Colchicine Prevents Myocardial Injury After Non-Cardiac Surgery Pilot Study

NCT04139655 | Withdrawn

• 1 other identifier: H19-02858
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

Brief Summary

Perioperative Myocardial Infarction (PMI) is a major contributor to perioperative mortality and morbidity with overall incidence of 5-16%. It is associated with increased 30-day mortality of 11.6% vs 2.2% of patients without PMI in non-cardiac surgical patients. However, its recognition and diagnosis remains challenging as the typical symptoms and findings of ischemic MI may be masked by post-operative changes and pain management. In this study, the investigators hope to determine if colchicine decreases the incidence of MINS in high risk surgical patients undergoing non-cardiac surgery and optimally establish colchicine as a viable therapy to improve perioperative cardiovascular outcome in those patients.

Conditions

Myocardial Infarction; Myocardial Injury; Major Adverse Cardiac Events; Infectious Complications

Keywords

MINS; Colchicine; Myocardial Injury; Major Adverse Cardiac Events; Myocardial Injury after Non-Cardiac Surgery; MACE

Outcome Measures

Primary Outcomes (1)

• Number of Patients Recruited

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

  3 months

Secondary Outcomes (4)

• Incidence of Myocardial Injury after Non-Cardiac Surgery (MINS)

  From Post-Operatively day one up to 7 days post-operatively

• Adverse Events

  Duration of hospital admission up to 7 days post-operatively

• Incidence of premature discontinuation of the study drug and Reasoning

  Post-Operatively until date of study drug discontinuation (up to 7 days post-operatively)

• Incidence of infectious complications

  Duration of hospital admission up to 7 days post-operatively

Other Outcomes (3)

• Medical comorbidities

  Duration of hospital admission up to 7 days post-operatively

• Clinical risk stratification scores

  Duration of hospital admission up to 7 days post-operatively

• Neutrophil to lymphocyte ratio (NLR)

  Pre-operatively up to 7 days post-operatively

Study Arms (2)

Colchicine Group

EXPERIMENTAL

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.

Drug: Colchicine 0.6 mg

Placebo Group

PLACEBO COMPARATOR

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.

Drug: Placebo oral tablet

Interventions

Colchicine 0.6 mg DRUG

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 Group

Placebo oral tablet DRUG

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 Group

Eligibility Criteria

• Age: 45 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Any patient undergoing non-cardiac surgery is eligible if (s)he is:
• Aged 45 years of age or older
• Expected to be admitted for \>48 hours
• Have a preoperative Brain natriuretic peptide (BNP) value of 92 or higher, or a N-terminal prohormone brain natriuretic peptide (NT-proBNP) value of 300 or higher,
• If a BNP or NT-proBNP is not available, then the patient must fulfill at least one of the criteria for moderate to high risk of perioperative myocardial injury (see below):
• Moderate to high risk for perioperative myocardial injury criteria:
• History of coronary artery disease
• History of peripheral artery disease
• History of stroke
• Undergoing major vascular surgery
• Any 3 of the following 9 criteria:
• Age 70 years or greater
• Undergoing intraperitoneal, retroperitoneal, intrathoracic, or major orthopaedic surgery
• History of heart failure
• History of transient ischemic attack

You may not qualify if:

• Patients will be ineligible for the study if (s)he has:
• An allergy to colchicine
• Myelodysplastic syndrome
• An estimated glomerular filtration rate (eGFR) of less than 30 mL/min/1.73m2
• Anticipated post-operative administration of cyclosporine, ketoconazole, itraconazole, protease inhibitors, or clarithromycin

Sponsors & Collaborators

• University of British Columbia: lead
• Providence Health & Services: collaborator
• Vancouver Coastal Health: collaborator

Study Sites (1)

St. Paul's Hospital

Vancouver, British Columbia, V6Z 1Y6, Canada

Location

Related Publications (10)

• Devereaux PJ, Xavier D, Pogue J, Guyatt G, Sigamani A, Garutti I, Leslie K, Rao-Melacini P, Chrolavicius S, Yang H, Macdonald C, Avezum A, Lanthier L, Hu W, Yusuf S; POISE (PeriOperative ISchemic Evaluation) Investigators. Characteristics and short-term prognosis of perioperative myocardial infarction in patients undergoing noncardiac surgery: a cohort study. Ann Intern Med. 2011 Apr 19;154(8):523-8. doi: 10.7326/0003-4819-154-8-201104190-00003.

  PMID: 21502650 BACKGROUND

• Puelacher C, Lurati Buse G, Seeberger D, Sazgary L, Marbot S, Lampart A, Espinola J, Kindler C, Hammerer A, Seeberger E, Strebel I, Wildi K, Twerenbold R, du Fay de Lavallaz J, Steiner L, Gurke L, Breidthardt T, Rentsch K, Buser A, Gualandro DM, Osswald S, Mueller C; BASEL-PMI Investigators. Perioperative Myocardial Injury After Noncardiac Surgery: Incidence, Mortality, and Characterization. Circulation. 2018 Mar 20;137(12):1221-1232. doi: 10.1161/CIRCULATIONAHA.117.030114. Epub 2017 Dec 4.

  PMID: 29203498 BACKGROUND

• Vascular Events In Noncardiac Surgery Patients Cohort Evaluation (VISION) Study Investigators; Devereaux PJ, Chan MT, Alonso-Coello P, Walsh M, Berwanger O, Villar JC, Wang CY, Garutti RI, Jacka MJ, Sigamani A, Srinathan S, Biccard BM, Chow CK, Abraham V, Tiboni M, Pettit S, Szczeklik W, Lurati Buse G, Botto F, Guyatt G, Heels-Ansdell D, Sessler DI, Thorlund K, Garg AX, Mrkobrada M, Thomas S, Rodseth RN, Pearse RM, Thabane L, McQueen MJ, VanHelder T, Bhandari M, Bosch J, Kurz A, Polanczyk C, Malaga G, Nagele P, Le Manach Y, Leuwer M, Yusuf S. Association between postoperative troponin levels and 30-day mortality among patients undergoing noncardiac surgery. JAMA. 2012 Jun 6;307(21):2295-304. doi: 10.1001/jama.2012.5502.

  PMID: 22706835 BACKGROUND

• Botto F, Alonso-Coello P, Chan MT, Villar JC, Xavier D, Srinathan S, Guyatt G, Cruz P, Graham M, Wang CY, Berwanger O, Pearse RM, Biccard BM, Abraham V, Malaga G, Hillis GS, Rodseth RN, Cook D, Polanczyk CA, Szczeklik W, Sessler DI, Sheth T, Ackland GL, Leuwer M, Garg AX, Lemanach Y, Pettit S, Heels-Ansdell D, Luratibuse G, Walsh M, Sapsford R, Schunemann HJ, Kurz A, Thomas S, Mrkobrada M, Thabane L, Gerstein H, Paniagua P, Nagele P, Raina P, Yusuf S, Devereaux PJ, Devereaux PJ, Sessler DI, Walsh M, Guyatt G, McQueen MJ, Bhandari M, Cook D, Bosch J, Buckley N, Yusuf S, Chow CK, Hillis GS, Halliwell R, Li S, Lee VW, Mooney J, Polanczyk CA, Furtado MV, Berwanger O, Suzumura E, Santucci E, Leite K, Santo JA, Jardim CA, Cavalcanti AB, Guimaraes HP, Jacka MJ, Graham M, McAlister F, McMurtry S, Townsend D, Pannu N, Bagshaw S, Bessissow A, Bhandari M, Duceppe E, Eikelboom J, Ganame J, Hankinson J, Hill S, Jolly S, Lamy A, Ling E, Magloire P, Pare G, Reddy D, Szalay D, Tittley J, Weitz J, Whitlock R, Darvish-Kazim S, Debeer J, Kavsak P, Kearon C, Mizera R, O'Donnell M, McQueen M, Pinthus J, Ribas S, Simunovic M, Tandon V, Vanhelder T, Winemaker M, Gerstein H, McDonald S, O'Bryne P, Patel A, Paul J, Punthakee Z, Raymer K, Salehian O, Spencer F, Walter S, Worster A, Adili A, Clase C, Cook D, Crowther M, Douketis J, Gangji A, Jackson P, Lim W, Lovrics P, Mazzadi S, Orovan W, Rudkowski J, Soth M, Tiboni M, Acedillo R, Garg A, Hildebrand A, Lam N, Macneil D, Mrkobrada M, Roshanov PS, Srinathan SK, Ramsey C, John PS, Thorlacius L, Siddiqui FS, Grocott HP, McKay A, Lee TW, Amadeo R, Funk D, McDonald H, Zacharias J, Villar JC, Cortes OL, Chaparro MS, Vasquez S, Castaneda A, Ferreira S, Coriat P, Monneret D, Goarin JP, Esteve CI, Royer C, Daas G, Chan MT, Choi GY, Gin T, Lit LC, Xavier D, Sigamani A, Faruqui A, Dhanpal R, Almeida S, Cherian J, Furruqh S, Abraham V, Afzal L, George P, Mala S, Schunemann H, Muti P, Vizza E, Wang CY, Ong GS, Mansor M, Tan AS, Shariffuddin II, Vasanthan V, Hashim NH, Undok AW, Ki U, Lai HY, Ahmad WA, Razack AH, Malaga G, Valderrama-Victoria V, Loza-Herrera JD, De Los Angeles Lazo M, Rotta-Rotta A, Szczeklik W, Sokolowska B, Musial J, Gorka J, Iwaszczuk P, Kozka M, Chwala M, Raczek M, Mrowiecki T, Kaczmarek B, Biccard B, Cassimjee H, Gopalan D, Kisten T, Mugabi A, Naidoo P, Naidoo R, Rodseth R, Skinner D, Torborg A, Paniagua P, Urrutia G, Maestre ML, Santalo M, Gonzalez R, Font A, Martinez C, Pelaez X, De Antonio M, Villamor JM, Garcia JA, Ferre MJ, Popova E, Alonso-Coello P, Garutti I, Cruz P, Fernandez C, Palencia M, Diaz S, Del Castillo T, Varela A, de Miguel A, Munoz M, Pineiro P, Cusati G, Del Barrio M, Membrillo MJ, Orozco D, Reyes F, Sapsford RJ, Barth J, Scott J, Hall A, Howell S, Lobley M, Woods J, Howard S, Fletcher J, Dewhirst N, Williams C, Rushton A, Welters I, Leuwer M, Pearse R, Ackland G, Khan A, Niebrzegowska E, Benton S, Wragg A, Archbold A, Smith A, McAlees E, Ramballi C, Macdonald N, Januszewska M, Stephens R, Reyes A, Paredes LG, Sultan P, Cain D, Whittle J, Del Arroyo AG, Sessler DI, Kurz A, Sun Z, Finnegan PS, Egan C, Honar H, Shahinyan A, Panjasawatwong K, Fu AY, Wang S, Reineks E, Nagele P, Blood J, Kalin M, Gibson D, Wildes T; Vascular events In noncardiac Surgery patIents cOhort evaluatioN (VISION) Writing Group, on behalf of The Vascular events In noncardiac Surgery patIents cOhort evaluatioN (VISION) Investigators; Appendix 1. The Vascular events In noncardiac Surgery patIents cOhort evaluatioN (VISION) Study Investigators Writing Group; Appendix 2. The Vascular events In noncardiac Surgery patIents cOhort evaluatioN Operations Committee; Vascular events In noncardiac Surgery patIents cOhort evaluatioN VISION Study Investigators. Myocardial injury after noncardiac surgery: a large, international, prospective cohort study establishing diagnostic criteria, characteristics, predictors, and 30-day outcomes. Anesthesiology. 2014 Mar;120(3):564-78. doi: 10.1097/ALN.0000000000000113.

  PMID: 24534856 BACKGROUND

• Duceppe E, Parlow J, MacDonald P, Lyons K, McMullen M, Srinathan S, Graham M, Tandon V, Styles K, Bessissow A, Sessler DI, Bryson G, Devereaux PJ. Canadian Cardiovascular Society Guidelines on Perioperative Cardiac Risk Assessment and Management for Patients Who Undergo Noncardiac Surgery. Can J Cardiol. 2017 Jan;33(1):17-32. doi: 10.1016/j.cjca.2016.09.008. Epub 2016 Oct 4.

  PMID: 27865641 BACKGROUND

• Parashar A, Agarwal S, Krishnaswamy A, Sud K, Poddar KL, Bassi M, Ellis S, Tuzcu EM, Menon V, Kapadia SR. Percutaneous Intervention for Myocardial Infarction After Noncardiac Surgery: Patient Characteristics and Outcomes. J Am Coll Cardiol. 2016 Jul 26;68(4):329-38. doi: 10.1016/j.jacc.2016.03.602.

  PMID: 27443427 BACKGROUND

• Lennerz C, Barman M, Tantawy M, Sopher M, Whittaker P. Colchicine for primary prevention of atrial fibrillation after open-heart surgery: Systematic review and meta-analysis. Int J Cardiol. 2017 Dec 15;249:127-137. doi: 10.1016/j.ijcard.2017.08.039. Epub 2017 Sep 1.

  PMID: 28918897 BACKGROUND

• Agarwal SK, Vallurupalli S, Uretsky BF, Hakeem A. Effectiveness of colchicine for the prevention of recurrent pericarditis and post-pericardiotomy syndrome: an updated meta-analysis of randomized clinical data. Eur Heart J Cardiovasc Pharmacother. 2015 Apr;1(2):117-25. doi: 10.1093/ehjcvp/pvv001. Epub 2015 Feb 19.

  PMID: 27533981 BACKGROUND

• Papageorgiou N, Briasoulis A, Lazaros G, Imazio M, Tousoulis D. Colchicine for prevention and treatment of cardiac diseases: A meta-analysis. Cardiovasc Ther. 2017 Feb;35(1):10-18. doi: 10.1111/1755-5922.12226.

  PMID: 27580061 BACKGROUND

• Hemkens LG, Ewald H, Gloy VL, Arpagaus A, Olu KK, Nidorf M, Glinz D, Nordmann AJ, Briel M. Cardiovascular effects and safety of long-term colchicine treatment: Cochrane review and meta-analysis. Heart. 2016 Apr;102(8):590-6. doi: 10.1136/heartjnl-2015-308542. Epub 2016 Feb 1.

  PMID: 26830663 BACKGROUND

MeSH Terms

Conditions

Myocardial Infarction; Cardiovascular Diseases

Interventions

Colchicine

Condition Hierarchy (Ancestors)

Myocardial Ischemia; Heart Diseases; Vascular Diseases; Infarction; Ischemia; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Necrosis

Intervention Hierarchy (Ancestors)

Alkaloids; Heterocyclic Compounds

Study Officials

• Ron Ree, MD

  Providence Health Care and UBC

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Masking Details: Double-Blinded
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Clinical Associate Professor

Model Details: Randomized Control Pilot Study

Study Record Dates

• First Submitted: September 25, 2019
• First Posted: October 25, 2019
• Study Start: September 1, 2020
• Primary Completion: September 1, 2021
• Study Completion: October 1, 2021
• Last Updated: November 19, 2021

Record last verified: 2021-11

Data Sharing

• IPD Sharing: Will not share

Locations

CA (1)