Study to Investigate the Treatment Effect of Colchicine in Patients With COVID-19

NCT04667780 | Completed Phase 3 DMC

• 1 other identifier: ATH/IRB/Colchicine/25.11.2020
• Study Type: interventional
• Target: 102
• Locations: 1 country
• Sites: 1

Brief Summary

COVID-19 is associated with a cytokine storm that leads to respiratory distress, multiorgan failure and elevated mortality. Oral Colchicine exhibits high anti-inflammatory capacity attributed to the inhibition of microtubules polymerization, inflammasome and production of IL-1β and IL-6, which could prevent the inflammatory storm in COVID-19 patients at risk. The investigators present a randomized, controlled, open-labeled, and pragmatic clinical trial to study the treatment effect of Colchicine in COVID-19 patients requiring hospitalization, but no intensive care yet. Colchicine will be started within the first 48 hours and continue for 14 days using a descending dose. The benefits will be studied in terms of clinical evolution (WHO 7-point scale) and IL-6 levels, as well as other clinical and biochemical secondary end-points. In the case of positive results, the clinical impact would be relevant given that this oral medication is affordable and widely accessible which would help to prevent the inflammatory complications associated with COVID-19.

Conditions

COVID-19

Outcome Measures

Primary Outcomes (2)

• Changes in the patients' clinical status through the 7 points ordinal scale WHO R&D Blueprint expert group

  Improvement in the clinical evolution of patients

  up to 14 days

• Changes in IL-6 concentrations

  Improvement in cytokine level

  up to 14 days

Secondary Outcomes (18)

• Improvement in the clinical status

  up to 14 days

• Changes in the score for the Sequential Organ Failure Assessment (SOFA score)

  up to 14 days

• Changes in the punctuation in the National Early Warning Score

  up to 14 days

• Number of days with invasive mechanical ventilation

  up to 14 days

• Number of days with high flow oxygen therapy

  up to 14 days

Study Arms (2)

Colchicine

EXPERIMENTAL

This arm will receive Standard COVID-19 care + Colchicine The Colchicine treatment includes an initial dose of 1.5 mg (1 mg and 0.5 mg two hours after), followed by 0.5 mg every 12 hours during the next 7 days and 0.5 mg every 24 hours until the completion of 14 days of total treatment. In patients receiving ritonavir or lopinavir or with reduced renal clearance (\<50 ml/min/1.37m2), weight \<70 kg or age \>75 years old, the dose will be adjusted to the half.

Drug: Colchicine; Drug: Standard COVID-19 care

Control - Standard COVID-19 care

OTHER

This arm will receive standard COVID-19 care as per the hospital guidelines.

Drug: Standard COVID-19 care

Interventions

Colchicine DRUG

Colchicine tablet 0.5 mg

Colchicine

Standard COVID-19 care DRUG

As per the hospital guidelines

Colchicine; Control - Standard COVID-19 care

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• SARS-CoV-2 infection confirmed by PCR.
• Admitted in the hospital in the previous 48 hours, with clinical status 3, 4 or 5 of WHO classification.
• Age above 18 years old.
• Informed written consent.

You may not qualify if:

• Invasive mechanical ventilation needed.
• Established limitation of the therapeutic effort
• Inflammatory bowel disease (IBD: Chron Syndrome or Ulcerative colitis), chronic diarrhea or malabsorption.
• Previous neuromuscular disease.
• Other disease with an estimated vital prognosis under 1 year.
• Severe renal insufficiency (glomerular filtration rate \<30 mL/min/1.73m2)
• Medical records of cirrhosis, active chronic hepatitis or severe hepatic disease defined by GOT or GPT levels three times above the normal upper limit.
• Patients with previous colchicine treatment for other diseases (mainly chronic prescriptions for familial Mediterranean fever or gout). Clearance period will not be required for patients treated with colchicine who stopped the treatment before the randomization.
• Patients with history of allergic reaction or significant sensitivity to colchicine.
• Pregnant or breastfeeding female, confirmed by a positive result in the human chorionic gonadotropin (hCG) test.
• Fertile woman, or post-menopausal during less than one year and non-surgically sterilized. Women of fertile age may be included if using at least one contraceptive method and preferably two complementary contraceptive methods.

Sponsors & Collaborators

• Ayub Teaching Hospital: lead
• Universidad de Murcia: collaborator

Study Sites (1)

Ayub Teaching Hospital

Abbottabad, Khyber Pakhtunkhwa, 22010, Pakistan

Location

Related Publications (2)

• 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.

  PMID: 32579195 BACKGROUND

• Scarsi M, Piantoni S, Colombo E, Airo P, Richini D, Miclini M, Bertasi V, Bianchi M, Bottone D, Civelli P, Cotelli MS, Damiolini E, Galbassini G, Gatta D, Ghirardelli ML, Magri R, Malamani P, Mendeni M, Molinari S, Morotti A, Salada L, Turla M, Vender A, Tincani A, Brucato A, Franceschini F, Furloni R, Andreoli L. Association between treatment with colchicine and improved survival in a single-centre cohort of adult hospitalised patients with COVID-19 pneumonia and acute respiratory distress syndrome. Ann Rheum Dis. 2020 Oct;79(10):1286-1289. doi: 10.1136/annrheumdis-2020-217712. Epub 2020 Jul 30.

  PMID: 32732245 BACKGROUND

MeSH Terms

Conditions

COVID-19

Interventions

Colchicine

Condition Hierarchy (Ancestors)

Pneumonia, Viral; Pneumonia; Respiratory Tract Infections; Infections; Virus Diseases; Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Alkaloids; Heterocyclic Compounds

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Phase III, prospective, randomized, controlled, open-label and pragmatic trial, comparing the administration of Colchicine plus standard treatment vs. standard therapy, in hospitalized patients with COVID-19, within the first 48 hours, and no severity criteria.

Study Record Dates

• First Submitted: December 11, 2020
• First Posted: December 16, 2020
• Study Start: December 1, 2020
• Primary Completion: July 9, 2021
• Study Completion: July 9, 2021
• Last Updated: January 5, 2023

Record last verified: 2023-01

Data Sharing

• IPD Sharing: Will not share

Locations

PA (1)