Colchicine Counteracting Inflammation in COVID-19 Pneumonia

Pneumonia, Viral Clinical Trial

— ColCOVID-19  

Official title:

Colchicine to Counteract Inflammatory Response in COVID-19 Pneumonia

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04322565
• Other study ID #: ColCOVID-19
• Status: Completed
• Phase: Phase 2
• Start date: April 20, 2020
• Est. completion date: October 1, 2021

Study information

• Verified date: July 2022
• Source: Azienda Ospedaliero-Universitaria di Parma
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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].

Recruitment information / eligibility

• Status: Completed
• Enrollment: 193
• Est. completion date: October 1, 2021
• Est. primary completion date: September 1, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 100 Years

Eligibility

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.

Related Conditions & MeSH terms

• Coronavirus Infections
• COVID-19
• Pneumonia
• Pneumonia, Viral

Intervention

Drug:
• Colchicine
Cochicine 1mg/day

Locations

Country	Name	City	State
Italy	Azienda Ospedaliero Universitaria di Parma	Parma	PR

Sponsors (1)

Lead Sponsor	Collaborator
Azienda Ospedaliero-Universitaria di Parma

Country where clinical trial is conducted

Italy, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	Hospital discharge	Live discharge from the hospital (whatever comes first)	Day 28
Secondary	Death	Number of death patients	Day 28
Secondary	Clinical status	7-category ordinal scale	Day 7, Day 14
Secondary	Mechanical ventilhation	Number of patients with mechanical ventilhation	Day 28
Secondary	Hospitalization	Days of hospitalization	Day 28
Secondary	Time from treatment initiation to death	Days to death from treatment initiation	Day 28
Secondary	Time to Negativization COVID 19	negativization of two consecutive pharyngo-nasal swab 24-72 hrs apart	Day 21
Secondary	Fever	Time to remission of fever in patients with T>37.5°C at enrollment	Day 1,4,7,14,21,28