Effect of Inflammasome Inhibitor on hsCRP in Patients After PCI

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

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.

Study Overview

• Status: Completed
• Conditions: Percutaneous Coronary Intervention; NLRP3; hsCRP
• Intervention / Treatment: Drug: Colchicine; Drug: Tranilast; Drug: Oridonin

• Study Type: Interventional
• Enrollment (Actual): 132
• Phase: Phase 4

Contacts and Locations

Study Locations

• China
  • Hubei
    • Wuhan, Hubei, China
      • Wuhan Union Hospital
    • Wuhan, Hubei, China, 430022
      • Department of Cardiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: NONE

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Colchicine group; 1 tablet (0.5mg) / time, once a day	Drug: Colchicine; 1 tablet (0.5mg) / time, once a day
EXPERIMENTAL: Tranilast group; 1 capsule (0.1g) / time, 3 times a day;	Drug: Tranilast; 1 capsule (0.1g) / time, 3 times a day
EXPERIMENTAL: Oridonin group; 2 tablets (0.5g) / time, 3 times a day	Drug: Oridonin; 2 tablets (0.5g) / time, 3 times a day;
NO_INTERVENTION: Non-intervention group

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage change in hsCRP	Percentage change in hsCRP at the end of 4 weeks compared with baseline	4 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
Bleeding	Time to occurrence of bleeding	4 weeks
Proteomics analysis	Proteomics analysis using cardiovascular II/III panel by Olink company	4 weeks

Collaborators and Investigators

• Sponsor: Wuhan Union Hospital, China

Study record dates

Study Major Dates

• Study Start (ACTUAL): November 15, 2021
• Primary Completion (ACTUAL): February 1, 2023
• Study Completion (ACTUAL): February 1, 2023

Study Registration Dates

• First Submitted: November 20, 2021
• First Submitted That Met QC Criteria: November 20, 2021
• First Posted (ACTUAL): November 23, 2021

Study Record Updates

• Last Update Posted (ACTUAL): February 8, 2023
• Last Update Submitted That Met QC Criteria: February 6, 2023
• Last Verified: February 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Peripheral Nervous System Agents; Analgesics; Sensory System Agents; Anti-Inflammatory Agents, Non-Steroidal; Analgesics, Non-Narcotic; Anti-Inflammatory Agents; Antirheumatic Agents; Platelet Aggregation Inhibitors; Antineoplastic Agents; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Membrane Transport Modulators; Calcium-Regulating Hormones and Agents; Calcium Channel Blockers; Anti-Allergic Agents; Histamine H1 Antagonists; Histamine Antagonists; Histamine Agents; Gout Suppressants; Colchicine; Tranilast
• Other Study ID Numbers: NLRP3-CRP

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No