Back to resultsTrial to Study the Benefit of Colchicine in Patients With COVID-19 (COL-COVID)
Primary Purpose
COVID19
Status
Completed
Phase
Phase 3
Locations
Spain
Study Type
Interventional
Intervention
Colchicine Tablets
Standard therapy for COVID-19 according to the stablished hospital protocols.
Sponsored by
About this trial
This is an interventional treatment trial for COVID19
Eligibility Criteria
Inclusion Criteria:
- 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.
Exclusion Criteria:
- 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.
- Treatment with immunosuppressive agents, corticoids or interleukine-1 antagonists for 6 months before inclusion.
- 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.
- Use of other investigational drugs in the moment of inclusion, or during 30 days previous to inclusion.
Sites / Locations
- Virgen de la Arrixaca University Clinical Hospital
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Placebo Comparator
Arm Label
COLCHICINE
control group
Arm Description
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.
Standard therapy for COVID-19 according to the stablished hospital protocols.
Outcomes
Primary Outcome Measures
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
Changes in IL-6 concentrations
improve in the clinical evolution of patients hospitalized
Secondary Outcome Measures
Improvement in the clinical status
time needed to reduce at least 2 points in the 7-point Ordinal Scale for Clinical Improvement by WHO R&D Blueprint expert group (0-7)
Changes in the score for the Sequential Organ Failure Assessment (SOFA score)
Sequential Organ Failure Assessment (SOFA score) (0-14)
Changes in the punctuation in the National Early Warning Score
National Early Warning Score (NEWS scale
Number of days with invasive mechanical ventilation
Number of days with high flow oxygen therapy
Changes in other inflammatory markers
C-reactive protein,
Changes in other inflammatory markers
TNF-alfa,
Changes in other inflammatory markers
GDF-15,
Changes in other inflammatory markers
IL-1β
Changes in severity markers
D-dimer
Changes in severity markers
leucocytes
Changes in severity markers
lymphocytes
Changes in severity markers
platelets
Changes in severity markers
LDH
Changes in severity markers
ferritin
Changes in myocardial damage
myocardial stress markers hsTnT
Changes in myocardial damage
myocardial stress markers NT-proBNP
Time until reaching a virus negative status
RT-PCR assay
Length of hospital stay
Length of hospital stay
Number of days in the intensive care unit.
Number of days in the intensive care unit.
Mortality
Mortality
Full Information
NCT ID
NCT04350320
First Posted
April 14, 2020
Last Updated
January 11, 2021
Sponsor
Fundacion para la Formacion e Investigacion Sanitarias de la Region de Murcia
1. Study Identification
Unique Protocol Identification Number
NCT04350320
Brief Title
Trial to Study the Benefit of Colchicine in Patients With COVID-19
Acronym
COL-COVID
Official Title
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 Type
Interventional
2. Study Status
Record Verification Date
January 2021
Overall Recruitment Status
Completed
Study Start Date
April 30, 2020 (Actual)
Primary Completion Date
October 20, 2020 (Actual)
Study Completion Date
December 30, 2020 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Fundacion para la Formacion e Investigacion Sanitarias de la Region de Murcia
4. Oversight
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
Data Monitoring Committee
No
5. Study Description
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.
Detailed Description
This is a Phase III, prospective, pragmatic, randomized, controlled and open-label trial, comparing standard of care vs. standard of care plus COLCHICINE for four weeks, in patients hospitalized due to COVID-19 and confirmed infection by SARSCov2, within the first 48 hours after the hospital admission. Patients meeting severity criteria will be excluded, defined as established limitation of therapeutic effort or need for invasive mechanical ventilation at the time of inclusion. 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.
Patients meeting all the inclusion criteria and none of the exclusion ones (see below), after signing the informed consent, will be centrally randomized to "colchicine" or "control" group. Patients in both groups will receive the standard therapy for COVID-19 according to the stablished hospital protocols. Randomization will be controlled by: age, sex, time from initiation of symptoms, cardiovascular disease, the 7 point WHO and levels of C-reactive protein, ferritin, D-dimer, IL-6 and lymphocyte levels.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
COVID19
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Model Description
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
Masking
None (Open Label)
Allocation
Randomized
Enrollment
102 (Actual)
8. Arms, Groups, and Interventions
Arm Title
COLCHICINE
Arm Type
Experimental
Arm Description
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.
Arm Title
control group
Arm Type
Placebo Comparator
Arm Description
Standard therapy for COVID-19 according to the stablished hospital protocols.
Intervention Type
Drug
Intervention Name(s)
Colchicine Tablets
Intervention Description
standard therapy for COVID-19 according to the stablished hospital protocols.
Intervention Type
Drug
Intervention Name(s)
Standard therapy for COVID-19 according to the stablished hospital protocols.
Intervention Description
standard therapy for COVID-19 according to the stablished hospital protocols.
Primary Outcome Measure Information:
Title
Changes in the patients' clinical status through the 7 points ordinal scale WHO R&D Blueprint expert group
Description
improve in the clinical evolution of patients hospitalized
Time Frame
7,14,28 Days
Title
Changes in IL-6 concentrations
Description
improve in the clinical evolution of patients hospitalized
Time Frame
up to day 28.
Secondary Outcome Measure Information:
Title
Improvement in the clinical status
Description
time needed to reduce at least 2 points in the 7-point Ordinal Scale for Clinical Improvement by WHO R&D Blueprint expert group (0-7)
Time Frame
up to day 28.
Title
Changes in the score for the Sequential Organ Failure Assessment (SOFA score)
Description
Sequential Organ Failure Assessment (SOFA score) (0-14)
Time Frame
up to day 28.
Title
Changes in the punctuation in the National Early Warning Score
Description
National Early Warning Score (NEWS scale
Time Frame
up to day 28.
Title
Number of days with invasive mechanical ventilation
Time Frame
up to day 28.
Title
Number of days with high flow oxygen therapy
Time Frame
up to day 28.
Title
Changes in other inflammatory markers
Description
C-reactive protein,
Time Frame
up to day 28
Title
Changes in other inflammatory markers
Description
TNF-alfa,
Time Frame
up to day 28
Title
Changes in other inflammatory markers
Description
GDF-15,
Time Frame
up to day 28
Title
Changes in other inflammatory markers
Description
IL-1β
Time Frame
up to day 28
Title
Changes in severity markers
Description
D-dimer
Time Frame
up to day 28
Title
Changes in severity markers
Description
leucocytes
Time Frame
up to day 28
Title
Changes in severity markers
Description
lymphocytes
Time Frame
up to day 28
Title
Changes in severity markers
Description
platelets
Time Frame
up to day 28
Title
Changes in severity markers
Description
LDH
Time Frame
up to day 28
Title
Changes in severity markers
Description
ferritin
Time Frame
up to day 28
Title
Changes in myocardial damage
Description
myocardial stress markers hsTnT
Time Frame
up to day 28
Title
Changes in myocardial damage
Description
myocardial stress markers NT-proBNP
Time Frame
up to day 28
Title
Time until reaching a virus negative status
Description
RT-PCR assay
Time Frame
up to day 28
Title
Length of hospital stay
Description
Length of hospital stay
Time Frame
up to day 28
Title
Number of days in the intensive care unit.
Description
Number of days in the intensive care unit.
Time Frame
up to day 28
Title
Mortality
Description
Mortality
Time Frame
up to day 28
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
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.
Exclusion Criteria:
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.
Treatment with immunosuppressive agents, corticoids or interleukine-1 antagonists for 6 months before inclusion.
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.
Use of other investigational drugs in the moment of inclusion, or during 30 days previous to inclusion.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Domingo A Pascual Figal, MD
Organizational Affiliation
HCUVA
Official's Role
Principal Investigator
Facility Information:
Facility Name
Virgen de la Arrixaca University Clinical Hospital
City
Murcia
ZIP/Postal Code
30120
Country
Spain
12. IPD Sharing Statement
Plan to Share IPD
No
Citations:
PubMed Identifier
34658014
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.
Results Reference
derived
PubMed Identifier
34539185
Citation
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.
Results Reference
derived
Learn more about this trial
Trial to Study the Benefit of Colchicine in Patients With COVID-19
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