Effect of Inflammasome Inhibitor on hsCRP in Patients After PCI

Phase 4

Completed

• Conditions: NLRP3; Percutaneous Coronary Intervention; hsCRP
• Interventions: Drug: Colchicine; Drug: Oridonin; Drug: Tranilast

• Registration Number: NCT05130892
• Lead Sponsor: Wuhan Union Hospital, China

Brief Summary

Coronary artery disease (CAD) comprises the major contributor to a global epidemic of cardiovascular disease. Patients with CAD undergoing percutaneous coronary intervention (PCI) have a high-risk for adverse clinical outcomes.

Residual inflammatory risk (RIR) in patients with CAD after standardized treatment is the main cause of adverse events such as recurrent myocardial infarction, stroke, and death, which has gained much interest in recent years. Inflammation plays an important role in the development of CAD. However, several randomized controlled clinical studies (RCT) of anti-inflammatory treatments ended in failure previously. Since 2017, the success of three large-scale RCTs (CANTOS, COLCOT and LoDoCo2) points to targeting the NLRP3 - IL-1 β- IL-6 pathway for anti-inflammatory treatment of CAD. The inhibition of this pathway eventually leads to the decrease of high-sensitivity C-reactive protein (hsCRP), consistent with an anti-inflammatory effect. Therefore, the change of hsCRP may serve as a biomarker to screen anti-inflammatory drugs in this pathway.

Targeting the NLRP3 - IL-1 β- IL-6 pathway with monoclonal antibodies is limited by high prices of the biological agents. Thus, researchers focused on the upstream molecule NLRP3. Currently, NLRP3 inhibitors that are clinically available include colchicine , tranilast and oridonin. Although several studies have indicated the effective effects of colchicine in CAD, the other two NLRP3 inhibitors lack sufficient data on anti-inflammatory treatment of CAD. Therefore, we intend to use NLRP3 inhibitors (colchicine, tranilast and oridonin) to treat patients after PCI for 4 weeks, compare the changes of hsCRP, and explore the effectiveness and safety of these different drugs, and screen the optimal anti-inflammatory drugs for coronary heart disease.

Detailed Description

Not available

Study Timeline

• Study Start: 2021-11-15
• Study First Submitted: 2021-11-20
• Study First Submitted QC: 2021-11-20
• Study First Posted: 2021-11-23
• Status Verified: 2023-02
• Primary Completion: 2023-02-01
• Study Completion: 2023-02-01
• Last Update Submitted: 2023-02-06
• Last Update Posted: 2023-02-08

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 132

Inclusion Criteria

1. Voluntarily participate, and sign the informed consent form;
2. Age ≥ 18 and ≤ 80 years, regardless of sex;
3. Patients after completion of planned percutaneous coronary intervention for 4 weeks.

Exclusion Criteria

1. Allergic to colchicine, tranilast or oridonin;
2. Taking colchicine, tranilast or oridonin before the screening period (10 days);
3. Abnormal liver function (ALT > 3 times the upper limit of normal value);
4. Abnormal renal function (creatinine clearance < 45 ml / min);
5. Thrombocytopenia (PLT < 100g / L);
6. Uncontrolled infectious diseases;
7. Complicated with immune diseases or immune related diseases such as systemic lupus erythematosus, asthma, inflammatory bowel disease, gout, and malignant tumor, etc.
8. Nonsteroidal anti-inflammatory drugs, hormones, immunomodulatory and chemotherapeutic drugs been taken;
9. History of surgery within 6 months before the screening period;
10. Pregnant women, lactating women or women of childbearing age who do not use effective contraceptives;
11. Other circumstances in which the investigator judges that the patient is not suitable to participate in the clinical trial.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Colchicine group	Colchicine	1 tablet (0.5mg) / time, once a day
Oridonin group	Oridonin	2 tablets (0.5g) / time, 3 times a day
Tranilast group	Tranilast	1 capsule (0.1g) / time, 3 times a day;

Primary Outcome Measures

Name	Time	Method
Percentage change in hsCRP	4 weeks	Percentage change in hsCRP at the end of 4 weeks compared with baseline

Secondary Outcome Measures

Name	Time	Method
Bleeding	4 weeks	Time to occurrence of bleeding
Proteomics analysis	4 weeks	Proteomics analysis using cardiovascular II/III panel by Olink company
MACE (composite endpoint of all-cause death, nonfatal myocardial infarction, nonfatal stroke, revascularization due to ischemia, or hospitalization due to unstable angina pectoris)	4 weeks	Time to occurrence of MACE

Trial Locations

Locations (2)

Wuhan Union Hospital; 🇨🇳 Wuhan, Hubei, China

Department of Cardiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology; 🇨🇳 Wuhan, Hubei, China