Atrial Fibrillation
Conditions
Keywords
atrial fibrillation, catheter ablation, colchicine, c reactive protein, CRP
Brief summary
Colchicine will lower C-reactive protein (CRP) in chronic atrial fibrillation and reduce the rise in CRP which occurs following atrial fibrillation ablation
Detailed description
Three groups of patients will be randomized to colchicine 0.6 mg PO bis in die (BID) or matching placebo: 1. Paroxysmal atrial fibrillation, pre-ablation 2. Persistent atrial fibrillation, pre-ablation 3. Chronic persistent atrial fibrillation
Interventions
DRUGColchicine, 0.6 mg PO BID
Colchicine tablets will be over-encapsulated by the research pharmacy to be indistinguishable from placebo
DRUGMatching placebo
Matching placebo tablets will be encapsulated by the research pharmacy to be indistinguishable from active drug
Sponsors
Takeda
Detiger Funds
Mayo Clinic
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
21 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Group 1: Persistent or chronic AF presenting for evaluation in cardiology offices. Diagnosis of AF will be made based on the 12 -lead surface ECG. * Group 2: Paroxysmal AF scheduled to go AF ablation presenting to the electrophysiology laboratory for the procedure in sinus rhythm.. * Group 3:Chronic AF scheduled to go clinically indicated AF ablation, and presenting in the electrophysiology laboratory in atrial fibrillation .
Exclusion criteria
1. Abnormal liver function with elevated enzymes\> 1.5 times the normal. 2. Abnormal kidney function with glomerular filtration rate \< 50 ml/min 3. Increased levels of creatine kinase or known myopathy 4. Neutropenia 5. Known GI disorders 6. Women of childbearing age who have not had surgical sterilization and are not using oral contraceptives, or who's spouse has not had surgical sterilization will be excluded due to the length of the trial and the possibility that they could become pregnant after entry. 7. Pregnant and lactating women 8. Lactose intolerance 9. Known sensitivity, allergy, or contraindication to colchicine use
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in C-reactive Protein | baseline, day 28 | Plasma levels of C-reactive protein was determined by the immunoprecipitation method using an in vitro diagnostic assay. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Subjects With Atrial Fibrillation | day 28 | All subjects will have 12 lead ECG on day 28 to measure the number of subjects with normal sinus rhythm and atrial fibrillation. |
| Time Course of C-reactive Protein Levels | baseline, day 3, day 7, day 14, day 28 | Plasma levels of C-reactive protein was determined by the immunoprecipitation method using an in vitro diagnostic assay. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Chronic Atrial Fibrillation, Colchicine Colchicine 0.6 mg PO BID
Colchicine, 0.6 mg PO BID: Colchicine tablets will be over-encapsulated by the research pharmacy to be indistinguishable from placebo Subjects not undergoing ablation. | 5 |
| Chronic Atrial Fibrillation, Placebo Matching placebo
Matching placebo: Matching placebo tablets will be encapsulated by the research pharmacy to be indistinguishable from active drug Subjects not undergoing ablation. | 5 |
| Pre-ablation, Sinus Rhythm, Colchicine Colchicine 0.6 mg PO BID
Colchicine, 0.6 mg PO BID: Colchicine tablets will be over-encapsulated by the research pharmacy to be indistinguishable from placebo Subjects undergoing ablation. | 4 |
| Pre-ablation, Sinus Rhythm, Placebo Matching placebo
Matching placebo: Matching placebo tablets will be encapsulated by the research pharmacy to be indistinguishable from active drug Subjects undergoing ablation. | 5 |
| Pre-ablation, AF, Colchicine Colchicine 0.6 mg PO BID
Colchicine, 0.6 mg PO BID: Colchicine tablets will be over-encapsulated by the research pharmacy to be indistinguishable from placebo Subjects undergoing ablation. | 4 |
| Pre-ablation, AF, Placebo Matching placebo
Matching placebo: Matching placebo tablets will be encapsulated by the research pharmacy to be indistinguishable from active drug Subjects undergoing ablation. | 3 |
| Total | 26 |
Baseline characteristics
| Characteristic | Total | Pre-ablation, AF, Placebo | Pre-ablation, AF, Colchicine | Pre-ablation, Sinus Rhythm, Placebo | Pre-ablation, Sinus Rhythm, Colchicine | Chronic Atrial Fibrillation, Placebo | Chronic Atrial Fibrillation, Colchicine |
|---|---|---|---|---|---|---|---|
| Age, Continuous | 68 years STANDARD_DEVIATION 8.5 | 62 years STANDARD_DEVIATION 18 | 68 years STANDARD_DEVIATION 7 | 69 years STANDARD_DEVIATION 6 | 65 years STANDARD_DEVIATION 5 | 73 years STANDARD_DEVIATION 8 | 71 years STANDARD_DEVIATION 7 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 25 Participants | 3 Participants | 4 Participants | 5 Participants | 4 Participants | 4 Participants | 5 Participants |
| Region of Enrollment United States | 26 Participants | 3 Participants | 4 Participants | 5 Participants | 4 Participants | 5 Participants | 5 Participants |
| Sex: Female, Male Female | 4 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 1 Participants | 2 Participants |
| Sex: Female, Male Male | 22 Participants | 3 Participants | 4 Participants | 4 Participants | 4 Participants | 4 Participants | 3 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk |
|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 5 | 0 / 5 | 0 / 4 | 0 / 5 | 0 / 4 | 0 / 3 |
| other Total, other adverse events | 0 / 5 | 0 / 5 | 0 / 4 | 0 / 5 | 0 / 4 | 0 / 3 |
| serious Total, serious adverse events | 0 / 5 | 0 / 5 | 0 / 4 | 0 / 5 | 0 / 4 | 0 / 3 |
Outcome results
Primary
Change in C-reactive Protein
Plasma levels of C-reactive protein was determined by the immunoprecipitation method using an in vitro diagnostic assay.
Time frame: baseline, day 28
Population: Not all subjects had sample available at all timepoints to measure C-reactive protein levels. Sample was either not collected or insufficient volume to run assay.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Chronic Atrial Fibrillation, Colchicine | Change in C-reactive Protein | Baseline | 6.4 ng/mL | Standard Deviation 7.2 |
| Chronic Atrial Fibrillation, Colchicine | Change in C-reactive Protein | day 28 | 1.8 ng/mL | Standard Deviation 2 |
| Chronic Atrial Fibrillation, Placebo | Change in C-reactive Protein | Baseline | 2.7 ng/mL | Standard Deviation 2.9 |
| Chronic Atrial Fibrillation, Placebo | Change in C-reactive Protein | day 28 | 2.7 ng/mL | Standard Deviation 1.4 |
| Pre-ablation, Sinus Rhythm, Colchicine | Change in C-reactive Protein | day 28 | 1.0 ng/mL | Standard Deviation 0.7 |
| Pre-ablation, Sinus Rhythm, Colchicine | Change in C-reactive Protein | Baseline | 2.9 ng/mL | Standard Deviation 1.6 |
| Pre-ablation, Sinus Rhythm, Placebo | Change in C-reactive Protein | Baseline | 5.9 ng/mL | Standard Deviation 5.5 |
| Pre-ablation, Sinus Rhythm, Placebo | Change in C-reactive Protein | day 28 | 2.5 ng/mL | Standard Deviation 1.7 |
| Pre-ablation, AF, Colchicine | Change in C-reactive Protein | Baseline | 2.6 ng/mL | Standard Deviation 2.7 |
| Pre-ablation, AF, Colchicine | Change in C-reactive Protein | day 28 | 1.2 ng/mL | Standard Deviation 1 |
| Pre-ablation, AF, Placebo | Change in C-reactive Protein | day 28 | 5.2 ng/mL | Standard Deviation 5.1 |
| Pre-ablation, AF, Placebo | Change in C-reactive Protein | Baseline | 2.3 ng/mL | Standard Deviation 1.7 |
Comparison: Baseline C-reactive protein vs day 28 C-reactive proteinp-value: 0.038t-test, 2 sided
Comparison: Baseline C-reactive protein vs day 28 C-reactive proteinp-value: 0.98t-test, 2 sided
Comparison: difference between placebo and colchicine levels at day 28p-value: 0.072t-test, 2 sided
Secondary
Number of Subjects With Atrial Fibrillation
All subjects will have 12 lead ECG on day 28 to measure the number of subjects with normal sinus rhythm and atrial fibrillation.
Time frame: day 28
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Chronic Atrial Fibrillation, Colchicine | Number of Subjects With Atrial Fibrillation | Sinus rhythm | 5 Participants |
| Chronic Atrial Fibrillation, Colchicine | Number of Subjects With Atrial Fibrillation | Atrial fibrillation | 0 Participants |
| Chronic Atrial Fibrillation, Placebo | Number of Subjects With Atrial Fibrillation | Sinus rhythm | 1 Participants |
| Chronic Atrial Fibrillation, Placebo | Number of Subjects With Atrial Fibrillation | Atrial fibrillation | 4 Participants |
| Pre-ablation, Sinus Rhythm, Colchicine | Number of Subjects With Atrial Fibrillation | Sinus rhythm | 4 Participants |
| Pre-ablation, Sinus Rhythm, Colchicine | Number of Subjects With Atrial Fibrillation | Atrial fibrillation | 0 Participants |
| Pre-ablation, Sinus Rhythm, Placebo | Number of Subjects With Atrial Fibrillation | Sinus rhythm | 3 Participants |
| Pre-ablation, Sinus Rhythm, Placebo | Number of Subjects With Atrial Fibrillation | Atrial fibrillation | 1 Participants |
| Pre-ablation, AF, Colchicine | Number of Subjects With Atrial Fibrillation | Sinus rhythm | 4 Participants |
| Pre-ablation, AF, Colchicine | Number of Subjects With Atrial Fibrillation | Atrial fibrillation | 0 Participants |
| Pre-ablation, AF, Placebo | Number of Subjects With Atrial Fibrillation | Sinus rhythm | 1 Participants |
| Pre-ablation, AF, Placebo | Number of Subjects With Atrial Fibrillation | Atrial fibrillation | 2 Participants |
Comparison: placebo vs colchicinep-value: 0.08t-test, 2 sided
Secondary
Time Course of C-reactive Protein Levels
Plasma levels of C-reactive protein was determined by the immunoprecipitation method using an in vitro diagnostic assay.
Time frame: baseline, day 3, day 7, day 14, day 28
Population: Not all subjects had sample available at all timepoints to measure C-reactive protein levels. Sample was either not collected or insufficient volume to run assay.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Chronic Atrial Fibrillation, Colchicine | Time Course of C-reactive Protein Levels | Day 14 | 4.3 ng/ml | Standard Deviation 7.8 |
| Chronic Atrial Fibrillation, Colchicine | Time Course of C-reactive Protein Levels | Day 7 | 3.2 ng/ml | Standard Deviation 4.8 |
| Chronic Atrial Fibrillation, Colchicine | Time Course of C-reactive Protein Levels | Baseline | 6.4 ng/ml | Standard Deviation 7.2 |
| Chronic Atrial Fibrillation, Colchicine | Time Course of C-reactive Protein Levels | Day 28 | 1.8 ng/ml | Standard Deviation 2 |
| Chronic Atrial Fibrillation, Colchicine | Time Course of C-reactive Protein Levels | Day 3 | 4.3 ng/ml | Standard Deviation 5.1 |
| Chronic Atrial Fibrillation, Placebo | Time Course of C-reactive Protein Levels | Day 3 | 2.9 ng/ml | Standard Deviation 2.2 |
| Chronic Atrial Fibrillation, Placebo | Time Course of C-reactive Protein Levels | Day 7 | 3.2 ng/ml | Standard Deviation 2.2 |
| Chronic Atrial Fibrillation, Placebo | Time Course of C-reactive Protein Levels | Day 14 | 3.2 ng/ml | Standard Deviation 2.3 |
| Chronic Atrial Fibrillation, Placebo | Time Course of C-reactive Protein Levels | Baseline | 2.7 ng/ml | Standard Deviation 2.9 |
| Chronic Atrial Fibrillation, Placebo | Time Course of C-reactive Protein Levels | Day 28 | 2.7 ng/ml | Standard Deviation 1.4 |
| Pre-ablation, Sinus Rhythm, Colchicine | Time Course of C-reactive Protein Levels | Day 28 | 1.0 ng/ml | Standard Deviation 0.7 |
| Pre-ablation, Sinus Rhythm, Colchicine | Time Course of C-reactive Protein Levels | Baseline | 2.9 ng/ml | Standard Deviation 1.6 |
| Pre-ablation, Sinus Rhythm, Colchicine | Time Course of C-reactive Protein Levels | Day 3 | 24.9 ng/ml | Standard Deviation 19.5 |
| Pre-ablation, Sinus Rhythm, Colchicine | Time Course of C-reactive Protein Levels | Day 7 | 5.0 ng/ml | Standard Deviation 2.2 |
| Pre-ablation, Sinus Rhythm, Colchicine | Time Course of C-reactive Protein Levels | Day 14 | 1.9 ng/ml | Standard Deviation 1.2 |
| Pre-ablation, Sinus Rhythm, Placebo | Time Course of C-reactive Protein Levels | Baseline | 5.9 ng/ml | Standard Deviation 5.5 |
| Pre-ablation, Sinus Rhythm, Placebo | Time Course of C-reactive Protein Levels | Day 14 | 4.1 ng/ml | Standard Deviation 3 |
| Pre-ablation, Sinus Rhythm, Placebo | Time Course of C-reactive Protein Levels | Day 7 | 6.6 ng/ml | Standard Deviation 5.8 |
| Pre-ablation, Sinus Rhythm, Placebo | Time Course of C-reactive Protein Levels | Day 28 | 2.5 ng/ml | Standard Deviation 1.7 |
| Pre-ablation, Sinus Rhythm, Placebo | Time Course of C-reactive Protein Levels | Day 3 | 27.8 ng/ml | Standard Deviation 2.82 |
| Pre-ablation, AF, Colchicine | Time Course of C-reactive Protein Levels | Day 3 | 4.4 ng/ml | Standard Deviation 1.1 |
| Pre-ablation, AF, Colchicine | Time Course of C-reactive Protein Levels | Day 7 | 1.9 ng/ml | Standard Deviation 1.2 |
| Pre-ablation, AF, Colchicine | Time Course of C-reactive Protein Levels | Day 14 | 2.0 ng/ml | Standard Deviation 1.9 |
| Pre-ablation, AF, Colchicine | Time Course of C-reactive Protein Levels | Baseline | 2.6 ng/ml | Standard Deviation 2.7 |
| Pre-ablation, AF, Colchicine | Time Course of C-reactive Protein Levels | Day 28 | 1.2 ng/ml | Standard Deviation 1 |
| Pre-ablation, AF, Placebo | Time Course of C-reactive Protein Levels | Day 3 | 48.2 ng/ml | Standard Deviation 59 |
| Pre-ablation, AF, Placebo | Time Course of C-reactive Protein Levels | Baseline | 2.3 ng/ml | Standard Deviation 1.7 |
| Pre-ablation, AF, Placebo | Time Course of C-reactive Protein Levels | Day 28 | 5.2 ng/ml | Standard Deviation 5.1 |
| Pre-ablation, AF, Placebo | Time Course of C-reactive Protein Levels | Day 7 | 15.4 ng/ml | Standard Deviation 17.1 |
| Pre-ablation, AF, Placebo | Time Course of C-reactive Protein Levels | Day 14 | 5.3 ng/ml | Standard Deviation 0.9 |