Colchicine in Patients at Cardiac Risk Undergoing Major Non-Cardiac Surgery

Summary

Perioperative myocardial injury and major adverse cardiovascular events (MACE) are common causes of morbidity and mortality in patients at increased cardiovascular risk undergoing non-cardiac surgery. However, research in recent years has yielded limited preventive and therapeutic measures for myocardial injury/MACE. Recent studies in patients with chronic and acute coronary artery disease have shown that colchicine administration can reduce the risk of cardiovascular events. These encouraging results in non-surgical patients ask for a similar investigation in patients undergoing major non-cardiac surgery. The aim of the proposed study is to investigate the effects of perioperative colchicine administration on the incidence of myocardial injury/MACE.

Eligibility

Inclusion Criteria:

undergoing major non-cardiac surgery in general anaesthesia will be included. Major non-cardiac surgery is defined as:

* vascular surgery (with the exception of arteriovenous shunt, vein stripping procedures and carotid endarterectomies)
* intraperitoneal surgery
* intrathoracic surgery
* major orthopaedic surgery (spinal surgery or joint replacement surgery)
* at cardiovascular risk, defined as meeting at least 1 of the following 6 criteria:

  * preoperative n-terminal pro brain natriuretic peptide (NT-proBNP) ≥ 200 ng/l
  * history of coronary artery disease
  * history of peripheral vascular disease
  * history of stroke
  * undergoing major vascular surgery, with the exception of arteriovenous shunt, vein stripping procedures and carotid endarterectomies
  * fulfilment of any 3 of the 8 following criteria:

    * undergoing major surgery (intrathoracic, intraperitoneal or supra-inguinal vascular surgery)
    * any history of congestive heart failure or history of pulmonary oedema
    * anamnestic transient ischemic attack (TIA)
    * diabetes under treatment with either oral antidiabetic agent or insulin
    * age \> 70 years
    * history of hypertension
    * serum creatinine \> 175 mumol/l or calculated creatinine clearance \< 60 ml/min/1.73m2 (cockcroft gault)
    * history of smoking within 2 years of surgery
    * planned surgical time ≥ 90 minutes
    * planned postoperative hospital stay at least 1 night

Exclusion Criteria:

* no written consent
* inclusion in other clinical trial with direct impact on perioperative medication
* previously reported side effects or reported intolerance from colchicine (e.g., allergic reaction or significant sensitivity to colchicine or an auxiliary substance of the IMP)
* pregnancy or planned pregnancy and/or breast feeding
* clinically significant history of drug or alcohol abuse within the last year
* very severe frailty (≥ 8 clinical frailty scale)
* patient with inflammatory bowel disease (e.g., Morbus Crohn or Colitis ulcerosa)
* patient taking colchicine for other indications (e.g., familial Mediterranean fever, gout)
* severe renal impairment (eGFR \< 30 ml min -1 1.73 m2 -1) or end-stage renal disease with indication for haemodialysis
* history of solid organ or bone marrow transplantation
* systemic immune-suppression (medication (steroids \>30mg cortisol-equivalent per day, tacrolimus etc...) or disease (e.g., myelodysplastic syndrome)
* severe hepatic impairment with history of cirrhosis
* chronic active hepatitis or functional disorders defined as alanine aminotransferase greater than three times the upper limit of normal
* anticipated post-operative administration of CYP3A4 metabolized substances like cyclosporine, ketoconazole, clarithromycin, verapamil, quinidine, diltiazem or ritonavir
* Any other condition that the investigator would consider a risk to the patient if the latter were to participate in the study.

Conditions6

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