Colchicine Counteracting Inflammation in COVID-19 Pneumonia

Зөвхөн бүртгэлтэй хэрэглэгчид л нийтлэл орчуулах боломжтой

Нэвтрэх / Бүртгүүлэх

Холбоосыг санах ойд хадгалдаг

СтатусАжилд авах

Ивээн тэтгэгчид

Azienda Ospedaliero-Universitaria di Parma

ЭМНЭЛ ЗҮЙН ТУРШИЛТ: NCT04322565

BioSeek: nct04322565

Түлхүүр үгс

Хураангуй

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].

Огноо

Сүүлд баталгаажуулсан:	06/30/2020
Эхлээд оруулсан:	03/23/2020
Тооцоолсон элсэлтийг оруулсан:	03/23/2020
Эхлээд нийтэлсэн:	03/25/2020
Сүүлийн шинэчлэлтийг оруулсан:	07/08/2020
Сүүлийн шинэчлэлтийг нийтэлсэн:	07/09/2020
Сургалтын бодит эхлэх огноо:	04/19/2020
Тооцоолсон анхан шатны ажил дуусах огноо:	12/19/2020
Судалгааны ажлыг дуусгах өдөр:	12/20/2020

Нөхцөл байдал эсвэл өвчин

Coronavirus Infections

Pneumonia, Viral

Хөндлөнгийн оролцоо / эмчилгээ

Drug: Colchicine

Үе шат

Үе шат 2

Arm Groups

Гар	Хөндлөнгийн оролцоо / эмчилгээ
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

Эрхийн шалгуур

Суралцах боломжтой нас	18 Years Хэнд 18 Years
Суралцах боломжтой хүйс	All
Эрүүл сайн дурын ажилтнуудыг хүлээн авдаг	Тийм ээ
Шалгуур үзүүлэлтүүд	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.

Үр дүн

Анхан шатны үр дүнгийн арга хэмжээ

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)

Хоёрдогч үр дүнгийн арга хэмжээ

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

Түлхүүр үгс

ковид-19

brucellosis

pneumonia

coronavirus infections

үрэвсэл

fever

gout

colchicine

гемодиализ