Colchicine Counteracting Inflammation in COVID-19 Pneumonia

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Přihlášení Registrace

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PostaveníNábor

Sponzoři

Azienda Ospedaliero-Universitaria di Parma

KLINICKÉ HODNOCENÍ: NCT04322565

BioSeek: nct04322565

Klíčová slova

Abstraktní

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].

Termíny

Poslední ověření:	06/30/2020
První předloženo:	03/23/2020
Odhadovaná registrace vložena:	03/23/2020
První zveřejnění:	03/25/2020
Poslední aktualizace byla odeslána:	07/08/2020
Poslední aktualizace zveřejněna:	07/09/2020
Aktuální datum zahájení studie:	04/19/2020
Odhadované datum dokončení primární:	12/19/2020
Odhadované datum dokončení studie:	12/20/2020

Stav nebo nemoc

Coronavirus Infections

Pneumonia, Viral

Intervence / léčba

Drug: Colchicine

Fáze

Fáze 2

Skupiny zbraní

Paže	Intervence / léčba
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

Kritéria způsobilosti

Věky způsobilé ke studiu	18 Years Na 18 Years
Pohlaví způsobilá ke studiu	All
Přijímá zdravé dobrovolníky	Ano
Kritéria	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.

Výsledek

Primární výsledná opatření

1. Clinical improvement [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 [Day 28]

Live discharge from the hospital (whatever comes first)

Měření sekundárních výsledků

1. Death [Day 28]

Number of death patients

2. Clinical status [Day 7, Day 14]

7-category ordinal scale

3. Mechanical ventilhation [Day 28]

Number of patients with mechanical ventilhation

4. Hospitalization [Day 28]

Days of hospitalization

5. Time from treatment initiation to death [Day 28]

Days to death from treatment initiation

6. Time to Negativization COVID 19 [Day 21]

negativization of two consecutive pharyngo-nasal swab 24-72 hrs apart

7. Fever [Day 1,4,7,14,21,28]

Time to remission of fever in patients with T>37.5°C at enrollment

Colchicine Counteracting Inflammation in COVID-19 Pneumonia

Klíčová slova

covid-19

brucelóza

pneumonia

coronavirus infections

zánět

horečka

dna

colchicine

hemodialýza