The Efficacy and Safety of Ketotifen in Primary PCI Patients With STEMI

Study Overview
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Brief Summary
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The purpose of this study was to evaluate the efficacy and safety of ketotifen (MC stabilizer) on the basis of standard treatment after primary PCI in STEMI patients. The ketotifen group and the control group were the ketotifen group and the control group. The control group continued to receive STEMI standard treatment. The ketotifen group received ketotifen for 3 months on the basis of standard treatment within 24 hours after primary PCI, and was followed up for 1 year. Infarct size, as well as differences in echocardiography, markers of two-dimensional speckle tracking, inflammatory factors and MC markers, and major adverse cardiovascular events.

Detailed Description
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Percutaneous coronary intervention (PCI) is the best way to improve the prognosis of patients with acute ST-segment elevation myocardial infarction (STEMI). However, STEMI after PCI may still have ischemia-reperfusion injury, inappropriate ventricular remodeling and myocardial fibrosis, which may be related to the inflammatory response of STEMI. Mast cells (MCs) and their degranulation products play an important role in the inflammatory response as well as inducing a series of inflammatory factors. It has been observed in animal experiments that MC stabilizers can improve the ejection fraction, reduce myocardial infarction size and myocardial fibrosis in patients with STEMI, but there is a lack of clinical studies to confirm the role of MC stabilizers in STEMI. The purpose of this study was to evaluate the efficacy and safety of ketotifen (MC stabilizer) on the basis of standard treatment after primary PCI in STEMI patients. The ketotifen group and the control group were the ketotifen group and the control group. The control group continued to receive STEMI standard treatment. The ketotifen group received ketotifen for 3 months on the basis of standard treatment within 24 hours after primary PCI, and was followed up for 1 year. Infarct size, as well as differences in echocardiography, markers of two-dimensional speckle tracking, inflammatory factors and MC markers, and major adverse cardiovascular events, to demonstrate that ketotifen can reduce ischemia-reperfusion injury and improve ventricular reperfusion in AMI. It provides new ideas for the treatment of AMI and a new basis for the optimization of STEMI treatment strategies.

Official Title
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A Randomized Controlled Study on the Efficacy and Safety of Ketotifen in Primary PCI Patients With STEMI

Conditions
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ST-segment Elevation Myocardial Infarction (STEMI)

Intervention / Treatment
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* Drug: Ketotifen Fumarate
* Drug: standard treatment


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Ages above 18 and below 80, gender is not limited; Meet the diagnostic criteria for STEMI (diagnostic criteria: ischemic chest pain lasting ≥30 min; ST segment elevation in two or more adjacent leads on the ECG or new left bundle branch block; with or without elevation of myocardial markers) , have completed primary PCI, and received standard treatment according to the Chinese Guidelines for the Diagnosis and Treatment of Acute ST-segment Elevation Myocardial Infarction (2019), including dual antiplatelet, anticoagulation, beta receptor Blockers, statins, etc. No contraindications to ketotifen; Agree and cooperate with participating in this research. Exclusion Criteria: Severe heart failure, such as Killip grade III-IV or LVEF <35%; Coronary artery bypass grafting within the past 3 years or planned; The patient is using or planning to use long-term oral or intravenous glucocorticoids (inhaled and topical hormones are allowed); Patients with severe liver and kidney disease; Patients with a history of cancer or lymphoproliferative diseases in the past 3 years; Implanted metal in the body or claustrophobia cannot accept cardiac MRI; Pregnancy or breastfeeding.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: ketotifen<br>Ketotifen was added to the standard treatment within 24 hours after the completion of primary PCI for 3 months, taking 1 mg each time, 1-2 times a day according to the patient's tolerance. | Drug: Ketotifen Fumarate<br>* Ketotifen treatment for 3 months, 1 mg each time, 1-2 times a day according to the patient's tolerance<br>* Other names: Ketotifen;|
| Sham Comparator: Control group<br>Standard treatment according to guidelines | Drug: standard treatment<br>* Standard treatment methods will be determined according to the Guidelines for the Diagnosis and Treatment of Acute ST-segment Elevation Myocardial Infarction (2019) [19], including primary PCI, dual antiplatelet, anticoagulation, ACEI/ARB/ARNI, β-receptor blockade drugs, statins, etc.<br>* Other names: standard;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Myocardial infarct size | Myocardial infarct size was assessed by cardiac MRI | 3 months after myocardial infarction | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| left ventricular systolic function | Transthoracic echocardiography to measure LVEF, left ventricular end-diastolic diameter, Em/Sm | 24 hours, 1 month, 3 months, and 12 months after myocardial infarction | 
| Left ventricular ultrasound strain | Two-dimensional speckle tracking imaging measures the movement in the long-axis direction as the overall longitudinal strain, the movement in the short-axis direction as the overall radial strain, reflecting the degree of wall systolic thickening, and the annular motion in the short-axis direction as the overall circumferential strain | 24 hours, 1 month, 3 months, and 12 months after myocardial infarction | 
| inflammatory factors and MC markers | Analysis of inflammatory factors (such as TNF-α, IL1, IL6, etc.) and MC markers (chymotrypsin) | 24 hours, 1 month, 3 months, and 12 months after myocardial infarction | 
| major adverse cardiovascular events | MACE events (death, nonfatal myocardial infarction, unplanned revascularization, hospitalization for angina and readmission for heart failure) | 12 months | 
| Drug-Related Adverse Reactions | Fatigue, lethargy and lethargy, nausea and other gastrointestinal adverse reactions | 12 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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ketotifen, STEMI, mast cell, prognosis