None listed
Conditions
Brief summary
COLCARDIO-ACS Main study: Inflammation plays a pivotal role in atherosclerosis, offering new opportunities for the prevention and treatment of coronary artery disease. Colchicine is a commonly used anti-inflammatory medication approved for the treatment of gout, Familial Mediterranean Fever, and acute/recurrent pericarditis. There is an increasing body of evidence in the medical literature supporting a beneficial role of long term colchicine therapy in prevention of cardiovascular disease, via modulation of inflammatory cytokine production and tubulin-mediated mitosis inhibition. This includes both primary prevention in patients treated with colchicine for gout or Familial Mediterranean Fever, and secondary prevention in patients with stable coronary artery disease who are also being treated with statins and anti-platelet agents. Low-dose colchicine use has also been proven to be safe, well tolerated, and is inexpensive and readily available. The aim of this project is to assess the effect of colchicine (0.5 mg/day) in addition to optimal medical therapy on cardiovascular outcomes in ACS patients with evidence of persistent coronary inflammation (based on hsCRP). We hypothesise that addition of colchicine to optimal medical therapy in patients post-ACS, who have biomarker evidence of persistent inflammation will reduce recurrent cardiovascular events. COLCHICINE-COG Sub-study: Dementia affects over 400,000 Australians at a cost to the economy of $30 billion per year and is a Commonwealth Government National Health Priority. It is the third leading cause of death overall and the largest reason for disability in older Australians. Cardiovascular disease (CVD) has been identified as the earliest and strongest pathological marker for dementia. Oxidative stress is characterised by an imbalance in the redox state of cells (either via the overproduction of reactive oxygen species of antioxidant system dysfunction) and is posited to be a key mechanistic pathway underpinning the relationship between CVD and cognitive decline. Importantly, research suggests that the pathology leading to dementia occurs 10-20 years before the onset of clinical symptoms. Therefore, it is critical that interventions target CVD in those ‘at risk’ to prevent onset and reduce cognitive decline. The aim of this study is to examine the effect of long term low-dose colchicine on cognition and brain health patients with established coronary artery disease.
Interventions
Oral Colchicine 0.5 mg tablet taken daily for median of 3 years. Eligible and consenting participants will be registered and then commenced on Run-In treatment consisting of 1 oral tablet (0.5mg of colchicine) a day for 28 days additional to standard of care medication prescribed by treating physician. The Run-In treatment will be dispensed to participants in a single blinded manner. Upon completion of the Run-In treatment participants will be asked to return to site for a safety and compliance
Oral Colchicine 0.5 mg tablet taken daily for median of 3 years. Eligible and consenting participants will be registered and then commenced on Run-In treatment consisting of 1 oral tablet (0.5mg of colchicine) a day for 28 days additional to standard of care medication prescribed by treating physician. The Run-In treatment will be dispensed to participants in a single blinded manner. Upon completion of the Run-In treatment participants will be asked to return to site for a safety and compliance check before being randomised to receive either oral Colchicine 0.5mg taken daily or matched oral Placebo tablet taken daily for a median of 3 years and 600 primary endpoint events have occurred. Ongoing study treatment will be dispensed on a 6 monthly basis and participants will attend annual in clinic visits for clinical assessments and compliance check. Eligible and consenting participants to the COLCHICINE-COG sub study will have additional assessments including 30-minute online neuropsychological assessments (baseline, 12, 24 and 36 months), blood collection performed at the same time as collection for the main study (baseline, 12 and 36 months) and 30-60 minute MRI assessments in a sub-set of participants (n=40) at baseline and 12 months.
COLCARDIO-ACS Study
Oral Colchicine (0.5 mg) or matched placebo tablet taken daily in addition to optimal medical therapy for a median of 3 years.
Screened participants eligible to take part in the run-in phase will receive a tablet for 28 days in addition to standard of care medication prescribed by their treating physician. At the end of the run-in phase, participant eligibility will be reviewed.
After the completion of run-in, participants that remain eligible will be randomised for the t
COLCARDIO-ACS Study Oral Colchicine (0.5 mg) or matched placebo tablet taken daily in addition to optimal medical therapy for a median of 3 years. Screened participants eligible to take part in the run-in phase will receive a tablet for 28 days in addition to standard of care medication prescribed by their treating physician. At the end of the run-in phase, participant eligibility will be reviewed. After the completion of run-in, participants that remain eligible will be randomised for the treatment phase to receive Colchicine (0.5 mg) or matched placebo daily in addition to optimal medical therapy as per national guidelines. Treatment will continue daily until the end of the study (approximately 3-years or until at least 600 primary end points have occurred), or early discontinuation. COLCHICINE-COG Sub-study Participants at Royal Prince Alfred Hospital who consent to participate in the COLCARDIO-ACS Study will be invited to participate in the COLCHICINE-COG Sub-study. Consenting participants will complete web-based cognitive assessments and a subset will undergo magnetic resonance imaging (MRI). Blood samples collected during the COLCARDIO-ACS Study will be analysed for blood-based biomarkers of neurodegenerative pathology.
Sponsors
University of Sydney
Study design
Allocation
Randomised controlled trial
Intervention model
Parallel
Primary purpose
Treatment
Masking
Blinded (masking used) (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
All
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Patients aged equal or greater than 18 years 2. Presentation with an Acute Coronary Syndrome (defined as acute myocardial infarction, with or without electrocardiographic evidence of ST-segment elevation, or high-risk unstable angina) and commenced on optimal medical therapy 3. hs-CRP equal or greater than 2mg/L (at time of registration 4 - 52 weeks after discharge for an Acute Coronary Syndrome event) 4. Willing and able to comply with all study requirements, including treatment, timing and/or nature of required assessments 5. Signed written informed consent COLCHICINE-COG Inclusion criteria: 1. Be enrolled in COLCARDIO-ACS; 2. Be aged 40 - 65 years (at the time of enrolment); 3. Be willing and able to comply with sub-study visit schedule and nature of required assessments; and 4. Provide signed written informed consent
Exclusion criteria
1. Any known intolerance to Colchicine 2. Pre-existing Colchicine treatment within the last 3 months 3. Any known myopathy (any grade or myopathy in present or prior history within the last 3 months or CK >3 x upper limit of normal) 4. Severe liver disease or aminotransferase level > 3x upper limit of normal, within the last 3 months 5. Blood dyscrasia (white cell count or platelet count < lower limit of normal), within the last 3 months 6. Estimated glomerular filtration rate (eGFR) <45 mL/min per 1.73m2 at time of registration 7. Prior or current therapy with a strong CYP3A4 inhibitor or inducer or calcineurin inhibitor 8. Active autoimmune disease or chronic inflammatory bowel disease (defined as any disease requiring long-term or frequent immunosuppression) 9. Haematological malignancy which remains uncured or antineoplastic therapy within the last 3 months 10. Concurrent illness, including severe infection that may jeopardise the ability of the patient to undergo the procedures outlined in this protocol with reasonable safety 11. Any known comorbidities or conditions (e.g. psychiatric) or concomitant medications which may interact with the investigational product(s) or may compromise assessment of key outcomes. 12. Life expectancy of less than 3 years 13. Serious medical or psychiatric conditions that might limit the ability of the patient to comply with the protocol. 14. Pregnancy, lactation, or inadequate contraception. Women must be post-menopausal, infertile, or use a reliable means of contraception. Women of childbearing potential must have a negative pregnancy test done within 7 days prior to registration. Men must have been surgically sterilised or use a (double if required) barrier method of contraception. COLCHICINE-COG Exclusion criteria: 1. Suspected or established dementia diagnosis (MMSE <23); 2. Intellectual or developmental disability; 3. History of head injury with loss of consciousness >30 minutes; 4. History of major neurological illness (e.g. stroke, epilepsy); 5. History of psychiatric illness (other than affective disorder e.g. schizophrenia, bipolar disorder); 6. History of electroconvulsive therapy or deep brain stimulation; 7. Current/past alcohol or substance dependence (other than nicotine); 8. Any known medical condition which may affect cognition (e.g. cancer, chronic fatigue syndrome); and/or 9. Contraindications to magnetic resonance imaging scanning (e.g. aneurysm clip, pacemaker, etc.).
Outcome results
None listed