Colchicine Counteracting Inflammation in COVID-19 Pneumonia

Study Overview
=================
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].

Official Title
-----------------
Colchicine to Counteract Inflammatory Response in COVID-19 Pneumonia

Conditions
-----------------
Coronavirus Infections, Pneumonia, Viral

Intervention / Treatment
-----------------
* Drug: Colchicine


Participation Criteria
=================
Eligibility Criteria
-----------------
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.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 100 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Colchicine<br>Administration of Colchicine 1mg (or 0.5 mg in CKD)/day + standard of care for COVID-19 pneumonia | Drug: Colchicine<br>* Cochicine 1mg/day<br>|
| No Intervention: Standard of care<br>Standard of care for COVID-19 pneumonia | |

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Clinical improvement | 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 | Day 28 | 
| Hospital discharge | Live discharge from the hospital (whatever comes first) | Day 28 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Death | Number of death patients | Day 28 | 
| Clinical status | 7-category ordinal scale | Day 7, Day 14 | 
| Mechanical ventilhation | Number of patients with mechanical ventilhation | Day 28 | 
| Hospitalization | Days of hospitalization | Day 28 | 
| Time from treatment initiation to death | Days to death from treatment initiation | Day 28 | 
| Time to Negativization COVID 19 | negativization of two consecutive pharyngo-nasal swab 24-72 hrs apart | Day 21 | 
| Fever | Time to remission of fever in patients with T>37.5°C at enrollment | Day 1,4,7,14,21,28 | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Colchicine, Corona Virus Infection, COVID-19