Early Intracoronary N-Acetylcysteine During Primary PCI in STEMI: A Pilot Randomized Trial of Reperfusion Injury Biomarkers and Functional Recovery

September 28, 2026 updated by: dr. Ahmad Yasa, Sp.JP, Subsp.K.I.(K), M.Kes, FIHA, FasCC, FA

Myocardial ischemia-reperfusion injury still poses a major therapeutic challenge in patients with ST-segment elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (PPCI). N-acetylcysteine (NAC) is a thiol-containing antioxidant and precursor to glutathione, and may attenuate oxidative stress, inflammatory activation, apoptosis-related signaling and myocardial damage during early reperfusion. However, evidence from clinical trials exploring early intracoronary NAC delivery during PPCI is still limited.

We performed a pilot randomised, double-blind, placebo-controlled trial to determine whether early intracoronary N-acetylcysteine (NAC) administration during primary percutaneous coronary intervention (PPCI) reduces biomarker responses to reperfusion injury and is associated with functional recovery in patients with ST elevation myocardial infarction (STEMI). Participants will be randomized to intracoronary NAC or intracoronary placebo in addition to standard PPCI and guideline based STEMI therapy. The main outcome is the change in malondialdehyde (MDA) from baseline to 24 hours after PPCI. Secondary outcomes include changes in high-sensitivity troponin I, interleukin-6 and caspase-3 and global longitudinal strain and metabolic equivalents derived from the six-minute walk test during follow-up.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

The standard reperfusion strategy for patients with ST-segment elevation myocardial infarction is primary percutaneous coronary intervention. While PPCI restores epicardial coronary blood flow and limits ischemic myocardial injury, the process of reperfusion itself may contribute to additional myocardial damage through myocardial ischemia-reperfusion injury. It is mediated through several interacting mechanisms including generation of reactive oxygen species, lipid peroxidation, inflammatory activation, endothelial dysfunction, mitochondrial injury, calcium overload, and programmed cell death.

N-acetylcysteine is an antioxidant with a thiol group and a glutathione precursor which may have cardioprotective effects in ischemia-reperfusion. NAC may reduce oxidative stress by donating thiols, by repleting intracellular glutathione, and by modulating reactive oxygen species . It may also modulate pathways involved in inflammation and apoptosis that are activated during early myocardial reperfusion. Prior studies in the clinical setting of NAC in acute myocardial infarction have largely been administered orally or intravenously. Evidence is limited for direct intracoronary delivery of NAC during PPCI.

This is a pilot, randomized, double-blind, placebo-controlled trial of early intracoronary NAC administration in STEMI patients undergoing PPCI. Eligible patients are adults undergoing PPCI for STEMI who give written informed consent. Participants will be randomized 1:1 to intracoronary NAC or intracoronary placebo in addition to standard PPCI and guideline-directed medical therapy.

In the intervention arm intracoronary NAC is given at a dose of 480 mg diluted in 10 mL normal saline. NAC is administered as early as possible during reperfusion after guidewire crossing when any antegrade coronary flow has been established. If crossing the guidewire alone does not restore flow, NAC is given after initial balloon dilatation when minimal flow is obtained. Solution is delivered through a microcatheter positioned proximal to the culprit lesion over 10 minutes. In the control arm, participants receive an intracoronary placebo of 10 mL normal saline by the same method and duration. The placebo solution appears and has the same volume as the NAC solution to maintain the blinding.

The primary end point was change in serum malondialdehyde from baseline to 24 h after PPCI. Circulating marker of oxidative stress and lipid peroxidation in early reperfusion. MDA . Secondary mechanistic end points are change from baseline to 24 hours after PPCI in high-sensitivity troponin I, interleukin-6, and caspase-3. High-sensitivity troponin I is used as a marker for release of the biomarker of myocardial injury, interleukin-6 as a marker for inflammatory response, and caspase-3 as a marker related to apoptosis.

Secondary functional end points are global longitudinal strain and metabolic equivalents from the six-minute walk test. Two-dimensional speckle-tracking echocardiography is used to measure global longitudinal strain at admission, discharge and 6 months after admission. Functional capacity was measured by the six-minute walk test at discharge and at 6 months, and the walking distance was expressed in metabolic equivalents.

This trial is intended to provide mechanistic and hypothesis-generating evidence regarding whether early intracoronary NAC during PPCI can attenuate reperfusion injury biomarker responses and support functional recovery signals in STEMI patients.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
110

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Indonesia
    • Central of Java
      • Surakarta, Central of Java, Indonesia, 57126
        • Dr. Moewardi General Hospital

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years to 65 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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 18-65 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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Double

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: Intracoronary NAC

The intervention group will have intracoronary NAC 480 mg immediately after the lesion is opened during primary PCI is performed besides standard treatment of STEMI before further evaluation.
Drug: Antipac

The first group is the NAC group, which will get intracoronary NAC 480 mg immediately after the lesion is opened during primary PCI. And the second group will have placebo immediately after the lesion is opened during primary PCI.
Placebo Comparator: Control

The intervention group will have intracoronary N-AC 480 mg immediately after the lesion is opened during primary PCI besides standard treatment of STEMI before further evaluation.
Drug: Antipac

The first group is the NAC group, which will get intracoronary NAC 480 mg immediately after the lesion is opened during primary PCI. And the second group will have placebo immediately after the lesion is opened during primary PCI.

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Malondialdehyde (ng/ml)
Time Frame: Baseline and 24 hours after intervention

Improvements in Biomolecular Parameters (Oxidative Stress)
Baseline and 24 hours after intervention

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
hs-Troponin I (ng/L)
Time Frame: Baseline and 24 hours after intervention

Myocardial necrosis parameter
Baseline and 24 hours after intervention
Caspase-3 (pg/dl)
Time Frame: Baseline and 24 hours after intervention

Apoptosis parameter
Baseline and 24 hours after intervention
IL-6 (pg/dl)
Time Frame: Baseline and 24 hours after intervention

Inflammation parameter
Baseline and 24 hours after intervention
Global Longitudinal Strain (%)
Time Frame: Baseline, discharge at day-5, and 1 weeks after discharge

Improvements in Echocardiographic Parameters
Baseline, discharge at day-5, and 1 weeks after discharge
Improvements in Physical Parameters
Time Frame: Day-5 after intervention (at discharge) and 6-month after discharge

6 Minutes Walking Test (METs)
Day-5 after intervention (at discharge) and 6-month after discharge

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
dr. Ahmad Yasa, Sp.JP, Subsp.K.I.(K), M.Kes, FIHA, FasCC, FA

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Ahmad Yasa, MD, Universitas Sebelas Maret
  • Principal Investigator: Trisulo Wasyanto, Prof. DR.dr., Universitas Sebelas Maret

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
April 1, 2025

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
March 30, 2026

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
April 30, 2026

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
February 23, 2025

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
February 23, 2025

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
February 27, 2025

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
October 2, 2026

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
September 28, 2026

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
September 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • 374/II/HREC/2025

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

IPD Plan Description

This study was conducted as part of the final project for doctoral program, there was no sponsorship during this study therefore the IPD cannot be shared

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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