Atrial Fibrillation (AF)Phase 4SMART-VERAPAFNCT07445789
SMART-VERAPAF: Self-MAnagement and Random Therapy With VERApamil or Metoprolol in Paroxysmal Atrial Fibrillation
A Phase 4 study testing Verapamil 240 mg slow-release tablet and metoprolol 100 mg slow-release tablet in people with Atrial Fibrillation (AF), run by Martini Hospital Groningen.
Trial summary
The SMART-VERAPAF study investigates the effects of different heart rate-lowering medications in patients with paroxysmal atrial fibrillation (AF). This heart rhythm disorder is associated with a large number of emergency room visits and hospitalizations for cardioversions and ablations. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Atrial Fibrillation (AF)
- What is being tested?
- Verapamil 240 mg slow-release tablet and metoprolol 100 mg slow-release tablet
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 436 participants
- Where
- No sites listed yet
- Study dates
- Jun 2026to Jun 2029
- 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 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
7.2 Inclusion criteria
In order to be eligible to participate in this study, a subject must meet all of the following criteria:
- Age ≥ 18 years old
- ECG documented diagnosis of paroxysmal AF
- Presence of symptomatic paroxysmal AF, defined as recurrent self-terminating AF (≥ 2 episodes in last 4 months) documented by typical symptoms, ECG or photoplethysmo-gram
- Able and willing to sign informed consent.
For SMART sub study only:
- Own a smartphone
7.3 Exclusion criteria
A potential subject who meets any of the following criteria will be excluded from participation in this study:
- A history of electrical cardioversion for persistent AF
- History of AF episode > 7 days
- Previous or current chronic amiodaron use.
- A history of pulmonary vein ablation
- Taking part in another randomized trial
- Reduced life-expectancy of < 1 year
- Presence of contra-indication for verapamil or metoprolol
- Pregnant or breastfeeding women. Or women who are planning to become pregnant during the study period.
- For substudy patients: already participating in an eHealth program
Contraindications for verapamil or metoprolol:
- Known hypersensitivity, intolerance or allergy to verapamil, metoprolol, or any excipi-ents.
- Current use of verapamil, diltiazem, beta-blockers or digoxin, or < 5 half-lives ago at the time of randomization.
- Concomitant use of medications with absolute contraindications for verapamil or metoprolol (e.g., strong CYP3A4 inhibitors).*
- Resting heart rate < 50 beats per minute at baseline.
- Symptomatic hypotension (or systolic blood pressure < 100 mmHg).
- Second- or third-degree atrioventricular block.
- Sick sinus syndrome or sinus node disease.
- Wolff-Parkinson-White syndrome.
- Severe heart failure (NYHA class III-IV or left ventricular ejection fraction < 45%).
- Clinically significant constipation requiring medical intervention.
- Severe bronchial asthma or COPD with bronchial hyperreactivity.
- Untreated pheochromocytoma (unless patient is concomitantly treated with an α-blocker).
- Type 1 diabetes mellitus with frequent symptomatic hypoglycaemia where β-blocker use would pose unacceptable risk due to masking of symptoms.
- Severe symptomatic peripheral arterial disease or disabling Raynaud's phenomenon.
- Pacemaker therapy in place. An implanted loop recorder is not a contraindication.
- Severe hepatic impairment (Child-Pugh class C).
- Severe renal impairment (eGFR < 30 ml/min/1.73m²). *Patients using statins can be switched to an equivalent dose of rosuvastatin prior to ran-domization. Patients using oral anticoagulation need to be switched to apixaban or rivaroxa-ban.
Trial locations and contacts
No sites are listed yet. Contact the study team or a site near you to ask about taking part.
About this study
The SMART-VERAPAF study investigates the effects of different heart rate-lowering medications in patients with paroxysmal atrial fibrillation (AF). This heart rhythm disorder is associated with a large number of emergency room visits and hospitalizations for cardioversions and ablations. In this study, patients with symptomatic paroxysmal AF are randomized to treatment with heart rate reduction using verapamil or metoprolol, both licensed for this indication. In addition, in a subset of patients, the effect of centrally guided self-care using smartwatch data will be evaluated.
The hypothesis is that both verapamil and guided self-care will lead to better heart rate control and fewer cardioversions and pulmonary vein ablations in patients with paroxysmal AF. This will also result in fewer hospital admissions, outpatient visits, and costs, as well as improved quality of life.
Read the detailed description
Rationale
In patients with paroxysmal atrial fibrillation (AF), heart rate-suppressing therapy is used to reduce symptoms and prevent heart failure. However, recent studies show that more than 30% of paroxysmal AF patients experience inappropriate high heart rates for over 50% of the time while in AF. Most patients are treated with beta-blockers for adequate rate control, while less than 5% are treated with verapamil.
Hypothesis and objectives
The investigators hypothesize that treatment with verapamil is superior for heart rate suppression in patients with paroxysmal AF, because dose titration is not hampered by sinus bradycardia outside AF episodes. This advantage is expected to lead to less clinical progression of AF and therefore fewer AF-related hospital admissions, fewer cardioversions, and fewer referrals for ablation. Additionally, the investigators hypothesize that guided self-management using smartwatch data improves the quality of heart rate suppression, resulting in fewer symptoms, fewer unplanned hospital admissions, fewer cardioversions, and fewer referrals for ablation.
Main trial endpoints
The primary outcome measure is the time to hospitalization for AF, cardioversion, or referral for pulmonary vein ablation during at least 1 year follow-up after randomization.
Secondary trial endpoints
Secondary outcome measures include hospitalizations for heart failure, the number of AF-related hospital days, outpatient visits for AF, echocardiographic parameters, heart rate and blood pressure, quality of life, symptoms, activity level, and costs.
Trial design
This is a multicenter, prospective, double-blind randomized study with blinded endpoint assessment. A sub-study will investigate feasibility and efficacy of guided self-management using smartwatches. Follow-up duration is at least 1 year after randomization.
Trial population Symptomatic patients with paroxysmal AF, ≥18 years of age, who have an indication for rate-control therapy. Patients with contraindications for verapamil or metoprolol, a history of persistent AF, or prior pulmonary vein ablation will be excluded.
Interventions
A total of 436 participants will be randomized to receive oral verapamil 240 mg slow-release or metoprolol 100 mg retard. A subset of participants will monitor heart rate using a smartwatch and adjust the study medication dose using heart rate data and a flow chart supported by a central service center.
Sample size and data analysis
A total of 436 patients with paroxysmal AF will be randomized. Endpoints will be analyzed according to the intention-to-treat (ITT) principle using standard statistical techniques.
- Conditions
- Atrial Fibrillation (AF)
- Being tested
- Verapamil 240 mg slow-release tablet, metoprolol 100 mg slow-release tablet
- Keywords
- atrial fibrillation, verapamil, metoprolol, rate control, rhythm control, paroxysmal
- Medical subject headings
- Atrial Fibrillation
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Verapamil 240 mg slow-release tabletDrug
rate control with verapamil 240 mg od
metoprolol 100 mg slow-release tabletDrug
Rate control with metoprolol 100 mg od
| Study group | Role | What they receive |
|---|---|---|
| verapamil | Experimental | rate control with verapamil 240 mg od Receives: Drug: Verapamil 240 mg slow-release tablet |
| metoprolol | Active comparator | rate control with metoprolol 100 mg od Receives: Drug: metoprolol 100 mg slow-release tablet |
What is being measured
The primary outcome is the main question the study is designed to answer.
The time to hospitalization for AF, cardioversion, or referral for pulmonary vein ablation
Measured: follow-up duration is at least 1 year after randomisation and can range from 1 to 3 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted3 Mar 2026
- Study startJun 2026 (estimated)
- Primary completionJun 2029 (estimated)
- Study completionJun 2029 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Atrial Fibrillation (AF)Studies 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
- Double blind randomised controlled trial comparing 2 medications
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 436 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Martini Hospital Groningen
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Robert G Tieleman, MD, PhD, Principal investigator, Martini Hospital Groningen
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07445789
- Sponsor's protocol ID
- SMART-VERAPAF
- Other IDs
- 10141022410031, 2025-524245-27-00, 2025
- Acronym
- SMART-VERAPAF
- Status last verified
- Mar 2026
- First submitted
- 25 Feb 2026
- Last updated
- 27 Mar 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: De-identified individual participant data (IPD) that underlie the results reported in publications (text, tables, figures, and appendices) will be shared. This includes baseline characteristics, outcome measures, and adverse event data.
Study at a glance
From the registry record, last updated by the sponsor on 27 Mar 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- SMART-VERAPAF: Self-MAnagement and Random Therapy With VERApamil or Metoprolol in Paroxysmal Atrial Fibrillation
- ClinicalTrials.gov ID
- NCT07445789
- Acronym / sponsor ID
- SMART-VERAPAF / SMART-VERAPAF
- Conditions
- Atrial Fibrillation (AF)
- Keywords
- atrial fibrillation, verapamil, metoprolol, rate control, rhythm control, paroxysmal
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Not yet recruiting
- Enrolment
- 436 participants (estimated)
- Lead sponsor
- Martini Hospital GroningenUniversity, hospital or other
- Study start
- Jun 2026 (estimated)
- Primary completion
- Jun 2029 (estimated)
- Study completion
- Jun 2029 (estimated)
- First posted
- 3 Mar 2026 (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.
The SMART-VERAPAF study investigates the effects of different heart rate-lowering medications in patients with paroxysmal atrial fibrillation (AF). This heart rhythm disorder is associated with a large number of emergency room visits and hospitalizations for cardioversions and ablations. In this study, patients with symptomatic paroxysmal AF are randomized to treatment with heart rate reduction using verapamil or metoprolol, both licensed for this indication. In addition, in a subset of patients, the effect of centrally guided self-care using smartwatch data will be evaluated.
The hypothesis is that both verapamil and guided self-care will lead to better heart rate control and fewer cardioversions and pulmonary vein ablations in patients with paroxysmal AF. This will also result in fewer hospital admissions, outpatient visits, and costs, as well as improved quality of life.
Detailed description
Rationale
In patients with paroxysmal atrial fibrillation (AF), heart rate-suppressing therapy is used to reduce symptoms and prevent heart failure. However, recent studies show that more than 30% of paroxysmal AF patients experience inappropriate high heart rates for over 50% of the time while in AF. Most patients are treated with beta-blockers for adequate rate control, while less than 5% are treated with verapamil.
Hypothesis and objectives
The investigators hypothesize that treatment with verapamil is superior for heart rate suppression in patients with paroxysmal AF, because dose titration is not hampered by sinus bradycardia outside AF episodes. This advantage is expected to lead to less clinical progression of AF and therefore fewer AF-related hospital admissions, fewer cardioversions, and fewer referrals for ablation. Additionally, the investigators hypothesize that guided self-management using smartwatch data improves the quality of heart rate suppression, resulting in fewer symptoms, fewer unplanned hospital admissions, fewer cardioversions, and fewer referrals for ablation.
Main trial endpoints
The primary outcome measure is the time to hospitalization for AF, cardioversion, or referral for pulmonary vein ablation during at least 1 year follow-up after randomization.
Secondary trial endpoints
Secondary outcome measures include hospitalizations for heart failure, the number of AF-related hospital days, outpatient visits for AF, echocardiographic parameters, heart rate and blood pressure, quality of life, symptoms, activity level, and costs.
Trial design
This is a multicenter, prospective, double-blind randomized study with blinded endpoint assessment. A sub-study will investigate feasibility and efficacy of guided self-management using smartwatches. Follow-up duration is at least 1 year after randomization.
Trial population Symptomatic patients with paroxysmal AF, ≥18 years of age, who have an indication for rate-control therapy. Patients with contraindications for verapamil or metoprolol, a history of persistent AF, or prior pulmonary vein ablation will be excluded.
Interventions
A total of 436 participants will be randomized to receive oral verapamil 240 mg slow-release or metoprolol 100 mg retard. A subset of participants will monitor heart rate using a smartwatch and adjust the study medication dose using heart rate data and a flow chart supported by a central service center.
Sample size and data analysis
A total of 436 patients with paroxysmal AF will be randomized. Endpoints will be analyzed according to the intention-to-treat (ITT) principle using standard statistical techniques.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
- Model description
- Double blind randomised controlled trial comparing 2 medications
| Arm | Type | Receives |
|---|---|---|
| verapamil | Experimental | Drug: Verapamil 240 mg slow-release tabletrate control with verapamil 240 mg od |
| metoprolol | Active comparator | Drug: metoprolol 100 mg slow-release tabletrate control with metoprolol 100 mg od |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
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 |
|---|---|---|
| Verapamil 240 mg slow-release tabletrate control with verapamil 240 mg od | Drug | verapamil |
| metoprolol 100 mg slow-release tabletRate control with metoprolol 100 mg od | Drug | metoprolol |
Primary outcome
The time to hospitalization for AF, cardioversion, or referral for pulmonary vein ablation
Time frame: follow-up duration is at least 1 year after randomisation and can range from 1 to 3 years
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 27 Mar 2026.
- Dutch description of the study on Funding Organisation of the Dutch GovernmentLink provided by the sponsor.
- Individual participant dataSharing planned: Yes. De-identified individual participant data (IPD) that underlie the results reported in publications (text, tables, figures, and appendices) will be shared. This includes baseline characteristics, outcome measures, and adverse event data.
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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.
Robert G Tieleman, MD, PhD principal investigator
Martini Hospital Groningen
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Verapamil 240 mg slow-release tablet and metoprolol 100 mg slow-release tablet in people with Atrial Fibrillation (AF), run by Martini Hospital Groningen.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
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 27 Mar 2026. Status can change between updates, so confirm with the study contact before making plans.
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 Robert G Tieleman, MD, PhD (+31505245245, r.tieleman@gmail.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
The time to hospitalization for AF, cardioversion, or referral for pulmonary vein ablation (time frame: follow-up duration is at least 1 year after randomisation and can range from 1 to 3 years). 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 27 Mar 2026.