Trial to Study the Benefit of Colchicine in Patients With COVID-19

NCT04350320 | Completed Phase 3

• 1 other identifier: IMIB-COLVID-2020-03
• 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. We present a randomized clinical trial, controlled, open-label and pragmatic, including COVID-19 patients requiring hospitalization but no intensive care yet. Colchicine will be started within the first 48 hours and then administered for four weeks using a descending dose. The benefit will be study 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 widely accessible which would help to prevent the inflammatory complications associated with COVID-19.

Conditions

COVID19

Outcome Measures

Primary Outcomes (2)

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

  improve in the clinical evolution of patients hospitalized

  7,14,28 Days

• Changes in IL-6 concentrations

  improve in the clinical evolution of patients hospitalized

  up to day 28.

Secondary Outcomes (21)

• Improvement in the clinical status

  up to day 28.

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

  up to day 28.

• Changes in the punctuation in the National Early Warning Score

  up to day 28.

• Number of days with invasive mechanical ventilation

  up to day 28.

• Number of days with high flow oxygen therapy

  up to day 28.

Study Arms (2)

COLCHICINE

EXPERIMENTAL

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 28 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. \+ standard therapy for COVID-19 according to the stablished hospital protocols.

Drug: Colchicine Tablets; Drug: Standard therapy for COVID-19 according to the stablished hospital protocols.

control group

PLACEBO COMPARATOR

Standard therapy for COVID-19 according to the stablished hospital protocols.

Drug: Standard therapy for COVID-19 according to the stablished hospital protocols.

Interventions

Colchicine Tablets DRUG

standard therapy for COVID-19 according to the stablished hospital protocols.

COLCHICINE

Standard therapy for COVID-19 according to the stablished hospital protocols. DRUG

standard therapy for COVID-19 according to the stablished hospital protocols.

COLCHICINE; control group

Eligibility Criteria

• Age: 18 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

• Fundacion para la Formacion e Investigacion Sanitarias de la Region de Murcia: lead

Study Sites (1)

Virgen de la Arrixaca University Clinical Hospital

Murcia, 30120, Spain

Location

Related Publications (2)

• 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.

  PMID: 34658014 DERIVED

• Pascual-Figal DA, Roura-Piloto AE, Moral-Escudero E, Bernal E, Albendin-Iglesias H, Perez-Martinez MT, Noguera-Velasco JA, Cebreiros-Lopez I, Hernandez-Vicente A, Vazquez-Andres D, Sanchez-Perez C, Khan A, Sanchez-Cabo F, Garcia-Vazquez E; COL-COVID Investigators. Colchicine in Recently Hospitalized Patients with COVID-19: A Randomized Controlled Trial (COL-COVID). Int J Gen Med. 2021 Sep 11;14:5517-5526. doi: 10.2147/IJGM.S329810. eCollection 2021.

  PMID: 34539185 DERIVED

MeSH Terms

Conditions

COVID-19

Interventions

Colchicine; Standard of Care

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; Quality Indicators, Health Care; Quality of Health Care; Health Services Administration; Health Care Quality, Access, and Evaluation

Study Officials

• Domingo A Pascual Figal, MD

  HCUVA

  PRINCIPAL INVESTIGATOR

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: April 14, 2020
• First Posted: April 17, 2020
• Study Start: April 30, 2020
• Primary Completion: October 20, 2020
• Study Completion: December 30, 2020
• Last Updated: January 12, 2021

Record last verified: 2021-01

Data Sharing

• IPD Sharing: Will not share

Locations

ES (1)