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

NCT04365257 | Terminated Phase 2 Results DMC FDA Drug

• 2 other identifiers: IRB00246659COV2001
• Study Type: interventional
• Target: 5
• Locations: 1 country
• Sites: 1

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).

Conditions

COVID-19

Keywords

SARS-CoV-2; Coronavirus disease 2019; COVID-19; Cytokine Storm Syndrome; Acute Respiratory Distress Syndrome; Prazosin; Alpha-1 receptor antagonist

Outcome Measures

Primary Outcomes (6)

• Death

  Number of participants in each arm who expire.

  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.

  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).

  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.

  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.

  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.

  up to day 60

Secondary Outcomes (4)

• Number of Participants With Laboratory Abnormalities in Peripheral Blood

  up to day 60

• Duration of Laboratory Abnormalities in Peripheral Blood

  up to day 60

• Number of Participants With Laboratory Abnormalities in Plasma

  up to day 60

• Duration of Laboratory Abnormalities in Plasma

  up to day 60

Study Arms (2)

Prazosin

EXPERIMENTAL

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.

Drug: Prazosin

Standard of care

ACTIVE COMPARATOR

Subjects randomized to this arm will receive standard of care.

Other: Standard of care

Interventions

Prazosin DRUG

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

Also known as: Minipress, alpha-1 adrenergic receptor antagonist, alpha blocker

Prazosin

Standard of care OTHER

Participants in this arm will receive standard of care.

Standard of care

Eligibility Criteria

• Age: 45 Years - 85 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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)

Sponsors & Collaborators

• Johns Hopkins University: lead
• Fast Grants: collaborator

Study Sites (1)

Johns Hopkins Hospital

Baltimore, Maryland, 21287, United States

Location

MeSH Terms

Conditions

COVID-19; Cytokine Release Syndrome; Respiratory Distress Syndrome

Interventions

Prazosin; Adrenergic alpha-1 Receptor Antagonists; Adrenergic alpha-Antagonists; Standard of Care

Condition Hierarchy (Ancestors)

Pneumonia, Viral; Pneumonia; Respiratory Tract Infections; Infections; Virus Diseases; Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Lung Diseases; Respiratory Tract Diseases; Systemic Inflammatory Response Syndrome; Inflammation; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Shock; Respiration Disorders

Intervention Hierarchy (Ancestors)

Quinazolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Adrenergic Antagonists; Adrenergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Pharmacologic Actions; Chemical Actions and Uses; Physiological Effects of Drugs; Quality Indicators, Health Care; Quality of Health Care; Health Services Administration; Health Care Quality, Access, and Evaluation

Results Point of Contact

• Title: Chetan Bettegowda
• Organization: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

cbetteg1@jhmi.edu

4109558620

Study Officials

• Chetan Bettegowda, MD/PhD

  Johns Hopkins University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 24, 2020
• First Posted: April 28, 2020
• Study Start: May 13, 2020
• Primary Completion: March 31, 2022
• Study Completion: March 31, 2022
• Last Updated: April 10, 2023
• Results First Posted: January 31, 2023

Record last verified: 2023-03

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)