Anti-inflammatory Therapy for Recurrent In-stent Restenosis

Study Overview
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Brief Summary
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This study is aimed at making a comparison of the safety and efficacy of standard drug therapy (control group), standard drugs combined with lose-dose colchicine therapy (colchicine group) and standard drug combined with prednisone therapy (prednisone group) in patients with coronary heart disease who suffered from recurrent In-stent restenosis (RISR).

Detailed Description
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This is a prospective, randomized, open-label, blinded-endpoint evaluation, single-center Study. A total of 252 RISR patients are planned to be enrolled in Fuwai Hospital, China. Then those included subjects will be randomized to standard drug therapy (control group), standard drugs combined with lose-dose colchicine therapy (colchicine group) and standard drug combined with prednisone therapy (prednisone group). The primary endpoint of the current study is target lesion ISR confirmed by coronary angiography for 12 months, and the secondary endpoint is Major adverse cardiovascular events (MACE: a composite of death, non-fatal myocardial infarction, non-fatal stroke, and target vascular revascularization) and each MACE component, target lesion revascularization, or other coronary artery disease revascularization for 12 months. The safety endpoint is adverse reactions to colchicine, adverse reactions of prednisone, or discontinued medication due to adverse reactions. In summary, the present study is to provide new evidence and strategy about anti-inflammatory therapy for recurrent In-stent restenosis after coronary intervention.

Official Title
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Safety and Efficacy of Low Dose Colchicine or Prednisone Combining With Standard Drug in Patients With Recurrent In-stent Restenosis: a Prospective, Randomized, Open-label Trial

Conditions
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In-stent Restenosis

Intervention / Treatment
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* Drug: Colchicine
* Drug: Prednisone
* Drug: Aspirin
* Drug: P2Y12 Receptor Antagonist
* Drug: Lipid-lowering drug


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: (1) CAD patients over 18 years old; (2) At least one coronary artery lesion meets the RISR criteria: target lesion ≥ 2 ISRs (stenosis of lumen diameter within the stent segment and within 5mm near and far of the stent ≥ 50%); (3) Intended intervention treatment for RISR lesions; (4) Acceptable for standard secondary prevention drug therapy for coronary heart disease, including dual antiplatelet therapy (DAPT) and statins; (5) Willing to participate in the trial and complete follow-up, signing an informed consent form approved by the ethics committee Exclusion Criteria: (1) The previous interventional treatment situation is unknown; (2) The mechanism of intracavitary imaging to clarify ISR is operator-related (poor stent adhesion, incomplete dilation, and stent fracture); (3) Clearly diagnose vascular inflammatory diseases or connective tissue diseases (including arteritis, Behcet's disease, systemic lupus erythematosus, etc.) involving the coronary artery; (4) Immunosuppressive drugs, including glucocorticoids, have been used in the past 30 days; (5) There are contraindications to the use of prednisone or colchicine, including: serious infectious diseases, including active infection, hepatitis B, hepatitis C or AIDS patients; Hematological diseases, such as thrombocytopenia, severe anemia, leukemia, etc; Uncontrolled diabetes; Severe liver and kidney function damage; Active peptic ulcer or gastrointestinal bleeding; Severe osteoporosis (with previous pathological fractures); Inflammatory bowel disease or chronic diarrhea; (6) A history of malignant tumors within 3 years; (7) Cognitive impairment; (8) Not willing to participate or follow up

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: control group<br>DAPT (aspirin+1 P2Y12 receptor antagonist) + Lipid-lowering drugs + hypoglycemic drugs and hypotensive drugs (if necessary) | Drug: Aspirin<br>* Patients who have re-implanted DES should receive aspirin for at least 1 year after intervention; Patients who have underwent DEB expansion should apply aspirin for at least 3 months after intervention.<br>* Other names: Acetylsalicylic Acid;Drug: P2Y12 Receptor Antagonist<br>* Patients who have re-implanted DES should receive 1 P2Y12 receptor antagonist for at least 1 year after intervention; Patients who have underwent DEB expansion should apply the P2Y12 receptor antagonist for at least 3 months after intervention.<br>Drug: Lipid-lowering drug<br>* Formulate the lipid-lowering drug regimen with LDL-C<1.4mmol/L as the target on the basis of moderate intensity or above statins.<br>|
| Experimental: Colchicine group<br>DAPT (aspirin+1 P2Y12 receptor antagonist) + Lipid-lowering drugs + hypoglycemic drugs and hypotensive drugs (if necessary) + Colchicine (0.5mg QD, orally) | Drug: Colchicine<br>* Add 0.5mg QD orally and start using it within 48 hours after intervention.<br>Drug: Aspirin<br>* Patients who have re-implanted DES should receive aspirin for at least 1 year after intervention; Patients who have underwent DEB expansion should apply aspirin for at least 3 months after intervention.<br>* Other names: Acetylsalicylic Acid;Drug: P2Y12 Receptor Antagonist<br>* Patients who have re-implanted DES should receive 1 P2Y12 receptor antagonist for at least 1 year after intervention; Patients who have underwent DEB expansion should apply the P2Y12 receptor antagonist for at least 3 months after intervention.<br>Drug: Lipid-lowering drug<br>* Formulate the lipid-lowering drug regimen with LDL-C<1.4mmol/L as the target on the basis of moderate intensity or above statins.<br>|
| Experimental: Prednisone group<br>DAPT (aspirin+1 P2Y12 receptor antagonist) + Lipid-lowering drugs + hypoglycemic drugs and hypotensive drugs (if necessary) + Prednisone (0.5mg/kg QD, orally) | Drug: Prednisone<br>* 0.5mg/kg QD orally and the dosage was reduced at a rate of 5mg/d per month until 5-10mg/d, maintained for 1 year after PCI.<br>Drug: Aspirin<br>* Patients who have re-implanted DES should receive aspirin for at least 1 year after intervention; Patients who have underwent DEB expansion should apply aspirin for at least 3 months after intervention.<br>* Other names: Acetylsalicylic Acid;Drug: P2Y12 Receptor Antagonist<br>* Patients who have re-implanted DES should receive 1 P2Y12 receptor antagonist for at least 1 year after intervention; Patients who have underwent DEB expansion should apply the P2Y12 receptor antagonist for at least 3 months after intervention.<br>Drug: Lipid-lowering drug<br>* Formulate the lipid-lowering drug regimen with LDL-C<1.4mmol/L as the target on the basis of moderate intensity or above statins.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| target lesion ISR | target lesion ISR confirmed by coronary angiography for 12 months | 12 months after randomization | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Major Adverse Cardiovascular Events | a composite of mortality, non-fatal myocardial infarction, non-fatal stroke and target vascular revascularization | 12 months after randomization | 
| target lesion revascularization | target lesion revascularization | 12 months after randomization | 
| other coronary artery disease revascularization | other coronary artery disease revascularization | 12 months after randomization | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Anti-inflammatory therapy, In-stent Restenosis, Colchicine, Prednisone