Clinical trial NCT06850831: Effect of Intracoronary N-Acetylcysteine in Patients With ST-Elevation Myocardial Infarction Undergoing Primary Percutaneous Coronary Intervention
Official title: Effect of Intracoronary N-Acetylcysteine on Malondialdehyde, Interleukin-6, High Sensitivity Troponin I, Caspase-3, Global Longitudinal Strain, and 6-Minutes Walking Test in Patients With ST-Elevation Myocardial Infarction Undergoing Primary Percutaneous Coronary Intervention
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: PHASE2
Conditions: STEMI - ST Elevation Myocardial Infarction (MI)
Primary PCI - STEMI
Keywords: STEMI
Primary PCI
Intracoronary NAC
Reperfusion Injury
Apoptosis
Necrosis
Oxidative Stress
Remodelling
Left ventricular dysfunction
Physical Recovery
Lead sponsor: Universitas Sebelas Maret
Sponsor class: OTHER
First posted: 2025-02-27
Enrollment: 32
Sex: ALL
Minimum age (years): 30
Maximum age (years): 60
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Randomized Controlled Trial and Double Blind (Researcher \& Patients)
Primary purpose: TREATMENT

Brief summary: Primary percutaneous coronary intervention (PCI) is the gold standard for reperfusion therapy in patients with ST-elevation myocardial infarction (STEMI), as it restores blood flow by clearing the blocked coronary artery. This process helps reoxygenate the previously hypoxic myocardium, potentially preventing further myocardial cell death. However, despite its benefits, reperfusion therapy, including primary PCI, can also lead to reperfusion injury, which may worsen myocardial damage, increase infarct size, and negatively impact patient outcomes. One of the key contributors to reperfusion injury is reactive oxygen species (ROS), which can induce oncosis, necrosis, and apoptosis, ultimately promoting cell death, myocardial remodeling, left ventricular systolic dysfunction and poorer clinical outcomes. N-Acetylcysteine (NAC), widely known for its mucolytic properties, has also been recognized for its antioxidant and cardioprotective effects. By reducing oxidative stress, NAC has been shown to decrease oncosis, necrosis, and apoptosis, as evidenced by lower levels of malondialdehyde, IL-6, troponin, caspase-3, and major adverse cardiac events in STEMI patients. However, existing research on NAC has only explored oral and intravenous administration. Given that reperfusion injury occurs rapidly, an optimal approach would involve delivering cardioprotective agents directly to the target site, specifically coronary artery endothelial cells. To date, no studies have directly investigated the effects of intracoronary NAC administration in STEMI patients undergoing primary PCI.

Detailed description: This study is a double-blind, randomized controlled trial, single-center study in STEMI patients undergoing primary PCI patients held in Moewardi General Hospital, Central Java, Indonesia. The investigator divided 32 patients with STEMI into two groups, the first is the NAC group, which will get 480 mg of intracoronary NAC immediately after the lesion is opened during primary PCI is performed and the second group will have a normal saline bolus. Each patient will be checked for malondialdehyde, IL-6, hs-troponin I, and caspase-3 just before the primary PCI is performed and 24 hours after intervention. Meanwhile, GLS and 6MWT examinations were carried out 1 week after the patient returned home from hospitalization. The study was approved by the hospital ethics committee. The clinical parameters above will then be analyzed. To determine the mean difference between each group (intervention and control) before and after treatment a paired T-test is used if the data distribution is normal (if not, the Wilcoxon test is used). To determine the mean difference between unpaired groups (treatment and control), an independent T-test is used if the distribution is normal (if not, the Mann-Whitney test is used). Normality testing is performed using the Shapiro-Wilk test, considering the sample size is less than 50.

Eligibility criteria: Inclusion Criteria:

1. STEMI patients according to The Fourth Universal Definition of Myocardial Infarction from the European Society of Cardiology, American College of Cardiology, American Heart Association, and World Heart Federation Treated by Primary PCI.
2. Aged 30-60 years
3. Willing to participate in the study and sign informed consent.

Exclusion Criteria:

1. Patients with cardiogenic shock (SBP ≤ 80 mmHg, cold extremities, urine output \<0.5 ml/kg/hour) \<24 hours before randomization
2. Patients with a history of myocardial infarction
3. Patients with a history of chronic heart failure before the onset of AMI
4. Patients scheduled for coronary artery bypass surgery
5. Patients with chronic renal failure or requiring dialysis
6. Patients with chronic inflammation
7. Patients with malignancy
8. Patients with a history of hyper/hypothyroidism
9. Patients with acute infection
10. Patients with sepsis
11. Patients with acute stroke
12. Patients with pulmonary fibrosis
13. Patients with a history of autoimmune disease
14. Patients with a history of anti-inflammatory / antioxidant supplementation
15. Patients with allergy to N-acetylcysteine
16. Pregnant and lactating patients

Primary outcomes:
measure: Improvements in Biomolecular Parameters (Oxidative Stress)
timeFrame: 24 hours
measure: Improvements in Biomolecular Parameters (Inflammation)
timeFrame: 24 hours
measure: Improvements in Biomolecular Parameters (Necrosis)
timeFrame: 24 hours
measure: Improvements in Biomolecular Parameters (Apoptosis)
timeFrame: 24 hours
Secondary outcomes:
measure: Improvements in Echocardiographic Parameters
timeFrame: 1 weeks
measure: Improvements in Physical Parameters
timeFrame: 1 week
Other outcomes:
Locations:
city: Surakarta
country: Indonesia
facility: Dr. Moewardi General Hospital
state: Central of Java
Study officials:
affiliation: Universitas Sebelas Maret
name: Ahmad Yasa, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Universitas Sebelas Maret
name: Trisulo Wasyanto, Prof. DR.dr.
role: PRINCIPAL_INVESTIGATOR
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