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

NCT06279000 | Recruiting Phase 3

• 1 other identifier: CTU 22/025
• Study Type: interventional
• Target: 880
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Cardiovascular Diseases; Cardiovascular Complication; Perioperative Complication; Myocardial Injury; Myocardial Injury After Noncardiac Surgery (MINS)

Keywords

Perioperative Cardiovascular Risk; myocardial injury; major adverse cardiac events; colchicine

Outcome Measures

Primary Outcomes (2)

• Major Adverse Cardiovascular Events

  Proportion of patients developing MACE in the peri- postoperative course. MACE is defined as a composite of any of the following within 30 days following surgery: * Acute coronary syndrome * New/worsening congestive heart failure * Coronary revascularization * Stroke * All-cause mortality * Cardiovascular death

  until postoperative day 30

• Myocardial Injury

  Proportion of patients developing myocardial injury in the peri- postoperative course. The primary outcome is a composite of myocardial injury and 30-day MACE. Myocardial injury is defined as an absolute perioperative rise in hs-cTnT of ≥ 14 ng/l above preoperative values (or between two postoperative measurements, if preoperative hs-cTnT is missing).

  until postoperative day 4

Secondary Outcomes (3)

• New onset Atrial fibrillation

  From beginning of surgery/surgical procedures until the date of first documented occurrence or until postoperative day 30/discharge from hospital, whatever comes first

• postoperative high sensitive cardiac Troponin T concentrations

  until postoperative day 4

• long term cardiovascular outcome

  until 1 year after surgery

Other Outcomes (1)

• Gastrointestinal adverse events

  From the first intake of the study drug until 72 hours after the last intake of the study drug (i.e., postoperative day 6) or until discharge from the hospital, whatever comes first

Study Arms (2)

Colchicine

EXPERIMENTAL

The first dose of the IMP is administered in the evening prior to the surgical procedure. Administrations of the study drug follow a 1-0-1 schedule (colchicine 0.5 mg per intake). The last study drug is administered in the evening of the third postoperative day.

Drug: Colchicine

Control (Placebo)

PLACEBO COMPARATOR

Patients in the control group will receive the same perioperative anaesthetic, surgical and medical treatment as patients in the experimental group, the sole difference being that patients will be given a placebo instead of the IMP colchicine. The first dose of the placebo is administered in the evening prior to the surgical procedure. Administrations of the placebo follow a 1-0-1 schedule. The last placebo is administered in the evening of the third postoperative day.

Drug: Placebo

Interventions

Colchicine DRUG

Colchicine Group: IMP = Colchicine (0.5 mg, enteral) first application in the evening before day of surgery, following a 1-0-1 regimen until the third postoperative day, ending with the application of the ninth dose. Colchicine tablets are provided as 1 mg tablets with a score, which must be divided before ingestion.

Colchicine

Placebo DRUG

Placebo Group: Placebo (identical to IMP in appearance and application) first application in the evening before day of surgery, following a 1-0-1 regimen until the third postoperative day, ending with the application of the ninth dose. Placebo tablets are provided as tablets with a score, which must be divided before ingestion.

Also known as: Control

Control (Placebo)

Eligibility Criteria

• Age: 45 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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)

You may not qualify if:

• no written consent
• 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.

Sponsors & Collaborators

• Cantonal Hospital of St. Gallen: lead

Study Sites (1)

Cantonal Hospital St. Gallen

Sankt Gallen, Canton of St. Gallen, 9007, Switzerland

RECRUITING

MeSH Terms

Conditions

Cardiovascular Diseases

Interventions

Colchicine

Intervention Hierarchy (Ancestors)

Alkaloids; Heterocyclic Compounds

Central Study Contacts

Timur Yurttas, MD

CONTACT

0041 714949158; timur.yurttas@kssg.ch

Miodrag Filipovic, Prof. MD.

CONTACT

0041714941111; miodrag.filipovic@kssg.ch

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Patients, anaesthesia providers and all other health care workers involved in the treatment and the study personal will be blinded to the group allocation by provision of equal looking study drugs (verum and placebo), which are repacked for blinding.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator, Senior Anaesthesiologist

Model Details: randomized, double-blinded, placebo-controlled, multicenter

Study Record Dates

• First Submitted: February 12, 2024
• First Posted: February 26, 2024
• Study Start: April 20, 2025
• Primary Completion (Estimated): March 30, 2028
• Study Completion (Estimated): March 30, 2029
• Last Updated: April 24, 2025

Record last verified: 2024-09

Locations

CH (1)