Colchicine Adverse ReactionPhase 4COCSNCT04224545
COlchicine in Cardiac Surgery
A Phase 4 study testing Colchicine Pill in people with Colchicine Adverse Reaction and Atrial Fibrillation New Onset, run by Bakulev Scientific Center of Cardiovascular Surgery at 2 sites in Russia.
Trial summary
Postoperative atrial fibrillation (POAF) is a major complication of cardiac surgery, which could lead to high morbidity and mortality, increase duration of hospital stay and increase the cost of treatment. Colchicine possesses both anti-inflammatory and sympatholytic properties, so it has been studied to prevent POAF. Read more about this study
- Who is it for?
- Ages 40 to 80 years
- Conditions the study is for
- Colchicine Adverse Reaction, Atrial Fibrillation New Onset
- What is being tested?
- Colchicine Pill
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 267 participants
- Where
- 2 sitesRussia
- Study dates
- 23 Dec 2019to 23 Aug 2022
- Phase
- Phase 4
- 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 40 to 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Adult patients awaiting elective cardiac surgery (CABG and/or AVR (aortic valve replacement), who are willing and able to give informed consent for participation in the study and who are in sinus rhythm and not taking any antiarrhythmic medication, except beta-adrenergic blocking agents, at the time before surgery.
Who cannot join
- History of persistent or long-term atrial fibrillation/atrial flutter
- Congenital heart disease, except the bicuspid AV
- Frequent VE/SVE, AV block 2-3 degrees
- Use of corticosteroids during the last month
- Taking any antiarrhythmic drugs, except beta-blockers, within the last 1 month
- Prior "open" heart surgery
Show all 10Show fewer
- Moderate to severe renal failure (creatinine clearance < 50 ml / min)
- History of obstructive hepato-biliary disease or other serious hepatic disease
- Significant mitral valve disease (moderate or severe mitral regurgitation-eg. > grade II and/or mitral stenosis \& mitral annular calcification).
- Patient participation in another clinical trial
Trial locations and contacts
2 sites in 1 country.
Russia2 sites
Federal Center for Cardiovascular Surgery (Astrakhan)
Astrakhan
Bakulev National Medical Research Center for Cardiovascular Surgery
Moscow
About this study
Official title: Colchicine for Prevention Atrial Fibrillation After Cardiac Surgery in the Early Postoperative Period
Postoperative atrial fibrillation (POAF) is a major complication of cardiac surgery, which could lead to high morbidity and mortality, increase duration of hospital stay and increase the cost of treatment. Colchicine possesses both anti-inflammatory and sympatholytic properties, so it has been studied to prevent POAF. The ACC/AHA guidelines for colchicine contain a class IIB recommendation, but the ESC guidelines do not recommend this drug. More researches are needed to focus on reducing of side effects by optimizing the colchicine regimen to reduce the incidence of gastrointestinal side effects. It is believed that further research is needed to investigate the efficacy and safety of colchicine in these conditions.
This research is aimed to study the effectiveness of short-term administration of the drug.
Read the detailed description
Postoperative atrial fibrillation (POAF) is a major complication of cardiac surgery, which could lead to high morbidity and mortality, increase duration of hospital stay and increase the cost of treatment. Postoperative AF is considered as a multifactorial phenomenon. Its pathogenesis is characterized by inflammation, oxidative stress and autonomic dysfunction. Several predisposing factors lead to the development of POAF, including pre -, intra-and postoperative factors. The main of them are age, previous history of major cardiovascular risk factors and ischemic reperfusion injury during surgery. Treatment of POAF involves drugs to control the frequency of rhythm in hemodynamically stable patients and other treatment regimens usually used for the treatment of AF. Intraoperative administration of beta-blockers and some antiarrhythmic drugs is recommended by international clinical guidelines. In addition, previous treatment consisting of the use of colchicine, magnesium sulfate, statins and antioxidants have reduced the incidence of postoperative AF. However, the results of large-scale randomized trials have observed the development of undesirable adverse reactions.
Despite these recommendations, the question of the correct regimen for prevention of POAF remains controversial. Colchicine possesses both anti-inflammatory and sympatholytic properties, so it has been studied to prevent POAF. The ACC/AHA guidelines for colchicine contain a class IIB recommendation, but the ESC guidelines do not recommend this drug.
Two studies sequentially COPPS-1 and COPPS-2 evaluated the effect of colchicine on the incidence of POAF after open heart surgery (COPPS-1) and the development of postcardiotomy syndrome (COPPS-2). In COPPS-1, patients (n=336) were treated with colchicine from the third day after surgery for a month and showed a significant decrease of POAF after heart surgery over the entire follow-up period. 360 patients were evaluated in the COPPS-2 study. The incidence of POAF between the colchicine and placebo groups was comparable, although colchicine significantly reduced postpericardiotomy syndrome. The main limitation of the COPSS-2 study was the high rate of cessation of intervention (20% of participants), which had a significant impact on the outcome of the trial.
Based on the latest meta-analysis of the colchicine effect on POAF after heart surgery, it was found that it still reduces POAF compared with control (HR = 0.69, 95% IM 0.57-0.84, p = 0.0002) and the duration of hospital stay was reduced by 1.2 days (95% IM -1.89 to -0.44, p = 0.002); however, the frequency of adverse gastrointestinal events increased significantly (HR = 2.52, 95% IM 1.62-3.93, p < 0.0001). Despite the high level of side effects, a significant reduction of POAF outweighs the balance in the favor of its use. However, more researches are needed to focus on reducing of side effects by optimizing the colchicine regimen to reduce the incidence of gastrointestinal side effects. It is believed that further research is needed to investigate the efficacy and safety of colchicine in these conditions.
This research is aimed to study the effectiveness of short-term administration of the drug.
- Being tested
- Colchicine Pill, Placebo
- Keywords
- Colchicine, Postoperative atrial fibrillation, Anti-inflammatory, Cardiac surgery, Sympatholytic
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Colchicine PillDrug
Also called group C
Colchicine at a dose of 1 mg a day before surgery, 2, 3, 4, 5 days after surgery.
PlaceboDrug
Also called group P
Placebo started a day before surgery, 2, 3, 4, 5 days after surgery.
| Study group | Role | What they receive |
|---|---|---|
| Colchicine | Experimental | Colchicine 1 mg day (COLCHICINA LIRCA ® ACARPIA Farmaceutici S.r.l.) Receives: Drug: Colchicine Pill |
| Placebo | Placebo comparator | Sugar pill Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of participants with postoperative atrial fibrillation.
POAF detected on continuous ECG monitoring.
Measured: Monitoring is carried out immediately after surgery and will be continued until the end of the 7th postoperative day.
Secondary outcomes (6)
Number of participants with lethal and non-lethal events.
The main nosocomial lethal and non-lethal events (death, stroke, myocardial infarction, heart failure).
Measured: Participants will be followed for the duration of the postoperative period up to the day of initial discharge from the hospital, an expected average of 7 days.
Fluid in the pericardium.
Fluid in the pericardium evaluated by echocardiography.
Measured: Diagnostics will be carried out on the 3rd and 5th day after surgery.
Fluid in the pleura.
Fluid in the pleura evaluated by echocardiography.
Measured: Diagnostics will be carried out on the 3rd and 5th day after surgery.
Acute kidney damage (according to the dynamics of creatinine clearance).
Dynamics of creatinine clearance.
Measured: Diagnostics will be carried out a day before surgery and on the 3rd and 5th day after surgery.
Inflammation in blood plasma.
Dynamics of biomarker of inflammation in blood plasma (neutrophils).
Measured: Diagnostics will be carried out a day before surgery and on the 3rd and 5th day after surgery.
Liver damage
Dynamics of biomarkers of liver damage (aspartate aminotransferase, alanine aminotransferase).
Measured: Diagnostics will be carried out a day before surgery and on the 3rd and 5th day after surgery.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 Jan 2020
- Study start23 Dec 2019
- Primary completion15 Aug 2022
- Study completion23 Aug 2022
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Colchicine Adverse ReactionStudies 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 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- A randomized double-blind controlled trial in two groups
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 267 participants (actual)
Sponsor and investigators
- Lead sponsor
- Bakulev Scientific Center of Cardiovascular Surgery
- Sponsor type
- Other government
- Responsible party
- Sponsor
- Investigators
- Vladimir Shvartz, Principal investigator, Bakulev National Medical Research Center for Cardiovascular Surgery
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04224545
- Sponsor's protocol ID
- #2.20122019
- Acronym
- COCS
- Status last verified
- Feb 2024
- First submitted
- 27 Dec 2019
- Last updated
- 20 Feb 2024
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: The datasets analyzed during the current study are publicly available. The data is available in the general repository "Open Science Framework" at the link
Publications
Shvartz V, Le T, Kryukov Y, Sokolskaya M, Ispiryan A, Khugaeva E, Yurkulieva G, Shvartz E, Petrosyan A, Bockeria L, Bockeria O. Colchicine for Prevention of Atrial Fibrillation after Cardiac Surgery in the Early Postoperative Period. J Clin Med. 2022 Mar 3;11(5):1387. doi: 10.3390/jcm11051387.
PubMed 35268478Shvartz V, Le T, Enginoev S, Sokolskaya M, Ispiryan A, Shvartz E, Nudel D, Araslanova N, Petrosyan A, Donakanyan S, Chernov I, Bockeria L, Golukhova E. Colchicine in Cardiac Surgery: The COCS Randomized Clinical Trial. J Cardiovasc Dev Dis. 2022 Oct 20;9(10):363. doi: 10.3390/jcdd9100363.
PubMed 36286314Shvartz V.A., Le T.G., Enginoev S.T., Sokolskaya M.A., Ispiryan A.Yu., Shvartz E.N., Nudel D.V., Araslanova N.Kh., Petrosyan A.D., Talibova S.M., Donakanyan S.A., Chernov I.I., Boсkeria L.A., Golukhova E.Z. Association of new markers of systemic inflammation with the risk of developing for the first time postoperative atrial fibrillation when using colchicine in patients undergoing open heart surgery. Annals of arrhythmology. 2023; 20(1): 22-33. (In Russian).
Study at a glance
From the registry record, last updated by the sponsor on 20 Feb 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Colchicine for Prevention Atrial Fibrillation After Cardiac Surgery in the Early Postoperative Period
- ClinicalTrials.gov ID
- NCT04224545
- Acronym / sponsor ID
- COCS / #2.20122019
- Keywords
- Colchicine, Postoperative atrial fibrillation, Anti-inflammatory, Cardiac surgery, Sympatholytic
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 267 participants (actual)
- Lead sponsor
- Bakulev Scientific Center of Cardiovascular SurgeryOther government
- Study start
- 23 Dec 2019 (actual)
- Primary completion
- 15 Aug 2022 (actual)
- Study completion
- 23 Aug 2022 (actual)
- First posted
- 13 Jan 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.
Postoperative atrial fibrillation (POAF) is a major complication of cardiac surgery, which could lead to high morbidity and mortality, increase duration of hospital stay and increase the cost of treatment. Colchicine possesses both anti-inflammatory and sympatholytic properties, so it has been studied to prevent POAF. The ACC/AHA guidelines for colchicine contain a class IIB recommendation, but the ESC guidelines do not recommend this drug. More researches are needed to focus on reducing of side effects by optimizing the colchicine regimen to reduce the incidence of gastrointestinal side effects. It is believed that further research is needed to investigate the efficacy and safety of colchicine in these conditions.
This research is aimed to study the effectiveness of short-term administration of the drug.
Detailed description
Postoperative atrial fibrillation (POAF) is a major complication of cardiac surgery, which could lead to high morbidity and mortality, increase duration of hospital stay and increase the cost of treatment. Postoperative AF is considered as a multifactorial phenomenon. Its pathogenesis is characterized by inflammation, oxidative stress and autonomic dysfunction. Several predisposing factors lead to the development of POAF, including pre -, intra-and postoperative factors. The main of them are age, previous history of major cardiovascular risk factors and ischemic reperfusion injury during surgery. Treatment of POAF involves drugs to control the frequency of rhythm in hemodynamically stable patients and other treatment regimens usually used for the treatment of AF. Intraoperative administration of beta-blockers and some antiarrhythmic drugs is recommended by international clinical guidelines. In addition, previous treatment consisting of the use of colchicine, magnesium sulfate, statins and antioxidants have reduced the incidence of postoperative AF. However, the results of large-scale randomized trials have observed the development of undesirable adverse reactions.
Despite these recommendations, the question of the correct regimen for prevention of POAF remains controversial. Colchicine possesses both anti-inflammatory and sympatholytic properties, so it has been studied to prevent POAF. The ACC/AHA guidelines for colchicine contain a class IIB recommendation, but the ESC guidelines do not recommend this drug.
Two studies sequentially COPPS-1 and COPPS-2 evaluated the effect of colchicine on the incidence of POAF after open heart surgery (COPPS-1) and the development of postcardiotomy syndrome (COPPS-2). In COPPS-1, patients (n=336) were treated with colchicine from the third day after surgery for a month and showed a significant decrease of POAF after heart surgery over the entire follow-up period. 360 patients were evaluated in the COPPS-2 study. The incidence of POAF between the colchicine and placebo groups was comparable, although colchicine significantly reduced postpericardiotomy syndrome. The main limitation of the COPSS-2 study was the high rate of cessation of intervention (20% of participants), which had a significant impact on the outcome of the trial.
Based on the latest meta-analysis of the colchicine effect on POAF after heart surgery, it was found that it still reduces POAF compared with control (HR = 0.69, 95% IM 0.57-0.84, p = 0.0002) and the duration of hospital stay was reduced by 1.2 days (95% IM -1.89 to -0.44, p = 0.002); however, the frequency of adverse gastrointestinal events increased significantly (HR = 2.52, 95% IM 1.62-3.93, p < 0.0001). Despite the high level of side effects, a significant reduction of POAF outweighs the balance in the favor of its use. However, more researches are needed to focus on reducing of side effects by optimizing the colchicine regimen to reduce the incidence of gastrointestinal side effects. It is believed that further research is needed to investigate the efficacy and safety of colchicine in these conditions.
This research is aimed to study the effectiveness of short-term administration of the drug.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 2
- Model description
- A randomized double-blind controlled trial in two groups
| Arm | Type | Receives |
|---|---|---|
| Colchicine | Experimental | Drug: Colchicine PillColchicine 1 mg day (COLCHICINA LIRCA ® ACARPIA Farmaceutici S.r.l.) |
| Placebo | Placebo comparator | Drug: PlaceboSugar pill |
Who may qualify
- Ages
- 40 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (1 listed)
- Adult patients awaiting elective cardiac surgery (CABG and/or AVR (aortic valve replacement), who are willing and able to give informed consent for participation in the study and who are in sinus rhythm and not taking any antiarrhythmic medication, except beta-adrenergic blocking agents, at the time before surgery.
Key exclusion criteria (10 listed)
- History of persistent or long-term atrial fibrillation/atrial flutter
- Congenital heart disease, except the bicuspid AV
- Frequent VE/SVE, AV block 2-3 degrees
- Use of corticosteroids during the last month
- Taking any antiarrhythmic drugs, except beta-blockers, within the last 1 month
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 PillAlso: group CColchicine at a dose of 1 mg a day before surgery, 2, 3, 4, 5 days after surgery. | Drug | Colchicine |
| PlaceboAlso: group PPlacebo started a day before surgery, 2, 3, 4, 5 days after surgery. | Drug | Placebo |
Primary outcome
Number of participants with postoperative atrial fibrillation.
Time frame: Monitoring is carried out immediately after surgery and will be continued until the end of the 7th postoperative day.
POAF detected on continuous ECG monitoring.
6 secondary outcomes
Number of participants with lethal and non-lethal events.
Time frame: Participants will be followed for the duration of the postoperative period up to the day of initial discharge from the hospital, an expected average of 7 days.
Fluid in the pericardium.
Time frame: Diagnostics will be carried out on the 3rd and 5th day after surgery.
Fluid in the pleura.
Time frame: Diagnostics will be carried out on the 3rd and 5th day after surgery.
Acute kidney damage (according to the dynamics of creatinine clearance).
Time frame: Diagnostics will be carried out a day before surgery and on the 3rd and 5th day after surgery.
Inflammation in blood plasma.
Time frame: Diagnostics will be carried out a day before surgery and on the 3rd and 5th day after surgery.
Liver damage
Time frame: Diagnostics will be carried out a day before surgery and on the 3rd and 5th day after surgery.
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 20 Feb 2024.
- Results publication: PubMed 35268478Shvartz V, Le T, Kryukov Y, Sokolskaya M, Ispiryan A, Khugaeva E, Yurkulieva G, Shvartz E, Petrosyan A, Bockeria L, Bockeria O. Colchicine for Prevention of Atrial Fibrillation after Cardiac Surgery in the Early Postoperative Period. J Clin Med. 2022 Mar 3;11(5):1387. doi: 10.3390/jcm11051387.
- Results publication: PubMed 36286314Shvartz V, Le T, Enginoev S, Sokolskaya M, Ispiryan A, Shvartz E, Nudel D, Araslanova N, Petrosyan A, Donakanyan S, Chernov I, Bockeria L, Golukhova E. Colchicine in Cardiac Surgery: The COCS Randomized Clinical Trial. J Cardiovasc Dev Dis. 2022 Oct 20;9(10):363. doi: 10.3390/jcdd9100363.
- Results publicationShvartz V.A., Le T.G., Enginoev S.T., Sokolskaya M.A., Ispiryan A.Yu., Shvartz E.N., Nudel D.V., Araslanova N.Kh., Petrosyan A.D., Talibova S.M., Donakanyan S.A., Chernov I.I., Boсkeria L.A., Golukhova E.Z. Association of new markers of systemic inflammation with the risk of developing for the first time postoperative atrial fibrillation when using colchicine in patients undergoing open heart surgery. Annals of arrhythmology. 2023; 20(1): 22-33. (In Russian).
- Individual participant dataSharing planned: Yes. The datasets analyzed during the current study are publicly available. The data is available in the general repository "Open Science Framework" at the link
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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.
Vladimir Shvartz principal investigator
Bakulev National Medical Research Center for Cardiovascular Surgery
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Colchicine Pill in people with Colchicine Adverse Reaction and Atrial Fibrillation New Onset, run by Bakulev Scientific Center of Cardiovascular Surgery at 2 sites in Russia.
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 1 inclusion and 10 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 20 Feb 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in Russia. 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 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
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?
Number of participants with postoperative atrial fibrillation. (time frame: Monitoring is carried out immediately after surgery and will be continued until the end of the 7th postoperative day.). 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 NCT04224545, which also lists 3 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 20 Feb 2024; AzTrials last refreshed its copy on 27 Oct 2026.