Propranolol vs Ivabradine for POTS

Overseen By Shahana Safdar

Age: 18 - 65

Sex: Any

Trial Phase: Phase 2

Sponsor: University of Calgary

Must not be taking: Antiarrhythmics, Calcium channel blockers

Disqualifiers: Heart disease, Diabetes, Asthma, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 4

20 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores two medications, propranolol and ivabradine, to determine which better alleviates postural tachycardia syndrome (POTS), a condition causing symptoms like palpitations and dizziness when standing. Researchers aim to assess how each drug affects heart rate and symptoms in POTS patients. Participants will try both medications and a placebo over several weeks to identify the most effective option. This trial may suit those diagnosed with POTS who frequently experience dizziness or rapid heartbeats when standing. As a Phase 2 trial, this research focuses on evaluating the treatment's effectiveness in an initial, smaller group, offering participants a chance to contribute to early-stage findings.

Will I have to stop taking my current medications?

Participants must stop taking certain medications before joining the trial. There is a 7-day washout period (time without taking certain medications) required before starting the study treatments. If you are currently on beta-blockers or ivabradine, you need to be able to safely stop them before the study.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that both propranolol and ivabradine are generally well-tolerated by people with postural orthostatic tachycardia syndrome (POTS).

For ivabradine, one study found that only about 9.58% of patients experienced side effects, suggesting it is quite safe for many with POTS. It also appears to help with symptoms like a racing heart and can improve overall health for some patients.

Propranolol has also been studied for POTS. Research indicates that low doses can slow fast heart rates and improve symptoms when standing. However, higher doses might not provide additional benefits and could worsen symptoms.

Both treatments are usually safe, but side effects can occur. Discuss any concerns with a doctor before starting treatment. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about Ivabradine and Propranolol for treating Postural Orthostatic Tachycardia Syndrome (POTS) because they offer different approaches to managing the condition. Unlike the standard treatments, which often focus on increasing blood volume or vasoconstriction, Ivabradine works by specifically reducing heart rate without affecting blood pressure, thanks to its action on the If current in the sinoatrial node. Propranolol, on the other hand, is a beta-blocker that helps by decreasing heart rate and the force of the heartbeat, providing an alternative mechanism of action. These differences in how the drugs work offer new possibilities for symptom relief in POTS patients who may not respond well to existing treatments.

What evidence suggests that this trial's treatments could be effective for POTS?

This trial will compare the effectiveness of ivabradine and propranolol for managing POTS, a condition that causes a fast heart rate. Research has shown that ivabradine can improve symptoms in about 91% of patients and lower the heart rate by about 14 beats per minute. Similarly, propranolol, a beta-blocker, reduces the fast heart rate and improves symptoms, with benefits mostly seen at low doses. Participants in this trial will receive either ivabradine or propranolol to assess their effectiveness in managing POTS symptoms, focusing on heart rate control. ^{1 2 3 5 6}

Who Is on the Research Team?

Satish R Raj, MD

Principal Investigator

University of Calgary

Are You a Good Fit for This Trial?

This trial is for adults aged 18-60 with Postural Tachycardia Syndrome (POTS) who can consent to participate. Excluded are those with low heart rates or blood pressure, structural heart disease, diabetes, uncontrolled asthma, pregnancy, severe liver issues, certain medication use and specific heart rhythm problems.

Inclusion Criteria

I am either a man or a woman.

I have been diagnosed with Postural Tachycardia Syndrome.

Able and willing to provide informed consent

Exclusion Criteria

I am not taking specific heart rhythm or blood pressure medications.

I am not taking strong medications that affect liver enzyme CYP 3A4.

Your blood pressure while lying down is lower than 90/60 mmHg.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

1-2 weeks

1 visit (in-person)

Treatment Phase 1

Participants receive a 4-week course of either ivabradine, propranolol, or placebo, followed by a 7-day washout period.

5 weeks

1 visit (in-person) at the end of the phase

Treatment Phase 2

Participants receive a 4-week course of the second treatment (ivabradine, propranolol, or placebo), followed by a 7-day washout period.

5 weeks

1 visit (in-person) at the end of the phase

Treatment Phase 3

Participants receive a 4-week course of the final treatment (ivabradine, propranolol, or placebo).

4 weeks

1 visit (in-person) at the end of the phase

Follow-up

Participants are monitored for safety and effectiveness after treatment.

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Ivabradine
• Propranolol

Trial Overview

The study tests the effectiveness of Ivabradine versus Propranolol in managing POTS symptoms and heart rate upon standing. It's a double-blind placebo-controlled crossover trial where participants try each treatment for 4 weeks with breaks in between.

How Is the Trial Designed?

Group I: 1st drug Ivabradine Active Control 3 Interventions

Patients will take Ivabradine first followed by Propranolol and Placebo

Group II: 2nd drug Ivabradine Active Control 3 Interventions

Patients will take either Propranolol or placebo first and then Ivabradine

Group III: 3rd drug Ivabradine Active Control 3 Interventions

Patients will take Propranolol and placebo first and then Ivabradine

Ivabradine is already approved in United States, European Union, Canada for the following indications:

Approved in United States as Corlanor for:

• Heart failure
• Angina

Approved in European Union as Procoralan for:

• Angina
• Heart failure

Approved in Canada as Lancora for:

• Angina
• Heart failure

Who Is Running the Clinical Trial?

University of Calgary

Lead Sponsor

Trials

827

Recruited

902,000+

Dysautonomia International

Collaborator

Trials

6

Recruited

420+

Published Research Related to This Trial

Controlled-release formulations of propranolol, specifically Elanol and Inderal LA, provide smoother serum level profiles and delayed peak times compared to conventional propranolol, indicating a potentially more stable therapeutic effect.

Elanol showed greater bioavailability than Inderal LA, suggesting that long-acting formulations can be effective without the drawbacks of reduced bioavailability due to first-pass metabolism.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pharmacokinetic and pharmacodynamic studies with a new controlled-release formulation of propranolol in normal volunteers: a comparison with other commercially available formulations. Perucca, E., Grimaldi, R., Gatti, G., et al.[2019]

In a study involving anesthetized dogs, four beta-adrenergic receptor antagonists (sotalol, nadolol, atenolol, and propranolol) were found to equally increase the electrical threshold for inducing ventricular fibrillation, indicating their potential effectiveness in preventing dangerous heart rhythms.

The antifibrillatory effects of these drugs were not linked to their beta-blocking abilities or changes in heart conduction and excitability, suggesting that their mechanism of action may involve other cardiac properties beyond just beta-adrenergic blockade.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Antifibrillatory properties of the beta-adrenergic receptor antagonists, nadolol, sotalol, atenolol and propranolol, in the anesthetized dog. Patterson, E., Lucchesi, BR.[2018]

In a study of 37 patients with a history of heart issues and inducible ventricular tachycardia (VT), adding propranolol to conventional antiarrhythmic drugs significantly increased the ventricular effective refractory period and VT cycle length, enhancing the antiarrhythmic effects.

Propranolol alone or in combination with type I antiarrhythmic drugs rendered 10 patients noninducible for VT, demonstrating its potential as an effective treatment option, with a follow-up showing only one sudden death and manageable recurrence rates over 20 months.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effectiveness of propranolol added to a type I antiarrhythmic agent for sustained ventricular tachycardia secondary to coronary artery disease. Friehling, TD., Lipshutz, H., Marinchak, RA., et al.[2019]

The long-acting propranolol hydrochloride (LA 60 mg) formulation shows sustained-release characteristics, with a longer half-life and delayed peak concentration compared to conventional propranolol (20 mg tid), indicating it may provide more stable drug levels over time.

Pharmacodynamic effects, such as heart rate and blood pressure response, were similar between LA 60 mg and the conventional 20 mg dosing, suggesting that LA 60 mg can effectively replace the more frequent dosing without compromising efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pharmacokinetics and pharmacodynamics of long-acting propranolol 60-mg capsules: a comparative evaluation. Marino, MR., Dey, M., Garg, DC., et al.[2019]

In a single-blind study involving 13 patients with mild to moderately severe hypertension, the combination of propranolol (80 mg) and bendrofluazide (2.5 mg) effectively controlled blood pressure in 12 patients over a 12-week period.

The treatment did not result in significant changes in biochemical parameters or ECG readings, and no serious side effects were reported, indicating a favorable safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Fixed ratio combination of propranolol and bendrofluazide in the treatment of hypertension. Pandhi, P., Sharma, BK., Sharma, PL., et al.[2013]

A study involving six healthy adult volunteers tested four different brands of propranolol (Inderal, Ciplar, Corbeta, and Propal) to assess variations in how the body absorbs and responds to the medication.

The results showed no significant differences in the pharmacokinetic (how the drug is processed in the body) and pharmacodynamic (the drug's effects on the body) parameters among the brands, indicating they are likely interchangeable in terms of efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparative pharmacokinetic and pharmacodynamic study of four different brands of propranolol in normal volunteers. Biswas, NR., Garg, SK., Kumar, N., et al.[2013]

Inderex, a combination of bendrofluazide and sustained-release propranolol, was found to be more effective in lowering blood pressure compared to either medication alone in a study of 21 patients.

The study indicated that there were no significant differences in treatment responses across different age groups, suggesting that Inderex is a suitable option for a wide range of patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treatment of hypertension with a fixed ratio combination of long-acting propranolol and bendrofluazide, and influence of age of the subject. Herrick, AL., Davis, JM., Weir, RJ.[2013]

In two pharmacokinetic studies involving 48 healthy volunteers, newly formulated generic propranolol HCl tablets were found to have the same rate and extent of absorption as the brand Inderal tablets, indicating bioequivalence.

Both studies showed no statistically significant differences in key pharmacokinetic parameters (AUC, Cmax, tmax, and Cmin) between the test and reference tablets, confirming that the generic formulation is as effective as the branded version.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Bioavailability of propranolol hydrochloride tablet formulations: application of multiple dose crossover studies. Eldon, MA., Kinkel, AW., Daniel, JE., et al.[2019]

Long-acting propranolol (Inderal LA) provides a controlled release of the medication, maintaining higher plasma concentrations over 24 hours compared to conventional tablets, which helps ensure consistent beta-adrenoceptor blockade.

This formulation is equally effective for treating conditions like angina pectoris, hypertension, and hyperthyroidism, while potentially improving patient adherence to treatment due to simplified dosing regimens.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-acting propranolol (Inderal LA): pharmacokinetics, pharmacodynamics and therapeutic use. Mishriki, AA., Weidler, DJ.[2019]

In a study of 181 patients with organic heart disease, sotalol demonstrated a significantly greater reduction in ventricular premature complexes (VPCs) per hour compared to propranolol, achieving an 80% reduction versus 50%.

Sotalol was also more effective in suppressing ventricular tachycardia events, with an 89% reduction compared to 78% for propranolol, highlighting its superior antiarrhythmic efficacy due to its combined type II and type III properties.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Sotalol Is More Powerful Than Propranolol in Suppressing Complex Ventricular Arrhythmias. Deedwania, PC.[2019]

Citations

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pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC7255540/

Ivabradine in Postural Orthostatic Tachycardia Syndrome

However, there has been evidence of beneficial outcomes with the use of ivabradine in POTS patients, as seen in prospective and retrospective ...

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jacc.org

jacc.org/doi/10.1016/j.jaccas.2025.104167

A Case of Postural Orthostatic Tachycardia Syndrome in ...

This patient with POTS had significant health improvements with the use of ivabradine. Previous studies have highlighted the efficacy of this ...

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ahajournals.org

ahajournals.org/doi/10.1161/circ.150.suppl_1.4144538

Abstract 4144538: Ivabradine in Patients With Postural ...

The analysis showed an improvement of symptoms in 90.89% (95% CI: 80.34-98.07;) of patients, and a decrease of 14.46 bpm in HR (95% CI: 7.69- ...

4.

clinicaltrials.gov

clinicaltrials.gov/study/NCT03182725

Effect of Ivabradine on Patients With Postural Orthostatic ...

The hypothesis for this experiment is that Ivabradine will reduce tachycardia and improve functional status in patients with POTS.

5.

sciencedirect.com

sciencedirect.com/science/article/pii/S0735109720381316

Randomized Trial of Ivabradine in Patients With ...

Ivabradine is safe and effective in significantly improving heart rate and QOL in patients with hyperadrenergic POTS as the predominant subtype.

6.

newsroom.uvahealth.com

newsroom.uvahealth.com/2025/07/31/heart-failure-drug-relieves-pots-symptoms-study-finds/

Heart Failure Drug Relieves POTS Symptoms, Study Finds

In an analysis of 10 patients with POTS, the researchers found that the drug reduced their heart racing while significantly improving other ...