Post-Acute Sequelae of Coronavirus-19 (COVID-19) With Dyspnea on Exertion And Associated TaChycardia TrEatment Study (PEACE)

November 26, 2024 updated by: Hackensack Meridian Health

Post-Acute Sequelae of Coronavirus-19 (COVID-19) With DysPnEA on ExertIon And Associated TaChycardia TrEatment Study

Most patients with acute COVID-19 (Coronavirus 19) recover within weeks, however a significant number of individuals will develop the post-acute COVID 19 syndrome (PASC). As of July 2021, the post COVID syndrome qualifies as a disability under the Americans with Disabilities Act. The symptoms which comprise this condition are highly variable and often extraordinarily debilitating. They may be distinct from the initial presentation or may mimic those which defined the initial infection. The post COVID syndrome can be diagnosed when symptoms persist longer than 3 months and may extend to beyond one year. There are risks for permanent levels of disability. Patients who seemingly did not have active COVID-19 symptoms in the days following infectious exposure may also develop post Covid syndromes. These syndromes are considered to constitute a distinct clinical entity which has of yet no clearly defined pathogenic mechanism or validated treatment algorithms.

International investigative efforts are now underway to determine who might develop the post COVID syndrome, it's long term consequences and how best to treat its many problematic symptoms.

Study Overview

Status

Terminated

Conditions

Intervention / Treatment

Detailed Description

Although the long Covid syndrome or PASC is a well recognized syndrome, its pathogenesis is poorly understood. Hypotheses have included persistent viral remnants with consequent provocation of the generalized symptoms characteristic of systemic inflammation. The virus may continue to infect heart, lung or neurologic tissue rendering various organs dysfunctional. Alternatively there could be persistently infected or damaged endothelial cells which line blood vessels and thereby create perturbations of blood flow.

The altered blood flow might then explain the many reported symptoms. However the pathogenesis can be distinguished and studied independently from the physiological disturbance. Existing and accepted therapies for tachycardia and shortness of breath, although they might not reverse the virus caused injury, could be used to reduce the resultant physiologic abnormalities which in turn produce the symptoms of the long Covid syndrome. Beta blockers are standard therapies in sinus tachycardias, (1,2) and postural orthostatic tachycardia syndrome (POTS) (3,4) which are often characterized by high levels of sympathetic drive which beta blockers are designed to modulate.

Thus it is reasonable to hypothesize that that treatment with beta blockers may be an effective intervention as Covid-19 directly infects the nerve and vascular tissues which regulate sympathetic excess which in turn may produce the cardiovascular symptoms of PASC. Moreover it is important to specifically study beta blockers in PASC because they are currently actively in use for this indication. Yet the possibility remains that although the symptoms are similar to those in which beta blockers have been effective, the pathologic processes in PASC will not be responsive to beta blocker therapy. If this were to be true, beta blockers would prove ineffective and might carry a risk of harm. Equally as important is to properly determine the effective dose as the therapeutic window for these agents is wide.

Metoprolol which is a widely used agent in cardiovascular disease is approved in doses ranging from 25 to 400 mg per day. The proposed study will compare 6 minute walk distances (pre and post the treatment), the echocardiographic measurement of the impact of sympathetic excess on the heart's ability to empty effectively and a quality of life survey. Each of these study elements will be measured before and after progressively increased doses of beta blocker.

Our study is thus designed to study two issues:

  1. Whether beta blockers which have been utilized to treat tachycardias, POTS (postural orthostatic tachycardia syndrome), and hypertension will have similar effectiveness in PASC
  2. To determine appropriate dosing which may be different than those used on non PASC conditions.

Study Type

Interventional

Enrollment (Actual)

14

Phase

  • Early Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • New Jersey
      • Hackensack, New Jersey, United States, 07601
        • Hackensack Univeristy Medical Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 40 years (Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  1. Subject should be between the ages of 18 and 40 with DOE (dyspnea on exertion) for 3 - 12 months
  2. Subjects recovered from acute, polymerase chain reaction (PCR) positive, COVID-19 infection
  3. Recovery from COVID-19 will be defined as substantial improvement in or essential resolution of initial clinical symptoms
  4. Demonstration of tachycardia and/or dyspnea with minimal activity (subjectively different than pre-COVID 19 infection state)
  5. Abnormal HUTT (heads up tilt test)
  6. Normal chest x-ray
  7. Left ventricular ejection fraction (LVEF) >50% by transthoracic echocardiography
  8. Zva >3.5 as calculated from TTE (transthoracic echocardiogram).
  9. Hemoglobin/Hematocrit within normal laboratory standards
  10. Thyroid-stimulating hormone (TSH) within normal laboratory standards

Exclusion Criteria:

  1. Active pregnancy (negative pregnancy test is the standard of care prior to HUTT)

  2. Demonstrate a primary cause of appropriate DOE and sinus tachycardia

    1. Fevers/infection
    2. Hypovolemia
    3. Anemia
    4. Hyperthyroidism
    5. Alcohol/drug/medication withdrawal
  3. Currently taking beta blocker medications
  4. Currently being treated for pre-existing neurally mediated hypotension/syncope or known dysautonomia.
  5. Medical history of chronic lung disease or reactive airway syndrome.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Study arm - Metoprolol Succinate.
The beta blocker metoprolol succinate will be initiated at a starting low dose of 25 mg daily for two weeks and will be escalated if well tolerated every 2 weeks to a maximum dose of 400 mg po daily.
Drug: Metoprolol Succinate
The beta blocker metoprolol succinate will be initiated at a starting low dose of 25 mg daily for two weeks and will be escalated if well tolerated every 2 weeks to a maximum dose of 400 mg po daily.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change in 6 Minute Walk Test at the End of Treatment Period
Time Frame: 12 weeks from baseline walk test
To assess the reduction of symptoms in patients with PASC Dyspnea on Exertion (DOE) and associated tachycardia when treated with beta blockers as captured in patients walk test. Walk test will be performed at day 1 (baseline) and at 2-4 weeks post treatment completion which consists of 8 weeks metoprolol succinate (approximately 12 weeks from baseline).
12 weeks from baseline walk test
Change in Zva Measurement at the End of Treatment Period
Time Frame: 12 weeks from baseline transthoracic echocardiogram (TTE).

To assess the reduction of symptoms in patients with PASC Dyspnea on Exertion (DOE) and associated tachycardia when treated with beta blockers as captured in Zva measurement calculated from patient's TTE (transthoracic echocardiogram).

TTE (and Zva) will be performed at day 1 (baseline) and at 2-4 weeks post treatment completion which consists of 8 weeks metoprolol succinate (approximately 12 weeks from baseline).
12 weeks from baseline transthoracic echocardiogram (TTE).

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change in Minnesota Living With Heart Failure Score at the End of Treatment Period
Time Frame: 12 weeks from baseline

Subjective improvement in Dyspnea on Exertion (DOE), tachycardia and well being score as measured by the Minnesota Living with Heart Failure.

The Minnesota Living with Heart Failure questionnaire will be administered at day 1 (baseline) and at 2-4 weeks post treatment completion which consists of 8 weeks metoprolol succinate (approximately 12 weeks from baseline). Minnesota Living with Heart Failure questionnaire is a 21-item questionnaire with each item having a 6 point Likert scale (0-5), Zero represents "No symptom" and 5 represents high intensity of symptom. The questionnaire has 3 dimension and they measure Physical, socio-economic and emotional/psychological aspects respectively. The total score is the sum of all item responses for total and dimension scores.
12 weeks from baseline

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Hackensack Meridian Health

Investigators

  • Principal Investigator: David Landers, MD, Hackensack Meridian Health

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

March 23, 2022

Primary Completion (Actual)

September 12, 2023

Study Completion (Actual)

September 12, 2023

Study Registration Dates

First Submitted

October 25, 2021

First Submitted That Met QC Criteria

October 25, 2021

First Posted (Actual)

October 27, 2021

Study Record Updates

Last Update Posted (Actual)

December 3, 2024

Last Update Submitted That Met QC Criteria

November 26, 2024

Last Verified

November 1, 2024

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • Pro2021-1100

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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