Colchicine Counteracting Inflammation in COVID-19 Pneumonia

NCT04322565 | Completed Phase 2 DMC

• 1 other identifier: ColCOVID-19
• Study Type: interventional
• Target: 193
• Locations: 1 country
• Sites: 1

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 \[4\].

Conditions

Coronavirus Infections; Pneumonia, Viral

Keywords

Colchicine; Corona Virus Infection; COVID-19

Outcome Measures

Primary Outcomes (2)

• 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 Outcomes (7)

• Death

  Day 28

• Clinical status

  Day 7, Day 14

• Mechanical ventilhation

  Day 28

• Hospitalization

  Day 28

• Time from treatment initiation to death

  Day 28

Study Arms (2)

Colchicine

EXPERIMENTAL

Administration of Colchicine 1mg (or 0.5 mg in CKD)/day + standard of care for COVID-19 pneumonia

Drug: Colchicine

Standard of care

NO INTERVENTION

Standard of care for COVID-19 pneumonia

Interventions

Colchicine DRUG

Cochicine 1mg/day

Colchicine

Eligibility Criteria

• Age: 18 Years - 100 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• Azienda Ospedaliero-Universitaria di Parma: lead

Study Sites (1)

Azienda Ospedaliero Universitaria di Parma

Parma, PR, 43100, Italy

Location

Related Publications (1)

• 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.

  PMID: 34658014 DERIVED

MeSH Terms

Conditions

Coronavirus Infections; Pneumonia, Viral; COVID-19

Interventions

Colchicine

Condition Hierarchy (Ancestors)

Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Virus Diseases; Infections; Pneumonia; Respiratory Tract Infections; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Alkaloids; Heterocyclic Compounds

Study Officials

• Umberto Maggiore, MD

  Azienda Ospedaliero-Universitaria di Parma

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: MD

Study Record Dates

• First Submitted: March 24, 2020
• First Posted: March 26, 2020
• Study Start: April 20, 2020
• Primary Completion: September 1, 2021
• Study Completion: October 1, 2021
• Last Updated: July 20, 2022

Record last verified: 2022-07

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, 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

Locations

IT (1)