Anti-inflammatory Therapy for Recurrent In-stent Restenosis

Official title

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

Overview

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

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.

Interventions

• Drug Colchicine
  Add 0.5mg QD orally and start using it within 48 hours after intervention.
• Drug Prednisone
  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.
• Drug Aspirin
  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.
• Drug P2Y12 Receptor Antagonist
  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.
• Drug Lipid-lowering drug
  Formulate the lipid-lowering drug regimen with LDL-C\<1.4mmol/L as the target on the basis of moderate intensity or above statins.

Primary outcome measures

• target lesion ISR [Time frame: 12 months after randomization]

Secondary outcome measures (3)

• Major Adverse Cardiovascular Events [Time frame: 12 months after randomization]
• target lesion revascularization [Time frame: 12 months after randomization]
• other coronary artery disease revascularization [Time frame: 12 months after randomization]

Eligibility criteria

Inclusion criteria

• CAD patients over 18 years old;
• 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%);
• Intended intervention treatment for RISR lesions;
• Acceptable for standard secondary prevention drug therapy for coronary heart disease, including dual antiplatelet therapy (DAPT) and statins;
• Willing to participate in the trial and complete follow-up, signing an informed consent form approved by the ethics committee

Exclusion criteria

• The previous interventional treatment situation is unknown;
• The mechanism of intracavitary imaging to clarify ISR is operator-related (poor stent adhesion, incomplete dilation, and stent fracture);
• Clearly diagnose vascular inflammatory diseases or connective tissue diseases (including arteritis, Behcet's disease, systemic lupus erythematosus, etc.) involving the coronary artery;
• Immunosuppressive drugs, including glucocorticoids, have been used in the past 30 days;
• 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;
• A history of malignant tumors within 3 years;
• Cognitive impairment;
• Not willing to participate or follow up

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Open label

Primary purpose

Treatment

Study locations

China · 4 centers

• Beijing Anzhen Hospital, Capital Medical University — Beijing
• Beijing Friendship Hospital — Beijing
• Beijing Luhe Hospital — Beijing
• Fuwai Hospital — Beijing

Publications

• Yu M, Jiang Y, Song Z, Wei ZY, Tan F, Liu X, Zhang X, Zhu F, Shi Y, Huang J, Yang WX, Qian HY. Anti-inflammatory therapy for recurrent in-stent restenosis (AI-ISR): study protocol for a prospective, randomised, open-label, multicentre clinical trial. BMJ Open. 2025 Oct 27;15(10):e092235. doi: 10.1136/bmjopen-2024-092235. PMID 41145262

Identifiers

NCT: NCT06090890 · 2023-GSP-GG-32

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗