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Low-dose Colchicine Inhibit Abdominal Aortic Aneurysm Growth Trial (COIN)

Primary Purpose

Colchicine, Abdominal Aortic Aneurysm, Progression

Status
Not yet recruiting
Phase
Not Applicable
Locations
Study Type
Interventional
Intervention
colchicine
Placebo
Sponsored by
Guangdong Provincial People's Hospital
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Colchicine

Eligibility Criteria

55 Years - 85 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • 1. Aged over 55 and under 85; 2. Diagnosis of infrarenal abdominal aortic aneurysm within 3 months by CTA; 3. No indication for endovascular repair or surgery of abdominal aortic aneurysm

Exclusion Criteria:

  • 1. Currently using colchicine; 2. Allergic to colchicine; 3. History of abdominal aortic aneurysm repair or surgery; 4. Combined with aortic dissection, thoracic aortic aneurysm, penetrating aortic ulcer (ulcer width>2cm and depth>1cm) and other aortic diseases requiring intervention; 5. Abdominal aortic aneurysm involving the renal artery or suprarenal abdominal aortic aneurysm; 6.Diameter of iliac aneurysm >29mm; 7. Renal artery stenosis or iliac artery stenosis planned for immediate intervention; 8. AAA caused by connective tissue disease (eg, collagen vascular disease), hereditary or genetic syndrome (eg, Marfan syndrome, Ehlers-Danlos syndrome); 9. Severe renal dysfunction (serum creatinine >176.8umol/L or eGFR <30ml/min) in the last 3 months 10. Severe liver dysfunction (ALT>2 ULN or TBIL>2 ULN)in the last 3 months; 11.Abnormal blood routine (hemoglobin <115g/L, white blood cell count<3.0×10^9/L, or platelet count <110×10^9/L) in the last 3 months; 12. Presence of inflammatory bowel disease or chronic diarrhea; 13. Current or planned usage of systemic immunosuppressants (eg, prednisone, azathioprine, methotrexate, cyclosporine for autoimmune disease or after bone marrow, heart, liver, lung, or other solid organ transplantation) ; 14.Patients with malignant tumors and autoimmune diseases; 15. Unable to take care of themselves, frail or expected survival time < 2 years; 16. Peripheral neuritis, myositis, or statin-related elevation of muscle enzymes; 17. Premenopausal, pregnant or lactating female patients; 18. Participated in other clinical studies of interventional therapy or drug therapy, which may interfere with the research results; 19. Refused or unable to sign informed consent to enter clinical research or to follow the research protocol and follow up.

Sites / Locations

    Arms of the Study

    Arm 1

    Arm 2

    Arm Type

    Experimental

    Placebo Comparator

    Arm Label

    low-dose colchicine group

    placebo group

    Arm Description

    colchicine 0.5mg per day for 24 months

    placebo 0.5mg per day for 24 months

    Outcomes

    Primary Outcome Measures

    changes of the maximum diameter of abdominal aortic aneurysm
    the changes of the maximum diameter of abdominal aortic aneurysm on CTA in 24 months

    Secondary Outcome Measures

    changes of the maximum volume of abdominal aortic aneurysm
    the changes of the maximum volume of abdominal aortic aneurysm on CTA in 24 months
    aorta-related adverse events
    rupture of abdominal aortic aneurysm, endovascular repair or surgery repair of abdominal aortic aneurysm,aortic-related death
    major adverse cardiovascular events
    cardiovascular death, acute coronary syndrome, interventon for coronary artery disease, ischemic stroke or transient ischemic attack
    all-cause mortality
    all-cause mortality
    aortic-related mortality
    aortic-related mortality
    cardiovascular -related mortality
    cardiovascular -related mortality
    change of inflammatory biomarkers
    change of CRP,D-dimer,MMP-9, IL-1β, IL-18
    change of living quality
    SF - 36 questionnaires

    Full Information

    First Posted
    April 30, 2022
    Last Updated
    April 30, 2022
    Sponsor
    Guangdong Provincial People's Hospital
    Collaborators
    The First Affiliated Hospital of Guangzhou Medical University, Shenzhen People's Hospital, Peking University Shougang Hospital, Peking Union Medical College Hospital, The Second Xianya Hospital of Central South University, Zhongshan People's Hospital, Guangdong, China, Shenzhen Bao an People's Hospital
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    1. Study Identification

    Unique Protocol Identification Number
    NCT05361772
    Brief Title
    Low-dose Colchicine Inhibit Abdominal Aortic Aneurysm Growth Trial
    Acronym
    COIN
    Official Title
    Low-dose Colchicine Inhibit Abdominal Aortic Aneurysm Growth Trial
    Study Type
    Interventional

    2. Study Status

    Record Verification Date
    April 2022
    Overall Recruitment Status
    Not yet recruiting
    Study Start Date
    June 1, 2022 (Anticipated)
    Primary Completion Date
    June 1, 2024 (Anticipated)
    Study Completion Date
    December 31, 2025 (Anticipated)

    3. Sponsor/Collaborators

    Responsible Party, by Official Title
    Principal Investigator
    Name of the Sponsor
    Guangdong Provincial People's Hospital
    Collaborators
    The First Affiliated Hospital of Guangzhou Medical University, Shenzhen People's Hospital, Peking University Shougang Hospital, Peking Union Medical College Hospital, The Second Xianya Hospital of Central South University, Zhongshan People's Hospital, Guangdong, China, Shenzhen Bao an People's Hospital

    4. Oversight

    Studies a U.S. FDA-regulated Drug Product
    No
    Studies a U.S. FDA-regulated Device Product
    No
    Data Monitoring Committee
    Yes

    5. Study Description

    Brief Summary
    COIN trial is a a prospective, randomized, placebo-controlled, double-blind, multicenter clinical study. Approximately 230 patients with small abdominal aortic aneurysms (AAA) will be randomly allocated to low-dose colchicine group or placebo group. All study patients will be followed up in the outpatient clinic every 3 months and undergo CTA scans after 24 months from randomization. The primary objective is to test the hypothesis that low dose colchicine can inhibit the progression of AAA diameter. The secondary objective is to test the hypothesis that low dose colchicine can inhibit the progression of AAA volume, reduce the incidence of clinical outcomes associated with AAA, reduce the incidence of major adverse cardiovascular events and all-cause mortality.
    Detailed Description
    This study is a prospective, randomized, placebo-controlled, double-blind, multicenter clinical study to test the research hypothesis that low-dose colchicine (0.5 mg/d) can delay the progression of AAA. The study will enroll patients with infrarenal abdominal aortic aneurysms with a maximum diameter of 30-50 mm and no indication for surgical or endovascular treatment. All patients will receive the best standard medical treatment. Before randomization, all patients will undergo a 1-month lead-in period, during which open-label colchicine 0.5 mg/d will be administered. If there is colchicine intolerance, they will not be randomized. The study center performed computer-generated block randomization (block size 8). Randomization method and block size will not unblinded until all data analyses are completed. Enrolled patients will randomly assigned to each hospital in a 1:1 ratio by the randomization center through sequentially coded, sealed, light-tight envelopes, to colchicine and placebo groups. After randomization, patients will receive low-dose colchicine (0.5 mg/d) or placebo, respectively, and will be followed up for 24 months. We will evulate whether low-dose colchicine can delay the progression of AAA by assessing the change in maximum aneurysm diameter by CTA. At the same time, its effects on abdominal aortic aneurysm-related and cardiovascular-related clinical events will be observed.

    6. Conditions and Keywords

    Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
    Colchicine, Abdominal Aortic Aneurysm, Progression

    7. Study Design

    Primary Purpose
    Treatment
    Study Phase
    Not Applicable
    Interventional Study Model
    Parallel Assignment
    Masking
    ParticipantCare ProviderInvestigator
    Allocation
    Randomized
    Enrollment
    230 (Anticipated)

    8. Arms, Groups, and Interventions

    Arm Title
    low-dose colchicine group
    Arm Type
    Experimental
    Arm Description
    colchicine 0.5mg per day for 24 months
    Arm Title
    placebo group
    Arm Type
    Placebo Comparator
    Arm Description
    placebo 0.5mg per day for 24 months
    Intervention Type
    Drug
    Intervention Name(s)
    colchicine
    Intervention Description
    colchicine 0.5mg per day for 24 months
    Intervention Type
    Drug
    Intervention Name(s)
    Placebo
    Intervention Description
    placebo 0.5mg per day for 24 months
    Primary Outcome Measure Information:
    Title
    changes of the maximum diameter of abdominal aortic aneurysm
    Description
    the changes of the maximum diameter of abdominal aortic aneurysm on CTA in 24 months
    Time Frame
    24 months
    Secondary Outcome Measure Information:
    Title
    changes of the maximum volume of abdominal aortic aneurysm
    Description
    the changes of the maximum volume of abdominal aortic aneurysm on CTA in 24 months
    Time Frame
    24 months
    Title
    aorta-related adverse events
    Description
    rupture of abdominal aortic aneurysm, endovascular repair or surgery repair of abdominal aortic aneurysm,aortic-related death
    Time Frame
    24 months
    Title
    major adverse cardiovascular events
    Description
    cardiovascular death, acute coronary syndrome, interventon for coronary artery disease, ischemic stroke or transient ischemic attack
    Time Frame
    24 months
    Title
    all-cause mortality
    Description
    all-cause mortality
    Time Frame
    24 months
    Title
    aortic-related mortality
    Description
    aortic-related mortality
    Time Frame
    24 months
    Title
    cardiovascular -related mortality
    Description
    cardiovascular -related mortality
    Time Frame
    24 months
    Title
    change of inflammatory biomarkers
    Description
    change of CRP,D-dimer,MMP-9, IL-1β, IL-18
    Time Frame
    24 months
    Title
    change of living quality
    Description
    SF - 36 questionnaires
    Time Frame
    24 months

    10. Eligibility

    Sex
    All
    Minimum Age & Unit of Time
    55 Years
    Maximum Age & Unit of Time
    85 Years
    Accepts Healthy Volunteers
    No
    Eligibility Criteria
    Inclusion Criteria: 1. Aged over 55 and under 85; 2. Diagnosis of infrarenal abdominal aortic aneurysm within 3 months by CTA; 3. No indication for endovascular repair or surgery of abdominal aortic aneurysm Exclusion Criteria: 1. Currently using colchicine; 2. Allergic to colchicine; 3. History of abdominal aortic aneurysm repair or surgery; 4. Combined with aortic dissection, thoracic aortic aneurysm, penetrating aortic ulcer (ulcer width>2cm and depth>1cm) and other aortic diseases requiring intervention; 5. Abdominal aortic aneurysm involving the renal artery or suprarenal abdominal aortic aneurysm; 6.Diameter of iliac aneurysm >29mm; 7. Renal artery stenosis or iliac artery stenosis planned for immediate intervention; 8. AAA caused by connective tissue disease (eg, collagen vascular disease), hereditary or genetic syndrome (eg, Marfan syndrome, Ehlers-Danlos syndrome); 9. Severe renal dysfunction (serum creatinine >176.8umol/L or eGFR <30ml/min) in the last 3 months 10. Severe liver dysfunction (ALT>2 ULN or TBIL>2 ULN)in the last 3 months; 11.Abnormal blood routine (hemoglobin <115g/L, white blood cell count<3.0×10^9/L, or platelet count <110×10^9/L) in the last 3 months; 12. Presence of inflammatory bowel disease or chronic diarrhea; 13. Current or planned usage of systemic immunosuppressants (eg, prednisone, azathioprine, methotrexate, cyclosporine for autoimmune disease or after bone marrow, heart, liver, lung, or other solid organ transplantation) ; 14.Patients with malignant tumors and autoimmune diseases; 15. Unable to take care of themselves, frail or expected survival time < 2 years; 16. Peripheral neuritis, myositis, or statin-related elevation of muscle enzymes; 17. Premenopausal, pregnant or lactating female patients; 18. Participated in other clinical studies of interventional therapy or drug therapy, which may interfere with the research results; 19. Refused or unable to sign informed consent to enter clinical research or to follow the research protocol and follow up.
    Central Contact Person:
    First Name & Middle Initial & Last Name or Official Title & Degree
    Songyuan Luo, MD
    Phone
    +86-13570337597
    Email
    656781257@qq.com
    First Name & Middle Initial & Last Name or Official Title & Degree
    Guokui Zhang, MM
    Phone
    +86-13622266656
    Email
    772379801@qq.com
    Overall Study Officials:
    First Name & Middle Initial & Last Name & Degree
    Jianfang Luo, MD
    Organizational Affiliation
    Guangdong Provincial People's Hospital
    Official's Role
    Study Chair

    12. IPD Sharing Statement

    Plan to Share IPD
    No
    Citations:
    PubMed Identifier
    30337540
    Citation
    Sakalihasan N, Michel JB, Katsargyris A, Kuivaniemi H, Defraigne JO, Nchimi A, Powell JT, Yoshimura K, Hultgren R. Abdominal aortic aneurysms. Nat Rev Dis Primers. 2018 Oct 18;4(1):34. doi: 10.1038/s41572-018-0030-7.
    Results Reference
    background
    PubMed Identifier
    28527818
    Citation
    Li W, Luo S, Luo J, Liu Y, Ning B, Huang W, Xue L, Chen J. Predictors Associated With Increased Prevalence of Abdominal Aortic Aneurysm in Chinese Patients with Atherosclerotic Risk Factors. Eur J Vasc Endovasc Surg. 2017 Jul;54(1):43-49. doi: 10.1016/j.ejvs.2017.04.004. Epub 2017 May 17.
    Results Reference
    background
    PubMed Identifier
    31821436
    Citation
    Guirguis-Blake JM, Beil TL, Senger CA, Coppola EL. Primary Care Screening for Abdominal Aortic Aneurysm: Updated Evidence Report and Systematic Review for the US Preventive Services Task Force. JAMA. 2019 Dec 10;322(22):2219-2238. doi: 10.1001/jama.2019.17021.
    Results Reference
    background
    PubMed Identifier
    22794334
    Citation
    Kuivaniemi H, Elmore JR. Opportunities in abdominal aortic aneurysm research: epidemiology, genetics, and pathophysiology. Ann Vasc Surg. 2012 Aug;26(6):862-70. doi: 10.1016/j.avsg.2012.02.005.
    Results Reference
    background
    PubMed Identifier
    30523221
    Citation
    Umebayashi R, Uchida HA, Wada J. Abdominal aortic aneurysm in aged population. Aging (Albany NY). 2018 Dec 6;10(12):3650-3651. doi: 10.18632/aging.101702. No abstract available.
    Results Reference
    background
    PubMed Identifier
    31821481
    Citation
    Liu CL, Ren J, Wang Y, Zhang X, Sukhova GK, Liao M, Santos M, Luo S, Yang D, Xia M, Inouye K, Hotamisligil GS, Lu G, Upchurch GR, Libby P, Guo J, Zhang J, Shi GP. Adipocytes promote interleukin-18 binding to its receptors during abdominal aortic aneurysm formation in mice. Eur Heart J. 2020 Jul 7;41(26):2456-2468. doi: 10.1093/eurheartj/ehz856.
    Results Reference
    background
    PubMed Identifier
    30443031
    Citation
    Golledge J. Abdominal aortic aneurysm: update on pathogenesis and medical treatments. Nat Rev Cardiol. 2019 Apr;16(4):225-242. doi: 10.1038/s41569-018-0114-9.
    Results Reference
    background
    PubMed Identifier
    30636430
    Citation
    Oliver-Williams C, Sweeting MJ, Jacomelli J, Summers L, Stevenson A, Lees T, Earnshaw JJ. Safety of Men With Small and Medium Abdominal Aortic Aneurysms Under Surveillance in the NAAASP. Circulation. 2019 Mar 12;139(11):1371-1380. doi: 10.1161/CIRCULATIONAHA.118.036966.
    Results Reference
    background
    PubMed Identifier
    18268154
    Citation
    Freiberg MS, Arnold AM, Newman AB, Edwards MS, Kraemer KL, Kuller LH. Abdominal aortic aneurysms, increasing infrarenal aortic diameter, and risk of total mortality and incident cardiovascular disease events: 10-year follow-up data from the Cardiovascular Health Study. Circulation. 2008 Feb 26;117(8):1010-7. doi: 10.1161/CIRCULATIONAHA.107.720219. Epub 2008 Feb 11.
    Results Reference
    background
    PubMed Identifier
    29406857
    Citation
    Forsythe RO, Dweck MR, McBride OMB, Vesey AT, Semple SI, Shah ASV, Adamson PD, Wallace WA, Kaczynski J, Ho W, van Beek EJR, Gray CD, Fletcher A, Lucatelli C, Marin A, Burns P, Tambyraja A, Chalmers RTA, Weir G, Mitchard N, Tavares A, Robson JMJ, Newby DE. 18F-Sodium Fluoride Uptake in Abdominal Aortic Aneurysms: The SoFIA3 Study. J Am Coll Cardiol. 2018 Feb 6;71(5):513-523. doi: 10.1016/j.jacc.2017.11.053.
    Results Reference
    background
    PubMed Identifier
    28720724
    Citation
    MA3RS Study Investigators. Aortic Wall Inflammation Predicts Abdominal Aortic Aneurysm Expansion, Rupture, and Need for Surgical Repair. Circulation. 2017 Aug 29;136(9):787-797. doi: 10.1161/CIRCULATIONAHA.117.028433. Epub 2017 Jul 18.
    Results Reference
    background
    PubMed Identifier
    12615785
    Citation
    Vainas T, Lubbers T, Stassen FR, Herngreen SB, van Dieijen-Visser MP, Bruggeman CA, Kitslaar PJ, Schurink GW. Serum C-reactive protein level is associated with abdominal aortic aneurysm size and may be produced by aneurysmal tissue. Circulation. 2003 Mar 4;107(8):1103-5. doi: 10.1161/01.cir.0000059938.95404.92.
    Results Reference
    background

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