Ivabradine for Long COVID Syndrome
(RECOVER-AUTO Trial)
Recruiting in Palo Alto (17 mi)
+1 other location
Age: 18+
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 2
Recruiting
Sponsor: Duke University
Must not be taking: Clonidine, Amphetamines, SNRIs, others
Disqualifiers: Pregnancy, Lactation, Hepatic impairment, others
No Placebo Group
Prior Safety Data
Approved in 6 Jurisdictions
Trial Summary
What is the purpose of this trial?This study is a platform protocol designed to be flexible so that it is suitable for a wide range of settings within health care systems and in community settings where it can be integrated into COVID-19 programs and subsequent treatment plans.
This protocol is a prospective, multi-center, multi-arm, randomized, controlled platform trial evaluating various interventions for use in the treatment of autonomic dysfunction symptoms, including cardiovascular complications and postural orthostatic tachycardia syndrome (POTS), in PASC participants. The interventions tested will include non-pharmacologic care and pharmacologic therapies with study drugs.
Will I have to stop taking my current medications?
You may need to stop taking certain medications like clonidine, tizanidine, amphetamines, and some antidepressants, unless you are on a stable dose of specific drugs like beta-blockers or calcium channel blockers. It's best to discuss your current medications with the trial team to see if any changes are needed.
How does the drug Ivabradine differ from other treatments for long COVID?
Ivabradine is unique because it specifically targets and reduces heart rate by inhibiting the 'funny' current (a specific electrical current in the heart), which may help alleviate cardiovascular symptoms like high heart rate and palpitations in long COVID, unlike other treatments that do not directly address these symptoms.
12345Eligibility Criteria
This trial is for individuals with long-term symptoms after COVID-19, known as Long COVID or PASC, who experience rapid heart rate upon standing (orthostatic tachycardia) and related symptoms. Participants should have a specific score on a questionnaire assessing autonomic dysfunction and not be enrolled in certain other sub-studies.Inclusion Criteria
I feel dizzy and my heart races when I stand up.
COMPASS-31 Score > 25 and not enrolled in the IVIG appendix
Exclusion Criteria
I have severe liver problems.
I am taking verapamil or diltiazem.
Lactating and breast-feeding women
+10 more
Trial Timeline
Screening
Participants are screened for eligibility to participate in the trial
2-4 weeks
Treatment
Participants receive Ivabradine or placebo with usual or coordinated care. The starting dose is 5 mg twice a day, adjusted at the 1-month clinic visit based on heart rate.
3 months
1 visit (in-person) at 1 month for dose adjustment
Follow-up
Participants are monitored for safety and effectiveness after treatment, including incidence of SAEs and ESIs.
6 months
Participant Groups
The study compares the effects of Ivabradine, a heart rate reducing medication, against a placebo. It also evaluates coordinated care versus usual healthcare practices to manage post-COVID autonomic dysfunction including cardiovascular issues and POTS.
4Treatment groups
Experimental Treatment
Group I: Ivabradine Placebo + Usual CareExperimental Treatment2 Interventions
Group II: Ivabradine Placebo + Coordinated CareExperimental Treatment2 Interventions
Group III: Ivabradine + Usual CareExperimental Treatment2 Interventions
The starting dose will be 5 mg twice a day, and the dose will be modified if needed at the 1 month clinic visit. At this visit, HR will be measured and the dose will be modified as applicable. The maximum dose will be 7.5 mg twice daily if HR is Λ 90 bpm.
The table below provides the dosing of ivabradine based on HR.
Supine Resting HR 60-80 2.5 mg BID Supine Resting HR \>80 5 mg BID Supine Resting HR \>90 7.5 mg BID
\*Resting HR should be measured 5 minutes after lying down
Group IV: Ivabradine + Coordinated CareExperimental Treatment2 Interventions
The starting dose will be 5 mg twice a day, and the dose will be modified if needed at the 1 month clinic visit. At this visit, HR will be measured and the dose will be modified as applicable. The maximum dose will be 7.5 mg twice daily if HR is Λ 90 bpm.
The table below provides the dosing of ivabradine based on HR.
Supine Resting HR 60-80 2.5 mg BID Supine Resting HR \>80 5 mg BID Supine Resting HR \>90 7.5 mg BID
\*Resting HR should be measured 5 minutes after lying down
Ivabradine is already approved in United States, European Union, Canada for the following indications:
πΊπΈ Approved in United States as Corlanor for:
- Heart failure
- Angina
πͺπΊ Approved in European Union as Procoralan for:
- Angina
- Heart failure
π¨π¦ Approved in Canada as Lancora for:
- Angina
- Heart failure
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
NorthShore University HealthSystem - Evanston HospitalEvanston, IL
All sites listed under NCT06305780Durham, NC
Loading ...
Who Is Running the Clinical Trial?
Duke UniversityLead Sponsor
Kanecia Obie ZimmermanLead Sponsor
References
Cardiovascular and autonomic dysfunction in long-COVID syndrome and the potential role of non-invasive therapeutic strategies on cardiovascular outcomes. [2023]A significant percentage of COVID-19 survivors develop long-lasting cardiovascular sequelae linked to autonomic nervous system dysfunction, including fatigue, arrhythmias, and hypertension. This post-COVID-19 cardiovascular syndrome is one facet of "long-COVID," generally defined as long-term health problems persisting/appearing after the typical recovery period of COVID-19. Despite the fact that this syndrome is not fully understood, it is urgent to develop strategies for diagnosing/managing long-COVID due to the immense potential for future disease burden. New diagnostic/therapeutic tools should provide health personnel with the ability to manage the consequences of long-COVID and preserve/improve patient quality of life. It has been shown that cardiovascular rehabilitation programs (CRPs) stimulate the parasympathetic nervous system, improve cardiorespiratory fitness (CRF), and reduce cardiovascular risk factors, hospitalization rates, and cognitive impairment in patients suffering from cardiovascular diseases. Given their efficacy in improving patient outcomes, CRPs may have salutary potential for the treatment of cardiovascular sequelae of long-COVID. Indeed, there are several public and private initiatives testing the potential of CRPs in treating fatigue and dysautonomia in long-COVID subjects. The application of these established rehabilitation techniques to COVID-19 cardiovascular syndrome represents a promising approach to improving functional capacity and quality of life. In this brief review, we will focus on the long-lasting cardiovascular and autonomic sequelae occurring after COVID-19 infection, as well as exploring the potential of classic and novel CRPs for managing COVID-19 cardiovascular syndrome. Finally, we expect this review will encourage health care professionals and private/public health organizations to evaluate/implement non-invasive techniques for the management of COVID-19 cardiovascular sequalae.
Antihistamines improve cardiovascular manifestations and other symptoms of long-COVID attributed to mast cell activation. [2023]Long-COVID is a broadly defined condition and there are no effective therapies. Cardiovascular manifestations of long-COVID include high heart rate, postural tachycardia, and palpitations. Previous studies have suggested that mast cell activation (MCA) may play a role in the pathophysiology of long-COVID, including in the mechanisms of its cardiovascular manifestations. The present study aimed to evaluate the effectiveness of a treatment with blockers of histamine receptors in patients with long-COVID who did not respond to other therapies.
Long-COVID Syndrome and the Cardiovascular System: A Review of Neurocardiologic Effects on Multiple Systems. [2023]Long-COVID syndrome is a multi-organ disorder that persists beyond 12 weeks post-acute SARS-CoV-2 infection (COVID-19). Here, we provide a definition for this syndrome and discuss neuro-cardiology involvement due to the effects of (1) angiotensin-converting enzyme 2 receptors (the entry points for the virus), (2) inflammation, and (3) oxidative stress (the resultant effects of the virus).
Unmasking Pandemic Echoes: An In-Depth Review of Long COVID's Unabated Cardiovascular Consequences beyond 2020. [2023]At the beginning of 2020, coronavirus disease 2019 (COVID-19) emerged as a new pandemic, leading to a worldwide health crisis and overwhelming healthcare systems due to high numbers of hospital admissions, insufficient resources, and a lack of standardized therapeutic protocols. Multiple genetic variants of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have been detected since its first public declaration in 2020, some of them being considered variants of concern (VOCs) corresponding to several pandemic waves. Nevertheless, a growing number of COVID-19 patients are continuously discharged from hospitals, remaining symptomatic even months after their first episode of COVID-19 infection. Long COVID-19 or 'post-acute COVID-19 syndrome' emerged as the new pandemic, being characterized by a high variability of clinical manifestations ranging from cardiorespiratory and neurological symptoms such as chest pain, exertional dyspnoea or cognitive disturbance to psychological disturbances, e.g., depression, anxiety or sleep disturbance with a crucial impact on patients' quality of life. Moreover, Long COVID is viewed as a new cardiovascular risk factor capable of modifying the trajectory of current and future cardiovascular diseases, altering the patients' prognosis. Therefore, in this review we address the current definitions of Long COVID and its pathophysiology, with a focus on cardiovascular manifestations. Furthermore, we aim to review the mechanisms of acute and chronic cardiac injury and the variety of cardiovascular sequelae observed in recovered COVID-19 patients, in addition to the potential role of Long COVID clinics in the medical management of this new condition. We will further address the role of future research for a better understanding of the actual impact of Long COVID and future therapeutic directions.
Outpatient treatment of COVID-19 and incidence of post-COVID-19 condition over 10 months (COVID-OUT): a multicentre, randomised, quadruple-blind, parallel-group, phase 3 trial. [2023]Post-COVID-19 condition (also known as long COVID) is an emerging chronic illness potentially affecting millions of people. We aimed to evaluate whether outpatient COVID-19 treatment with metformin, ivermectin, or fluvoxamine soon after SARS-CoV-2 infection could reduce the risk of long COVID.