Colchicine Counteracting Inflammation in COVID-19 Pneumonia (ColCOVID-19)

Colchicine to Counteract Inflammatory Response in COVID-19 Pneumonia

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].

Study Overview

• Status: Completed
• Conditions: Coronavirus Infections; Pneumonia, Viral
• Intervention / Treatment: Drug: Colchicine

• Study Type: Interventional
• Enrollment (Actual): 193
• Phase: Phase 2

Contacts and Locations

Study Locations

• Italy
  • PR
    • Parma, PR, Italy, 43100
      • Azienda Ospedaliero Universitaria di Parma

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 100 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / 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

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

Collaborators and Investigators

• Sponsor: Azienda Ospedaliero-Universitaria di Parma
• Investigators: Principal Investigator: Umberto Maggiore, MD, Azienda Ospedaliero-Universitaria di Parma

Publications and helpful links

General Publications

• Mikolajewska A, Fischer AL, Piechotta V, Mueller A, Metzendorf MI, Becker M, Dorando E, Pacheco RL, Martimbianco ALC, Riera R, Skoetz N, Stegemann M. Colchicine for the treatment of COVID-19. Cochrane Database Syst Rev. 2021 Oct 18;10(10):CD015045. doi: 10.1002/14651858.CD015045.

Study record dates

Study Major Dates

• Study Start (Actual): April 20, 2020
• Primary Completion (Actual): September 1, 2021
• Study Completion (Actual): October 1, 2021

Study Registration Dates

• First Submitted: March 24, 2020
• First Submitted That Met QC Criteria: March 24, 2020
• First Posted (Actual): March 26, 2020

Study Record Updates

• Last Update Posted (Actual): July 20, 2022
• Last Update Submitted That Met QC Criteria: July 19, 2022
• Last Verified: July 1, 2022

More Information

Terms related to this study

• Keywords: COVID-19; Colchicine; Corona Virus Infection
• Additional Relevant MeSH Terms: Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Virus Diseases; Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Lung Diseases; COVID-19; Coronavirus Infections; Pneumonia; Pneumonia, Viral; Molecular Mechanisms of Pharmacological Action; Antirheumatic Agents; Antineoplastic Agents; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Gout Suppressants; Colchicine
• Other Study ID Numbers: ColCOVID-19

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Yes
• IPD Sharing Time Frame: Data will be avaliable from July 2020 and documentation will be shared for 10 years
• IPD Sharing Access Criteria: The sponsor recognizes the importance of communicating study data and will disclose and publish the results in a suitable form regardless of outcome. The sponsor will publish the results of this study in scientific journals
• IPD Sharing Supporting Information Type: Study Protocol; Statistical Analysis Plan (SAP); Informed Consent Form (ICF); Clinical Study Report (CSR); Analytic Code

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No