Combined Antioxidant Therapy Against Myocardial Reperfusion Injury. Phase I Study.

NCT05215743 | Completed Phase 1

• 1 other identifier: FONDECYT 1211850
• Study Type: interventional
• Target: 18
• Locations: 1 country
• Sites: 1

Brief Summary

Background: Acute myocardial infarction (AMI) has remained a leading cause of mortality and disability worldwide. Although percutaneous coronary angioplasty (PCA) is the best treatment for these patients, paradoxically this procedure causes reperfusion injury. Considerable efforts aimed to reduce this damage have been made, but the results are disappointing and there is still no effective therapy for preventing the damage. Previously, the investigators have achieved a reduction of infarct size in an experimental model of an isolated rat heart, through a synergistic effect of three compounds in a "combined antioxidant therapy" (CAT). In this study, the investigators aim to describe the pharmacokinetics and safety of CAT intravenously administered to healthy subjects. This is the first step to a later clinical application of CAT in AMI patients. Methodology: The safety and pharmacokinetics of the CAT (deferoxamine, N-acetylcysteine, and ascorbate) will be assessed in healthy volunteers in a "phase I clinical trial". Two different formulations (mass of CAT components by bag) with different infusion rates each one will be tested (CAT1 and CAT2). Subjects (18-35 years old, n=18) will be randomized 1:2 to receive a placebo or CAT for 90 minutes. Blood concentrations of each CAT component will be measured in plasma at 0, 15, 30, 60, 90, 120, and 180 minutes after the infusion onset. Adverse events will be registered from the onset of infusion until day 30.

Conditions

Acute Myocardial Infarction; Ischemia-reperfusion Injury; Reperfusion Injury, Myocardial; Reperfusion Arrhythmias; Reperfusion Injury

Keywords

antioxidants; acute myocardial infarction; reperfusion injury; randomized clinical trial; multi-target interventions

Outcome Measures

Primary Outcomes (7)

• Peak plasma concentration (Cmax) of each CAT component

  Cmax of deferoxamine, n-acetylcysteine and ascorbate

  180 minutes (just before the infusion onset up to 90 minutes after infusion ending)

• Half-life time (T1/2) of each CAT component

  T1/2 of deferoxamine, n-acetylcysteine and ascorbate

  180 minutes (just before the infusion onset up to 90 minutes after infusion ending)

• Area under the plasma concentration versus time curve (AUC) of each CAT component

  AUC of deferoxamine, n-acetylcysteine and ascorbate

  180 minutes (just before the infusion onset up to 90 minutes after infusion ending)

• Volume of distribution (Vd) of each CAT component

  Vd of deferoxamine, n-acetylcysteine and ascorbate

  180 minutes (just before the infusion onset up to 90 minutes after infusion ending)

• Clearence (CL) of each CAT component

  CL of deferoxamine, n-acetylcysteine and ascorbate

  180 minutes (just before the infusion onset up to 90 minutes after infusion ending)

• Elimination rate constant (Ke) of each CAT component

  Ke of deferoxamine, n-acetylcysteine and ascorbate

  180 minutes (just before the infusion onset up to 90 minutes after infusion ending)

• Incidence of serious adverse events during combined antioxidant therapy infusion or along the 30-day follow-up

  Number of new events that began during I.V infusion, the 90 minutes of observation after the infusion end, or during the 30-day follow-up, and that resulted in death, disability, life-threatening, or medical admission of a patient according to medical records

  From day 0 to day 30 after the intervention

Secondary Outcomes (4)

• Incidence of any adverse event (serious and non-serious) up to thirty days after infusion ending

  From day 0 to day 30 after the intervention

• Number of patients with any adverse event (severe and non-severe) up to thirty days after infusion ending

  From day 0 to day 30 after the intervention

• Plasma levels of oxidative stress biomarkers over the time

  0 (just before infusion onset) and 30, 90 and120 minutes after infusion onset.

• Plasma concentrations over the time of each CAT component

  0 (just before infusion onset) and 30, 60, 90, 120 and 180 minutes after infusion onset.

Study Arms (2)

Combined antioxidant therapy (CAT)

EXPERIMENTAL

Intravenous administration of deferoxamine, n-acetylcysteine, and ascorbate over 90 minutes.

Drug: Antioxidant therapy

Placebo

PLACEBO COMPARATOR

Intravenous administration of NaCl 0.9% over 90 minutes

Drug: NaCl 0.9%

Interventions

Antioxidant therapy DRUG

Active therapy

Also known as: ascorbate, n-acetylcysteine, deferoxamine

Combined antioxidant therapy (CAT)

NaCl 0.9% DRUG

Placebo

Also known as: saline solution

Placebo

Eligibility Criteria

• Age: 18 Years - 35 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Healthy subjects from 18 to 35 years old
• Not obese (BMI 19-29.9 kg/m2)

You may not qualify if:

• Impaired renal function (creatinine \> 1.5 mg/dL)
• Liver impairment (liver enzymes more than 3 times over normal values)
• Glucose 6-phosphate dehydrogenase deficiency
• Any chronic disease
• Any acute disease in the last two weeks
• To be enrolled in another clinical study

Sponsors & Collaborators

• University of Chile: lead
• Fondo Nacional de Desarrollo Científico y Tecnológico, Chile: collaborator

Study Sites (1)

University of Chile

Santiago, Chile

Location

MeSH Terms

Conditions

Reperfusion Injury; Myocardial Reperfusion Injury

Interventions

Acetylcysteine; Deferoxamine; Sodium Chloride; Saline Solution

Condition Hierarchy (Ancestors)

Vascular Diseases; Cardiovascular Diseases; Postoperative Complications; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Cardiomyopathies; Heart Diseases; Myocardial Ischemia

Intervention Hierarchy (Ancestors)

Cysteine; Amino Acids, Sulfur; Sulfur Compounds; Organic Chemicals; Amino Acids; Amino Acids, Peptides, and Proteins; Hydroxamic Acids; Hydroxylamines; Amines; Hydroxy Acids; Carboxylic Acids; Chlorides; Hydrochloric Acid; Chlorine Compounds; Inorganic Chemicals; Sodium Compounds; Crystalloid Solutions; Isotonic Solutions; Solutions; Pharmaceutical Preparations

Study Officials

• Ramón Rodrigo, Prof.

  Program of Pharmacology, ICBM, Faculty of Medicine, University of Chile

  STUDY DIRECTOR

• Abraham IJ Gajardo, MD, PhD

  Intensive Care Unit, Hospital Clínico Universidad de Chile

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Full Professor

Model Details: Combined antioxidant therapy (CAT) and placebo

Study Record Dates

• First Submitted: January 17, 2022
• First Posted: January 31, 2022
• Study Start: August 9, 2022
• Primary Completion: November 22, 2022
• Study Completion: December 22, 2022
• Last Updated: January 12, 2024

Record last verified: 2024-01

Data Sharing

• IPD Sharing: Will not share

Locations

CL (1)