Atrial Fibrillation
Conditions
Brief summary
The purpose of this study to investigate the effects of colchicine on atrial fibrillation recurrence and vascular and cardiac function in patients with atrial fibrillation.
Detailed description
The study is an investigator-initiated, prospective, double-blind, placebo-controlled, randomized clinical trial investigating the effects of colchicine in patients with atrial fibrillation (AF). The study population will consist of approximately 500 patients aged 18 years and above with a diagnosis of paroxysmic or persistent AF with a successful outcome of cardioversion. Patients will be randomized to either low-dose colchicine treatment (0,5 mg once daily) or placebo. Treatment will continue for 12 months. Patients will be assessed by measurement of time to first admission with AF (Electro Cardio Gram (ECG) confirmed), echocardiography, cardiac Magnetic Resonance Imaging (MRI), and blood samples at baseline and after 6 + 12 months.
Interventions
DRUGColchicine
Colchicine 0.5 mg once daily
DRUGPlacebo
Placebo once daily
Sponsors
Herlev and Gentofte Hospital
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Living address in the Capital Region of Denmark 2. Age \> 18 3. Diagnosed with paroxysmic/persistent AF. 4. Planned or acute admission for cardioversion of AF with successful outcome. 5. Female participants should either not be of childbearing potential, defined as postmenopausal for at least 1 year or surgically sterile, or is of childbearing potential and practicing one of the following methods of contraception throughout the study and for 30 days after study completion: Hormonal contraception (oral contraceptives, contraceptive implant, injectable birth control, contraceptive patch, or vaginal ring) or intrauterine device 6. Participants will have given written, informed consent and are able and willing to comply with the requirements of the study protocol. 7. Optimal background therapy (in relation to comorbidities and development of heart failure / thromboembolic event) for AF as judged by the investigator.
Exclusion criteria
1. Colchicine treatment for another cause, e.g. gout 2. Allergy/hypersensitivity to colchicine 3. Uncontrolled hypertension (systolic BP \>180 mmHg or diastolic BP \>110 mmHg) 4. History of malignancy of any organ system excluding a successfully treated non-metastatic cutaneous squamous cell or basal cell carcinoma, localized prostate cancer and/or localized carcinoma in situ of the cervix 5. Cirrhosis, chronic active hepatitis or other severe hepatic disease 6. Hemodialysis 7. Estimated glomerular filtration rate (eGFR) \< 60 mL/min/1.73 m2 8. Systemic treatment with moderate or strong cytochrome P450 3A4 (CYP3A4) inhibitors or P-glycoprotein inhibitors (list in Appendix 1) 9. Permanent AF 10. Female participants who are pregnant, lactating, or considering becoming pregnant during the study or for 6 months after study completion 11. Significant drug or alcohol abuse during the last year 12. Current use of or plans to initiate chronic systemic steroid therapy during the study (topical or inhaled steroids are allowed) 13. Planned ablation procedure as treatment for AF 14. If cardiovascular surgery or ablation has been done the past three months prior to inclusion. 15. Chronic inflammatory bowel disease (Crohn's disease or ulcerative colitis) or chronic diarrhea 16. Use of other investigational drugs within 30 days of the time of enrollment 17. Any surgical or medical condition, which in the opinion of the investigator, may place the patient at higher risk from his/her participation in the study, or is likely to prevent the patient from complying with the requirements of the study or completing the study. 18. Suspected AF, confirmed with ECG, at time of inclusion and randomization
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Between-group difference in change in time to first AF admission measured in days | 12 months |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Between-group difference in change in accumulated number of readmissions for symptomatic AF | 12 months | — |
| Between-group difference in change in Left Atrial Volume (LAV) assessed by echocardiography | 12 months | — |
| Between-group difference in change in Atrial Fibrillation Effect On Quality-Of-Life Questionnaire (AFEQT) score | 12 months | Score of 0 being the worst outcome and score of 100 being the best outcome |
Other
| Measure | Time frame |
|---|---|
| Between-group difference in change in LV posterior wall thickness assessed by echocardiography | 12 months |
| Between-group difference in change in Left Ventricle Ejection Fraction (LVEF) assessed by echocardiography | 12 months |
| Between-group difference in change in E/A ratio assessed by echocardiography | 12 months |
| Between-group difference in change in e' assessed by echocardiography | 12 months |
| Between-group difference in change in E/e' ratio assessed by echocardiography | 12 months |
| Between-group difference in change in Global Longitudinal Strain (GLS) assessed by echocardiography | 12 months |
| Between-group difference in change in aortic distensibility assessed by echocardiography | 12 months |
| Between-group difference in change in aortic strain assessed by echocardiography | 12 months |
| Between-group difference in change in plasma concentration of high sensitivity C-Reactive Protein (hs-CRP) | 12 months |
| Between-group difference in change in LV posterior wall thickness assessed by cardiac MRI | 12 months |
| Between-group difference in change in LVEF assessed by cardiac MRI | 12 months |
| Between-group difference in change in myocardial fibrosis assessed by cardiac MRI | 12 months |
| Between-group difference in change in myocardial inflammation assessed by cardiac MRI | 12 months |
| Between-group difference in change in plasma concentration of Tumor Necrosis Factor alpha (TNF-α) | 12 months |
| Between-group difference in change in plasma concentration of pro Brain Natriuretic Peptide (pro-BNP) | 12 months |
| Between-group difference in change in accumulated number of cardiovascular-related hospital visits | 12 months |
| Between-group difference in change in LV septal wall thickness assessed by cardiac MRI | 12 months |
| Between-group difference in change in plasma concentration of high sensitivity Troponin I (hs-TnI) | 12 months |
| Between-group difference in change in Left Ventricle (LV) septal wall thickness assessed by echocardiography | 12 months |
| Between-group difference in change in LV mass index assessed by echocardiography | 12 months |
Countries
Denmark
Contacts
Primary ContactAdam Femerling Langhoff, M.D.
Backup ContactTor Biering-Sørensen, MD, PhD, MPH
Outcome results
None listed