COVID19Phase 3COL-COVIDNCT04350320
Trial to Study the Benefit of Colchicine in Patients With COVID-19
A Phase 3 study testing Colchicine Tablets and Standard therapy for COVID-19 according to the stablished hospital protocols. in people with COVID19, run by Fundacion para la Formacion e Investigacion Sanitarias de la Region de Murcia at 1 site in Spain.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- COVID19
- What is being tested?
- Colchicine Tablets and Standard therapy for COVID-19 according to the stablished hospital protocols.
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 102 participants
- Where
- 1 siteSpain
- Study dates
- 30 Apr 2020to 30 Dec 2020
- Phase
- Phase 3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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)
Show all 13Show fewer
- 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.
Trial locations and contacts
1 site in 1 country.
About this study
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.
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.
Read the 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.
- Conditions
- COVID19
- Being tested
- Colchicine Tablets, Standard therapy for COVID-19 according to the stablished hospital protocols.
- Medical subject headings
- COVID-19
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Colchicine TabletsDrug
standard therapy for COVID-19 according to the stablished hospital protocols.
Standard therapy for COVID-19 according to the stablished hospital protocols.Drug
standard therapy for COVID-19 according to the stablished hospital protocols.
| Study group | Role | What they receive |
|---|---|---|
| COLCHICINE | Experimental | 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. Receives: Drug: Colchicine Tablets; Drug: Standard therapy for COVID-19 according to the stablished hospital protocols. |
| control group | Placebo comparator | Standard therapy for COVID-19 according to the stablished hospital protocols. Receives: Drug: Standard therapy for COVID-19 according to the stablished hospital protocols. |
What is being measured
The primary outcome is the main question the study is designed to answer.
Changes in the patients' clinical status through the 7 points ordinal scale WHO R&D Blueprint expert group
improve in the clinical evolution of patients hospitalized
Measured: 7,14,28 Days
Changes in IL-6 concentrations
improve in the clinical evolution of patients hospitalized
Measured: up to day 28.
Secondary outcomes (21)
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)
Measured: up to day 28.
Changes in the score for the Sequential Organ Failure Assessment (SOFA score)
Sequential Organ Failure Assessment (SOFA score) (0-14)
Measured: up to day 28.
Changes in the punctuation in the National Early Warning Score
National Early Warning Score (NEWS scale
Measured: up to day 28.
Number of days with invasive mechanical ventilation
Measured: up to day 28.
Number of days with high flow oxygen therapy
Measured: up to day 28.
Changes in other inflammatory markers
C-reactive protein,
Measured: up to day 28
Changes in other inflammatory markers
TNF-alfa,
Measured: up to day 28
Changes in other inflammatory markers
GDF-15,
Measured: up to day 28
Changes in other inflammatory markers
IL-1β
Measured: up to day 28
Changes in severity markers
D-dimer
Measured: up to day 28
Changes in severity markers
leucocytes
Measured: up to day 28
Changes in severity markers
lymphocytes
Measured: up to day 28
Changes in severity markers
platelets
Measured: up to day 28
Changes in severity markers
LDH
Measured: up to day 28
Changes in severity markers
ferritin
Measured: up to day 28
Changes in myocardial damage
myocardial stress markers hsTnT
Measured: up to day 28
Changes in myocardial damage
myocardial stress markers NT-proBNP
Measured: up to day 28
Time until reaching a virus negative status
RT-PCR assay
Measured: up to day 28
Length of hospital stay
Length of hospital stay
Measured: up to day 28
Number of days in the intensive care unit.
Number of days in the intensive care unit.
Measured: up to day 28
Mortality
Mortality
Measured: up to day 28
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted17 Apr 2020
- Study start30 Apr 2020
- Primary completion20 Oct 2020
- Study completion30 Dec 2020
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for COVID19Studies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- 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)
- Enrolment
- 102 participants (actual)
Sponsor and investigators
- Lead sponsor
- Fundacion para la Formacion e Investigacion Sanitarias de la Region de Murcia
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Domingo A Pascual Figal, MD, Principal investigator, HCUVA
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04350320
- Sponsor's protocol ID
- IMIB-COLVID-2020-03
- Acronym
- COL-COVID
- Status last verified
- Jan 2021
- First submitted
- 14 Apr 2020
- Last updated
- 12 Jan 2021
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Mikolajewska A, Fischer AL, Piechotta V, Mueller A, Metzendorf MI, Becker M, Dorando E, Pacheco RL, Martimbianco ALC, Riera R, Skoetz N, Stegemann M. Colchicine for the treatment of COVID-19. Cochrane Database Syst Rev. 2021 Oct 18;10(10):CD015045. doi: 10.1002/14651858.CD015045.
PubMed 34658014Pascual-Figal DA, Roura-Piloto AE, Moral-Escudero E, Bernal E, Albendin-Iglesias H, Perez-Martinez MT, Noguera-Velasco JA, Cebreiros-Lopez I, Hernandez-Vicente A, Vazquez-Andres D, Sanchez-Perez C, Khan A, Sanchez-Cabo F, Garcia-Vazquez E; COL-COVID Investigators. Colchicine in Recently Hospitalized Patients with COVID-19: A Randomized Controlled Trial (COL-COVID). Int J Gen Med. 2021 Sep 11;14:5517-5526. doi: 10.2147/IJGM.S329810. eCollection 2021.
PubMed 34539185
Study at a glance
From the registry record, last updated by the sponsor on 12 Jan 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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.
- ClinicalTrials.gov ID
- NCT04350320
- Acronym / sponsor ID
- COL-COVID / IMIB-COLVID-2020-03
- Conditions
- COVID19
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 102 participants (actual)
- Lead sponsor
- Fundacion para la Formacion e Investigacion Sanitarias de la Region de MurciaUniversity, hospital or other
- Study start
- 30 Apr 2020 (actual)
- Primary completion
- 20 Oct 2020 (actual)
- Study completion
- 30 Dec 2020 (actual)
- First posted
- 17 Apr 2020 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
- 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
| Arm | Type | Receives |
|---|---|---|
| COLCHICINE | Experimental | Drug: Colchicine Tablets, Drug: Standard therapy for COVID-19 according to the stablished hospital protocols.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. |
| control group | Placebo comparator | Drug: Standard therapy for COVID-19 according to the stablished hospital protocols.Standard therapy for COVID-19 according to the stablished hospital protocols. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- 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.
Key exclusion criteria (13 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Colchicine Tabletsstandard therapy for COVID-19 according to the stablished hospital protocols. | Drug | COLCHICINE |
| Standard therapy for COVID-19 according to the stablished hospital protocols.standard therapy for COVID-19 according to the stablished hospital protocols. | Drug | COLCHICINE, control group |
Primary outcome
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
Changes in IL-6 concentrations
Time frame: up to day 28.
improve in the clinical evolution of patients hospitalized
21 secondary outcomes
Improvement in the clinical status
Time frame: up to day 28.
Changes in the score for the Sequential Organ Failure Assessment (SOFA score)
Time frame: up to day 28.
Changes in the punctuation in the National Early Warning Score
Time frame: up to day 28.
Number of days with invasive mechanical ventilation
Time frame: up to day 28.
Number of days with high flow oxygen therapy
Time frame: up to day 28.
Changes in other inflammatory markers
Time frame: up to day 28
Changes in other inflammatory markers
Time frame: up to day 28
Changes in other inflammatory markers
Time frame: up to day 28
Changes in other inflammatory markers
Time frame: up to day 28
Changes in severity markers
Time frame: up to day 28
Changes in severity markers
Time frame: up to day 28
Changes in severity markers
Time frame: up to day 28
Changes in severity markers
Time frame: up to day 28
Changes in severity markers
Time frame: up to day 28
Changes in severity markers
Time frame: up to day 28
Changes in myocardial damage
Time frame: up to day 28
Changes in myocardial damage
Time frame: up to day 28
Time until reaching a virus negative status
Time frame: up to day 28
Length of hospital stay
Time frame: up to day 28
Number of days in the intensive care unit.
Time frame: up to day 28
Mortality
Time frame: up to day 28
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 12 Jan 2021.
- Derived from this study: PubMed 34658014Mikolajewska A, Fischer AL, Piechotta V, Mueller A, Metzendorf MI, Becker M, Dorando E, Pacheco RL, Martimbianco ALC, Riera R, Skoetz N, Stegemann M. Colchicine for the treatment of COVID-19. Cochrane Database Syst Rev. 2021 Oct 18;10(10):CD015045. doi: 10.1002/14651858.CD015045.
- Derived from this study: PubMed 34539185Pascual-Figal DA, Roura-Piloto AE, Moral-Escudero E, Bernal E, Albendin-Iglesias H, Perez-Martinez MT, Noguera-Velasco JA, Cebreiros-Lopez I, Hernandez-Vicente A, Vazquez-Andres D, Sanchez-Perez C, Khan A, Sanchez-Cabo F, Garcia-Vazquez E; COL-COVID Investigators. Colchicine in Recently Hospitalized Patients with COVID-19: A Randomized Controlled Trial (COL-COVID). Int J Gen Med. 2021 Sep 11;14:5517-5526. doi: 10.2147/IJGM.S329810. eCollection 2021.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Domingo A Pascual Figal, MD principal investigator
HCUVA
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Colchicine Tablets and Standard therapy for COVID-19 according to the stablished hospital protocols. in people with COVID19, run by Fundacion para la Formacion e Investigacion Sanitarias de la Region de Murcia at 1 site in Spain.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 13 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 12 Jan 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Spain. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Changes in the patients' clinical status through the 7 points ordinal scale WHO R&D Blueprint expert group (time frame: 7,14,28 Days). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04350320, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 12 Jan 2021.