Coronavirus Infections, Pneumonia, Viral
Conditions
Keywords
Colchicine, Corona Virus Infection, COVID-19
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 \[4\].
Interventions
DRUGColchicine
Cochicine 1mg/day
Sponsors
Azienda Ospedaliero-Universitaria di Parma
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 100 Years
Healthy volunteers
No
Inclusion criteria
* 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 * 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% * Positive swab for COVID-19 * 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
* Pregnant or breast feeding * MEWS \>=3 * Hepatic failure Child-Pugh C * Enrollment in other pharmacological studies * Ongoing treatment with colchicine * Ongoing treatment with antiviral drugs that include ritonavir or cobicistat * Any medical condition or disease which in the opinion of the Investigator may place the patient at unacceptable risk for study participation.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| Hospitalization | Day 28 | Days of hospitalization |
| Time from treatment initiation to death | Day 28 | Days to death from treatment initiation |
| Fever | Day 1,4,7,14,21,28 | Time to remission of fever in patients with T\>37.5°C at enrollment |
| Death | Day 28 | Number of death patients |
| Clinical status | Day 7, Day 14 | 7-category ordinal scale |
| Time to Negativization COVID 19 | Day 21 | negativization of two consecutive pharyngo-nasal swab 24-72 hrs apart |
| Mechanical ventilhation | Day 28 | Number of patients with mechanical ventilhation |
Countries
Italy
Outcome results
None listed