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

Phase 2TerminatedNCT04365257

Johns Hopkins University5 enrolled

Overview

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).

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.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

COVID-19

Interventions

PrazosinDRUG

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

Standard of careOTHER

Participants in this arm will receive standard of care.

Eligibility

Sex: ALLMin age: 45 YearsMax age: 85 Years

Medical Language ↔ Plain English

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)

Locations (1)

Johns Hopkins Hospital

Baltimore, Maryland, United States

Outcomes

Primary Outcomes

Death

Number of participants in each arm who expire.

Time frame: up to day 60

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.

Time frame: up to day 60

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).

Time frame: up to day 60

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.

Time frame: up to day 60

Number of Participants With Serious Adverse Events

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

Time frame: up to day 60

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.

Time frame: up to day 60

Secondary Outcomes

Number of Participants With Laboratory Abnormalities in Peripheral Blood

Data from ClinicalTrials.gov

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