Clinical trial NCT04818489: Colchicine and Post-COVID-19 Pulmonary Fibrosis
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
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE4
Conditions: Covid19
Pulmonary Fibrosis Interstitial
Keywords: COVID19
Pulmonary Fibrosis
Colchicine
Clinical outcomes
Lead sponsor: ClinAmygate
Sponsor class: OTHER
First posted: 2021-03-26
Enrollment: 260
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Clinical status
timeFrame: Two weeks
measure: Pulmonary fibrosis at week 2
timeFrame: Two weeks
measure: Pulmonary fibrosis at 45 days
timeFrame: 45 days
Secondary outcomes:
measure: C-reactive protein
timeFrame: Two weeks
measure: Ferritin
timeFrame: Two weeks
measure: Erythrocyte sedimentation rate
timeFrame: Two weeks
measure: Lactate dehydrogenase
timeFrame: Two weeks
measure: Adverse events
timeFrame: 45 days
measure: Pulmonary function test: FVC
timeFrame: 45 days
measure: Pulmonary function test: FEV1
timeFrame: 45 days
Other outcomes:
Locations:
city: Cairo
country: Egypt
facility: El-Demerdash Hospital
Study officials:
affiliation: Ain Shams Univeristy
name: Emad Issak
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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.