ColCOVID-19: Colchicine Counteracting Inflammation in COVID-19 Pneumonia

Sponsor
Azienda Ospedaliero-Universitaria di Parma (Other)
Overall Status
Completed
CT.gov ID
NCT04322565
Collaborator
(none)
193
1
2
17.4
11.1

Study Details

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
Phase 2

Study Design

Study Type:
Interventional
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 :
Apr 20, 2020
Actual Primary Completion Date :
Sep 1, 2021
Actual Study Completion Date :
Oct 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 [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 [Day 28]

    Live discharge from the hospital (whatever comes first)

Secondary Outcome Measures

  1. Death [Day 28]

    Number of death patients

  2. Clinical status [Day 7, Day 14]

    7-category ordinal scale

  3. Mechanical ventilhation [Day 28]

    Number of patients with mechanical ventilhation

  4. Hospitalization [Day 28]

    Days of hospitalization

  5. Time from treatment initiation to death [Day 28]

    Days to death from treatment initiation

  6. Time to Negativization COVID 19 [Day 21]

    negativization of two consecutive pharyngo-nasal swab 24-72 hrs apart

  7. Fever [Day 1,4,7,14,21,28]

    Time to remission of fever in patients with T>37.5°C at enrollment

Eligibility Criteria

Criteria

Ages Eligible for Study:
18 Years to 100 Years
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
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

Site City State Country Postal Code
1 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

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.
Responsible Party:
Umberto Maggiore, MD, Azienda Ospedaliero-Universitaria di Parma
ClinicalTrials.gov Identifier:
NCT04322565
Other Study ID Numbers:
  • ColCOVID-19
First Posted:
Mar 26, 2020
Last Update Posted:
Jul 20, 2022
Last Verified:
Jul 1, 2022
Individual Participant Data (IPD) Sharing Statement:
Yes
Plan to Share IPD:
Yes
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, MD, Azienda Ospedaliero-Universitaria di Parma
Additional relevant MeSH terms:

Study Results

No Results Posted as of Jul 20, 2022