Colchicine and Post-COVID-19 Pulmonary Fibrosis

Sponsor
ClinAmygate (Other)
Overall Status
Completed
CT.gov ID
NCT04818489
Collaborator
(none)
260
1
2
6.9
37.9

Study Details

Study Description

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.

Condition or Disease Intervention/Treatment Phase
  • Drug: Colchicine 0.5 MG
  • Other: the standard protocol only
Phase 4

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 Design

Study Type:
Interventional
Actual Enrollment :
260 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Single (Outcomes Assessor)
Masking Description:
The radiologist who will assess the CT scans will be blinded
Primary Purpose:
Treatment
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
Actual Study Start Date :
Mar 25, 2021
Actual Primary Completion Date :
Aug 25, 2021
Actual Study Completion Date :
Oct 20, 2021

Arms and Interventions

Arm Intervention/Treatment
Experimental: 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

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 Names:
  • Colchicine
  • Other: the standard protocol only
    the local standard protocol for COVID19
    Other Names:
  • the local standard protocol for COVID19
  • Placebo Comparator: Control group

    the local standard protocol of COVID19 management

    Other: the standard protocol only
    the local standard protocol for COVID19
    Other Names:
  • the local standard protocol for COVID19
  • Outcome Measures

    Primary Outcome Measures

    1. Clinical status [Two weeks]

      Seven-category ordinal scale: minimum 1 is the best and a maximum is 6

    2. Pulmonary fibrosis at week 2 [Two weeks]

      Percent of Participants with pulmonary fibrosis

    3. Pulmonary fibrosis at 45 days [45 days]

      Percent of Participants with pulmonary fibrosis

    Secondary Outcome Measures

    1. C-reactive protein [Two weeks]

      Change in the levels of C-reactive protein

    2. Ferritin [Two weeks]

      Change in the levels of Ferritin

    3. Erythrocyte sedimentation rate [Two weeks]

      Change in the levels of Erythrocyte sedimentation rate

    4. Lactate dehydrogenase [Two weeks]

      Change in the levels of Lactate dehydrogenase

    5. Adverse events [45 days]

      Adverse events related to the study medication

    6. Pulmonary function test: FVC [45 days]

      Pulmonary function test: FVC

    7. Pulmonary function test: FEV1 [45 days]

      Pulmonary function test: FEV1

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    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

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 El-Demerdash Hospital Cairo Egypt

    Sponsors and Collaborators

    • ClinAmygate

    Investigators

    • Principal Investigator: Emad Issak, Ain Shams Univeristy

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    Responsible Party:
    Emad R Issak, Doctor, ClinAmygate
    ClinicalTrials.gov Identifier:
    NCT04818489
    Other Study ID Numbers:
    • PR00202
    First Posted:
    Mar 26, 2021
    Last Update Posted:
    Nov 9, 2021
    Last Verified:
    Nov 1, 2021
    Individual Participant Data (IPD) Sharing Statement:
    No
    Plan to Share IPD:
    No
    Studies a U.S. FDA-regulated Drug Product:
    No
    Studies a U.S. FDA-regulated Device Product:
    No
    Product Manufactured in and Exported from the U.S.:
    No
    Keywords provided by Emad R Issak, Doctor, ClinAmygate
    Additional relevant MeSH terms:

    Study Results

    No Results Posted as of Nov 9, 2021