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| ID | Type | Description | Link |
|---|---|---|---|
| COV2001 | Other Identifier | Johns Hopkins University |
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Lack of recruitment
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| Name | Class |
|---|---|
| Fast Grants | OTHER |
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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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Prazosin | Experimental |
If BP monitoring is not available, repeated occurrences of postural dizziness should trigger drug dose reduction or BP monitoring. |
|
| Standard of care | Active Comparator | Subjects randomized to this arm will receive standard of care. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Prazosin | Drug | Participants in this arm will receive the study drug as outlined in the arm description. |
|
| Measure | Description | Time Frame |
|---|---|---|
| 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 |
| Measure | Description | Time Frame |
|---|---|---|
| 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 |
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Inclusion Criteria:
(*)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:
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| Name | Affiliation | Role |
|---|---|---|
| Chetan Bettegowda, MD/PhD | Johns Hopkins University | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Johns Hopkins Hospital | Baltimore | Maryland | 21287 | United States |
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| ID | Title | Description |
|---|---|---|
| FG000 | Prazosin |
If BP monitoring is not available, repeated occurrences of postural dizziness should trigger drug dose reduction or BP monitoring. Prazosin: Participants in this arm will receive the study drug as outlined in the arm description. |
| FG001 | Standard of Care | Subjects randomized to this arm will receive standard of care. Standard of care: Participants in this arm will receive standard of care. |
| Title | Milestones | Reasons Not Completed | |||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
|
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| ID | Title | Description |
|---|---|---|
| BG000 | Prazosin |
If BP monitoring is not available, repeated occurrences of postural dizziness should trigger drug dose reduction or BP monitoring. Prazosin: Participants in this arm will receive the study drug as outlined in the arm description. |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Death | Number of participants in each arm who expire. | Posted | Count of Participants | Participants | up to day 60 |
|
60 days
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Prazosin |
If BP monitoring is not available, repeated occurrences of postural dizziness should trigger drug dose reduction or BP monitoring. Prazosin: Participants in this arm will receive the study drug as outlined in the arm description. |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Constipation | Gastrointestinal disorders | Systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Chetan Bettegowda | Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins | 4109558620 | cbetteg1@jhmi.edu |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot_SAP | Yes | Yes | No | Study Protocol and Statistical Analysis Plan | Jun 12, 2020 | Nov 30, 2022 | Prot_SAP_000.pdf |
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| ID | Term |
|---|---|
| D000086382 | COVID-19 |
| D000080424 | Cytokine Release Syndrome |
| D012128 | Respiratory Distress Syndrome |
| ID | Term |
|---|---|
| D011024 | Pneumonia, Viral |
| D011014 | Pneumonia |
| D012141 | Respiratory Tract Infections |
| D007239 | Infections |
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| ID | Term |
|---|---|
| D011224 | Prazosin |
| D058668 | Adrenergic alpha-1 Receptor Antagonists |
| D000317 | Adrenergic alpha-Antagonists |
| D059039 | Standard of Care |
| ID | Term |
|---|---|
| D011799 | Quinazolines |
| D006574 | Heterocyclic Compounds, 2-Ring |
| D000072471 | Heterocyclic Compounds, Fused-Ring |
| D006571 | Heterocyclic Compounds |
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| Standard of care | Other | Participants in this arm will receive standard of care. |
|
| 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 |
| 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 |
| Duration of Laboratory Abnormalities in Plasma | Number of days with laboratory abnormalities in fractionated plasma catecholamines and plasma metanephrines. | up to day 60 |
| Withdrawal by Subject |
|
| BG001 | Standard of Care | Subjects randomized to this arm will receive standard of care. Standard of care: Participants in this arm will receive standard of care. |
| BG002 | Total | Total of all reporting groups |
| Participants |
|
| Age, Continuous | Median | Full Range | years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Race (NIH/OMB) | Count of Participants | Participants |
|
| OG001 | Standard of Care | Subjects randomized to this arm will receive standard of care. Standard of care: Participants in this arm will receive standard of care. |
|
|
| 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. | Posted | Count of Participants | Participants | 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). | Posted | Count of Participants | Participants | 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. | Posted | Count of Participants | Participants | 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. | Posted | Count of Participants | Participants | 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. | Posted | Count of Participants | Participants | 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. | Posted | Count of Participants | Participants | 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. | Data was not collected because no participant had laboratory abnormalities in peripheral blood. | Posted | 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. | Posted | Count of Participants | Participants | up to day 60 |
|
|
|
| Secondary | Duration of Laboratory Abnormalities in Plasma | Number of days with laboratory abnormalities in fractionated plasma catecholamines and plasma metanephrines. | Data was not collected because no participant had laboratory abnormalities in plasma. | Posted | up to day 60 |
|
|
| 0 |
| 3 |
| 0 |
| 3 |
| 1 |
| 3 |
| EG001 | Standard of Care | Subjects randomized to this arm will receive standard of care. Standard of care: Participants in this arm will receive standard of care. | 0 | 2 | 0 | 2 | 1 | 2 |
| back pain | Musculoskeletal and connective tissue disorders | Systematic Assessment |
|
| dizziness | General disorders | Systematic Assessment |
|
| urinary urgency | Renal and urinary disorders | Systematic Assessment |
|
| Hypotension | Cardiac disorders | Systematic Assessment |
|
| Hypoxia during the night | General disorders | Systematic Assessment |
|
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| D014777 |
| Virus Diseases |
| D018352 | Coronavirus Infections |
| D003333 | Coronaviridae Infections |
| D030341 | Nidovirales Infections |
| D012327 | RNA Virus Infections |
| D008171 | Lung Diseases |
| D012140 | Respiratory Tract Diseases |
| D018746 | Systemic Inflammatory Response Syndrome |
| D007249 | Inflammation |
| D010335 | Pathologic Processes |
| D013568 | Pathological Conditions, Signs and Symptoms |
| D012769 | Shock |
| D012120 | Respiration Disorders |
| D018674 | Adrenergic Antagonists |
| D018663 | Adrenergic Agents |
| D018377 | Neurotransmitter Agents |
| D045504 | Molecular Mechanisms of Pharmacological Action |
| D020228 | Pharmacologic Actions |
| D020164 | Chemical Actions and Uses |
| D045505 | Physiological Effects of Drugs |
| D019984 | Quality Indicators, Health Care |
| D011787 | Quality of Health Care |
| D006298 | Health Services Administration |
| D017530 | Health Care Quality, Access, and Evaluation |