Combined Antioxidant Therapy for Acute Myocardial Infarction (CAT-AMI)

August 16, 2026 updated by: Ramon Rodrigo, University of Chile

Pharmacological Protection Against Reperfusion Injury in Patients With Acute Myocardial Infarction: a Phase 2 Randomized Controlled Trial of a Combined Antioxidant Therapy (CAT-AMI Trial)

The goal of this clinical trial is to learn if a combined antioxidant therapy (CAT) can reduce heart damage caused by the return of blood flow after blocked arteries are reopened in adults with ST-elevation myocardial infarction (STEMI) treated with primary percutaneous coronary intervention (PCI). It will also learn about the safety of this treatment. The main questions it aims to answer are:

  1. Does combined antioxidant therapy lower infarct size, measured by cardiac magnetic resonance imaging (CMR), compared with placebo?
  2. Does combined antioxidant therapy improve heart function, blood biomarkers of heart injury, and short-term clinical outcomes?
  3. What problems do participants have when receiving the therapy?

Researchers will compare CAT to placebo (a look-alike infusion with no active drug) to see if the treatment lowers infarct size after STEMI.

Participants will:

  • Be randomly assigned to receive either CAT or placebo
  • Receive the study infusion before and during primary PCI, in addition to standard treatment for STEMI
  • Have blood tests to measure heart injury, oxidative stress, inflammation, and drug levels
  • Undergo cardiac magnetic resonance imaging about 3 to 7 days after STEMI.
  • Be followed for clinical outcomes and safety for 30 days.

Study Overview

Status

Not yet recruiting

Conditions

Intervention / Treatment

Detailed Description

Acute myocardial infarction (AMI) remains as a leading cause of morbidity and mortality worldwide. In patients with ST-segment elevation myocardial infarction (STEMI), early reperfusion with primary percutaneous coronary intervention (PCI) is the standard treatment to limit myocardial injury. However, reperfusion induces additional damage, referred to as ischemia-reperfusion injury (IRI), which has been estimated to account for up to 50% of final infarct size. Oxidative stress is a key mechanism in IRI and contributes to lipid peroxidation, inflammation, and regulated cell death pathways. Prior pharmacologic approaches directed at single components of this process have shown limited and inconsistent clinical benefit, supporting evaluation of multitarget strategies.

This study is a phase II, randomized, double-blind, placebo-controlled, parallel-group superiority trial designed to evaluate the efficacy and safety of a combined antioxidant therapy (CAT) in patients with acute STEMI undergoing primary PCI. CAT consists of ascorbate, N-acetylcysteine, and deferoxamine. These agents were selected to target complementary mechanisms relevant to IRI: reactive oxygen species scavenging, glutathione replenishment, redox modulation and inflammatory response, and iron chelation with inhibition of iron-dependent lipid peroxidation. The study will randomly assign participants in a 1:1 ratio to receive CAT or matching placebo in addition to guideline-based STEMI treatment.

The intervention will be initiated before reperfusion and maintained during primary PCI in order to ensure drug exposure during the early reperfusion phase. Both groups will receive standard-of-care treatment for STEMI, including primary PCI and guideline-directed medical therapy.

The trial is designed as a signal-seeking phase II study using infarct size as the primary efficacy endpoint. Infarct size measured by cardiac magnetic resonance (CMR) is a mechanistically relevant endpoint in cardioprotection trials and has established prognostic value. In this study, CMR will be performed during the index hospitalization to quantify infarct size as a percentage of left ventricular mass. Additional imaging variables, myocardial injury biomarkers, oxidative stress and inflammatory biomarkers, pharmacokinetic measurements, short-term clinical outcomes, and safety data will be collected to support interpretation of the primary analysis. These assessments include left ventricular systolic function, hs-cTnI, CK, CK-MB, plasma concentrations of the study drugs, and 30-day follow-up for clinical events and adverse events.

The planned sample size is 46 participants. The study is powered to detect a large between-group difference in infarct size, consistent with its exploratory phase II design. Accordingly, the trial is intended to determine whether CAT demonstrates a sufficiently large efficacy signal, together with an acceptable safety profile, to support further evaluation in a larger trial.

Safety monitoring will include systematic collection of adverse events and serious adverse events during hospitalization and through day 30. Events will be recorded using Medical Dictionary for Regulatory Activities (MedDRA) terminology.

This trial will provide phase II data on the efficacy, safety, pharmacokinetics, and mechanistic effects of a multitarget antioxidant strategy administered during primary PCI in patients with STEMI.

Study Type

Interventional

Enrollment (Estimated)

46

Phase

  • 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 Contact

Study Contact Backup

Study Locations

  • Chile
    • Santiago Metropolitan
      • Santiago, Santiago Metropolitan, Chile, 8170000

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

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • Age 18 years or older
  • First anterior ST-segment elevation myocardial infarction (STEMI)
  • Symptom onset within 6 hours before presentation
  • Eligible for primary percutaneous coronary intervention (PCI)
  • Provision of informed consent by the participant or a legally authorized representative, according to local ethics requirements

Exclusion Criteria:

  • Prior myocardial infarction
  • Cardiogenic shock, defined as Society for Cardiovascular Angiography and Interventions (SCAI) shock class D or E.
  • Prior thrombolytic therapy for the index event.
  • Chronic kidney disease, defined as serum creatinine greater than 1.5 mg/dL or dialysis.
  • Liver cirrhosis
  • Advanced heart failure, defined as New York Heart Association (NYHA) class III or IV
  • Glucose-6-phosphate dehydrogenase (G6PD) deficiency
  • Nephrolithiasis
  • Life expectancy less than 6 months
  • Implanted cardiac device, including pacemaker, implantable cardioverter-defibrillator, or cardiac resynchronization device
  • Prior coronary artery bypass graft (CABG) surgery
  • Pregnancy
  • Claustrophobia
  • Other contraindications to cardiac magnetic resonance imaging (CMR), according to local protocol

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: Quadruple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Combined Antioxidant Therapy
Participants receive combined antioxidant therapy consisting of ascorbate, N-acetylcysteine, and deferoxamine, initiated before reperfusion and maintained during primary PCI, in addition to standard-of-care treatment for STEMI.
Drug: Combined antioxidant therapy
Combined Antioxidant Therapy consisting of ascorbate, N-acetylcysteine and deferoxamine
Placebo Comparator: Placebo
Participants receive matching placebo infusion initiated before reperfusion and maintained during primary PCI, in addition to standard-of-care treatment for STEMI.
Drug: Placebo
Matching placebo infusion administered before reperfusion and during primary PCI.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Infarct Size
Time Frame: 3-7 days after Primary Coronary Intervention
Infarct size by CMR: infarct size will be expressed as a percentage of left ventricular (LV) mass (%LV). Infarct size will be measured using late gadolinium enhancement with manual contouring.
3-7 days after Primary Coronary Intervention

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Cardiac Function and structure by CMR
Time Frame: 3-7 days after Primary Percutaneous Coronary Intervention
Left ventricular ejection fraction (LVEF), left ventricular end-diastolic volume (LVEDV), left ventricular end-systolic volume (LVESV), and left ventricular mass measured by cardiac magnetic resonance imaging.
3-7 days after Primary Percutaneous Coronary Intervention
Cardiac function by Transthoracic echocardiography
Time Frame: Before hospital discharge, approximately 3-7 days after Primary Percutaneous Coronary Intervention
Left ventricular systolic and diastolic function parameters, regional wall motion abnormalities, cardiac chamber sizes, and right ventricle systolic function
Before hospital discharge, approximately 3-7 days after Primary Percutaneous Coronary Intervention
Myocardial Injury Biomarkers
Time Frame: Samples will be obtained at baseline (prior to infusion), immediately after Primary Percutaneous Coronary Intervention (PCI), and at 12 hours, 24 hours, and 48 hours after PCI.
High sensitivity cardiac Troponin I, creatine kinase (CK), and CK-MB. For each biomarker, peak value, area under the curve (AUC 0-48 hours), and change from baseline will be assessed.
Samples will be obtained at baseline (prior to infusion), immediately after Primary Percutaneous Coronary Intervention (PCI), and at 12 hours, 24 hours, and 48 hours after PCI.
Biomarkers of oxidative stress
Time Frame: Samples will be obtained at baseline (prior to infusion), immediately after Primary Percutaneous Coronary Intervention (PCI), and at 12 hours, 24 hours, and 48 hours after PCI.
Ferric reducing ability of plasma (FRAP), malondialdehyde, F2-isoprostanes, reduced glutathione/oxidized glutathione ratio (GSH/GSSG), enzymatic activity of superoxide dismutase, glutathione peroxidase, and catalase.
Samples will be obtained at baseline (prior to infusion), immediately after Primary Percutaneous Coronary Intervention (PCI), and at 12 hours, 24 hours, and 48 hours after PCI.
Biomarkers of inflammation
Time Frame: Samples will be obtained at baseline, 12 hours, and 24 hours after Primary Percutaneous Coronary Intervention.
C-reactive protein (CRP) and interleukin (IL)-18
Samples will be obtained at baseline, 12 hours, and 24 hours after Primary Percutaneous Coronary Intervention.
Clinical outcomes
Time Frame: 30 days after PCI
Clinical outcomes will include all-cause mortality, cardiovascular associated mortality, reinfarction, target-vessel revascularization, and heart failure.
30 days after PCI
Safety outcomes
Time Frame: Through hospitalization and up to day 30 after Primary Percutaneous Coronary Intervention.
Adverse events (AEs) and serious adverse events (SAEs) will be recorded regardless of suspected causality. Events will be coded using Medical Dictionary for Regulatory Activities (MedDRA) standardized terminology.
Through hospitalization and up to day 30 after Primary Percutaneous Coronary Intervention.

Collaborators and Investigators

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

Sponsor

University of Chile

Collaborators

Hospital San Juan de Dios,Chile

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 (Estimated)

September 1, 2026

Primary Completion (Estimated)

January 31, 2027

Study Completion (Estimated)

December 31, 2027

Study Registration Dates

First Submitted

August 10, 2026

First Submitted That Met QC Criteria

August 16, 2026

First Posted (Actual)

August 20, 2026

Study Record Updates

Last Update Posted (Actual)

August 20, 2026

Last Update Submitted That Met QC Criteria

August 16, 2026

Last Verified

August 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • Phase 2 - FONDECYT 1211850
  • FONDECYT 1211850 (Other Grant/Funding Number: Agencia Nacional de Investigacion y Desarrollo (ANID))

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

IPD Plan Description

Deidentified individual participant data will not be publicly shared because of ethical, confidentiality, and institutional restrictions. The study protocol and statistical analysis plan will be made available after publication of the main results.

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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