Using Mirabegron to Increase BP in Patients With POTS (RAISE BP)

Cedars-Sinai Medical Center

Status and phase: Enrolling; Phase 2

Conditions: Syncope; Postural Orthostatic Tachycardia Syndrome; Chronic Orthostatic Intolerance

Treatments: Drug: Mirabegron 50 MG; Drug: Mirabegron 25 MG

Study type: Interventional

Funder types: Other

Identifiers

NCT06133075

STUDY00002281

Details and patient eligibility

About

This is a pilot dose-finding study to test the hypothesis that mirabegron increases systolic blood pressure (BP), prevents syncope/presyncope, and improves the quality of life (QOL), functional capacity, chest pain, and overactive bladder (OAB) symptoms in patients with postural orthostatic tachycardia syndrome (POTS) who have a documented history of hypotension inadequately responsive to conventional treatments. The American Heart Association funds this study.

Full description

This is a pilot dose-finding study to test the hypothesis that mirabegron increases systolic blood pressure (BP), prevents syncope/presyncope, and improves the quality of life (QOL), functional capacity, chest pain, and overactive bladder (OAB) symptoms in patients with postural orthostatic tachycardia syndrome (POTS) who have a documented history of hypotension inadequately responsive to conventional treatments. The investigators will perform 24-hour ambulatory blood pressure monitoring (ABPM) and ambulatory skin sympathetic nerve activity (SKNA) recording using a Bittium Faros electrocardiogram (ECG) monitor, assess the number of syncope and presyncope episodes and determine the symptoms using validated questionnaires at baseline. The patients will then be given mirabegron (either 25 mg once daily or 50 mg once daily) for eight weeks. Afterward, the patient will return to the clinic for clinical assessments, complete questionnaires, ABPM, and ambulatory SKNA recording while still on treatment. Mirabegron will be stopped when the data collection is complete. Because mirabegron has a long half-life, the investigators will schedule a video visit with the patient 12 weeks after beginning the treatment and inquire about the patient's symptoms. The investigators will repeat all pertinent questionnaires at that time.

Enrollment: 20 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

1. Provision of signed and dated informed consent form.

2. Age > 18 years old.

3. Documented history of chronic (> 3 months) of orthostatic intolerance.

4. Diagnosis of syncope or pre-syncope and documented intermittent hypotension unresponsive to conventional life-style modification therapy.

   1. A history of syncope (complete loss of consciousness) or presyncope (the sensation that one is about to pass out).
   2. At least one documented hypotensive episode with systolic BP < 90 mmHg on 24-hr ABPM.
   3. Inadequate response to conventional therapies.

Exclusion criteria

1. Patients with other potential etiologies of syncope

   1. Sustained tachyarrhythmias other than sinus tachycardia. Specifically, patients with a diagnosis of atrial fibrillation, sustained (> 30 seconds) arrhythmias including paroxysmal supraventricular tachycardia, atrial flutter, ventricular tachycardia, ventricular fibrillation.
   2. Symptomatic bradycardia before pacemaker implantation.

2. Heart failure with either preserved or reduced ejection fraction.

3. Wolff Parkinson-White Syndrome.

4. Stroke within the past 6 months.

5. Any history of myocardial infarction.

6. Active thyrotoxicosis.

7. Any experimental medication concomitantly or within 4 weeks of participation in the study.

8. Patients < 18 years old because mirabegron is not approved by FDA for use in children.

9. People with a history of allergy to ECG electrodes or adhesive tape.

10. Patients with known contraindications or precautions to mirabegron.

    1. Hypertension
    2. Severe renal impairment (calculated CrCl < 30ml/min)
    3. Hepatic disease (Child-Pugh Class B)
    4. Pregnant or lactation
    5. Geriatric patients in long term care facilities
    6. Patients who are known to be allergic to mirabegron
    7. Patients taking drugs that are CYP2D6 substrates, such as midodrine. An extensive list can be found at the following website: https://drug-interactions.medicine.iu.edu/MainTable.aspx

11. Prisoners

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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20 participants in 2 patient groups

50 mg group

Active Comparator group

Description:

Ten patients will receive 50 mg mirabegron for 8 weeks.

Treatment:

Drug: Mirabegron 50 MG

25 mg group

Active Comparator group

Description:

Ten patients will receive 25 mg mirabegron for 8 weeks.

Treatment:

Drug: Mirabegron 25 MG