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.
Drug: Prazosin
Participants in this arm will receive the study drug as outlined in the arm description.
Other Name: Array
Other: Standard of care
Participants in this arm will receive standard of care.
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)
Johns Hopkins Hospital
Baltimore, Maryland, United States
Chetan Bettegowda, MD/PhD, Principal Investigator
Johns Hopkins University