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

• ClinicalTrials.gov Identifier: NCT04322565
• Recruitment Status: Recruiting
• First Posted: March 26, 2020
• Last Update Posted: July 10, 2020
• 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)
• Estimated Enrollment: 310 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
• Estimated Primary Completion Date: December 20, 2020
• Estimated Study Completion Date: December 21, 2020

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

Contacts

Contact: Umberto Maggiore, MD; 00390521904760; umberto.maggiore@unipr.it

Contact: Lucio Manenti, MD; 00390521702013; lmanenti@ao.pr.it

Locations

Italy

Azienda Ospedaliero Universitaria di Parma; Recruiting

Parma, PR, Italy, 43100

Contact: Umberto Maggiore, MD 0521702009 umaggiore@ao.pr.it

Contact: MD

Sub-Investigator: Giuseppe Maglietta, PhD

Sub-Investigator: Caterina Caminiti, PhD

Sub-Investigator: Lucio Manenti, MD

Sponsors and Collaborators

Azienda Ospedaliero-Universitaria di Parma

Investigators

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

More Information

• 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 10, 2020
• Last Verified: July 2020

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:

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