Covid19, Pulmonary Fibrosis Interstitial
Conditions
Keywords
COVID19, Pulmonary Fibrosis, Colchicine, Clinical outcomes
Brief summary
Pulmonary fibrosis is a sequela to adult respiratory distress syndrome (ARDS). 40% of patients with corona virus disease 2019 (COVID-19) develop ARDS, and 20% of them are severe. Clinical, radiographic, and autopsy reports of pulmonary fibrosis were commonplace following SARS and MERS, and current evidence suggests pulmonary fibrosis could complicate infection by SARS-CoV-2 too. Colchicine has 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. It suppress secretion of cytokines and chemokines as well as in vitro platelet aggregation. All these are potentially beneficial effects that might diminish the COVID-19 inflammatory storm associated with severe cases.
Detailed description
Approximately 96 million people have been diagnosed with severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), and around two million people have died from this deadly disease worldwide. The pulmonary symptoms associated with SARS-CoV-2 vary from mild respiratory symptoms to severe respiratory failure. Of those infected with SARS-CoV-2, 40% will progress to ARDS. Radiologically, most of those infected by SARS COV 2 have bilateral lower lobes ground-glass opacities with or without consolidation. However, long term lung impairment may develop particularly interstitial lung disease (ILD), the fibrotic type. Besides, pulmonary fibrosis (PF) is recognized sequelae of ARDS, and several studies have shown that protective lung ventilation tends to diminish the radiographic abnormalities following ARDS. Colchicine has anti-fibrotic effects as a microtubule-destabilizing agent. In an in vitro study using human lung fibroblasts, colchicine inhibited myofibroblast differentiation via Rho/serum response factor (SRF) dependent. In COVID19 cases, colchicine was used by where they assessed its impact on the inflammatory biomarkers and clinical outcomes.
Interventions
DRUGColchicine 0.5 MG
colchicine 0.5 mg (2 tablets: 1 mg) twice per day as a loading dose, followed by one tablet 0.5 twice per day for three weeks in addition to the standard protocol
OTHERthe standard protocol only
the local standard protocol for COVID19
Sponsors
ClinAmygate
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
SINGLE (Outcomes Assessor)
Masking description
The radiologist who will assess the CT scans will be blinded
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Patients who are confirmed to have COVID-19 clinically, radiologically and PCR * Age above 18 years old * Informed written consent
Exclusion criteria
* History of hypersensitivity to colchicine * Pregnancy or breastfeeding women. * Patients with severe renal impairment (creatinine clearance (CCL) \<30 mL / min) * Patients with severe hepatic impairment (AST or ALT\> 5 times the normal limits in International Units (ULN) * Patients with blood dyscrasias, neutrophils \<1.000 / mmc or platelets \<50.000 / mmc * Patients with history of severe cardiac insufficiency * Patients with history of pulmonary fibrosis * Severe diarrhoea or bowel diverticulitis, or perforation * Patients who cannot take oral therapy * Patients already in ICU or requiring mechanical ventilation * Patients already enrolled in other clinical trials * Patients with taking P-glycoprotein inhibitor (e.g. ciclosporin, verapamil or quinidine) or a CYP3A4 inhibitor (e.g. ritonavir, remdesivir, atazanavir, indinavir, clarithromycin, telithromycin, itraconazole or ketaconazole) or Tocilizumab
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Clinical status | Two weeks | Seven-category ordinal scale: minimum 1 is the best and a maximum is 6 |
| Pulmonary fibrosis at week 2 | Two weeks | Percent of Participants with pulmonary fibrosis |
| Pulmonary fibrosis at 45 days | 45 days | Percent of Participants with pulmonary fibrosis |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Lactate dehydrogenase | Two weeks | Change in the levels of Lactate dehydrogenase |
| Adverse events | 45 days | Adverse events related to the study medication |
| C-reactive protein | Two weeks | Change in the levels of C-reactive protein |
| Pulmonary function test: FEV1 | 45 days | Pulmonary function test: FEV1 |
| Pulmonary function test: FVC | 45 days | Pulmonary function test: FVC |
| Ferritin | Two weeks | Change in the levels of Ferritin |
| Erythrocyte sedimentation rate | Two weeks | Change in the levels of Erythrocyte sedimentation rate |
Countries
Egypt
Outcome results
None listed