Atrial FibrillationPhase 2TIRO-AFNCT06802081
TIRzepatide for the Treatment of Obesity in Patients With Atrial Fibrillation
A Phase 2 study testing Tirzepatide in people with Atrial Fibrillation and Obesity, run by The Cleveland Clinic at 1 site in United States.
Trial summary
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… Read more about this study
- Who is it for?
- Ages 18 to 80 years
- Conditions the study is for
- Atrial Fibrillation, Obesity
- What is being tested?
- Tirzepatide
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 100 participants
- Where
- 1 siteUnited States
- Study dates
- 8 Apr 2025to 1 Jun 2027
- Phase
- Phase 2
- 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
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
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- 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.
Who cannot join
- 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
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- 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
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, 1 recruiting
- Recruiting
Cleveland Clinic
Cleveland, Ohio, 44195
Jeannine Ramsey, RN, BSN, RAMSEYJ8@ccf.org
Yuki Kuramochi, RN, BSN, 216-445-4063, kuramoy@ccf.org
About this study
Official title: TIRO-AF: TIRzepatide for the Treatment of Obesity in Patients With Atrial Fibrillation
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.
Read the detailed description
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.
- Conditions
- Atrial Fibrillation, Obesity
- Being tested
- Tirzepatide, Placebo
- Keywords
- Atrial Fibrillation, Obesity, tirzepatide
- Medical subject headings
- Atrial Fibrillation, Obesity
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
TirzepatideDrug
Also called Zepbound
Weekly subcutaneous injections starting with dose 2.5mg, then increase dose by 2.5mg at week 4 (5mg), week 8 (7.5mg) and at week12 (10mg) as tolerated.
PlaceboDrug
Also called Normal Saline
Weekly subcutaneous injections starting with dose 2.5mg, then increase dose by 2.5mg at week 4 (5mg), week 8 (7.5mg) and at week 12 (10mg).
| Study group | Role | What they receive |
|---|---|---|
| Tirzepatide | Experimental | 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. Receives: Drug: Tirzepatide |
| Control | Placebo comparator | 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). Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
AFib burden
Percentage total duration of being in AFIB
Measured: Up to 4 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted30 Jan 2025
- Study start8 Apr 2025
- Primary completion31 Dec 2026 (estimated)
- Study completion1 Jun 2027 (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.
- More trials run by The Cleveland ClinicThe sponsor's other registered studies.
- 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 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 100 participants (estimated)
Sponsor and investigators
- Lead sponsor
- The Cleveland Clinic
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Leslie Cho, MD, Principal investigator, The Cleveland Clinic
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06802081
- Sponsor's protocol ID
- 24-228
- Acronym
- TIRO-AF
- Status last verified
- Jan 2026
- First submitted
- 27 Jan 2025
- Last updated
- 13 Jan 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 13 Jan 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- TIRO-AF: TIRzepatide for the Treatment of Obesity in Patients With Atrial Fibrillation
- ClinicalTrials.gov ID
- NCT06802081
- Acronym / sponsor ID
- TIRO-AF / 24-228
- Conditions
- Atrial Fibrillation, Obesity
- Keywords
- Atrial Fibrillation, Obesity, tirzepatide
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 100 participants (estimated)
- Lead sponsor
- The Cleveland ClinicUniversity, hospital or other
- Study start
- 8 Apr 2025 (actual)
- Primary completion
- 31 Dec 2026 (estimated)
- Study completion
- 1 Jun 2027 (estimated)
- First posted
- 30 Jan 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.
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.
Detailed description
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Tirzepatide | Experimental | Drug: TirzepatideParticipants 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. |
| Control | Placebo comparator | Drug: PlaceboParticipants 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). |
Who may qualify
- Ages
- 18 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (13 listed)
- Sinus rhythm at randomization
- Age ≥18 to ≤80 years old
- BMI ≥ 27 and ≤60 kg/m2
- AFIB criteria:
- All anti-diabetic medication (including insulin) must be stable for at least 3 months prior to enrollment,
Key exclusion criteria (26 listed)
- 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
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 |
|---|---|---|
| TirzepatideAlso: ZepboundWeekly subcutaneous injections starting with dose 2.5mg, then increase dose by 2.5mg at week 4 (5mg), week 8 (7.5mg) and at week12 (10mg) as tolerated. | Drug | Tirzepatide |
| PlaceboAlso: Normal SalineWeekly subcutaneous injections starting with dose 2.5mg, then increase dose by 2.5mg at week 4 (5mg), week 8 (7.5mg) and at week 12 (10mg). | Drug | Control |
Primary outcome
AFib burden
Time frame: Up to 4 weeks
Percentage total duration of being in AFIB
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 13 Jan 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.
Leslie Cho, MD principal investigator
The Cleveland Clinic
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Tirzepatide in people with Atrial Fibrillation and Obesity, run by The Cleveland Clinic 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 13 inclusion and 26 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: looking for participants now, as of the sponsor's last update on 13 Jan 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. Some participants in this study may receive a placebo. 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
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 Jeannine M Ramsey, RN, BSN (216-559-7942, ramseyj8@ccf.org), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
AFib burden (time frame: Up to 4 weeks). 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 13 Jan 2026; AzTrials last refreshed its copy on 8 Nov 2026.