Colchicine and Post-COVID-19 Pulmonary Fibrosis

Phase 4

Active, not recruiting

• Conditions: Covid19; Pulmonary Fibrosis Interstitial
• Interventions: Drug: Colchicine 0.5 MG; Other: the standard protocol only

• Registration Number: NCT04818489
• Lead Sponsor: ClinAmygate

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.

Study Timeline

• Study First Submitted: 2021-02-13
• Study Start: 2021-03-25
• Study First Submitted QC: 2021-03-25
• Study First Posted: 2021-03-26
• Primary Completion: 2021-08-25
• Status Verified: 2023-09
• Last Update Submitted: 2023-09-04
• Last Update Posted: 2023-09-06
• Study Completion: 2023-10-20

Recruitment & Eligibility

• Status: ACTIVE_NOT_RECRUITING
• Sex: All
• Target Recruitment: 260

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Colchicine group	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 local standard protocol of COVID19 management
Colchicine group	the standard protocol only	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	the standard protocol only	the local standard protocol of COVID19 management

Primary Outcome Measures

Name	Time	Method
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
Clinical status	Two weeks	Seven-category ordinal scale: minimum 1 is the best and a maximum is 6

Secondary Outcome Measures

Name	Time	Method
Ferritin	Two weeks	Change in the levels of Ferritin
Pulmonary function test: FEV1	45 days	Pulmonary function test: FEV1
C-reactive protein	Two weeks	Change in the levels of C-reactive protein
Erythrocyte sedimentation rate	Two weeks	Change in the levels of Erythrocyte sedimentation rate
Pulmonary function test: FVC	45 days	Pulmonary function test: FVC
Adverse events	45 days	Adverse events related to the study medication
Lactate dehydrogenase	Two weeks	Change in the levels of Lactate dehydrogenase

Trial Locations

Locations (1)

El-Demerdash Hospital; 🇪🇬 Cairo, Egypt