ColCOVID-19: Colchicine Counteracting Inflammation in COVID-19 Pneumonia
Study Details
Study Description
Brief Summary
Cytokines and chemokines are thought to play an important role in immunity and immunopathology during virus infections [3]. Patients with severe COVID-19 have higher serum levels of pro-inflammatory cytokines (TNF-α, IL-1 and IL-6) and chemokines (IL-8) compared to individuals with mild disease or healthy controls, similar to patients with SARS or MERS . The change of laboratory parameters, including elevated serum cytokine, chemokine levels, and increased NLR in infected patients are correlated with the severity of the disease and adverse outcome, suggesting a possible role for hyper-inflammatory responses in COVID-19 pathogenesis. Importantly, previous studies showed that viroporin E, a component of SARS-associated coronavirus (SARS-CoV), forms Ca2C-permeable ion channels and activates the NLRP3 inflammasome. In addition, another viroporin 3a was found to induce NLRP3 inflammasome activation . The mechanisms are unclear.
Colchicine, an old drug used in auto-inflammatory disorders (i.e., Familiar Mediterranean Fever and Bechet disease) and in gout, counteracts the assembly of the NLRP3 inflammasome, thereby reducing the release of IL-1b and an array of other interleukins, including IL-6, that are formed in response to danger signals. Recently, colchicine has been successfully used in two cases of life-threatening post-transplant capillary leak syndrome. These patients had required mechanically ventilation for weeks and hemodialysis, before receiving colchicine, which abruptly restored normal respiratory function and diuresis over 48 hrs [4].
Condition or Disease | Intervention/Treatment | Phase |
---|---|---|
Phase 2 |
Study Design
Arms and Interventions
Arm | Intervention/Treatment |
---|---|
Experimental: Colchicine Administration of Colchicine 1mg (or 0.5 mg in CKD)/day + standard of care for COVID-19 pneumonia |
Drug: Colchicine
Cochicine 1mg/day
|
No Intervention: Standard of care Standard of care for COVID-19 pneumonia |
Outcome Measures
Primary Outcome Measures
- Clinical improvement [Day 28]
Time to clinical improvement: defined as time from randomization to an improvement of two points from the status at randomization on a seven-category ordinary scale
- Hospital discharge [Day 28]
Live discharge from the hospital (whatever comes first)
Secondary Outcome Measures
- Death [Day 28]
Number of death patients
- Clinical status [Day 7, Day 14]
7-category ordinal scale
- Mechanical ventilhation [Day 28]
Number of patients with mechanical ventilhation
- Hospitalization [Day 28]
Days of hospitalization
- Time from treatment initiation to death [Day 28]
Days to death from treatment initiation
- Time to Negativization COVID 19 [Day 21]
negativization of two consecutive pharyngo-nasal swab 24-72 hrs apart
- Fever [Day 1,4,7,14,21,28]
Time to remission of fever in patients with T>37.5°C at enrollment
Eligibility Criteria
Criteria
Inclusion Criteria:
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Positive nasopharyngeal swab for COVID-19, asymptomatic or paucisymptomatic, aged ≥70 years and/or with clinical risk factors for poor outcome (clinically relevant chronic lung disease, diabetes and/or heart disease) or
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symptomatic with respiratory or systemic symptoms, however clinically stable (MEWS<3) with CT imaging showing viral pneumonia and positive or pending pharyngo-nasal swab for COVID-19: Temperature 38°C and/or intensive cough, Respiratory rate < 25 /min, oxygen saturation (pulse oximetry) >95%
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Positive swab for COVID-19
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with respiratory and/or systemic symptoms and initial mild respiratory failure e with objective signs of lung involvement; the patient is in stable conditions (MEWS < 3) Temperature>38°C and or intensive cough, Respiratory rate ≥25 /min, or oxygen saturation 94- 95% in room air
Exclusion Criteria:
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Pregnant or breast feeding
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MEWS >=3
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Hepatic failure Child-Pugh C
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Enrollment in other pharmacological studies
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Ongoing treatment with colchicine
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Ongoing treatment with antiviral drugs that include ritonavir or cobicistat
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Any medical condition or disease which in the opinion of the Investigator may place the patient at unacceptable risk for study participation.
Contacts and Locations
Locations
Site | City | State | Country | Postal Code | |
---|---|---|---|---|---|
1 | Azienda Ospedaliero Universitaria di Parma | Parma | PR | Italy | 43100 |
Sponsors and Collaborators
- Azienda Ospedaliero-Universitaria di Parma
Investigators
- Principal Investigator: Umberto Maggiore, MD, Azienda Ospedaliero-Universitaria di Parma
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- ColCOVID-19