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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT05096884
Recruitment Status : Terminated (Low accrual)
First Posted : October 27, 2021
Last Update Posted : January 11, 2024
Sponsor:
Information provided by (Responsible Party):
Hackensack Meridian Health

Brief Summary:

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.


Condition or disease Intervention/treatment Phase
Tachycardia Dyspnea COVID-19 Drug: Metoprolol Succinate Early Phase 1

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.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 14 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Post-Acute Sequelae of Coronavirus-19 (COVID-19) With DysPnEA on ExertIon And Associated TaChycardia TrEatment Study
Actual Study Start Date : March 23, 2022
Actual Primary Completion Date : September 12, 2023
Actual Study Completion Date : September 12, 2023


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.




Primary Outcome Measures :
  1. 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).

  2. 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).



Secondary Outcome Measures :
  1. 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).




Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 40 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT05096884


Locations
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United States, New Jersey
Hackensack Univeristy Medical Center
Hackensack, New Jersey, United States, 07601
Sponsors and Collaborators
Hackensack Meridian Health
Investigators
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Principal Investigator: David Landers, MD Hackensack Meridian Health
Publications:

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Responsible Party: Hackensack Meridian Health
ClinicalTrials.gov Identifier: NCT05096884    
Other Study ID Numbers: Pro2021-1100
First Posted: October 27, 2021    Key Record Dates
Last Update Posted: January 11, 2024
Last Verified: January 2024
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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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
Keywords provided by Hackensack Meridian Health:
COVID-19
Post-COVID
Long-COVID
Tachycardia
Shortness of breath
Post-Acute Sequelae of COVID-19 (PASC)
Additional relevant MeSH terms:
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COVID-19
Dyspnea
Tachycardia
Pneumonia, Viral
Pneumonia
Respiratory Tract Infections
Infections
Virus Diseases
Coronavirus Infections
Coronaviridae Infections
Nidovirales Infections
RNA Virus Infections
Lung Diseases
Respiratory Tract Diseases
Arrhythmias, Cardiac
Heart Diseases
Cardiovascular Diseases
Cardiac Conduction System Disease
Pathologic Processes
Respiration Disorders
Signs and Symptoms, Respiratory
Metoprolol
Anti-Arrhythmia Agents
Antihypertensive Agents
Sympatholytics
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Adrenergic beta-1 Receptor Antagonists
Adrenergic beta-Antagonists