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

NCT ID: NCT04365257

Last Updated: 2023-04-10

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE2
• Total Enrollment: 5 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2020-05-13
• Study Completion Date: 2022-03-31

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.

Conditions

COVID-19

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Prazosin

1. Prazosin 1mg given to observe if medication is tolerated or if signs or symptoms of hypotension develop (e.g. dizziness, lightheadedness).

2. If the patient remains asymptomatic and BP >110/60 mmHg, prazosin is continued at 1mg every 8 hours (q8h).

3. Day 3: If the patient remains asymptomatic and BP >110/60 mmHg, increase dose to 2mg q8h.

4. Day 6: If the patient remains asymptomatic and BP >110/60 mmHg, increase dose to 5mg q8h.

5. 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.

6. 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.

Group Type: EXPERIMENTAL

Prazosin

Intervention Type: DRUG

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

Standard of care

Subjects randomized to this arm will receive standard of care.

Group Type: ACTIVE_COMPARATOR

Standard of care

Intervention Type: OTHER

Participants in this arm will receive standard of care.

Interventions

Prazosin

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

Intervention Type: DRUG

Standard of care

Participants in this arm will receive standard of care.

Intervention Type: OTHER

Other Intervention Names

Minipress; alpha-1 adrenergic receptor antagonist; alpha blocker

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)

• Minimum Eligible Age: 45 Years
• Maximum Eligible Age: 85 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Fast Grants

OTHER

Sponsor Role: collaborator

Johns Hopkins University

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Chetan Bettegowda, MD/PhD

Role: PRINCIPAL_INVESTIGATOR

Johns Hopkins University

Locations

Johns Hopkins Hospital

Baltimore, Maryland, United States

Countries

United States

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

COV2001

Identifier Type: OTHER

Identifier Source: secondary_id

IRB00246659

Identifier Type: -

Identifier Source: org_study_id