Administration of oral colchicine at 0.6 mg 1 hour prior to surgery, then 0.6 mg twice daily starting on the night after surgery for 7 days or until discharge from hospital, whichever occurs earlier. For patient under 60kg in body weight, daily dose will be 0.6 mg once daily. Medical and surgical management of the participant will be carried out under each institute's standard clinical practice.

Participants allocated to the control group will receive a placebo pill at the same dosing regimen as with treatment group. Perioperative and surgical care will not be different from standard clinical practice.

Myocardial Infarction

Myocardial Injury

Major Adverse Cardiac Events

Infectious Complications

Oral colchicine given at 0.6 mg 1 hour prior to surgery, then 0.6 mg twice daily starting on the night after surgery for 7 days or until discharge from hospital, whichever occurs earlier. For patient under 60kg in body weight, daily dose will be 0.6 mg once daily. Medical and surgical management of the participant will be carried out under each institute's standard clinical practice.

Colchicine 0.6 mg

Placebo oral tablet given at 0.6 mg 1 hour prior to surgery, then 0.6 mg twice daily starting on the night after surgery for 7 days or until discharge from hospital, whichever occurs earlier. For patient under 60kg in body weight, daily dose will be 0.6 mg once daily. Medical and surgical management of the participant will be carried out under each institute's standard clinical practice.

Placebo oral tablet

St. Paul's Hospital

Colchicine Prevents Myocardial Injury After Non-Cardiac Surgery Pilot Study

Colchicine Prevents Myocardial Injury After Non-Cardiac Surgery Pilot Study (COPMAN)

The number of eligible subjects recruited in 3 months after 2 weeks of run-in period in participating centres

The incidence of MINS in the treatment versus placebo group, as defined by high sensitivity troponin T level > 65 ng/L or Troponin level > 0.03 ng/mL. The incidence of MINS will be determined upon review of the troponin assay on post-operative day 0, 1, 2 and 3rd (or according to each participating institution's own MINS pathway) and electroncardiogram (ECG) on post-operative day 1, or as otherwise clinically indicated and ordered by the perioperative team. Information will be obtained by review of blood work results and ECG on institution's electronic health record and patient's bedside chart if necessary by our research team member.

We will collect adverse effects, whether or not associated with study drug through review of patient's bedside chart and discharge summary.

Incidence of premature discontinuation of the study drug will be recorded. If the subject chooses to discontinue the study drug and withdraw from the study, the duration of treatment before withdraw as well as reasons of withdraw will be recorded.

Incidence of infectious complications will also be recorded with review of chart and discharge summary. The determination of the complication will depend on patient's chart review, history and physical assessment by the primary care provider team, and associated imaging and laboratory investigations as clinically indicated. Complications include, but are not limited to: including but not limited to: pneumonia, surgical site infection, urinary tract infection, and sepsis during the hospital admission.

Revised cardiac risk index - RCRI scores based on patient charts.RCRI score is used and recommended by Canadian Cardiovascular Society as an evidence-based 30-day perioperative cardiovascular mortality and morbidity risk stratification tool

Based on patient charts, to be obtained from patient's pre-operative bloodwork. NLR is a marker of neutrophil predominant inflammatory state that is associated with Major Adverse Cardiac Events (MACE) in a systemic review

Ron Ree

Clinical Associate Professor

University of British Columbia

Providence Health & Services

Vancouver Coastal Health

In the Berberine Arm, patients will receive berberine 200 mg twice daily for 4±1 weeks (Stage 1); then, 300 mg twice daily for 4±1 weeks (Stage 2); then, 400 mg twice daily for 4±1 weeks (Stage 3) in addition to standard treatment, including aspirin 100 mg once daily and clopidogrel 75 mg once daily for 12±1 weeks.

In the Control Arm, patients will receive standard treatment, including aspirin 100 mg once daily and clopidogrel 75 mg once daily for 12±1 weeks.

Coronary Artery Disease

Percutaneous Coronary Intervention

Berberine 200 mg twice daily for 4±1 weeks (Stage 1); then, 300 mg twice daily for 4±1 weeks (Stage 2); then, 400 mg twice daily for 4 weeks (Stage 3).

Berberine

Standard treatment

Aspirin 100 mg once daily for 12±1 weeks.

Aspirin

Clopidogrel 75 mg once daily for 12±1 weeks.

Clopidogrel

Peking Union Medical College Hospital

Anti-platelet Effect of Berberine in Patients After Percutaneous Coronary Intervention

A Single-center, Randomized, Open-label, Controlled, Dose-escalating, Parallel-group Study to Assess the Anti-platelet Effect of Berberine in Patients Receiving Aspirin and Clopidogrel After Percutaneous Coronary Intervention

The P2Y12 reaction unit (PRU) assessed by VerifyNow assay 2-4 h after all the antiplatelet agents are taken simultaneously in the morning at the end of the treatment period (Visit 4, EOT), i.e., on the 12th (11th-13th) week of treatment

The P2Y12 reaction unit (PRU) assessed by VerifyNow assay 2-4 h after all the antiplatelet agents are taken simultaneously in the morning at the end of Stage 2 (Visit 3) [ i.e., on the 8th (7th-9th) week of treatment ]

The P2Y12 reaction unit (PRU) assessed by VerifyNow assay 2-4 h after all the antiplatelet agents are taken simultaneously in the morning at the end of Stage 1 (Visit 2) [ i.e., on the 4th (3rd-5th) week of treatment ]

The platelet reactivity index (PRI) assessed by vasodilator-stimulated phosphoprotein-phosphorylation (VASP-P) assay 2-4 h after all the antiplatelet agents are taken simultaneously in the morning at the end of the treatment period (Visit 4, EOT) [ i.e., on the 12th (11th-13th) week of treatment ]

The platelet reactivity index (PRI) assessed by vasodilator-stimulated phosphoprotein-phosphorylation (VASP-P) assay 2-4 h after all the antiplatelet agents are taken simultaneously in the morning at the end of Stage 2 (Visit 3) [ i.e., on the 8th (7th-9th) week of treatment ]

The platelet reactivity index (PRI) assessed by vasodilator-stimulated phosphoprotein-phosphorylation (VASP-P) assay 2-4 h after all the antiplatelet agents are taken simultaneously in the morning at the end of Stage 1 (Visit 2) [ i.e., on the 4th (3rd-5th) week of treatment ]

The urinary 11-dehydro-thromboxane B2 (11-dH-TXB2) assessed by enzyme-linked immunosorbent assay (ELISA) 2-4 h after all the antiplatelet agents are taken simultaneously in the morning at the end of the treatment period (Visit 4, EOT) [ i.e., on the 12th (11th-13th) week of treatment ]

The urinary 11-dehydro-thromboxane B2 (11-dH-TXB2) assessed by enzyme-linked immunosorbent assay (ELISA) 2-4 h after all the antiplatelet agents are taken simultaneously in the morning at the end of Stage 2 (Visit 3) [ i.e., on the 8th (7th-9th) week of treatment ]

The urinary 11-dehydro-thromboxane B2 (11-dH-TXB2) assessed by enzyme-linked immunosorbent assay (ELISA) 2-4 h after all the antiplatelet agents are taken simultaneously in the morning at the end of Stage 1 (Visit 2) [ i.e., on the 4th (3rd-5th) week of treatment ]

The composite of death, or myocardial infarction, or urgent coronary revascularization, or definite or possible stent thrombosis, up to the end of the treatment period (Visit 4, EOT), i.e., the 12th (11th-13th) week of treatment

The major bleeding according to platelet inhibition and patient outcomes (PLATO) definition up to the end of the treatment period (Visit 4, EOT), i.e., the 12th (11th-13th) week of treatment

The minor bleeding according to platelet inhibition and patient outcomes (PLATO) definition up to the end of the treatment period (Visit 4, EOT), i.e., the 12th (11th-13th) week of treatment

The minimal bleeding according to platelet inhibition and patient outcomes (PLATO) definition up to the end of the treatment period (Visit 4, EOT), i.e., the 12th (11th-13th) week of treatment

The major or minor bleeding according to platelet inhibition and patient outcomes (PLATO) definition up to the end of the treatment period (Visit 4, EOT), i.e., the 12th (11th-13th) week of treatment

The major or minor or minimal bleeding according to platelet inhibition and patient outcomes (PLATO) definition up to the end of the treatment period (Visit 4, EOT), i.e., the 12th (11th-13th) week of treatment

The P-selectin (CD62p) expression assessed by flow cytometry 2-4 h after all the antiplatelet agents are taken simultaneously in the morning at the end of the treatment period (Visit 4, EOT) [ i.e., the 12th (11th-13th) week of treatment ]

Serum soluble P-selectin (sCD62p) assessed by enzyme-linked immunosorbent assay (ELISA) 2-4 h after all the antiplatelet agents are taken simultaneously in the morning at the end of the treatment period (Visit 4, EOT) [ i.e., on the 12th (11th-13th) week of treatment ]

Serum soluble CD40 ligand (sCD40L) assessed by enzyme-linked immunosorbent assay (ELISA) 2-4 h after all the antiplatelet agents are taken simultaneously in the morning at the end of the treatment period (Visit 4, EOT) [ i.e., on the 12th (11th-13th) week of treatment ]

LiuZhenyu

Professor

On the first day of the treatment period (Visit 1), eligible patients will be randomized into the Berberine Arm and the Control Arm.
In the Berberine Arm, patients will receive berberine 200 mg twice daily for 4±1 weeks (Stage 1); then, 300 mg twice daily for 4±1 weeks (Stage 2); then, 400 mg twice daily for 4±1 weeks (Stage 3) in addition to standard treatment, including aspirin 100 mg once daily and clopidogrel 75 mg once daily for 12±1 weeks.
In the Control Arm, patients will receive standard treatment, including aspirin 100 mg once daily and clopidogrel 75 mg once daily for 12±1 weeks.

Examination of participants prior to chemotherapy. Venous occlusion plethysmography SphygmoCor 24hour blood pressure DEXA scan Laboratory blood samples

Examination of participants immediately after chemotherapy. Venous occlusion plethysmography SphygmoCor 24hour blood pressure DEXA scan Laboratory blood samples

Examination of participants one year after chemotherapy. Venous occlusion plethysmography SphygmoCor 24hour blood pressure DEXA scan Laboratory blood samples

Breast Neoplasms

Endothelial Dysfunction

Cardiovascular Disease

Metabolic Syndrome

To characterize endothelial function in vivo the effect of vasodilatating substances is measured in the forearm circuit. The substances is administered via a thin catheter placed in the Brachial artery near the elbow in local anesthesia. Once the vessels dilate, the blood flow in the forearm will increase and the flow change is a measure of the vasodilatory capacity of that substance. The change is measured with classical venous occlusion plethysmography. The method described is established at Aarhus University Hospital and has been used for several decades to illustrate the effect of vasoactive drugs on the human circulation, meaning it is a proven and well documented method.

Venous occlusion plethysmography

Applanation tonometry (pulse wave velocity and central blood pressure/arterial stiffness): The central blood pressure and the augmentation index is estimated from the shape of the radial pulse wave measured with a tonometer.
Pulse wave velocity (PWV) is calculated from the average difference between the pulse pressure wave measured with a tonometer and the R in an ECG recorded simultaneously.

SphygmoCor

24hour blood pressure

Measurements of body composition: Total body fat and fat free mass is measured by Dual Energy X-ray Absorptiometry (DEXA).

DEXA scan

Fasting blood tests are drawn from an antecubital placed catheter (albumin, ALAT/ASAT, alkaline phosphatase, bilirubin, gammaglutamyl transferase, coagulation factors, red and white blood cells, creatinin, potassium, sodium, fasting lipids, fasting glucose, hemoglobin A1C, insulin, sex hormones, von Willebrand factor, low grade inflammation markers, DNA and RNA for later analyses, including relevant coding genes).
Further more urine samples to determine possible systemic impact of cardiovascular disease.
We will create a biobank containing urine and blood samples from participants for future research, provided that the participant gives her permission.
Responsibility for the biobank lies with the project responsible physician, Anders Bonde Jensen.

Laboratory blood samples

Aarhus University Hospital

Anticancer Treatment of Breast Cancer Related to Cardiotoxicity and Dysfunctional Endothelium

P-Kolesterol, P-Kolesterol HDL, P-Kolesterol LDL, P-Triglyceride, P-Glukose, P-Progesteron, P-Testosteron, P-Von Willebrand-faktor, P-Natrium, P-Kalium, P-Kreatinin and P-Østradiol.

The SCORE-system is a well- established and validated method using age, gender, smoking status, systolic blood pressure and plasma cholesterol for risk stratification.

alkaloid/infarction

Colchicine Prevents Myocardial Injury After Non-Cardiac Surgery Pilot Study

Anti-platelet Effect of Berberine in Patients After Percutaneous Coronary Intervention

Anticancer Treatment of Breast Cancer Related to Cardiotoxicity and Dysfunctional Endothelium

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