 17 Apr 2026.