Clinical trial NCT04322565: Colchicine Counteracting Inflammation in COVID-19 Pneumonia
Official title: Colchicine to Counteract Inflammatory Response in COVID-19 Pneumonia
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Coronavirus Infections
Pneumonia, Viral
Keywords: Colchicine
Corona Virus Infection
COVID-19
Lead sponsor: Azienda Ospedaliero-Universitaria di Parma
Sponsor class: OTHER
First posted: 2020-03-26
Enrollment: 193
Sex: ALL
Minimum age (years): 18
Maximum age (years): 100
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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 \[4\].


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.

Primary outcomes:
measure: Clinical improvement
timeFrame: Day 28
measure: Hospital discharge
timeFrame: Day 28
Secondary outcomes:
measure: Death
timeFrame: Day 28
measure: Clinical status
timeFrame: Day 7, Day 14
measure: Mechanical ventilhation
timeFrame: Day 28
measure: Hospitalization
timeFrame: Day 28
measure: Time from treatment initiation to death
timeFrame: Day 28
measure: Time to Negativization COVID 19
timeFrame: Day 21
measure: Fever
timeFrame: Day 1,4,7,14,21,28
Other outcomes:
Locations:
city: Parma
country: Italy
facility: Azienda Ospedaliero Universitaria di Parma
state: PR
Study officials:
affiliation: Azienda Ospedaliero-Universitaria di Parma
name: Umberto Maggiore, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.