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Prazosin to Prevent COVID-19 (PREVENT-COVID Trial) (PREVENT)

Primary Purpose

COVID-19

Status

Terminated

Phase

Phase 2

Locations

United States

Study Type

Interventional

Intervention

Prazosin

Standard of care

About this trial

This is an interventional treatment trial for COVID-19 focused on measuring SARS-CoV-2, Coronavirus disease 2019, COVID-19, Cytokine Storm Syndrome, Acute Respiratory Distress Syndrome, Prazosin, Alpha-1 receptor antagonist

Eligibility Criteria

45 Years - 85 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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)

Sites / Locations

Johns Hopkins Hospital

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Active Comparator

Arm Label

Prazosin

Standard of care

Arm Description

Prazosin 1mg given to observe if medication is tolerated or if signs or symptoms of hypotension develop (e.g. dizziness, lightheadedness). If the patient remains asymptomatic and BP >110/60 mmHg, prazosin is continued at 1mg every 8 hours (q8h). Day 3: If the patient remains asymptomatic and BP >110/60 mmHg, increase dose to 2mg q8h. Day 6: If the patient remains asymptomatic and BP >110/60 mmHg, increase dose to 5mg q8h. 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. 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.

Subjects randomized to this arm will receive standard of care.

Outcomes

Primary Outcome Measures

Death

Number of participants in each arm who expire.

Hospitalized, Requiring Mechanical Ventilation and/or High Flow Nasal Cannula and/or ICU/CCU Admission (or Equivalent) and/or ECMO

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.

Hospitalized, Requiring Supplemental Oxygen, Not Requiring ICU/CCU Level Care (or Interventions Listed Under Outcome 2)

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).

Cumulative Incidence of Grade 3 and 4 Adverse Events

Number of participants in each arm who develop grade 3 and 4 adverse events during the study period.

Number of Participants With Serious Adverse Events

Number of participants in each arm who develop serious adverse events during the study period.

Incidence of Symptomatic Hypotension or Hypotension Requiring Cessation of Prazosin

Number of participants in each arm who develop symptomatic hypotension (systolic blood pressure <90 mmHg) or hypotension requiring cessation of prazosin.

Secondary Outcome Measures

Number of Participants With Laboratory Abnormalities in Peripheral Blood

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.

Duration of Laboratory Abnormalities in Peripheral Blood

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.

Number of Participants With Laboratory Abnormalities in Plasma

Number of participants with laboratory abnormalities in fractionated plasma catecholamines and plasma metanephrines.

Duration of Laboratory Abnormalities in Plasma

Number of days with laboratory abnormalities in fractionated plasma catecholamines and plasma metanephrines.

Full Information

NCT ID

NCT04365257

First Posted

April 24, 2020

Last Updated

March 16, 2023

Sponsor

Johns Hopkins University

Collaborators

Fast Grants

1. Study Identification

Unique Protocol Identification Number

NCT04365257

Brief Title

Prazosin to Prevent COVID-19 (PREVENT-COVID Trial)

Acronym

PREVENT

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

Study Type

Interventional

2. Study Status

Record Verification Date

March 2023

Overall Recruitment Status

Terminated

Why Stopped

Lack of recruitment

Study Start Date

May 13, 2020 (Actual)

Primary Completion Date

March 31, 2022 (Actual)

Study Completion Date

March 31, 2022 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Johns Hopkins University

Collaborators

Fast Grants

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Yes

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

Yes

5. Study Description

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).

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

COVID-19

Keywords

SARS-CoV-2, Coronavirus disease 2019, COVID-19, Cytokine Storm Syndrome, Acute Respiratory Distress Syndrome, Prazosin, Alpha-1 receptor antagonist

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Parallel Assignment

Masking

None (Open Label)

Allocation

Randomized

Enrollment

5 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Prazosin

Arm Type

Experimental

Arm Description

Arm Title

Standard of care

Arm Type

Active Comparator

Arm Description

Subjects randomized to this arm will receive standard of care.

Intervention Type

Drug

Intervention Name(s)

Prazosin

Other Intervention Name(s)

Minipress, alpha-1 adrenergic receptor antagonist, alpha blocker

Intervention Description

Participants in this arm will receive the study drug as outlined in the arm description.

Intervention Type

Other

Intervention Name(s)

Standard of care

Intervention Description

Participants in this arm will receive standard of care.

Primary Outcome Measure Information:

Title

Death

Description

Number of participants in each arm who expire.

Time Frame

up to day 60

Title

Hospitalized, Requiring Mechanical Ventilation and/or High Flow Nasal Cannula and/or ICU/CCU Admission (or Equivalent) and/or ECMO

Description

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.

Time Frame

up to day 60

Title

Hospitalized, Requiring Supplemental Oxygen, Not Requiring ICU/CCU Level Care (or Interventions Listed Under Outcome 2)

Description

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).

Time Frame

up to day 60

Title

Cumulative Incidence of Grade 3 and 4 Adverse Events

Description

Number of participants in each arm who develop grade 3 and 4 adverse events during the study period.

Time Frame

up to day 60

Title

Number of Participants With Serious Adverse Events

Description

Number of participants in each arm who develop serious adverse events during the study period.

Time Frame

up to day 60

Title

Incidence of Symptomatic Hypotension or Hypotension Requiring Cessation of Prazosin

Description

Number of participants in each arm who develop symptomatic hypotension (systolic blood pressure <90 mmHg) or hypotension requiring cessation of prazosin.

Time Frame

up to day 60

Secondary Outcome Measure Information:

Title

Number of Participants With Laboratory Abnormalities in Peripheral Blood

Description

Time Frame

up to day 60

Title

Duration of Laboratory Abnormalities in Peripheral Blood

Description

Time Frame

up to day 60

Title

Number of Participants With Laboratory Abnormalities in Plasma

Description

Number of participants with laboratory abnormalities in fractionated plasma catecholamines and plasma metanephrines.

Time Frame

up to day 60

Title

Duration of Laboratory Abnormalities in Plasma

Description

Number of days with laboratory abnormalities in fractionated plasma catecholamines and plasma metanephrines.

Time Frame

up to day 60

10. Eligibility

Sex

All

Minimum Age & Unit of Time

45 Years

Maximum Age & Unit of Time

85 Years

Accepts Healthy Volunteers

Eligibility 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)

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Chetan Bettegowda, MD/PhD

Organizational Affiliation

Johns Hopkins University

Official's Role

Principal Investigator

Facility Information:

Facility Name

Johns Hopkins Hospital

City

Baltimore

State/Province

Maryland

ZIP/Postal Code

21287

Country

United States

12. IPD Sharing Statement

Plan to Share IPD

Learn more about this trial

Prazosin to Prevent COVID-19 (PREVENT-COVID Trial)

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