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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.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Colchicine group | Experimental | 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 local standard protocol of COVID19 management |
|
| Control group | Placebo Comparator | the local standard protocol of COVID19 management |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Colchicine 0.5 MG | Drug | 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 |
| Measure | Description | Time Frame |
|---|---|---|
| Clinical status | Seven-category ordinal scale: minimum 1 is the best and a maximum is 6 | Two weeks |
| Pulmonary fibrosis at week 2 | Percent of Participants with pulmonary fibrosis | Two weeks |
| Pulmonary fibrosis at 45 days | Percent of Participants with pulmonary fibrosis | 45 days |
| Measure | Description | Time Frame |
|---|---|---|
| C-reactive protein | Change in the levels of C-reactive protein | Two weeks |
| Ferritin | Change in the levels of Ferritin | Two weeks |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Emad Issak | Ain Shams Univeristy | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| El-Demerdash Hospital | Cairo | Egypt |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 32579195 | Background | Deftereos SG, Giannopoulos G, Vrachatis DA, Siasos GD, Giotaki SG, Gargalianos P, Metallidis S, Sianos G, Baltagiannis S, Panagopoulos P, Dolianitis K, Randou E, Syrigos K, Kotanidou A, Koulouris NG, Milionis H, Sipsas N, Gogos C, Tsoukalas G, Olympios CD, Tsagalou E, Migdalis I, Gerakari S, Angelidis C, Alexopoulos D, Davlouros P, Hahalis G, Kanonidis I, Katritsis D, Kolettis T, Manolis AS, Michalis L, Naka KK, Pyrgakis VN, Toutouzas KP, Triposkiadis F, Tsioufis K, Vavouranakis E, Martinez-Dolz L, Reimers B, Stefanini GG, Cleman M, Goudevenos J, Tsiodras S, Tousoulis D, Iliodromitis E, Mehran R, Dangas G, Stefanadis C; GRECCO-19 investigators. Effect of Colchicine vs Standard Care on Cardiac and Inflammatory Biomarkers and Clinical Outcomes in Patients Hospitalized With Coronavirus Disease 2019: The GRECCO-19 Randomized Clinical Trial. JAMA Netw Open. 2020 Jun 1;3(6):e2013136. doi: 10.1001/jamanetworkopen.2020.13136. | |
| 34658014 |
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| ID | Term |
|---|---|
| D000086382 | COVID-19 |
| D011658 | Pulmonary Fibrosis |
| ID | Term |
|---|---|
| D011024 | Pneumonia, Viral |
| D011014 | Pneumonia |
| D012141 | Respiratory Tract Infections |
| D007239 | Infections |
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| ID | Term |
|---|---|
| D003078 | Colchicine |
| ID | Term |
|---|---|
| D000470 | Alkaloids |
| D006571 | Heterocyclic Compounds |
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The radiologist who will assess the CT scans will be blinded
|
| the standard protocol only | Other | the local standard protocol for COVID19 |
|
|
| Erythrocyte sedimentation rate | Change in the levels of Erythrocyte sedimentation rate | Two weeks |
| Lactate dehydrogenase | Change in the levels of Lactate dehydrogenase | Two weeks |
| Adverse events | Adverse events related to the study medication | 45 days |
| Pulmonary function test: FVC | Pulmonary function test: FVC | 45 days |
| Pulmonary function test: FEV1 | Pulmonary function test: FEV1 | 45 days |
| Derived |
| 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. |
| D014777 |
| Virus Diseases |
| D018352 | Coronavirus Infections |
| D003333 | Coronaviridae Infections |
| D030341 | Nidovirales Infections |
| D012327 | RNA Virus Infections |
| D008171 | Lung Diseases |
| D012140 | Respiratory Tract Diseases |
| D017563 | Lung Diseases, Interstitial |
| D005355 | Fibrosis |
| D010335 | Pathologic Processes |
| D013568 | Pathological Conditions, Signs and Symptoms |