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

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ClinicalTrials.gov Identifier: NCT04350320
Recruitment Status : Recruiting
First Posted : April 17, 2020
Last Update Posted : May 5, 2020
Sponsor:
Information provided by (Responsible Party):
Fundacion para la Formacion e Investigacion Sanitarias de la Region de Murcia

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.

Condition or disease Intervention/treatment Phase
COVID19 Drug: Colchicine Tablets Drug: Standard therapy for COVID-19 according to the stablished hospital protocols. Phase 3

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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 102 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention 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)
Primary Purpose: Treatment
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.
Actual Study Start Date : April 30, 2020
Estimated Primary Completion Date : October 20, 2020
Estimated Study Completion Date : November 20, 2020

Resource links provided by the National Library of Medicine

Drug Information available for: Colchicine

Arm Intervention/treatment
Experimental: 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 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
standard therapy for COVID-19 according to the stablished hospital protocols.

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

Placebo Comparator: control group
Standard therapy for COVID-19 according to the stablished hospital protocols.
Drug: Standard therapy for COVID-19 according to the stablished hospital protocols.
standard therapy for COVID-19 according to the stablished hospital protocols.




Primary Outcome Measures :
  1. Changes in the patients' clinical status through the 7 points ordinal scale WHO R&D Blueprint expert group [ Time Frame: 7,14,28 Days ]
    improve in the clinical evolution of patients hospitalized

  2. Changes in IL-6 concentrations [ Time Frame: up to day 28. ]
    improve in the clinical evolution of patients hospitalized


Secondary Outcome Measures :
  1. Improvement in the clinical status [ Time Frame: up to day 28. ]
    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)

  2. Changes in the score for the Sequential Organ Failure Assessment (SOFA score) [ Time Frame: up to day 28. ]
    Sequential Organ Failure Assessment (SOFA score) (0-14)

  3. Changes in the punctuation in the National Early Warning Score [ Time Frame: up to day 28. ]
    National Early Warning Score (NEWS scale

  4. Number of days with invasive mechanical ventilation [ Time Frame: up to day 28. ]
  5. Number of days with high flow oxygen therapy [ Time Frame: up to day 28. ]
  6. Changes in other inflammatory markers [ Time Frame: up to day 28 ]
    C-reactive protein,

  7. Changes in other inflammatory markers [ Time Frame: up to day 28 ]
    TNF-alfa,

  8. Changes in other inflammatory markers [ Time Frame: up to day 28 ]
    GDF-15,

  9. Changes in other inflammatory markers [ Time Frame: up to day 28 ]
    IL-1β

  10. Changes in severity markers [ Time Frame: up to day 28 ]
    D-dimer

  11. Changes in severity markers [ Time Frame: up to day 28 ]
    leucocytes

  12. Changes in severity markers [ Time Frame: up to day 28 ]
    lymphocytes

  13. Changes in severity markers [ Time Frame: up to day 28 ]
    platelets

  14. Changes in severity markers [ Time Frame: up to day 28 ]
    LDH

  15. Changes in severity markers [ Time Frame: up to day 28 ]
    ferritin

  16. Changes in myocardial damage [ Time Frame: up to day 28 ]
    myocardial stress markers hsTnT

  17. Changes in myocardial damage [ Time Frame: up to day 28 ]
    myocardial stress markers NT-proBNP

  18. Time until reaching a virus negative status [ Time Frame: up to day 28 ]
    RT-PCR assay

  19. Length of hospital stay [ Time Frame: up to day 28 ]
    Length of hospital stay

  20. Number of days in the intensive care unit. [ Time Frame: up to day 28 ]
    Number of days in the intensive care unit.

  21. Mortality [ Time Frame: up to day 28 ]
    Mortality



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

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

Exclusion Criteria:

  1. Invasive mechanical ventilation needed.
  2. Established limitation of the therapeutic effort
  3. Inflammatory bowel disease (IBD: Chron Syndrome or Ulcerative colitis), chronic diarrhea or malabsorption.
  4. Previous neuromuscular disease.
  5. Other disease with an estimated vital prognosis under 1 year.
  6. Severe renal insufficiency (glomerular filtration rate <30 mL/min/1.73m2)
  7. Medical records of cirrhosis, active chronic hepatitis or severe hepatic disease defined by GOT or GPT levels three times above the normal upper limit.
  8. 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.
  9. Patients with history of allergic reaction or significant sensitivity to colchicine.
  10. Treatment with immunosuppressive agents, corticoids or interleukine-1 antagonists for 6 months before inclusion.
  11. Pregnant or breastfeeding female, confirmed by a positive result in the human chorionic gonadotropin (hCG) test.
  12. 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.
  13. Use of other investigational drugs in the moment of inclusion, or during 30 days previous to inclusion.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04350320


Contacts
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Contact: Domingo A Pascual Figal, MD 968369500 dpascual@um.es
Contact: Elisa García Vazquez

Locations
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Spain
Virgen de la Arrixaca University Clinical Hospital Recruiting
Murcia, Spain, 30120
Sponsors and Collaborators
Fundacion para la Formacion e Investigacion Sanitarias de la Region de Murcia
Investigators
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Principal Investigator: Domingo A Pascual Figal, MD HCUVA
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Responsible Party: Fundacion para la Formacion e Investigacion Sanitarias de la Region de Murcia
ClinicalTrials.gov Identifier: NCT04350320    
Other Study ID Numbers: IMIB-COLVID-2020-03
First Posted: April 17, 2020    Key Record Dates
Last Update Posted: May 5, 2020
Last Verified: April 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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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
Additional relevant MeSH terms:
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Colchicine
Gout Suppressants
Antirheumatic Agents
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents