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Trial record 1 of 1 for:    COVID-19 | Prazosin
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Prazosin to Prevent COVID-19 (PREVENT-COVID Trial) (PREVENT)

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ClinicalTrials.gov Identifier: NCT04365257
Recruitment Status : Recruiting
First Posted : April 28, 2020
Last Update Posted : May 15, 2020
Sponsor:
Collaborator:
Fast Grants
Information provided by (Responsible Party):
Johns Hopkins University

Brief Summary:
The purpose of this study is to assess the efficacy and safety of prazosin to prevent cytokine storm syndrome and severe complications in hospitalized patients with Coronavirus disease 2019 (COVID-19).

Condition or disease Intervention/treatment Phase
COVID-19 Drug: Prazosin Other: Standard of care Phase 2

Detailed Description:

In Coronavirus disease 2019 (COVID-19), severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) elicits an exuberant local or systemic immune response ('hyperinflammation') in the lung and other sites of viral replication, compromising organ function and leading to high morbidity and mortality. Emerging evidence suggests that a subset of patients with COVID-19 develops a cytokine storm syndrome that is associated with elevation of pro-inflammatory cytokines.

Catecholamines enhance inflammatory injury by augmenting the production of IL-6 and other cytokines through a self-amplifying feed-forward loop in immune cells that requires alpha-1 adrenergic receptor (⍺1-AR) signaling. The ⍺1-AR antagonist prazosin prevents cytokine storm and markedly increased survival following inflammatory stimuli in preclinical models. In a retrospective study of outcomes in acute respiratory distress syndrome or pneumonia, patients who were taking ⍺1-AR antagonists had significantly lower probability of needing invasive mechanical ventilation and dying in the hospital compared to non-users.

Prazosin may blunt surges in catecholamines and self-amplifying cytokine production (including interleukin 6) and, as an early preemptive therapy in patients prior to disease progression, may prevent cytokine storm syndrome and severe complications of COVID-19.

In this study, patients with positive SARS-CoV-2 testing who are hospitalized (but are not requiring more than 4 liters/minute of supplemental oxygen by nasal cannula) will be screened for eligibility. Patients who provide informed consent and meet eligibility requirements will be randomized in a 1:1 ratio to receive either prazosin or standard of care. Participants randomized to the study drug will receive prazosin for 28 days and all patients will be followed for a total of 60 days to capture outcomes.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 220 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Alpha-1 Adrenergic Receptor Antagonism to Prevent COVID-19 Cytokine Storm Syndrome and Acute Respiratory Distress Syndrome: A Randomized Study Comparing the Efficacy of Prazosin vs. Standard of Care for SARS-CoV-2 Infection
Actual Study Start Date : May 13, 2020
Estimated Primary Completion Date : December 2020
Estimated Study Completion Date : December 2020


Arm Intervention/treatment
Experimental: Prazosin
  1. Prazosin 1mg given to observe if medication is tolerated or if signs or symptoms of hypotension develop (e.g. dizziness, lightheadedness).
  2. If the patient remains asymptomatic and BP >110/60 mmHg, prazosin is continued at 1mg every 8 hours (q8h).
  3. Day 3: If the patient remains asymptomatic and BP >110/60 mmHg, increase dose to 2mg q8h.
  4. Day 6: If the patient remains asymptomatic and BP >110/60 mmHg, increase dose to 5mg q8h.
  5. If the BP is <100/60 mmHg at any time, the next dose should be held, and patient continues with the highest previously tolerated dose 8 hours later.
  6. If the patient did not tolerate dose escalation to 5mg q8h, one attempt is made to increase dose to 3mg q8h. If this is not tolerated, the patient continues with the highest previously tolerated dose 8 hours later.

If BP monitoring is not available, repeated occurrences of postural dizziness should trigger drug dose reduction or BP monitoring.

Drug: Prazosin
Participants in this arm will receive the study drug as outlined in the arm description.
Other Names:
  • Minipress
  • alpha-1 adrenergic receptor antagonist
  • alpha blocker

Active Comparator: Standard of care
Subjects randomized to this arm will receive standard of care.
Other: Standard of care
Participants in this arm will receive standard of care.




Primary Outcome Measures :
  1. Death [ Time Frame: up to day 60 ]
    Number of participants in each arm who expire.

  2. Hospitalized, requiring mechanical ventilation and/or high flow nasal cannula and/or ICU/CCU admission (or equivalent) and/or ECMO [ Time Frame: up to day 60 ]
    Number of participants in each arm who are hospitalized and requiring mechanical ventilation and/or high flow nasal cannula and/or ICU/CCU admission (or equivalent) and/or ECMO.

  3. Hospitalized, requiring supplemental oxygen, not requiring ICU/CCU level care (or interventions listed under Outcome 2) [ Time Frame: up to day 60 ]
    Number of participants in each arm who are hospitalized and requiring supplemental oxygen, not requiring ICU/CCU level care (or interventions listed under Outcome 2).

  4. Cumulative incidence of grade 3 and 4 adverse events [ Time Frame: up to day 60 ]
    Number of participants in each arm who develop grade 3 and 4 adverse events during the study period.

  5. Number of participants with serious adverse events [ Time Frame: up to day 60 ]
    Number of participants in each arm who develop serious adverse events during the study period.

  6. Incidence of symptomatic hypotension or hypotension requiring cessation of prazosin [ Time Frame: up to day 60 ]
    Number of participants in each arm who develop symptomatic hypotension (systolic blood pressure <90 mmHg) or hypotension requiring cessation of prazosin.


Secondary Outcome Measures :
  1. Number of participants with laboratory abnormalities in peripheral blood [ Time Frame: up to day 60 ]
    Number of participants with laboratory abnormalities in peripheral blood (Lymphopenia, leukocytosis, anemia, thrombocytopenia, creatinine, AST/ALT, troponin I, pro-BNP, D-dimer, ferritin, interleukin (IL-6), soluble IL-2 receptor.

  2. Duration of laboratory abnormalities in peripheral blood [ Time Frame: up to day 60 ]
    Number of days with laboratory abnormalities in peripheral blood (Lymphopenia, leukocytosis, anemia, thrombocytopenia, creatinine, AST/ALT, troponin I, pro-BNP, D-dimer, ferritin, interleukin (IL-6), soluble IL-2 receptor.

  3. Number of participants with laboratory abnormalities in plasma [ Time Frame: up to day 60 ]
    Number of participants with laboratory abnormalities in fractionated plasma catecholamines and plasma metanephrines.

  4. Duration of laboratory abnormalities in plasma [ Time Frame: up to day 60 ]
    Number of days with laboratory abnormalities in fractionated plasma catecholamines and plasma metanephrines.



Information from the National Library of Medicine

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Ages Eligible for Study:   45 Years to 85 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Subjects must be 45 years of age or older
  • Provision of informed consent
  • Subjects who tested positive for SARS-CoV-2 AND have clinical symptoms of COVID-19* AND have been hospitalized, but are not requiring more than 4 liters/minute of supplemental oxygen by nasal cannula and are not requiring ICU/CCU-level care at time of enrollment

(*)Acute respiratory tract infection (sudden onset of at least one of the following: fever, chills, sore throat, myalgia, diarrhea, cough, or shortness of breath) AND with no other etiology that fully explains the clinical presentation

Exclusion Criteria:

  • Female subjects who identify as pregnant, self-reported positive pregnancy testing, or who are breastfeeding during the study period
  • Age >85 years
  • Known history of known orthostatic hypotension, unexplained history of syncope, postural orthostatic tachycardia syndrome (POTS), neurally-mediated hypotension, heart failure, myocardial infarction, stable or unstable angina, history of coronary artery bypass surgery, stroke, carotid artery disease, or moderate to severe mitral or aortic stenosis
  • Current use of tocilizumab, sarilumab, siltuximab, lopinavir/ritonavir, remdesivir, favipiravir, alpha-blockers, combined alpha/beta blockers (carvedilol, labetalol), sotalol, clonidine, phosphodiesterase type 5 inhibitors, asenapine, or alpha-methyldopa
  • Need for vasopressors, inotropes, or intra-aortic balloon pump at time of enrollment
  • Allergy or intolerance to quinazolines (including prazosin)
  • Requires oxygen supplementation beyond 4 liters of oxygen/minute per nasal cannula at time of enrollment (i.e. not requiring oxygenation by non-rebreather, high-flow nasal cannula, CPAP/BiPAP, or invasive mechanical ventilation)
  • Patients who are in the custody of state or federal entities (prisoners)

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): NCT04365257


Contacts
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Contact: Chetan Bettegowda, MD/PhD 410-955-8620 cbetteg1@jhmi.edu

Locations
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United States, Maryland
Johns Hopkins Hospital Recruiting
Baltimore, Maryland, United States, 21287
Contact: Chetan Bettegowda, MD/PhD    410-955-8620    cbetteg1@jhmi.edu   
Principal Investigator: Chetan Bettegowda, MD/PhD         
Sponsors and Collaborators
Johns Hopkins University
Fast Grants
Investigators
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Principal Investigator: Chetan Bettegowda, MD/PhD Johns Hopkins University
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Responsible Party: Johns Hopkins University
ClinicalTrials.gov Identifier: NCT04365257    
Other Study ID Numbers: IRB00246659
COV2001 ( Other Identifier: Johns Hopkins University )
First Posted: April 28, 2020    Key Record Dates
Last Update Posted: May 15, 2020
Last Verified: May 2020
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
Keywords provided by Johns Hopkins University:
SARS-CoV-2
Coronavirus disease 2019
COVID-19
Cytokine Storm Syndrome
Acute Respiratory Distress Syndrome
Prazosin
Alpha-1 receptor antagonist
Additional relevant MeSH terms:
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Prazosin
Adrenergic alpha-1 Receptor Antagonists
Adrenergic Antagonists
Antihypertensive Agents
Adrenergic alpha-Antagonists
Adrenergic Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Physiological Effects of Drugs