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

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ClinicalTrials.gov Identifier: NCT04667780
Recruitment Status : Recruiting
First Posted : December 16, 2020
Last Update Posted : December 16, 2020
Sponsor:
Collaborator:
Universidad de Murcia
Information provided by (Responsible Party):
Dr Umer Farooq, Ayub Teaching Hospital

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.

Condition or disease Intervention/treatment Phase
COVID-19 Drug: Colchicine Drug: Standard COVID-19 care 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 14 days, in patients hospitalized due to COVID-19 and confirmed infection by SARS-CoV-2, 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 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.

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 as per the 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: Study to Investigate the Treatment Effect of Colchicine in Patients With COVID-19
Actual Study Start Date : December 10, 2020
Estimated Primary Completion Date : May 9, 2021
Estimated Study Completion Date : July 9, 2021

Resource links provided by the National Library of Medicine

Drug Information available for: Colchicine

Arm Intervention/treatment
Experimental: Colchicine

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
Colchicine tablet 0.5 mg

Drug: Standard COVID-19 care
As per the hospital guidelines

Control - Standard COVID-19 care
This arm will receive standard COVID-19 care as per the hospital guidelines.
Drug: Standard COVID-19 care
As per the hospital guidelines




Primary Outcome Measures :
  1. Changes in the patients' clinical status through the 7 points ordinal scale WHO R&D Blueprint expert group [ Time Frame: up to 14 days ]
    Improvement in the clinical evolution of patients

  2. Changes in IL-6 concentrations [ Time Frame: up to 14 days ]
    Improvement in cytokine level


Secondary Outcome Measures :
  1. Improvement in the clinical status [ Time Frame: up to 14 days ]
    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 14 days ]
    Sequential Organ Failure Assessment (SOFA score) (0-14)

  3. Changes in the punctuation in the National Early Warning Score [ Time Frame: up to 14 days ]
    National Early Warning Score (NEWS scale)

  4. Number of days with invasive mechanical ventilation [ Time Frame: up to 14 days ]
  5. Number of days with high flow oxygen therapy [ Time Frame: up to 14 days ]
  6. Changes in other inflammatory markers [ Time Frame: up to 14 days ]
    C-reactive protein

  7. Changes in severity markers [ Time Frame: up to 14 days ]
    D-dimer

  8. Changes in severity markers [ Time Frame: up to 14 days ]
    Leukocytes

  9. Changes in severity markers [ Time Frame: up to 14 days ]
    Lymphocytes

  10. Changes in severity markers [ Time Frame: up to 14 days ]
    Platelets

  11. Changes in severity markers [ Time Frame: up to 14 days ]
    LDH

  12. Changes in severity markers [ Time Frame: up to 14 days ]
    Ferritin

  13. Changes in myocardial damage [ Time Frame: up to 14 days ]
    myocardial stress markers hsTnT

  14. Changes in myocardial damage [ Time Frame: up to 14 days ]
    myocardial stress markers NT-proBNP

  15. Time until reaching a virus negative status [ Time Frame: up to 14 days ]
    RT-PCR assay

  16. Length of hospital stay [ Time Frame: up to 14 days ]
    Length of hospital stay

  17. Number of days in the intensive care unit. [ Time Frame: up to 14 days ]
    Number of days in the intensive care unit.

  18. Mortality [ Time Frame: up to 14 days ]
    Mortality



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 65 Years   (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): NCT04667780


Contacts
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Contact: Dr. Zeeshan Haroon, MBBS + 92 3175564317 zeeshanharoon@yahoo.com

Locations
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Pakistan
Ayub Teaching Hospital Recruiting
Abbottabad, Khyber Pakhtunkhwa, Pakistan, 22010
Contact: Dr. Zeeshan Haroon, MBBS    + 92 317 5564317    zeeshanharoon@yahoo.com   
Sponsors and Collaborators
Ayub Teaching Hospital
Universidad de Murcia
Publications:
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, Martinèz-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.

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Responsible Party: Dr Umer Farooq, Professor, Ayub Teaching Hospital
ClinicalTrials.gov Identifier: NCT04667780    
Other Study ID Numbers: ATH/IRB/Colchicine/25.11.2020
First Posted: December 16, 2020    Key Record Dates
Last Update Posted: December 16, 2020
Last Verified: December 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