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

COVID-19 Clinical Trial

— 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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT04365257
• Other study ID #: IRB00246659
• Secondary ID: COV2001
• Status: Terminated
• Phase: Phase 2
• Start date: May 13, 2020
• Est. completion date: March 31, 2022

Study information

• Verified date: March 2023
• Source: Johns Hopkins University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 5
• Est. completion date: March 31, 2022
• Est. primary completion date: March 31, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 45 Years to 85 Years

Eligibility

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)

Related Conditions & MeSH terms

• COVID-19
• Respiratory Distress Syndrome

Intervention

Drug:
• Prazosin
Participants in this arm will receive the study drug as outlined in the arm description.

Other:
• Standard of care
Participants in this arm will receive standard of care.

Locations

Country	Name	City	State
United States	Johns Hopkins Hospital	Baltimore	Maryland

Sponsors (2)

Lead Sponsor	Collaborator
Johns Hopkins University	Fast Grants

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Death	Number of participants in each arm who expire.	up to day 60
Primary	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.	up to day 60
Primary	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).	up to day 60
Primary	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.	up to day 60
Primary	Number of Participants With Serious Adverse Events	Number of participants in each arm who develop serious adverse events during the study period.	up to day 60
Primary	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.	up to day 60
Secondary	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.	up to day 60
Secondary	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.	up to day 60
Secondary	Number of Participants With Laboratory Abnormalities in Plasma	Number of participants with laboratory abnormalities in fractionated plasma catecholamines and plasma metanephrines.	up to day 60
Secondary	Duration of Laboratory Abnormalities in Plasma	Number of days with laboratory abnormalities in fractionated plasma catecholamines and plasma metanephrines.	up to day 60