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

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ClinicalTrials.gov Identifier: NCT04603690
Recruitment Status : Withdrawn (No funding available)
First Posted : October 27, 2020
Last Update Posted : December 10, 2020
Sponsor:
Collaborator:
Universidad de Murcia
Information provided by (Responsible Party):
Prof. Dr. Ikram Din Ujjan, MBBS, PhD, Liaquat University of Medical & Health Sciences

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 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.

Patiens 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)
Actual Enrollment : 0 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: A Randomized, Open-labeled, and Controlled Trial to Study the Benefits of Colchicine in Patients With COVID-19
Estimated Study Start Date : December 15, 2020
Estimated Primary Completion Date : May 14, 2021
Estimated Study Completion Date : June 14, 2021

Resource links provided by the National Library of Medicine

Drug Information available for: Colchicine

Arm Intervention/treatment
Experimental: Colchicine

This arm will receive Colchicine + Standard care as per hospital guidelines.

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
1 mg tablet

No Intervention: Control group
This arm will receive standard care as per the hospital guidelines.



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

  2. Changes in IL-6 concentrations [ Time Frame: up to 14 days ]
    Improvement in the clinical status


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 or ECMO [ 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 (C-reactive protein, IL-6) from randomization [ Time Frame: up to 14 days ]
  7. Changes in severity markers (D-dimer, lymphocytes, and ferritin) from randomization [ Time Frame: up to 14 days ]
  8. Changes in myocardial damage and stress markers (hsTnT and NT-proBNP) from randomization. [ Time Frame: up to 14 days ]
  9. Time until reaching a virus negative status by RT-PCR assay [ Time Frame: up to 14 days ]
  10. Length of hospital stay [ Time Frame: up to 14 days ]
  11. Number of days in the intensive care unit [ Time Frame: up to 14 days ]
  12. Mortality by causes [ Time Frame: up to 14 days ]


Information from the National Library of Medicine

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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.
Additional Information:
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Responsible Party: Prof. Dr. Ikram Din Ujjan, MBBS, PhD, Professor of Pathology, Liaquat University of Medical & Health Sciences
ClinicalTrials.gov Identifier: NCT04603690    
Other Study ID Numbers: LUMHS/REC/893
First Posted: October 27, 2020    Key Record Dates
Last Update Posted: December 10, 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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COVID-19
Respiratory Tract Infections
Infections
Pneumonia, Viral
Pneumonia
Virus Diseases
Coronavirus Infections
Coronaviridae Infections
Nidovirales Infections
RNA Virus Infections
Lung Diseases
Respiratory Tract Diseases
Colchicine
Gout Suppressants
Antirheumatic Agents
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents