Ivabradine for Long-Term Effects of COVID-19 With POTS Cohort
NCT ID: NCT05481177
Last Updated: 2023-11-29
Study Results
The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.
Basic Information
Get a concise snapshot of the trial, including recruitment status, study phase, enrollment targets, and key timeline milestones.
RECRUITING
PHASE4
250 participants
INTERVENTIONAL
2023-06-14
2024-09-01
Brief Summary
Review the sponsor-provided synopsis that highlights what the study is about and why it is being conducted.
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.
Detailed Description
Dive into the extended narrative that explains the scientific background, objectives, and procedures in greater depth.
Those with confirmed POTS or Inappropriate sinus tachycardia (IST) will be randomized to ivabradine or placebo to determine efficacy in reducing heart rate as a putative surrogate for POTS disease as well as effects on POTS symptoms. The biopsychosocial mechanisms of LHC and POTS will also be explored. Specific objectives will be:
1. To assess the frequency and severity of fatigue, dyspnea, headache, and confusion and other suggestive symptoms among volunteers with and without LHC and measure the occurrence of clinically confirmed POTS or IST-in relation to these symptoms.
2. To assess whether treatment with ivabradine will significantly reduce heart rate and improve symptoms and quality of life among subjects manifesting typical POTS or similar autonomic dysregulation.
3. To characterize the immunoinflammatory and genomic factors associated with LHC and POTS among those with LHC. In particular, to determine whether those with POTS have differential expression of genes and/or proteins associated with autonomic nervous system function. To determine whether these factors reflect a genetic predisposition.
4. To determine whether wearable automated ambulatory monitoring with existing FDA-approved devices will permit improved diagnostic accuracy for POTS.
5. To determine the degree to which LHC induced autonomic instability and whether it is associated with induced inflammation and/or dysregulation
6. To evaluate potential contribution of psychological symptoms and the interplay between psychosocial symptoms, quality of life, cognitive symptoms, and physiologic responses induced by LHC.
7. To determine whether LHC improves following vaccination (in the limited number of cases where late vaccination occurs) and/or "breakthrough" clinical COVID-19 infection.
8. Assess whether individuals with LHC have different antibody and/or cellular immune responses to SARS-CoV-2 antigens compared to infected individuals who did not develop LHC.
9. Assess whether specific plasma protein markers of dysregulated blood coagulation, which were significantly correlated with immunothrombosis in severe COVID-19, persist in individuals with LHC.
Conditions
See the medical conditions and disease areas that this research is targeting or investigating.
Study Design
Understand how the trial is structured, including allocation methods, masking strategies, primary purpose, and other design elements.
RANDOMIZED
PARALLEL
TREATMENT
TRIPLE
Study Groups
Review each arm or cohort in the study, along with the interventions and objectives associated with them.
Long Haul COVID
Persistent signs and/or symptoms \>12 weeks post Covid-infection N = 200 evaluable subjects.
No interventions assigned to this group
Post COVID without LHC
No persistent signs and/or symptoms \>12 weeks N = 50 evaluable subjects.
No interventions assigned to this group
Ivabradine RCT Arms
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
Ivabradine
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.
Interventions
Learn about the drugs, procedures, or behavioral strategies being tested and how they are applied within this trial.
Ivabradine
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.
Eligibility Criteria
Check the participation requirements, including inclusion and exclusion rules, age limits, and whether healthy volunteers are accepted.
Inclusion Criteria
2. History of documented COVID-19 infection of any severity to include a positive COVID-19 PCR, or antibody test
3. Meets criteria for 'long-haul' COVID-19 with symptoms \>12 weeks following acute illness
4. Able and willing to provide informed consent and participate for study duration
5. Willing to participate in the nested randomized controlled trial of ivabradine if RCT enrollment criteria are met
6. Access to a primary healthcare provider and proof of health insurance
1. Age 18-80
2. History of documented COVID-19 infection of any severity to include a positive COVID-19 PCR, or antibody test
3. Does not meet criteria for 'long-haul' COVID-19
4. Able and willing to provide informed consent and participate for study duration
5. Willing to participate in the nested randomized controlled trial of ivabradine if RCT enrollment criteria are met
6. Access to a primary healthcare provider and proof of health insurance
1. Age 18-80; Meets criteria for 'long-haul' COVID-19
1. Documented history of COVID-19 infection made available to study team 1914
2. Lack of documented history, but evidence of infection from sensitive antibody tests
2. Able and willing to provide informed consent and participate for study duration
3. Volunteers with or without LHC combined with POTS based on an increase in comparing the supine heart rate to standing heart rate \>20 beats per minute with a drop in systolic blood pressure less than 20 mm Hg or a drop in diastolic blood pressure less than 10 mm Hg will be included, OR additionally, volunteers with or without LHC and a 24-hour mean heart rate of 90 beats per minute or more (in sinus rhythm) will be diagnosed with IST and be included.
4. For females of childbearing age - willing to use a highly effective form of contraceptive with \<1% failure rate or practice abstinence for the duration of the study
Exclusion Criteria
2. Atrial fibrillation
3. Supraventricular tachycardia
4. Allergic reaction or known contraindications to study drug
1. Acute decompensated heart failure
2. Clinically significant hypotension, defined as a drop in systolic BP \>20 mmHg or drop in diastolic \>10 mmHg during orthostatic vital signs testing.
3. Sick sinus syndrome, sinoatrial block or 3rd degree AV block, unless a functioning demand pacemaker is present
4. Clinically significant bradycardia
5. Severe hepatic impairment
6. Pacemaker dependence (heart rate maintained exclusively by the pacemaker)
7. Concomitant use of cytochrome P450 3A4 (CYP3A4) inhibitors or inducers
5. Pregnant/lactating females
6. Impaired gastrointestinal absorption that would preclude oral drug administration
7. Taking any of the following without discontinuation in consultation with the volunteer's healthcare provider and a one-week washout period:
1. ivabradine
2. beta-blockers
3. calcium- channel blockers
4. cholinesterase inhibitors (pyridostigmine),
5. vasoconstrictors (midodrine, octreotide, droxidopa, stimulants)
6. sympatholytics (clonidine, methyldopa)
7. blood volume enhancers (fludrocortisone, desmopressin, salt supplementation)
8. oral ketoconazole (contraindicated)
8. Acute suicidality identified at screening
\-
18 Years
80 Years
ALL
No
Sponsors
Meet the organizations funding or collaborating on the study and learn about their roles.
Uniformed Services University of the Health Sciences
FED
Responsible Party
Identify the individual or organization who holds primary responsibility for the study information submitted to regulators.
David Saunders
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
Principal Investigators
Learn about the lead researchers overseeing the trial and their institutional affiliations.
David L Saunders, MD, MPH
Role: PRINCIPAL_INVESTIGATOR
Uniformed Services University of the Health Sciences
Mark C Haigney, MD, FAHA
Role: STUDY_CHAIR
Uniformed Services University of the Health Sciences
Locations
Explore where the study is taking place and check the recruitment status at each participating site.
Uniformed Services University
Bethesda, Maryland, United States
Countries
Review the countries where the study has at least one active or historical site.
Central Contacts
Reach out to these primary contacts for questions about participation or study logistics.
References
Explore related publications, articles, or registry entries linked to this study.
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.
Provided Documents
Download supplemental materials such as informed consent forms, study protocols, or participant manuals.
Document Type: Informed Consent Form
Other Identifiers
Review additional registry numbers or institutional identifiers associated with this trial.
USUHS.2022-094
Identifier Type: -
Identifier Source: org_study_id