Double Blind Randomized Clinical Trial of Use of Colchicine Added to Standard Treatment in Hospitalized With Covid-19

Double Blind Randomized Clinical Trial of Use of Colchicine Added to Standard Treatment in Hospitalized Patients With Covid-19 Infection

EC CORONACOLCHI is a multicenter, double-blind and randomized clinical trial with two branches. Patients who meet all the inclusion criteria and none of the exclusion criteria will be randomized 1: 1 to be included in one of the following groups:

• Experimental group: colchicine for 2 weeks orally at the doses described, added to the standard treatment of COVID-19.
• Control group: placebo for 2 weeks orally added to standard COVID-19 treatment.

Study Overview

• Status: Active, not recruiting
• Conditions: COVID-19 Infection
• Intervention / Treatment: Drug: Colchcine

• Study Type: Interventional
• Enrollment (Anticipated): 752
• Phase: Phase 3

Contacts and Locations

Study Locations

• Spain
  • Guipuzcoa
    • San Sebastián, Guipuzcoa, Spain, 20014
      • Biodonostia Health Research Institute

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 99 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• 1 - Acute symptoms compatible with SARS-CoV-2 infection: fever, cough, myalgia, dysgeusia / ageusia, dyspnea, pulmonary infiltrates on X-ray / CT, or any sign / symptom attributable to said infection
• 2. Microbiologically confirmed infection by SARS-CoV-2 (PCR and / or CLIA or ELISA serology or with a valid microbiological diagnostic test with antigen test).
• 3.> 18 years.
• 4. <2 weeks from the onset of symptoms.
• 5. Admitted (with or without pneumonia) and ambulant (with pneumonia demonstrated by X-ray or CT)
• 6. Some analytical degree of moderate inflammation defined by PCR between 20 and 80 mg / L and / or ferritin between the high limit of normality (LAN) and 3 times said LAN
• 7. Signing of the Informed Consent, or acceptance of oral consent before witnesses.

Exclusion Criteria:

• 1. Drug allergy.
• 2. Intolerance to lactose and / or cow's milk proteins.
• 3. Renal failure with GFR <30 ml / min.
• 4. Liver cirrhosis or severe liver failure
• 5. Pregnancy or breastfeeding.
• 6. Blood dyscrasias or cardiac disorders that in the opinion of the investigator contraindicate the use of colchicine.
• 7. Pre-existing degenerative neuromuscular disease.
• 8. Acute or chronic diarrhea or malabsorptive syndrome that in the judgment of the clinician contraindicates the use of colchicine.
• 9. CRP> 80 mg / L or ferritin> 3 times LAN
• 10. Shock or hemodynamic instability.
• 11. Respiratory distress measured by PaO2 / FIO2 <300 or baseline O2 saturation ≤ 93%.
• 12. Patients undergoing mechanical ventilation.
• 13. Chronic treatment with any drug that, in the opinion of the investigator, interacts with colchicine and cannot be discontinued during the clinical trial, unacceptably increasing the risk of toxicity (digoxin, cyclosporine, etc.)
• 14. Have received any dose of colchicine, tocilizumab, any antiL6 or antiL1 drug.
• 15. Current treatment with corticosteroids (except chronic corticosteroid therapy without recent increase in dose).
• 16. Participation in any other clinical trial of patients with COVID-19.
• 17. Any other condition that, in the opinion of the investigator, contraindicates the use of colchicine or puts the subject at risk due to their participation in the study.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Colchicine; EC Experimental group: colchicine for 2 weeks orally added to standard treatment.	Drug: Colchcine; In patients not taking lopinavir / ritonavir or any other CYP3A4 or P-glycoprotein inhibitor drugs: Day 1: 1 single dose of 1 mg orally, in a single dose.; Days 2 to 6: 0.5 mg every 12 hours v.o.; Days 7 to 14: 0.5 mg / 24 hours v.o. In patients taking drugs that inhibit the CYP3A4 system or the P-glycoprotein, these drugs will be attempted to be discontinued. The dose in these cases will be: o 0.5 mg every 72 hours v.o. while taking the drug that interacts. or 0.5 mg every 24 hours v.o. when, after suspending the interacting drug, at least 5 half-lives of the suspended drug have elapsed, from the last intake of said drug (in the case of lopinavir / ritonavir this would be a total of 24-30 hours) until the 14th day. In patients older than 80 years or patients with CKD-EPI estimated glomerular renal failure filtration rate between 30 and 50 ml / min / 1.73 m2), the colchicine / placebo dose will be: o Days 1 to 14: 0.5 mg / day
Placebo Comparator: Placebo; Control group: placebo for 2 weeks added to standard treatment.	Drug: Colchcine; In patients not taking lopinavir / ritonavir or any other CYP3A4 or P-glycoprotein inhibitor drugs: Day 1: 1 single dose of 1 mg orally, in a single dose.; Days 2 to 6: 0.5 mg every 12 hours v.o.; Days 7 to 14: 0.5 mg / 24 hours v.o. In patients taking drugs that inhibit the CYP3A4 system or the P-glycoprotein, these drugs will be attempted to be discontinued. The dose in these cases will be: o 0.5 mg every 72 hours v.o. while taking the drug that interacts. or 0.5 mg every 24 hours v.o. when, after suspending the interacting drug, at least 5 half-lives of the suspended drug have elapsed, from the last intake of said drug (in the case of lopinavir / ritonavir this would be a total of 24-30 hours) until the 14th day. In patients older than 80 years or patients with CKD-EPI estimated glomerular renal failure filtration rate between 30 and 50 ml / min / 1.73 m2), the colchicine / placebo dose will be: o Days 1 to 14: 0.5 mg / day

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Proportion of patients who present death, need for mechanical ventilation or respiratory distress (Pa02 / FiO2 <300 or baseline O2 saturation ≤93%) on days +7, +14 and +30.	Although the definition of respiratory distress usually includes a radiological criterion, as long as the oxygenation deficit is not attributable to another cause by the clinician, we do not consider it essential to perform a chest X-ray to confirm the diagnosis of distress because it does not correspond to clinical practice routine and the X-ray result does not change the patient's management.	30 days (from day +1 to day +30)
Each of the items (proportion of patients who suffer death, need for mechanical ventilation and development of respiratory distress) separately on days +7, +14 and +30.		30 days (from day +1 to day +30)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Proportion of patients in each of the items of the clinical scale detailed below on days +3, +7, +14 and +30:	Not hospitalized, usual activities not limited; Not hospitalized with limitation for usual activities; Hospitalized, without oxygen requirements; Hospitalized with oxygen requirements; Hospitalized with oxygen in a reservoir, non-invasive mechanical ventilation or high-flow oxygen device; Hospitalized with the need for invasive mechanical ventilation; Deceased	30 days (from day +1 to day +30)
Time (days) until death		30 days (from day +1 to day +30)
Proportion of patients in whom fever ≥37.8 ºC persists on days +3, +7, +14 and +30.		30 days (from day +1 to day +30)
Evolution of the levels of C-Reactive Protein (CRP), LDH, D-dimer, ferritin, lymphocytes on days +3, +7, +14 and +30.		30 days (from day +1 to day +30)
Proportion of patients who have received tocilizumab / other antiL6 or antiL1 drug / corticosteroids on days +3, +7, +14 and +30.		30 days (from day +1 to day +30)
Proportion of patients experiencing serious unexpected adverse reactions that require discontinuation of the investigational product.		30 days (from day +1 to day +30)

Collaborators and Investigators

• Sponsor: Asociacion Instituto Biodonostia

Study record dates

Study Major Dates

• Study Start (Actual): September 8, 2020
• Primary Completion (Anticipated): September 1, 2021
• Study Completion (Anticipated): January 1, 2022

Study Registration Dates

• First Submitted: August 3, 2021
• First Submitted That Met QC Criteria: August 6, 2021
• First Posted (Actual): August 9, 2021

Study Record Updates

• Last Update Posted (Actual): August 9, 2021
• Last Update Submitted That Met QC Criteria: August 6, 2021
• Last Verified: August 1, 2021

More Information

Terms related to this study

• Keywords: covid-19; colchicine
• Additional Relevant MeSH Terms: Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Virus Diseases; Respiratory Tract Infections; Respiratory Tract Diseases; Pneumonia, Viral; Pneumonia; Lung Diseases; COVID-19; Infections
• Other Study ID Numbers: EC CORONACOLCHI

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• 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