Colchicine and Post-COVID-19 Pulmonary Fibrosis

NCT ID: NCT04818489

Last Updated: 2023-09-06

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE4
• Total Enrollment: 260 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2021-03-25
• Study Completion Date: 2023-10-20

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.

Conditions

Covid19; Pulmonary Fibrosis Interstitial

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: SINGLE

Study Groups

Colchicine group

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

Group Type: EXPERIMENTAL

Colchicine 0.5 MG

Intervention Type: 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

the standard protocol only

Intervention Type: OTHER

the local standard protocol for COVID19

Control group

the local standard protocol of COVID19 management

Group Type: PLACEBO_COMPARATOR

the standard protocol only

Intervention Type: OTHER

the local standard protocol for COVID19

Interventions

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

Intervention Type: DRUG

the standard protocol only

the local standard protocol for COVID19

Intervention Type: OTHER

Other Intervention Names

Colchicine; the local standard protocol for COVID19

Eligibility Criteria

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

ClinAmygate

OTHER

Sponsor Role: lead

Responsible Party

Emad R Issak

Doctor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Emad Issak

Role: PRINCIPAL_INVESTIGATOR

Ain Shams Univeristy

Locations

El-Demerdash Hospital

Cairo, , Egypt

Countries

Egypt

References

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.

Reference Type: BACKGROUND

PMID: 32579195 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 34658014 (View on PubMed)

Other Identifiers

PR00202

Identifier Type: -

Identifier Source: org_study_id