Ivabradine for Long-Term Effects of COVID-19 With POTS Cohort

NCT05481177 | Unknown Phase 4 DMC

• 1 other identifier: USUHS.2022-094
• Study Type: interventional
• Target: 250
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of the study is three-fold. The primary aim is to identify the proportion of Long-Haul COVID (LHC) and non-LHC volunteers with relevant symptoms actually have postural orthostatic tachycardia syndrome (POTS). The second is to determine benefit of ivabradine treatment. Ivabradine is a drug approved to treat tachycardia in persons with heart failure. The third is to characterize risk factors and outcomes among volunteers with and without LHC. This will include comparison with COVID-19-positive individuals who did not develop long-COVID symptoms. The study will improve basic and applied knowledge of LHC and its associated cardiovascular and autonomic consequences. Cellular and molecular characterization of LHC and non-LHC participants will be performed with a nested clinical trial for Ivabradine responsiveness on reduction of tachycardia. It is hoped that a greater understanding of LHC, and related autonomic dysfunction in particular will help to identify treatment paradigms and therapeutic targets for improving recovery and enhancing health for those affected.

Conditions

Long Haul COVID; Postural Orthostatic Tachycardia Syndrome

Outcome Measures

Primary Outcomes (1)

• Change in standing heart rate following 3 months treatment.

  The primary endpoint will be a reduction in standing heart rate at 3 months. Up to 200 evaluable subjects will be enrolled in the general LHC cohort with the expectation that at least 20% of those recruited will have POTS or otherwise IST causing symptoms appropriate for enrollment to the nested RCT (ivabradine vs. placebo). This will yield an RCT study population of at least 40 evaluable subjects. Study recruiting will be aimed at volunteers with features of POTS. Drop-outs in all cohorts may be replaced.

  3 months

Study Arms (3)

Long Haul COVID

NO INTERVENTION

Persistent signs and/or symptoms \>12 weeks post Covid-infection N = 200 evaluable subjects.

Post COVID without LHC

NO INTERVENTION

No persistent signs and/or symptoms \>12 weeks N = 50 evaluable subjects.

Ivabradine RCT Arms

PLACEBO COMPARATOR

If POTS or IST is present for participants within either of these cohorts, then they will be assigned to one of two arms of the Ivabradine RCT \[2:1 treatment:control\]. RCT Arms: at least 36 evaluable subjects will be enrolled to two arms in a 2:1 ratio. More may be enrolled, depending on the number from the overall COVID-19 cohort who qualify. IVA (Ivabradine) - at least 24 evaluable subjects Placebo - at least 12 evaluable subjects

Drug: Ivabradine

Interventions

Ivabradine DRUG

Ivabradine is a drug approved to treat tachycardia in volunteers with heart failure. This study is to determine benefit of ivabradine treatment in postural orthostatic tachycardia syndrome (POTS) in participants with Long haul Covid.

Ivabradine RCT Arms

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age 18-80
• History of documented COVID-19 infection of any severity to include a positive COVID-19 PCR, or antibody test
• Meets criteria for 'long-haul' COVID-19 with symptoms \>12 weeks following acute illness
• Able and willing to provide informed consent and participate for study duration
• Willing to participate in the nested randomized controlled trial of ivabradine if RCT enrollment criteria are met
• Access to a primary healthcare provider and proof of health insurance
• Age 18-80
• History of documented COVID-19 infection of any severity to include a positive COVID-19 PCR, or antibody test
• Does not meet criteria for 'long-haul' COVID-19
• Able and willing to provide informed consent and participate for study duration
• Willing to participate in the nested randomized controlled trial of ivabradine if RCT enrollment criteria are met
• Access to a primary healthcare provider and proof of health insurance
• Age 18-80; Meets criteria for 'long-haul' COVID-19
• Documented history of COVID-19 infection made available to study team 1914
• Lack of documented history, but evidence of infection from sensitive antibody tests

You may not qualify if:

• Resting heart rate \<60 bpm
• Atrial fibrillation
• Supraventricular tachycardia
• Allergic reaction or known contraindications to study drug
• Acute decompensated heart failure
• Clinically significant hypotension, defined as a drop in systolic BP \>20 mmHg or drop in diastolic \>10 mmHg during orthostatic vital signs testing.
• Sick sinus syndrome, sinoatrial block or 3rd degree AV block, unless a functioning demand pacemaker is present
• Clinically significant bradycardia
• Severe hepatic impairment
• Pacemaker dependence (heart rate maintained exclusively by the pacemaker)
• Concomitant use of cytochrome P450 3A4 (CYP3A4) inhibitors or inducers
• Pregnant/lactating females
• Impaired gastrointestinal absorption that would preclude oral drug administration
• Taking any of the following without discontinuation in consultation with the volunteer's healthcare provider and a one-week washout period:
• ivabradine

Sponsors & Collaborators

• Uniformed Services University of the Health Sciences: lead

Study Sites (1)

Uniformed Services University

Bethesda, Maryland, 20814, United States

RECRUITING

Related Publications (1)

• Saunders D, Arnold TB, Lavender JM, Bi D, Alcover K, Hellwig LD, Leazer ST, Mohammed R, Markos B, Perera K, Shaw D, Kobi P, Evans M, Mains A, Tanofsky-Kraff M, Goguet E, Mitre E, Pratt KP, Dalgard CL, Haigney MC. Comparative cohort study of post-acute COVID-19 infection with a nested, randomized controlled trial of ivabradine for those with postural orthostatic tachycardia syndrome (the COVIVA study). Front Neurol. 2025 Jul 7;16:1550636. doi: 10.3389/fneur.2025.1550636. eCollection 2025.

  PMID: 40692561 DERIVED

MeSH Terms

Conditions

Post-Acute COVID-19 Syndrome; Postural Orthostatic Tachycardia Syndrome

Interventions

Ivabradine

Condition Hierarchy (Ancestors)

COVID-19; Pneumonia, Viral; Pneumonia; Respiratory Tract Infections; Infections; Virus Diseases; Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Lung Diseases; Respiratory Tract Diseases; Post-Infectious Disorders; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Orthostatic Intolerance; Primary Dysautonomias; Autonomic Nervous System Diseases; Nervous System Diseases

Intervention Hierarchy (Ancestors)

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

Study Officials

• David L Saunders, MD, MPH

  Uniformed Services University of the Health Sciences

  PRINCIPAL INVESTIGATOR

• Mark C Haigney, MD, FAHA

  Uniformed Services University of the Health Sciences

  STUDY CHAIR

Central Study Contacts

Roshila Mohammed, MBBS

CONTACT

(301) 318-6024; clinical.research.unit.53-ggg@usuhs.edu

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: FED
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Colonel, Medical Corps, US Army, Professor of Medicine, Preventive Medicine and Biostatistics, Director, Translational Medicine Unit, Department of Medicine, Director, Division of Clinical Pharmacology and Medical Toxicology

Study Record Dates

• First Submitted: July 28, 2022
• First Posted: August 1, 2022
• Study Start: June 14, 2023
• Primary Completion: September 1, 2024
• Study Completion: September 1, 2024
• Last Updated: November 29, 2023

Record last verified: 2023-11

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)