Effect of Ivabradine on Patients With Postural Orthostatic Tachycardia Syndrome

NCT03182725 | Completed Phase 3 Results FDA Drug

• 1 other identifier: 170694
• Study Type: interventional
• Target: 37
• Locations: 1 country
• Sites: 1

Brief Summary

Postural orthostatic tachycardia syndrome (POTS) occurs in approximately 500,000 Americans, but predominates in women with a 5:1 ratio. Patients with POTS experience debilitating tachycardia upon postural changes such as standing that impairs their quality of life. Tachycardia is clinically defined as a heart rate greater than 100 beats/min; and in POTS patients, the prolonged heart rate increase is greater than 30 beats/min or increases to 120 beats/min within the first ten minutes of a diagnostic tilt table test without postural hypotension. There are currently no effective treatment methods for POTS. However, several studies suggest Ivabradine could be a main treatment option for POTS because Ivabradine specifically inhibits the f-channels (If) within the sinoatrial (SA) node, which slows the heart rate. Currently in the US, Ivabradine is mainly prescribed to treat chronic heart failure. It is well tolerated in patients, but it is not commonly prescribed for POTS. It has been also used for treatment of inappropriate sinus tachycardia with good benefit. The hypothesis for this experiment is that Ivabradine will reduce tachycardia and improve functional status in patients with POTS.

Conditions

Postural Orthostatic Tachycardia Syndrome

Keywords

POTS; tachycardia; ivabradine

Outcome Measures

Primary Outcomes (1)

• Change in Heart Rate

  Orthostatic heart rate monitoring will be used to gauge heart rate changes.

  Baseline and one month post-treatment

Secondary Outcomes (1)

• Change in Quality of Life Via SF-36 Survey

  Baseline and one month post-treatment

Study Arms (2)

Placebo

PLACEBO COMPARATOR

Patient will consume one placebo pill twice a day for one month.

Drug: Placebo

Ivabradine

EXPERIMENTAL

Patient will consume one dose of Ivabradine twice a day for one month.

Drug: Ivabradine

Interventions

Ivabradine DRUG

Ivabradine is prescribed for treatment of chronic heart failure through inhibition of the f-channels (If) within the sinoatrial node.

Ivabradine

Placebo DRUG

A substance that has no therapeutic effect and will act as a control.

Placebo

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Subjects aged 18-65.
• Subjects must have POTS diagnosis (Hyperadrenergic Subtype with NE\> 600pg/ml))
• Subjects with no structural heart disease
• Subject with no arrhythmias
• Subjects with norepinephrine levels greater than 600 pg/ml
• Subjects with normal CBC, Metabolic, and thyroid levels

You may not qualify if:

• Thyroid or adrenal disorders
• Drugs that interfere with Ivabradine (example: Cytochrome P450 drugs)
• Presentation of peripheral edema and discolored toes with peripheral autonomic neuropathy. Symptoms include: legs (reduced hair growth, cramps), toes (blue color), legs/feet (wounds, ulcers that do not heal), and muscles (numbness, heaviness)
• Subjects who have had a history of systemic illnesses (acute or chronic infectious); autoimmune/ inflammatory disease, cancer, COPD, anemia, diabetes, or psychiatric illness
• Subjects with resting heart rate\< 60beats/min, atrial fibrillation, advanced AV blocks, sinus disease, and acute decompensated heart failure and severe hepatic impairment.
• Smokers or alcohol abuse
• Pregnant or breastfeeding mothers
• Woman of childbearing potential who are unwilling to use highly effective contraception during treatment and for an additional one month after discontinuing the study drug

Sponsors & Collaborators

• University of California, San Diego: lead
• Amgen: collaborator

Study Sites (1)

University of California, San Diego

La Jolla, California, 92093, United States

Location

Related Publications (3)

• McDonald C, Frith J, Newton JL. Single centre experience of ivabradine in postural orthostatic tachycardia syndrome. Europace. 2011 Mar;13(3):427-30. doi: 10.1093/europace/euq390. Epub 2010 Nov 9.

  PMID: 21062792 RESULT

• Ewan V, Norton M, Newton JL. Symptom improvement in postural orthostatic tachycardia syndrome with the sinus node blocker ivabradine. Europace. 2007 Dec;9(12):1202. doi: 10.1093/europace/eum235. Epub 2007 Oct 19. No abstract available.

  PMID: 17951266 RESULT

• Barzilai M, Jacob G. The Effect of Ivabradine on the Heart Rate and Sympathovagal Balance in Postural Tachycardia Syndrome Patients. Rambam Maimonides Med J. 2015 Jul 30;6(3):e0028. doi: 10.5041/RMMJ.10213.

  PMID: 26241226 RESULT

MeSH Terms

Conditions

Postural Orthostatic Tachycardia Syndrome; Tachycardia

Interventions

Ivabradine

Condition Hierarchy (Ancestors)

Orthostatic Intolerance; Primary Dysautonomias; Autonomic Nervous System Diseases; Nervous System Diseases; Arrhythmias, Cardiac; Heart Diseases; Cardiovascular Diseases; Cardiac Conduction System Disease; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Benzazepines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Limitations and Caveats

* smaller sample size * many patients suspected they were on ivabradine * patients were only on 1 month of ivabradine; longer study duration may be warranted to assess potential long term effects

Results Point of Contact

• Title: Dr. Pam Taub
• Organization: University of California - San Diego Health

ptaub@health.ucsd.edu

858-246-2342

Study Officials

• Pam Taub, M.D.

  University of California, San Diego

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor of Medicine

Model Details: 20 patients with POTS will receive Ivabradine treatment vs placebo for one month. Then there will be a one-month wash out period prior to the cross over in which patients who received Ivabradine will receive the placebo, and patients who initially were on placebo will now receive Ivabradine.

Study Record Dates

• First Submitted: June 7, 2017
• First Posted: June 9, 2017
• Study Start: February 6, 2018
• Primary Completion: May 8, 2020
• Study Completion: May 8, 2020
• Last Updated: June 29, 2021
• Results First Posted: June 29, 2021

Record last verified: 2021-06

Locations

US (1)