Colchicine Counteracting Inflammation in COVID-19 Pneumonia

NCT ID: NCT04322565

Last Updated: 2022-07-20

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 193 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2020-04-20
• Study Completion Date: 2021-10-01

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

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Colchicine

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

Group Type: EXPERIMENTAL

Colchicine

Intervention Type: DRUG

Cochicine 1mg/day

Standard of care

Standard of care for COVID-19 pneumonia

Group Type: NO_INTERVENTION

No interventions assigned to this group

Interventions

Colchicine

Cochicine 1mg/day

Intervention Type: DRUG

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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 100 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Azienda Ospedaliero-Universitaria di Parma

OTHER

Sponsor Role: lead

Responsible Party

Umberto Maggiore

MD

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Umberto Maggiore, MD

Role: PRINCIPAL_INVESTIGATOR

Azienda Ospedaliero-Universitaria di Parma

Locations

Azienda Ospedaliero Universitaria di Parma

Parma, PR, Italy

Countries

Italy

References

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.

Reference Type: DERIVED

PMID: 34658014 (View on PubMed)

Other Identifiers

ColCOVID-19

Identifier Type: -

Identifier Source: org_study_id