Anti-il6 Treatment of Serious COVID-19 Disease With Threatening Respiratory Failure (TOCIVID)
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ClinicalTrials.gov Identifier: NCT04322773 |
Recruitment Status :
Terminated
(The study has been terminated due to changed clinical conditions and too few patients available)
First Posted : March 26, 2020
Last Update Posted : October 9, 2020
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Tracking Information | |||||||||||||
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First Submitted Date ICMJE | March 24, 2020 | ||||||||||||
First Posted Date ICMJE | March 26, 2020 | ||||||||||||
Last Update Posted Date | October 9, 2020 | ||||||||||||
Actual Study Start Date ICMJE | April 5, 2020 | ||||||||||||
Actual Primary Completion Date | October 8, 2020 (Final data collection date for primary outcome measure) | ||||||||||||
Current Primary Outcome Measures ICMJE |
Time to independence from supplementary oxygen therapy [ Time Frame: days from enrolment up 28 days ] | ||||||||||||
Original Primary Outcome Measures ICMJE |
Time to independence from supplementary oxygen therapy [ Time Frame: days from enrolment up 30 days ] | ||||||||||||
Change History | |||||||||||||
Current Secondary Outcome Measures ICMJE |
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Original Secondary Outcome Measures ICMJE |
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Current Other Pre-specified Outcome Measures | Not Provided | ||||||||||||
Original Other Pre-specified Outcome Measures | Not Provided | ||||||||||||
Descriptive Information | |||||||||||||
Brief Title ICMJE | Anti-il6 Treatment of Serious COVID-19 Disease With Threatening Respiratory Failure | ||||||||||||
Official Title ICMJE | Effectiveness of Interleukin-6 Receptor Inhibitors in the Management of Patients With Severe SARS-CoV-2 Pneumonia: An Open-Label, Multicenter Sequential and Cluster Randomized Trial | ||||||||||||
Brief Summary | Coronavirus disease 2019 (COVID-19) is caused by the newly discovered coronavirus, SARS-CoV-2. The median time from onset of symptoms of COVID-19 to development of acute respiratory distress syndrome (ARDS) has been reported as short as 9 days. No effective prophylactic or post-exposure therapy is currently available. According to data from the Danish Health Authority (www.sst.dk/corona), as of March 21st, 2020, there were 1326 patients infected with the disease in Denmark, more than 250 are admitted to a hospital, and >50 of them have required intensive care. Nearly 350.000 cases and 15.000 deaths have been reported globally. These numbers are likely to markedly increase during the coming weeks, challenging the capacity of health systems worldwide. In patients infected with SARS-CoV-2, it has been described that disease severity and outcomes are related to the characteristics of the immune response. Interleukin (IL)-6 and other components of the inflammatory cascade contribute to host defense against infections. However, exaggerated synthesis of IL-6 can lead to an acute severe systemic inflammatory response known as 'cytokine storm'. In the pathogenesis of SARS-CoV-2 pneumonia, a study found that a cytokine storm involving a considerable release of proinflammatory cytokines occurred, including IL-6, IL-12, and tumor necrosis factor α (TNF-α). Studies on the Middle East respiratory syndrome caused by another coronavirus (MERS-CoV), indicate that cytokine genes of IL-6, IL-1β, and IL-8 can be markedly upregulated. Similarly, patients with SARS-CoV-2 pneumonia admitted to an intensive care unit had higher plasma levels of cytokines including IL-6, IL-2, IL-7, IL-10, granulocyte-colony stimulating factor (G-CSF), interferon-γ-inducible protein (IP10), monocyte chemoattractant protein (MCP1), macrophage inflammatory protein 1 alpha (MIP1A), and TNF-α. These findings indicate that the magnitude and characteristics of the cytokine response is related to the severity and prognosis of patients with SARS-CoV-2 pneumonia. It has been suggested that IL-6 blockade may constitute a novel therapeutic strategy for other types of cytokine storm, such as the systemic inflammatory response syndrome including sepsis, macrophage activation syndrome and hemophagocytic lymphohistiocytosis. Remarkable beneficial effects of IL-6 blockade therapy using a IL-6 receptor inhibitor has been described in patients with severe SARS-CoV-2 pneumonia in a retrospective case series from China. Currently, there are two available drugs based on human monoclonal antibodies against IL-6 receptor, tocilizumab (RoActemra, Roche) and sarilumab (Kevzara, Sanofi). IL-6 receptor inhibitors are currently licensed for several autoimmune disorders and are considered well tolerated and safe in general. The most common side effects reported are upper respiratory tract infections, headache, hypertension, and abnormal liver function tests. The most serious side effects are serious infections, complications of diverticulitis, and hypersensitivity reactions. it is hypothesized that IL-6 might play a key role in the cytokine storm associated with serious adverse outcomes in patients infected with SARS-CoV-2 pneumonia, and that blockade of IL-6 would be suitable therapeutic target for these patients. The study will investigate the effect of different types of IL-6 inhibition versus no adjuvant treatment compared to standard of care in patients with severe SARS-CoV-2 pneumonia. Primary objective: To compare the effect of either one of three IL-6 inhibitor administrations, relative to the standard of care, on time to independence from supplementary oxygen therapy, measured in days from baseline to day 28, in patients with severe SARS-CoV-2 pneumonia. |
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Detailed Description | Not Provided | ||||||||||||
Study Type ICMJE | Interventional | ||||||||||||
Study Phase ICMJE | Phase 2 | ||||||||||||
Study Design ICMJE | Allocation: Randomized Intervention Model: Sequential Assignment Masking: None (Open Label) Primary Purpose: Treatment |
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Condition ICMJE | Corona Virus Disease | ||||||||||||
Intervention ICMJE |
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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 | Terminated | ||||||||||||
Actual Enrollment ICMJE |
20 | ||||||||||||
Original Estimated Enrollment ICMJE |
200 | ||||||||||||
Actual Study Completion Date ICMJE | October 8, 2020 | ||||||||||||
Actual Primary Completion Date | October 8, 2020 (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 | Denmark | ||||||||||||
Removed Location Countries | |||||||||||||
Administrative Information | |||||||||||||
NCT Number ICMJE | NCT04322773 | ||||||||||||
Other Study ID Numbers ICMJE | APPI2-CV-2020-01 | ||||||||||||
Has Data Monitoring Committee | No | ||||||||||||
U.S. FDA-regulated Product |
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IPD Sharing Statement ICMJE |
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Responsible Party | Marius Henriksen, Frederiksberg University Hospital | ||||||||||||
Study Sponsor ICMJE | Marius Henriksen | ||||||||||||
Collaborators ICMJE | Not Provided | ||||||||||||
Investigators ICMJE |
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PRS Account | Frederiksberg University Hospital | ||||||||||||
Verification Date | October 2020 | ||||||||||||
ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP |