Effect of Inflammasome Inhibitor on hsCRP in Patients After PCI

NCT05130892 | Completed Phase 4

• 1 other identifier: NLRP3-CRP
• Study Type: interventional
• Target: 132
• Locations: 1 country
• Sites: 2

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

Outcome Measures

Primary Outcomes (1)

• Percentage change in hsCRP

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

  4 weeks

Secondary Outcomes (3)

• 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

• Bleeding

  4 weeks

• Proteomics analysis

  4 weeks

Study Arms (4)

Colchicine group

EXPERIMENTAL

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

Drug: Colchicine

Tranilast group

EXPERIMENTAL

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

Drug: Tranilast

Oridonin group

EXPERIMENTAL

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

Drug: Oridonin

Non-intervention group

NO INTERVENTION

Interventions

Colchicine DRUG

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

Colchicine group

Tranilast DRUG

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

Tranilast group

Oridonin DRUG

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

Oridonin group

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

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

You may not qualify if:

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

Sponsors & Collaborators

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

Study Sites (2)

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

Wuhan, Hubei, 430022, China

Location

Wuhan Union Hospital

Wuhan, Hubei, China

Location

MeSH Terms

Interventions

Colchicine; tranilast; oridonin

Intervention Hierarchy (Ancestors)

Alkaloids; Heterocyclic Compounds

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Director of Cardiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology

Study Record Dates

• First Submitted: November 20, 2021
• First Posted: November 23, 2021
• Study Start: November 15, 2021
• Primary Completion: February 1, 2023
• Study Completion: February 1, 2023
• Last Updated: February 8, 2023

Record last verified: 2023-02

Data Sharing

• IPD Sharing: Will not share

Locations

CN (2)