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The ECLA PHRI COLCOVID Trial. Effects of Colchicine on Moderate/High-risk Hospitalized COVID-19 Patients. (COLCOVID)

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ClinicalTrials.gov Identifier: NCT04328480
Recruitment Status : Completed
First Posted : March 31, 2020
Last Update Posted : April 27, 2021
Sponsor:
Collaborator:
Population Health Research Institute
Information provided by (Responsible Party):
Estudios Clínicos Latino América

Brief Summary:
The ECLA PHRI COLCOVID Trial is a simple, pragmatic randomized open controlled trial to test the effects of colchicine on moderate/high-risk hospitalized COVID-19 patients with the aim of reducing mortality and/or new requirement for mechanical ventilation.

Condition or disease Intervention/treatment Phase
COVID-19 Drug: Colchicine Other: Local standard of care Phase 3

Detailed Description:

Various anti-viral treatments are being tested in clinical trials worldwide. The World Health Organization (WHO) launched a simple,pragmatic worldwide open-label trial to test Remdesivir, Lopinavir/Ritonavir, Interferon and Hydroxychloroquine or Chloroquine.The most important complication of COVID-19 severe cases is respiratory failure from severe acute respiratory syndrome (SARS), the leading cause of mortality. Accumulating evidence suggests that patients with severe COVID-19 might have a cytokine storm syndrome, a hyperinflammatory syndrome characterized by a fulminant and fatal hypercytokinemia and multiorgan failure.

The proposed pathophysiological mechanism of cytokine storm and inflammatory cascade activation is based on evidence collected primarily during the SARS-CoV and MERS-CoV epidemics (with a significant increase in IL1B, IL6, IL12, IFNγ, IP10, TNFα, IL15, and IL17 among others). The data collected during the pandemic with COVID-19 also shows a significant increase in inflammatory cytokines (GCSF, IP10, MCP1, MIP1A, and TNFα, among others) in sicker patients admitted to intensive care. In the absence of effective treatments for the management of patients with COVID-19 and respiratory failure, the immunomodulatory and anti-inflammatory effect of colchicine on cytokines involved in the hyper-inflammatory state is postulated. Several lines of research worldwide are testing powerful anti-inflammatory drugs for the pandemic, with different options including steroids, cytokine blockers, and other potent anti-inflammatory agents. Steroids are partially contraindicated in viral infections.

Colchicine is a powerful anti-inflammatory drug approved for the treatment or prevention of gout and Familial Mediterranean Fever at doses ranging between 0.3 mg and 2.4 mg/day. Its mechanism of action is through the inhibition of tubulin polymerization, as well as through potential effects on cellular adhesion molecules and inflammatory chemokines. It might also have direct anti-inflammatory effects by inhibiting key inflammatory signalling networks known as inflammasome and pro-inflammatory cytokines. Additionally, evidence suggests that colchicine exerts a direct anti-inflammatory effect by inhibiting the synthesis of tumor necrosis factor alpha and IL-6, monocyte migration, and the secretion of matrix metalloproteinase-9. Through the disruption of the cytoskeleton, colchicine is believed to suppress secretion of cytokines and chemokines as well as in vitro platelet aggregation. All these are potentially beneficial effects that might diminish or ameliorate the COVID-19 inflammatory storm associated with severe forms of the disease. Importantly, in one contemporary trial low-dose colchicine administered to patients who survived from acute coronary syndrome shows a statistically significantly reduction of cardiovascular complications.

We have therefore designed in a simple, pragmatic randomized controlled trial to test the effects of colchicine on severe hospitalized COVID-19 cases with the aim of reducing mortality.

Sample size calculation:

A minimum sample size of 1200 patients will provide 80% power to detect a relative risk reduction of approximately 30% in the treated group if the assumed composite rate (new requirement of intubation and / or death) in the control group is about 24%.

The ECLA PHRI COLCOVID Trial allows randomization to another trial, specifically patients included in the trial might be (or not) randomized to an antithrombotic strategy.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 1279 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: Simple pragmatic randomized open controlled trial
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: The ECLA PHRI COLCOVID Trial
Actual Study Start Date : April 17, 2020
Actual Primary Completion Date : April 25, 2021
Actual Study Completion Date : April 26, 2021

Resource links provided by the National Library of Medicine

Drug Information available for: Colchicine

Arm Intervention/treatment
Active Comparator: Local standard of care plus colchicine
Local standard of care plus colchicine (specific dosage schedule)
Drug: Colchicine

The colchicine dosage schedule will vary according to the following scenarios:

  1. In patients not receiving Lopinavir/Ritonavir

    • Loading dose of 1.5 mg followed by 0.5 mg after two hours (day 1)
    • The next day 0.5 mg bid for 14 days or until discharge.
  2. In patients receiving Lopinavir/Ritonavir

    • Loading dose of 0.5 mg (day 1)
    • After 72 hours from the loading dose, 0.5 mg every 72 hours for 14 days or until discharge.
  3. Patients under treatment with Colchicine that are starting with Lopinavir/Ritonavir

    • Dose of 0.5 mg 72 hours after starting Lopinavir/Ritonavir.
    • Continue with 0.5 mg every 72 hours for 14 days or until discharge.

Only the oral route will be used except in the case of patients associated with mechanical ventilation or with contraindications to the oral route, in whom it will be administered by nasogastric tube.

Other Name: Colchicina

Other: Local standard of care
Local standard of care for COVID-19 SARS moderate /high-risk patients

Local standard of care
Local standard of care for COVID-19 SARS moderate / high-risk patients
Other: Local standard of care
Local standard of care for COVID-19 SARS moderate /high-risk patients




Primary Outcome Measures :
  1. Composite outcome: New requirement for mechanical ventilation or death [ Time Frame: 28 days post randomization ]
    Number of participants who require new intubation for mechanical ventilation or die

  2. Mortality [ Time Frame: 28 days post randomization ]
    Number of participants who die


Secondary Outcome Measures :
  1. New requirement for mechanical ventilation or death from respiratory failure [ Time Frame: 28 days post randomization ]
    Number of participants who require new intubation for mechanical ventilation or die from respiratory failure

  2. New requirement for mechanical ventilation or death from non-respiratory failure [ Time Frame: 28 days post randomization ]
    Number of participants who require new intubation for mechanical ventilation or die from non-respiratory failure

  3. Mortality due to respiratory failure [ Time Frame: 28 days post randomization ]
    Number of participants who die from respiratory failure

  4. Mortality due to non-respiratory failure [ Time Frame: 28 days post randomization ]
    Number of participants who die from non-respiratory failure

  5. In hospital - Composite outcome [ Time Frame: During hospitalization or until death, whichever comes first, assessed up to 28 days ]
    Number of participants who require intubation for mechanical ventilation or die

  6. In hospital - Mortality [ Time Frame: During hospitalization or until death, whichever comes first, assessed up to 28 days ]
    Number of participants who die

  7. Composite outcome (New requirement for mechanical ventilation or death) evaluated in Non-intubated population [ Time Frame: 28 days post randomization ]
    Number of participants who were not intubated at randomization and require new intubation for mechanical ventilation or die

  8. Mortality evaluated in Non-intubated population [ Time Frame: 28 days post randomization ]
    Number of participants who were not intubated at randomization and die

  9. Mean WHO descriptive score of COVID-19 during hospitalization [ Time Frame: During hospitalization or until death, whichever comes first, assessed up to 28 days ]
    Mean WHO descriptive score of COVID-19 in the active treatment group compared to the placebo group

  10. Highest WHO descriptive score of COVID-19 during hospitalization [ Time Frame: During hospitalization or until death, whichever comes first, assessed up to 28 days ]
    Mean highest WHO descriptive score of COVID-19 in the active treatment group compared to the placebo group



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 (case definition)

  • Consented adults (age ≥18 years) and
  • COVID-19 suspicious and
  • Admitted to hospital or already in hospital and
  • COVID-19 suggestive symptoms (fever or febrile equivalent, loss of smell and taste, fatigue, etc.) that may be present or absent at randomization time and
  • SARS (severe acute respiratory syndrome)

    • shortness of breath (dyspnea) or
    • image of typical or atypical pneumonia or
    • oxygen desaturation (SpO2 ≤ 93)

Exclusion criteria

  • Clear indication or contraindication for the use of colchicine
  • Pregnant or breastfeeding female.
  • Chronic renal disease with creatinine clearance <15 ml/min/m2
  • Negative PCR test for SARS-COV2

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): NCT04328480


Locations
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Argentina
Sanatorio Parque
Rosario, Santa Fe, Argentina, 2000
Sponsors and Collaborators
Estudios Clínicos Latino América
Population Health Research Institute
Investigators
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Principal Investigator: Rafael Diaz, MD ECLA- ICR
Additional Information:
Publications of Results:
Other Publications:
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Responsible Party: Estudios Clínicos Latino América
ClinicalTrials.gov Identifier: NCT04328480    
Other Study ID Numbers: COLCOVID version 2.0
First Posted: March 31, 2020    Key Record Dates
Last Update Posted: April 27, 2021
Last Verified: April 2021
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