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Secondary to other study results, suspended for a scientific review
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| Name | Class |
|---|---|
| Washington State University | OTHER |
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Novel coronavirus SARS(Severe Acute Respiratory Syndrome)-CoV-2 was first identified during the outbreak in Wuhan, China in December 2019 with the now resulting pandemic. Aggressive supportive care is the mainstay of treatment currently and rescue with lung protective mechanical ventilation is essential for survival in patients with severe acute respiratory distress syndrome. Despite supportive care, mortality is significant in hospitalized patients in the U.S., especially among patients > 65 years of age. Pharmacologic treatments to decrease disease severity are urgently needed. Hydroxychloroquine is currently widely used for treatment of autoimmune disease including systemic lupus erythematosus and rheumatoid arthritis, and it has been used to prevent and treat malaria. In vitro and in vivo antiviral activity towards SARS-CoV-2 has been reported. Since hydroxychloroquine has been used for decades its properties as a drug are well known. The investigators propose a pragmatic trial of hydroxychloroquine in moderately ill hospitalized adults with SARS-CoV-2 pneumonia with the hypothesis that hydroxychloroquine reduces severity of acute lung injury caused by SARS-CoV-2 infection.
Novel coronavirus SARS-CoV-2 was first identified during the outbreak in Wuhan, China in December 2019 with the now resulting pandemic. Aggressive supportive care is the mainstay of treatment currently and rescue with lung protective mechanical ventilation is essential for survival in patients with severe acute respiratory distress syndrome. Despite supportive care, mortality is significant in hospitalized patients in the U.S., especially among patients > 65 years of age. Pharmacologic treatments to decrease disease severity are urgently needed. Candidate treatments with antiviral activity and/or immune-modulating effects include hydroxychloroquine (HCQ), lopinavir/ritonavir, remdesivir, and tocilizumab among others. There is limited high quality clinical data prompting a dilemma of how to use and review potential treatments and ensure patient safety now as the pandemic begins to peak. There are also significant limitations in drug supplies at many institutions.
Hydroxychloroquine is currently widely used for treatment of autoimmune disease including systemic lupus erythematosus and rheumatoid arthritis, and it has been used to prevent and treat malaria. In vitro and in vivo antiviral activity towards SARS-CoV-2 has been reported. Since hydroxychloroquine has been used for decades its properties as a drug are well known. Pertinent adverse events to monitor in a hospitalized patient include QTc (corrected QT interval) prolongation, elevation of liver enzymes/acute liver injury, and hypokalemia.
Acute lung injury and progressive respiratory failure is the major cause of mortality in SARS-CoV-2 infection. In acute lung injury and respiratory distress syndrome, the severity of hypoxia is categorized by the Pao2/FIO2 (fraction of inspired oxygen) ration as mild (200 mm Hg\
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Hydroxychloroquine (HCQ) | Experimental | Initial dose: HCQ 400mg x 2 (800mg) then 200mg by mouth, three times per day (600mg/24hr period) starting 8 hours after the initial dose for a total of 14 doses over 5 days Plus Usual Care (See below for full description) |
|
| Usual Care | No Intervention | The care of hospitalized patients with covid-19 is evolving with hospital guidelines arising across the U.S. with several commonalities. Patients receive clinical assessment, chest x-ray, covid-19 testing, basic labs (WBC, CMP), and additional labs based on protocol or clinical judgment (ABG, CRP, LDH), antibiotics for possible bacterial pneumonia, acetaminophen for fever, supplemental O2, and consideration for mechanical ventilation. Early intubation over escalating noninvasive support. Low tidal volume ventilation and prone positioning are lung protective strategies used in critically ill covid-19 patients that are based on management of acute respiratory distress syndrome generally. Conservative fluid replacement is used to avoid worsening oxygenation. |
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Hydroxychloroquine | Drug | Hydroxychloroquine is currently widely used for treatment of autoimmune disease including systemic lupus erythematosus and rheumatoid arthritis, and it has been used to prevent and treat malaria. |
| Measure | Description | Time Frame |
|---|---|---|
| Change from Baseline Oxygenation on Day 1 to Day 5 | paO2 | Day 1 of treatment to day 5 of treatment |
| Change from Baseline Oxygenation at Day 5 | FIO2 | Day 1 of treatment to day 5 of treatment |
| Measure | Description | Time Frame |
|---|---|---|
| Intensive Care length of stay | Length in hours | Day 0 to Day 28 |
| Required Mechanical Ventilation | Length in hours | Day 0 to Day 28 |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Sean Cook, D.O. | Kootenai Health | Principal Investigator |
| Jeanette Berg, MD, PhD | Kootenai Health | Principal Investigator |
| Sterling McPherson, PhD | Washington State University | Principal Investigator |
| John Roll, PhD | Washington State University | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Kootenai Health | Coeur d'Alene | Idaho | 83814 | United States |
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| ID | Term |
|---|---|
| D000086382 | COVID-19 |
| D011014 | Pneumonia |
| ID | Term |
|---|---|
| D011024 | Pneumonia, Viral |
| D012141 | Respiratory Tract Infections |
| D007239 | Infections |
| D014777 | Virus Diseases |
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| ID | Term |
|---|---|
| D006886 | Hydroxychloroquine |
| ID | Term |
|---|---|
| D002738 | Chloroquine |
| D000634 | Aminoquinolines |
| D011804 | Quinolines |
| D006574 | Heterocyclic Compounds, 2-Ring |
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Single-center pragmatic randomized open-label trial of hydroxychloroquine + usual care in hospitalized adults with confirmed SARS-CoV-2 infection and acute hypoxia compared to usual care.
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| Required Oxygen supplementation | Length in hours | Day 0 to Day 28 |
| Hospitalization length of Stay | Length in hours | Day 0 to Day 28 |
| Mortality | Date of Death | Day 0 to Day 28 |
| Cardiac Arrhythmia - Polymorphic Ventricular Tachycardia | Cardiologist Diagnostic Documentation | Day 0 to Day 28 |
| Cardiac Arrhythmia - Ventricular Tachycardia | Cardiologist Diagnostic Documentation | Day 0 to Day 28 |
| Cardiac Arrhythmia - Lengthening QTc | Cardiologist Diagnostic Documentation | Day 0 to Day 28 |
| D018352 |
| Coronavirus Infections |
| D003333 | Coronaviridae Infections |
| D030341 | Nidovirales Infections |
| D012327 | RNA Virus Infections |
| D008171 | Lung Diseases |
| D012140 | Respiratory Tract Diseases |
| D000072471 |
| Heterocyclic Compounds, Fused-Ring |
| D006571 | Heterocyclic Compounds |