Effect of Inflammasome Inhibitor on hsCRP in Patients After PCI

Huazhong University of Science and Technology

Status and phase: Completed; Phase 4

Conditions: NLRP3; Percutaneous Coronary Intervention; hsCRP

Treatments: Drug: Colchicine; Drug: Tranilast; Drug: Oridonin

Study type: Interventional

Funder types: Other

Identifiers

NCT05130892

NLRP3-CRP

Details and patient eligibility

About

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.

Enrollment: 132 patients

Sex: All

Ages: 18 to 80 years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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132 participants in 4 patient groups

Colchicine group

Experimental group

Description:

1 tablet (0.5mg) / time, once a day

Treatment:

Drug: Colchicine

Tranilast group

Experimental group

Description:

1 capsule (0.1g) / time, 3 times a day;

Treatment:

Drug: Tranilast

Oridonin group

Experimental group

Description:

2 tablets (0.5g) / time, 3 times a day

Treatment:

Drug: Oridonin

Non-intervention group

No Intervention group