Colchicine and Post-COVID-19 Pulmonary Fibrosis

Covid19 Clinical Trial

Official title:

Impact of Colchicine on the Clinical Outcome of COVID-19 and the Development of Post-COVID-19 Pulmonary Fibrosis: Randomized Controlled Clinical Trial

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT04818489
• Other study ID #: PR00202
• Status: Active, not recruiting
• Phase: Phase 4
• Start date: March 25, 2021
• Est. completion date: October 20, 2023

Study information

• Verified date: September 2023
• Source: ClinAmygate
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 260
• Est. completion date: October 20, 2023
• Est. primary completion date: August 25, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• COVID-19
• Covid19
• Fibrosis
• Pulmonary Fibrosis
• Pulmonary Fibrosis Interstitial

Intervention

Drug:
• Colchicine 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

Other:
• the standard protocol only
the local standard protocol for COVID19

Locations

Country	Name	City	State
Egypt	El-Demerdash Hospital	Cairo

Sponsors (1)

Lead Sponsor	Collaborator
ClinAmygate

Country where clinical trial is conducted

Egypt, 

References & Publications (1)

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Clinical status	Seven-category ordinal scale: minimum 1 is the best and a maximum is 6	Two weeks
Primary	Pulmonary fibrosis at week 2	Percent of Participants with pulmonary fibrosis	Two weeks
Primary	Pulmonary fibrosis at 45 days	Percent of Participants with pulmonary fibrosis	45 days
Secondary	C-reactive protein	Change in the levels of C-reactive protein	Two weeks
Secondary	Ferritin	Change in the levels of Ferritin	Two weeks
Secondary	Erythrocyte sedimentation rate	Change in the levels of Erythrocyte sedimentation rate	Two weeks
Secondary	Lactate dehydrogenase	Change in the levels of Lactate dehydrogenase	Two weeks
Secondary	Adverse events	Adverse events related to the study medication	45 days
Secondary	Pulmonary function test: FVC	Pulmonary function test: FVC	45 days
Secondary	Pulmonary function test: FEV1	Pulmonary function test: FEV1	45 days