The ECLA PHRI COLCOVID Trial. Effects of Colchicine on Moderate/High-risk Hospitalized COVID-19 Patients.
The ECLA PHRI COLCOVID Trial. Effects of Colchicine on Moderate/High-risk Hospitalized COVID-19 Patients.
The ECLA PHRI COLCOVID Trial is a simple, pragmatic randomized open controlled trial to test
 the effects of colchicine on moderate/high-risk hospitalized COVID-19 patients with the aim
 of reducing mortality and/or new requirement for mechanical ventilation.
Various anti-viral treatments are being tested in clinical trials worldwide. The World Health
 Organization (WHO) launched a simple,pragmatic worldwide open-label trial to test Remdesivir,
 Lopinavir/Ritonavir, Interferon and Hydroxychloroquine or Chloroquine.The most important
 complication of COVID-19 severe cases is respiratory failure from severe acute respiratory
 syndrome (SARS), the leading cause of mortality. Accumulating evidence suggests that patients
 with severe COVID-19 might have a cytokine storm syndrome, a hyperinflammatory syndrome
 characterized by a fulminant and fatal hypercytokinemia and multiorgan failure.

 The proposed pathophysiological mechanism of cytokine storm and inflammatory cascade
 activation is based on evidence collected primarily during the SARS-CoV and MERS-CoV
 epidemics (with a significant increase in IL1B, IL6, IL12, IFNγ, IP10, TNFα, IL15, and IL17
 among others). The data collected during the pandemic with COVID-19 also shows a significant
 increase in inflammatory cytokines (GCSF, IP10, MCP1, MIP1A, and TNFα, among others) in
 sicker patients admitted to intensive care. In the absence of effective treatments for the
 management of patients with COVID-19 and respiratory failure, the immunomodulatory and
 anti-inflammatory effect of colchicine on cytokines involved in the hyper-inflammatory state
 is postulated. Several lines of research worldwide are testing powerful anti-inflammatory
 drugs for the pandemic, with different options including steroids, cytokine blockers, and
 other potent anti-inflammatory agents. Steroids are partially contraindicated in viral
 infections.

 Colchicine is a powerful anti-inflammatory drug approved for the treatment or prevention of
 gout and Familial Mediterranean Fever at doses ranging between 0.3 mg and 2.4 mg/day. Its
 mechanism of action is through the inhibition of tubulin polymerization, as well as through
 potential effects on cellular adhesion molecules and inflammatory chemokines. It might also
 have direct anti-inflammatory effects by inhibiting key inflammatory signalling networks
 known as inflammasome and pro-inflammatory cytokines. Additionally, evidence suggests that
 colchicine exerts a direct anti-inflammatory effect by inhibiting the synthesis of tumor
 necrosis factor alpha and IL-6, monocyte migration, and the secretion of matrix
 metalloproteinase-9. Through the disruption of the cytoskeleton, colchicine is believed to
 suppress secretion of cytokines and chemokines as well as in vitro platelet aggregation. All
 these are potentially beneficial effects that might diminish or ameliorate the COVID-19
 inflammatory storm associated with severe forms of the disease. Importantly, in one
 contemporary trial low-dose colchicine administered to patients who survived from acute
 coronary syndrome shows a statistically significantly reduction of cardiovascular
 complications.

 We have therefore designed in a simple, pragmatic randomized controlled trial to test the
 effects of colchicine on severe hospitalized COVID-19 cases with the aim of reducing
 mortality.

 Sample size calculation:

 A minimum sample size of 1200 patients will provide 80% power to detect a relative risk
 reduction of approximately 30% in the treated group if the assumed composite rate (new
 requirement of intubation and / or death) in the control group is about 24%.

 The ECLA PHRI COLCOVID Trial allows randomization to another trial, specifically patients
 included in the trial might be (or not) randomized to an antithrombotic strategy.
Inclusion Criteria (case definition)

 -  Consented adults (age ≥18 years) and

 -  COVID-19 suspicious and

 -  Admitted to hospital or already in hospital and

 -  COVID-19 suggestive symptoms (fever or febrile equivalent, loss of smell and taste,
 fatigue, etc.) that may be present or absent at randomization time and

 -  SARS (severe acute respiratory syndrome)

 -  shortness of breath (dyspnea) or

 -  image of typical or atypical pneumonia or

 -  oxygen desaturation (SpO2 ≤ 93)

 Exclusion criteria

 -  Clear indication or contraindication for the use of colchicine

 -  Pregnant or breastfeeding female.

 -  Chronic renal disease with creatinine clearance <15 ml/min/m2

 -  Negative PCR test for SARS-COV2