A Phase 4 interventional study of Verapamil 240 mg slow-release tablet and metoprolol 100 mg slow-release tablet in Atrial Fibrillation (AF), sponsored by Martini Hospital Groningen. Not yet recruiting. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2026-03-27.
Sponsored by Martini Hospital Groningen · Phase 4, Interventional, and Treatment
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.
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.
4,009 studies on the registry are indexed under Atrial Fibrillation; 961 are open to participants now.
This study's planned enrollment of 436 is above the median of 150 across 2,476 interventional studies indexed under Atrial Fibrillation.
Browse Atrial Fibrillation studies →Martini Hospital Groningen is the lead sponsor of 14 studies on the registry; 4 are open to participants now.
Counted across the registry records on this site, refreshed daily.
Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.
In order to be eligible to participate in this study, a subject must meet all of the following criteria:
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:
Contraindications for verapamil or metoprolol:
Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
A recording of the heart’s electrical activity, taken with stickers on the chest, arms and legs. It takes a few minutes and does not hurt.
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
A reason a treatment, test or procedure should not be given to a particular person, such as an allergy, another illness or a medicine they take.
An allergy, or another reaction of the immune system, to a substance. “Hypersensitivity to the study drug” means a known allergic reaction to it — not every side effect a medicine can have.
CYP3A is a group of enzymes, mainly CYP3A4, in the liver and gut that break down many medicines. Some medicines, supplements and foods (grapefruit, St John’s wort) slow them down or speed them up, which changes how much of a study drug stays in the body.
Studies list them so they can be avoided or switched; bring a list of everything you take, including supplements.
The New York Heart Association’s four classes of how much heart failure limits physical activity.
Studies set their own limit — many outside heart failure leave out class III–IV, while heart failure studies may ask for a particular class. Check the class this study names.
The share of blood the heart’s main pumping chamber (the left ventricle) pushes out with each beat, measured by an echocardiogram (heart ultrasound) or a MUGA scan. About 50–70% is normal.
Judged by the study doctor to matter for your health or for the study. It is a doctor’s decision, so ask the study team if you are unsure whether something counts.
Chronic obstructive pulmonary disease: long-term lung disease that makes it hard to breathe out, including emphysema and chronic bronchitis.
A score of how well the liver works in people with liver disease such as cirrhosis: class A is mild, B moderate and C severe.
GFR (glomerular filtration rate) is how much blood the kidneys filter each minute. It is usually estimated from a blood test — eGFR, by formulas such as CKD-EPI or MDRD — and some studies ask for it to be measured directly instead. Usually given in mL/min/1.73 m².
Check the method, the units and the minimum the study states. A value of 90 or above is in the normal-or-high range, but kidney damage can show in other tests too.
ECG (electrocardiogram)
A recording of the heart’s electrical activity, taken with stickers on the chest, arms and legs. It takes a few minutes and does not hurt.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Informed consent
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Contraindication
A reason a treatment, test or procedure should not be given to a particular person, such as an allergy, another illness or a medicine they take.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Hypersensitivity
An allergy, or another reaction of the immune system, to a substance. “Hypersensitivity to the study drug” means a known allergic reaction to it — not every side effect a medicine can have.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
CYP3A (CYP3A4) inhibitors and inducers
CYP3A is a group of enzymes, mainly CYP3A4, in the liver and gut that break down many medicines. Some medicines, supplements and foods (grapefruit, St John’s wort) slow them down or speed them up, which changes how much of a study drug stays in the body.
Studies list them so they can be avoided or switched; bring a list of everything you take, including supplements.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
NYHA class (heart failure)
The New York Heart Association’s four classes of how much heart failure limits physical activity.
Studies set their own limit — many outside heart failure leave out class III–IV, while heart failure studies may ask for a particular class. Check the class this study names.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
LVEF (left ventricular ejection fraction)
The share of blood the heart’s main pumping chamber (the left ventricle) pushes out with each beat, measured by an echocardiogram (heart ultrasound) or a MUGA scan. About 50–70% is normal.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Clinically significant
Judged by the study doctor to matter for your health or for the study. It is a doctor’s decision, so ask the study team if you are unsure whether something counts.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
COPD
Chronic obstructive pulmonary disease: long-term lung disease that makes it hard to breathe out, including emphysema and chronic bronchitis.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Child-Pugh class
A score of how well the liver works in people with liver disease such as cirrhosis: class A is mild, B moderate and C severe.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
GFR and eGFR (kidney filtering)
GFR (glomerular filtration rate) is how much blood the kidneys filter each minute. It is usually estimated from a blood test — eGFR, by formulas such as CKD-EPI or MDRD — and some studies ask for it to be measured directly instead. Usually given in mL/min/1.73 m².
Check the method, the units and the minimum the study states. A value of 90 or above is in the normal-or-high range, but kidney damage can show in other tests too.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
rate control with verapamil 240 mg od
Drug: Verapamil 240 mg slow-release tablet
rate control with metoprolol 100 mg od
Drug: metoprolol 100 mg slow-release tablet
rate control with verapamil 240 mg od
Rate control with metoprolol 100 mg od
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
No study locations are listed for this record.
Plan to share: 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.
Supporting information: Study protocol, Statistical analysis plan, Informed consent form, Clinical study report, Analytic code
Time frame: Data will be available beginning 12 months following publication of the primary results and ending 5 years after publication.
Access criteria: Data will be made available to researchers who provide a methodologically sound proposal. Proposals should be directed to the PI (r.tieleman@gmail.com). To gain access, requestors will need to sign a data access agreement. Data will be shared for the purpose of achieving the aims outlined in the approved proposal.
Start is estimated for Jun 2026; primary completion for Jun 2029, 36 months later.
Of 129 non-industry phase 4 interventional studies under Atrial Fibrillation, half reached primary completion within 53 months of starting (the median), counting those still running; a quarter within 28 and three quarters within 81. This study's planned 36 months is below that.
Counting every sponsor, half of 141 studies reached it within 48 months; a quarter within 27 and three quarters within 81.
How these figures are worked out, and which studies are left out of them.
This study is not yet recruiting, as verified in Mar 2026. You cannot join it, but the record below documents what was studied.
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Studies of the drug tested here: Verapamil
Martini Hospital Groningen