Low-dose Colchicine Inhibit Abdominal Aortic Aneurysm Growth Trial

Not Applicable

Not yet recruiting

• Conditions: Colchicine; Progression; Abdominal Aortic Aneurysm
• Interventions: Drug: colchicine; Drug: Placebo

• Registration Number: NCT05361772
• Lead Sponsor: Guangdong Provincial People's Hospital

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.

Study Timeline

• Status Verified: 2022-04
• Study First Submitted: 2022-04-30
• Study First Submitted QC: 2022-04-30
• Last Update Submitted: 2022-04-30
• Study First Posted: 2022-05-05
• Last Update Posted: 2022-05-05
• Study Start: 2022-06-01
• Primary Completion: 2024-06-01
• Study Completion: 2025-12-31

Recruitment & Eligibility

• Status: NOT_YET_RECRUITING
• Sex: All
• Target Recruitment: 230

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

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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.

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
low-dose colchicine group	colchicine	colchicine 0.5mg per day for 24 months
placebo group	Placebo	placebo 0.5mg per day for 24 months

Primary Outcome Measures

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

Secondary Outcome Measures

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