Effect of Inflammasome Inhibitor on hsCRP in Patients After PCI

Percutaneous Coronary Intervention Clinical Trial

Official title:

Effect of Inflammasome Inhibitor on High-sensitivity C-reactive Protein in Patients After Percutaneous Coronary Intervention

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT05130892
• Other study ID #: NLRP3-CRP
• Status: Completed
• Phase: Phase 4
• Start date: November 15, 2021
• Est. completion date: February 1, 2023

Study information

• Verified date: February 2023
• Source: Wuhan Union Hospital, China
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 132
• Est. completion date: February 1, 2023
• Est. primary completion date: February 1, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 80 Years

Eligibility

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.

Related Conditions & MeSH terms

• hsCRP
• Percutaneous Coronary Intervention

Intervention

Drug:
• Colchicine
1 tablet (0.5mg) / time, once a day
• Tranilast
1 capsule (0.1g) / time, 3 times a day
• Oridonin
2 tablets (0.5g) / time, 3 times a day;

Locations

Country	Name	City	State
China	Department of Cardiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology	Wuhan	Hubei
China	Wuhan Union Hospital	Wuhan	Hubei

Sponsors (1)

Lead Sponsor	Collaborator
Wuhan Union Hospital, China

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percentage change in hsCRP	Percentage change in hsCRP at the end of 4 weeks compared with baseline	4 weeks
Secondary	MACE (composite endpoint of all-cause death, nonfatal myocardial infarction, nonfatal stroke, revascularization due to ischemia, or hospitalization due to unstable angina pectoris)	Time to occurrence of MACE	4 weeks
Secondary	Bleeding	Time to occurrence of bleeding	4 weeks
Secondary	Proteomics analysis	Proteomics analysis using cardiovascular II/III panel by Olink company	4 weeks