Back to resultsStudy to Investigate the Treatment Effect of Colchicine in Patients With COVID-19
Primary Purpose
COVID-19
Status
Completed
Phase
Phase 3
Locations
Pakistan
Study Type
Interventional
Intervention
Colchicine
Standard COVID-19 care
Sponsored by
About this trial
This is an interventional treatment trial for COVID-19
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
- Ayub Teaching Hospital
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Other
Arm Label
Colchicine
Control - Standard COVID-19 care
Arm Description
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.
This arm will receive standard COVID-19 care as per the hospital guidelines.
Outcomes
Primary Outcome Measures
Changes in the patients' clinical status through the 7 points ordinal scale WHO R&D Blueprint expert group
Improvement in the clinical evolution of patients
Changes in IL-6 concentrations
Improvement in cytokine level
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 severity markers
D-dimer
Changes in severity markers
Leukocytes
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
NCT04667780
First Posted
December 11, 2020
Last Updated
January 4, 2023
Sponsor
Ayub Teaching Hospital
Collaborators
Universidad de Murcia
1. Study Identification
Unique Protocol Identification Number
NCT04667780
Brief Title
Study to Investigate the Treatment Effect of Colchicine in Patients With COVID-19
Official Title
Study to Investigate the Treatment Effect of Colchicine in Patients With COVID-19
Study Type
Interventional
2. Study Status
Record Verification Date
January 2023
Overall Recruitment Status
Completed
Study Start Date
December 1, 2020 (Actual)
Primary Completion Date
July 9, 2021 (Actual)
Study Completion Date
July 9, 2021 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Ayub Teaching Hospital
Collaborators
Universidad 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
Yes
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. 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.
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
COVID-19
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
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.
Arm Title
Control - Standard COVID-19 care
Arm Type
Other
Arm Description
This arm will receive standard COVID-19 care as per the hospital guidelines.
Intervention Type
Drug
Intervention Name(s)
Colchicine
Intervention Description
Colchicine tablet 0.5 mg
Intervention Type
Drug
Intervention Name(s)
Standard COVID-19 care
Intervention Description
As per the hospital guidelines
Primary Outcome Measure Information:
Title
Changes in the patients' clinical status through the 7 points ordinal scale WHO R&D Blueprint expert group
Description
Improvement in the clinical evolution of patients
Time Frame
up to 14 days
Title
Changes in IL-6 concentrations
Description
Improvement in cytokine level
Time Frame
up to 14 days
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 14 days
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 14 days
Title
Changes in the punctuation in the National Early Warning Score
Description
National Early Warning Score (NEWS scale)
Time Frame
up to 14 days
Title
Number of days with invasive mechanical ventilation
Time Frame
up to 14 days
Title
Number of days with high flow oxygen therapy
Time Frame
up to 14 days
Title
Changes in other inflammatory markers
Description
C-reactive protein
Time Frame
up to 14 days
Title
Changes in severity markers
Description
D-dimer
Time Frame
up to 14 days
Title
Changes in severity markers
Description
Leukocytes
Time Frame
up to 14 days
Title
Changes in severity markers
Description
Lymphocytes
Time Frame
up to 14 days
Title
Changes in severity markers
Description
Platelets
Time Frame
up to 14 days
Title
Changes in severity markers
Description
LDH
Time Frame
up to 14 days
Title
Changes in severity markers
Description
Ferritin
Time Frame
up to 14 days
Title
Changes in myocardial damage
Description
myocardial stress markers hsTnT
Time Frame
up to 14 days
Title
Changes in myocardial damage
Description
myocardial stress markers NT-proBNP
Time Frame
up to 14 days
Title
Time until reaching a virus negative status
Description
RT-PCR assay
Time Frame
up to 14 days
Title
Length of hospital stay
Description
Length of hospital stay
Time Frame
up to 14 days
Title
Number of days in the intensive care unit.
Description
Number of days in the intensive care unit.
Time Frame
up to 14 days
Title
Mortality
Description
Mortality
Time Frame
up to 14 days
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
65 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.
Facility Information:
Facility Name
Ayub Teaching Hospital
City
Abbottabad
State/Province
Khyber Pakhtunkhwa
ZIP/Postal Code
22010
Country
Pakistan
12. IPD Sharing Statement
Plan to Share IPD
No
Citations:
PubMed Identifier
32579195
Citation
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, Martinez-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.
Results Reference
background
PubMed Identifier
32732245
Citation
Scarsi M, Piantoni S, Colombo E, Airo P, Richini D, Miclini M, Bertasi V, Bianchi M, Bottone D, Civelli P, Cotelli MS, Damiolini E, Galbassini G, Gatta D, Ghirardelli ML, Magri R, Malamani P, Mendeni M, Molinari S, Morotti A, Salada L, Turla M, Vender A, Tincani A, Brucato A, Franceschini F, Furloni R, Andreoli L. Association between treatment with colchicine and improved survival in a single-centre cohort of adult hospitalised patients with COVID-19 pneumonia and acute respiratory distress syndrome. Ann Rheum Dis. 2020 Oct;79(10):1286-1289. doi: 10.1136/annrheumdis-2020-217712. Epub 2020 Jul 30.
Results Reference
background
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Study to Investigate the Treatment Effect of Colchicine in Patients With COVID-19
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