Colchicine, Colchicine Adverse Reaction, Inflammation in Cardiac Surgery, Inflammatory Markers, Post Operative Atrial Fibrillation
Conditions
Brief summary
This study wants to see if the medicine colchicine can help lower inflammation and reduce the chance of developing an irregular heartbeat (atrial fibrillation) after heart bypass surgery. Adults having coronary artery bypass surgery (CABG) can join. Participants will be randomly placed into one of two groups: one group will receive colchicine along with usual care, and the other will receive a placebo (a look-alike capsule with no medicine) along with usual care. Everyone will take a study capsule, and neither the patients nor the study team will know which capsule is being given. Everyone in the study will take study capsule, and neither the patients nor the study team will know who is receiving colchicine or placebo. Blood samples and health information will be collected before surgery; at 24, 48, 72, and 96 hours after surgery; and again at 10 days after surgery or at hospital discharge, whichever comes first. The investigators will look at inflammation marker levels, whether atrial fibrillation happens, and any side effects. This small study will help to generate effect size estimates and safety data that will help plan a larger study in the future.
Interventions
Colchicine dosing is based on actual body weight and renal function (creatinine clearance). Subjects will initiate study medication (placebo or active drug) 5 days prior to surgery and continue therapy for 10 days postoperatively or until hospital discharge, whichever occurs first. For patients weighing ≥70 kg: If CrCl \>30 mL/min: Colchicine 0.6 mg twice daily If CrCl \<30 mL/min: Colchicine 0.3 mg once daily For patients weighing \<70 kg: If CrCl \>30 mL/min: Colchicine 0.6 mg once daily If CrCl \<30 mL/min: Colchicine 0.3 mg every other day
DRUGPlacebo
Placebo dosing is based on actual body weight and renal function (creatinine clearance). Subjects will initiate study medication (placebo or active drug) 5 days prior to surgery and continue therapy for 10 days postoperatively or until hospital discharge, whichever occurs first. For patients weighing ≥70 kg: If CrCl \>30 mL/min: Placebo 0.6 mg twice daily If CrCl \<30 mL/min: Placebo 0.3 mg once daily For patients weighing \<70 kg: If CrCl \>30 mL/min: Placebo 0.6 mg once daily If CrCl \<30 mL/min: Placebo 0.3 mg every other day
Sponsors
Ayesha Ather
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 99 Years
Healthy volunteers
No
Inclusion criteria
* Age 18 years and older * Coronary artery bypass graft (CABG) planned procedure
Exclusion criteria
* History of atrial fibrillation * Off-pump CABG procedure * Current treatment with colchicine for any cause * Hypersensitivity to colchicine (as indicated by rash; hives; itching; red, swollen, blistered, or peeling skin with or without fever) * Emergency cardiac surgery * Extracorporeal Membrane Oxygenation (ECMO) pre- or post-cardiac surgery * Heart transplant patients * Left ventricular assist device (LVAD) patients * Serum creatinine \>2.0 mg/dL * Preoperative elevated CK or known myopathy * Severe liver disease or elevation of serum transaminases (\>1.5 times the upper limit of 40 units/liter) * Chronic intestinal disease or blood dyscrasia * Unable to speak English * Pregnancy or lactation in women
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Inflammatory markers | Baseline (pre-surgery), 24, 48, 72, 96 hours post-surgery and 10 days postoperatively or at discharge, whichever occurs first. | markers of inflammation (IL-6, CRP, IL-18, IL-1β, IL-8, and TNF-α) will be measured at predefined time points. Blood samples will be obtained as part of routine clinical care and analyzed using commercially available ELISA assays. |
| Rate of post-operative atrial fibrillation (POAF) | Through discharge (up to 15 days) | Postoperative atrial fibrillation (POAF) incidence will be assessed through daily chart review. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of participants discontinuing treatment | Through discharge (up to 15 days) | treatment discontinuation rates due to adverse events will be measured |
| Change in Liver Function | Baseline and Post operatively (approximately 24 hours) | Assessed as the impact on clinical biomarkers, i.e., ALT, AST in units per liter. |
| Change in creatinine level | Baseline through discharge (up to 15 days) | Assessed as the impact on clinical biomarkers, i.e., creatinine level in mg/dl |
| Creatine kinase level | Through discharge (up to 15 days) | Assessed as the impact on clinical biomarkers, creatine kinase (i.e., CK level) in units per liter |
| Complete blood count (CBC). | Through discharge (up to 15 days) | Assessed as the impact on clinical biomarker complete blood count (CBC). |
Countries
United States
Contacts
CONTACTAyesha Ather
STUDY_DIRECTORSibu Saha, MD
University of Kentucky
Outcome results
None listed