Clinical trial NCT05361772: Low-dose Colchicine Inhibit Abdominal Aortic Aneurysm Growth Trial
Official title: Low-dose Colchicine Inhibit Abdominal Aortic Aneurysm Growth Trial
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: NA
Conditions: Colchicine
Abdominal Aortic Aneurysm
Progression
Lead sponsor: Guangdong Provincial People's Hospital
Sponsor class: OTHER
Collaborators: name: The First Affiliated Hospital of Guangzhou Medical University
name: Shenzhen People's Hospital
name: Peking University Shougang Hospital
name: Peking Union Medical College Hospital
name: The Second Xianya Hospital of Central South University
name: Zhongshan People's Hospital, Guangdong, China
name: Shenzhen Bao an People's Hospital
First posted: 2022-05-05
Enrollment: 230
Sex: ALL
Minimum age (years): 55
Maximum age (years): 85
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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.

Primary outcomes:
measure: changes of the maximum diameter of abdominal aortic aneurysm
timeFrame: 24 months
Secondary outcomes:
measure: changes of the maximum volume of abdominal aortic aneurysm
timeFrame: 24 months
measure: aorta-related adverse events
timeFrame: 24 months
measure: major adverse cardiovascular events
timeFrame: 24 months
measure: all-cause mortality
timeFrame: 24 months
measure: aortic-related mortality
timeFrame: 24 months
measure: cardiovascular -related mortality
timeFrame: 24 months
measure: change of inflammatory biomarkers
timeFrame: 24 months
measure: change of living quality
timeFrame: 24 months
Other outcomes:
Locations:
Study officials:
affiliation: Guangdong Provincial People's Hospital
name: Jianfang Luo, MD
role: STUDY_CHAIR
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