Effect of Inflammasome Inhibitor on hsCRP in Patients After PCI

NCT ID: NCT05130892

Last Updated: 2023-02-08

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE4
• Total Enrollment: 132 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2021-11-15
• Study Completion Date: 2023-02-01

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.

Conditions

NLRP3; hsCRP; Percutaneous Coronary Intervention

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Colchicine group

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

Group Type: EXPERIMENTAL

Colchicine

Intervention Type: DRUG

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

Tranilast group

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

Group Type: EXPERIMENTAL

Tranilast

Intervention Type: DRUG

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

Oridonin group

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

Group Type: EXPERIMENTAL

Oridonin

Intervention Type: DRUG

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

Non-intervention group

Group Type: NO_INTERVENTION

No interventions assigned to this group

Interventions

Colchicine

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

Intervention Type: DRUG

Tranilast

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

Intervention Type: DRUG

Oridonin

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

Intervention Type: DRUG

Eligibility Criteria

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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 80 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Union Hospital, Tongji Medical College, Huazhong University of Science and Technology

OTHER

Sponsor Role: lead

Responsible Party

Xiang Cheng

Director of Cardiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology

Responsibility Role: PRINCIPAL_INVESTIGATOR

Locations

Department of Cardiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology

Wuhan, Hubei, China

Wuhan Union Hospital

Wuhan, Hubei, China

Countries

China

Other Identifiers

NLRP3-CRP

Identifier Type: -

Identifier Source: org_study_id