Prazosin to Prevent COVID-19 (PREVENT-COVID Trial) (PREVENT)
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|ClinicalTrials.gov Identifier: NCT04365257|
Recruitment Status : Terminated (Lack of recruitment)
First Posted : April 28, 2020
Results First Posted : January 31, 2023
Last Update Posted : April 10, 2023
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|Condition or disease||Intervention/treatment||Phase|
|COVID-19||Drug: Prazosin Other: Standard of care||Phase 2|
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 (Clinical Trial)|
|Actual Enrollment :||5 participants|
|Intervention Model:||Parallel Assignment|
|Masking:||None (Open Label)|
|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|
|Actual Primary Completion Date :||March 31, 2022|
|Actual Study Completion Date :||March 31, 2022|
If BP monitoring is not available, repeated occurrences of postural dizziness should trigger drug dose reduction or BP monitoring.
Participants in this arm will receive the study drug as outlined in the arm description.
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.
- Death [ Time Frame: up to day 60 ]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 [ 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.
- 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).
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
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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|
- 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
- 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)
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
|United States, Maryland|
|Johns Hopkins Hospital|
|Baltimore, Maryland, United States, 21287|
|Principal Investigator:||Chetan Bettegowda, MD/PhD||Johns Hopkins University|
Documents provided by Johns Hopkins University:
|Responsible Party:||Johns Hopkins University|
|Other Study ID Numbers:||
COV2001 ( Other Identifier: Johns Hopkins University )
|First Posted:||April 28, 2020 Key Record Dates|
|Results First Posted:||January 31, 2023|
|Last Update Posted:||April 10, 2023|
|Last Verified:||March 2023|
|Individual Participant Data (IPD) Sharing Statement:|
|Plan to Share IPD:||No|
|Studies a U.S. FDA-regulated Drug Product:||Yes|
|Studies a U.S. FDA-regulated Device Product:||No|
Coronavirus disease 2019
Cytokine Storm Syndrome
Acute Respiratory Distress Syndrome
Alpha-1 receptor antagonist
Respiratory Distress Syndrome
Respiratory Tract Infections
RNA Virus Infections
Respiratory Tract Diseases
Adrenergic alpha-1 Receptor Antagonists
Molecular Mechanisms of Pharmacological Action
Physiological Effects of Drugs