Hydroxychloroquine in SARS-CoV-2 (COVID-19) Pneumonia Trial
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ClinicalTrials.gov Identifier: NCT04382625 |
Recruitment Status :
Withdrawn
(Secondary to other study results, suspended for a scientific review)
First Posted : May 11, 2020
Last Update Posted : February 5, 2021
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Tracking Information | |||||||||||||
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First Submitted Date ICMJE | April 14, 2020 | ||||||||||||
First Posted Date ICMJE | May 11, 2020 | ||||||||||||
Last Update Posted Date | February 5, 2021 | ||||||||||||
Estimated Study Start Date ICMJE | October 2020 | ||||||||||||
Estimated Primary Completion Date | January 1, 2022 (Final data collection date for primary outcome measure) | ||||||||||||
Current Primary Outcome Measures ICMJE |
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Original Primary Outcome Measures ICMJE | Same as current | ||||||||||||
Change History | |||||||||||||
Current Secondary Outcome Measures ICMJE |
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Original Secondary Outcome Measures ICMJE | Same as current | ||||||||||||
Current Other Pre-specified Outcome Measures | Not Provided | ||||||||||||
Original Other Pre-specified Outcome Measures | Not Provided | ||||||||||||
Descriptive Information | |||||||||||||
Brief Title ICMJE | Hydroxychloroquine in SARS-CoV-2 (COVID-19) Pneumonia Trial | ||||||||||||
Official Title ICMJE | Hydroxychloroquine in SARS-CoV-2 (COVID-19) Pneumonia Trial | ||||||||||||
Brief Summary | 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. | ||||||||||||
Detailed Description | 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<Pao2/Fio2≤300 mm Hg), moderate (100 mm Hg<Pao2/Fio2≤200 mm Hg), and severe (Pao2/Fio2 ≤100 mm Hg). A persistently low Pao2/Fio2 ratio is associated with worse outcomes and may be a marker of failure to respond to conventional therapy. PaO2/FIO2 is a clinically useful measure in patients regardless of if they are receiving noninvasive supplemental O2 or mechanical ventilation, and low ratios are associated with duration of ICU stay and hospital mortality. 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-C reactive protein, LDH), antibiotics for possible bacterial pneumonia, acetaminophen for fever, supplemental O2, close monitoring for worsening respiratory status and consideration for mechanical ventilation. Since covid-19 is a novel illness, there is no proven clinically efficacious drug treatment. Candidate drugs are being used, some in the context of trials and others by physician discretion. Early intubation over escalating noninvasive support (ie. High flow nasal canula and bipap) has been adopted due to the frequency of rapidly worsening oxygenation, hemodynamic instability, and to protect staff from virus aerosolization. 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. Arrhythmias, cardiomyopathy, and shock are serious complications from covid-19 that warrant avoidance of acidosis, electrolyte monitoring and replacement, and pressor support. Conservative fluid replacement is used to avoid worsening oxygenation. In sum, multiple factors including timeliness and quality of care likely affect patient outcomes. Hospitalists and pulmonary critical care physicians direct the care of covid-19 patients with support from specialists as needed including infectious disease, cardiology, and nephrology. Pragmatic trials focus on studying the real-world effect of an intervention, such as a medication, in the context of other care a patient is likely to receive. The intervention is delivered by staff normally taking care of the patient with monitoring that is routinely available. Advantages can include generalizability, increased physician participation due to less burdensome study protocols, and feasibility. Disadvantages include allowance of unblinded design, bias from physicians and patients about the intervention, and more heterogeneity in treatment than in a mechanistic protocolized trial. Efforts to minimize bias include selecting objective outcomes (e.g. PaO2/FIO2 rather than cough or dyspnea). |
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Study Type ICMJE | Interventional | ||||||||||||
Study Phase ICMJE | Phase 4 | ||||||||||||
Study Design ICMJE | Allocation: Randomized Intervention Model: Parallel Assignment Intervention Model Description: 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. Masking: None (Open Label)Primary Purpose: Treatment |
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Condition ICMJE |
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Intervention ICMJE | Drug: Hydroxychloroquine
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.
Other Name: Plaquenil
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Study Arms ICMJE |
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Publications * | Not Provided | ||||||||||||
* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline. |
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Recruitment Information | |||||||||||||
Recruitment Status ICMJE | Withdrawn | ||||||||||||
Actual Enrollment ICMJE |
0 | ||||||||||||
Original Estimated Enrollment ICMJE |
120 | ||||||||||||
Estimated Study Completion Date ICMJE | June 1, 2022 | ||||||||||||
Estimated Primary Completion Date | January 1, 2022 (Final data collection date for primary outcome measure) | ||||||||||||
Eligibility Criteria ICMJE | Inclusion Criteria:
Exclusion Criteria:
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Sex/Gender ICMJE |
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Ages ICMJE | 18 Years and older (Adult, Older Adult) | ||||||||||||
Accepts Healthy Volunteers ICMJE | No | ||||||||||||
Contacts ICMJE | Contact information is only displayed when the study is recruiting subjects | ||||||||||||
Listed Location Countries ICMJE | United States | ||||||||||||
Removed Location Countries | |||||||||||||
Administrative Information | |||||||||||||
NCT Number ICMJE | NCT04382625 | ||||||||||||
Other Study ID Numbers ICMJE | 18244 | ||||||||||||
Has Data Monitoring Committee | Yes | ||||||||||||
U.S. FDA-regulated Product |
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IPD Sharing Statement ICMJE |
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Current Responsible Party | Kootenai Health | ||||||||||||
Original Responsible Party | Same as current | ||||||||||||
Current Study Sponsor ICMJE | Kootenai Health | ||||||||||||
Original Study Sponsor ICMJE | Same as current | ||||||||||||
Collaborators ICMJE | Washington State University | ||||||||||||
Investigators ICMJE |
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PRS Account | Kootenai Health | ||||||||||||
Verification Date | May 2020 | ||||||||||||
ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP |