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

• ClinicalTrials.gov Identifier: NCT04322565
• Recruitment Status: Completed
• First Posted: March 26, 2020
• Last Update Posted: July 20, 2022
• Sponsor: Azienda Ospedaliero-Universitaria di Parma
• Information provided by (Responsible Party): Umberto Maggiore, Azienda Ospedaliero-Universitaria di Parma

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
Coronavirus Infections; Pneumonia, Viral	Drug: Colchicine	Phase 2

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 193 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Colchicine to Counteract Inflammatory Response in COVID-19 Pneumonia
• Actual Study Start Date: April 20, 2020
• Actual Primary Completion Date: September 1, 2021
• Actual Study Completion Date: October 1, 2021

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 :

1. Clinical improvement [ Time Frame: 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
2. Hospital discharge [ Time Frame: Day 28 ]
   Live discharge from the hospital (whatever comes first)

Secondary Outcome Measures :

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

Eligibility Criteria

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

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.

Contacts and Locations

Locations

Italy

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

More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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:CD015045. doi: 10.1002/14651858.CD015045. Review.

• Responsible Party: Umberto Maggiore, MD, Azienda Ospedaliero-Universitaria di Parma
• ClinicalTrials.gov Identifier: NCT04322565
• Other Study ID Numbers: ColCOVID-19
• First Posted: March 26, 2020
• Last Update Posted: July 20, 2022
• Last Verified: July 2022

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Yes
• Supporting Materials: Study Protocol; Statistical Analysis Plan (SAP); Informed Consent Form (ICF); Clinical Study Report (CSR); Analytic Code
• Time Frame: Data will be avaliable from July 2020 and documentation will be shared for 10 years
• 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

• 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

Keywords provided by Umberto Maggiore, Azienda Ospedaliero-Universitaria di Parma:

Colchicine; Corona Virus Infection; COVID-19

Additional relevant MeSH terms:

COVID-19; Pneumonia; Coronavirus Infections; Pneumonia, Viral; Infections; Respiratory Tract Infections; Virus Diseases; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Lung Diseases; Respiratory Tract Diseases; Colchicine; Gout Suppressants; Antirheumatic Agents; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents