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

Tracking Information

• First Submitted Date: March 24, 2020
• First Posted Date: March 26, 2020
• Last Update Posted Date: July 10, 2020
• Actual Study Start Date: April 20, 2020
• Estimated Primary Completion Date: December 20, 2020 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: March 24, 2020)

• 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
• Hospital discharge [ Time Frame: Day 28 ]
  Live discharge from the hospital (whatever comes first)

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: April 14, 2020)

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

Original Secondary Outcome Measures (submitted: March 24, 2020)

• Death [ Time Frame: Day 28 ]
• Clinical status [ Time Frame: Day 4, 7, Day 14, Day 21 ]
  7-category ordinal scale
• Mechanical venhtilation [ Time Frame: Day 28 ]
• Hospitalization [ Time Frame: Day 28 ]
• Time from death [ Time Frame: Day 28 ]
• Negativization COVID 19 [ Time Frame: Day 21 ]
  negativization of two consecutive pharyngo-nasal swab 24-72 hrs apart
• Fever [ Time Frame: Day 1,4,7,14,21,28 ]
  Time to remission of fever in patients with T>37.5°C at enrollment

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Colchicine Counteracting Inflammation in COVID-19 Pneumonia
• Official Title: Colchicine to Counteract Inflammatory Response in COVID-19 Pneumonia

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].

• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 2
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment

Condition

• Coronavirus Infections
• Pneumonia, Viral

Intervention

Drug: Colchicine

Cochicine 1mg/day

Study Arms

• Experimental: Colchicine
  Administration of Colchicine 1mg (or 0.5 mg in CKD)/day + standard of care for COVID-19 pneumonia
  Intervention: Drug: Colchicine
• No Intervention: Standard of care
  Standard of care for COVID-19 pneumonia

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: April 14, 2020): 310
• Original Estimated Enrollment (submitted: March 24, 2020): 100
• Estimated Study Completion Date: December 21, 2020
• Estimated Primary Completion Date: December 20, 2020 (Final data collection date for primary outcome measure)

Eligibility 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.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years to 100 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Contacts

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

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

• Listed Location Countries: Italy

Administrative Information

• NCT Number: NCT04322565
• Other Study ID Numbers: ColCOVID-19
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• 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

IPD Sharing Statement

• Plan to Share IPD: Yes
• Supporting Materials: Study Protocol
• Supporting Materials: Statistical Analysis Plan (SAP)
• Supporting Materials: Informed Consent Form (ICF)
• Supporting Materials: Clinical Study Report (CSR)
• Supporting Materials: 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

• Responsible Party: Umberto Maggiore, Azienda Ospedaliero-Universitaria di Parma
• Study Sponsor: Azienda Ospedaliero-Universitaria di Parma
• Collaborators: Not Provided

Investigators

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

• PRS Account: Azienda Ospedaliero-Universitaria di Parma
• Verification Date: July 2020