Acute Myocardial InfarctionPhase 1NCT05215743
Combined Antioxidant Therapy Against Myocardial Reperfusion Injury. Phase I Study.
A Phase 1 study testing Antioxidant therapy and NaCl 0.9% in people with Acute Myocardial Infarction and Ischemia-reperfusion Injury, run by University of Chile at 1 site in Chile.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 35 yearsHealthy volunteers can take part
- Conditions the study is for
- Acute Myocardial Infarction, Ischemia-reperfusion Injury, Reperfusion Injury, Myocardial
- What is being tested?
- Antioxidant therapy and NaCl 0.9%
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 18 participants
- Where
- 1 siteChile
- Study dates
- 9 Aug 2022to 22 Dec 2022
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 35 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- Healthy subjects from 18 to 35 years old
- Not obese (BMI 19-29.9 kg/m2)
Who cannot join
- 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
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Cardioprotection of Patients With Acute Myocardial Infarction Undergoing Percutaneous Coronary Angioplasty Through a Combined Antioxidant Therapy. A Phase I, Randomized Clinical Trial.
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.
Read the detailed description
In this single-blind trial, healthy subjects from 18-35 years old will be allocated to a placebo or an intravenous combined antioxidant therapy (CAT) following a fixed-dose scalation approach. Before the study onset, blood samples will be drawn from eligible subjects to measure a general health profile, and also a physician evaluation and medical exams will be scheduled to further confirm the healthy status two weeks after the CAT/placebo infusion.
Two different CAT formulations (named CAT1 and CAT2) will be tested, each one with a different dose of deferoxamine, N-acetylcysteine, and ascorbate. The infusions (CAT or placebo) will be administered at the "CREA" - Hospital Clínico Universidad de Chile. The first nine subjects will be randomized 1:2 to placebo (NaCl 0.9%) or CAT1, infused at two different rates (one in the first 30 min, and another one in the following 60 minutes). If the stopping rules are not observed (see below), then the next nine subjects will be randomized 1:2 to placebo or CAT2 to be infused I.V over 90 min at a constant rate. The protocol will be stopped at any time if more than 33% of the subjects in a group (2 volunteers) suffer a serious adverse event, following the international definitions (death, disability, life-threatening, medical admission).
Vital signs will be continuously assessed during the IV infusion and for the following 90 minutes after the infusion ends, together with adverse events assessment in this 180-minute observation period. Blood samples will be collected at 0, 15, 30, 60, 90, 120, and 180 minutes. Concentrations of ascorbate, deferoxamine, and N-acetylcysteine will be measured, as well as oxidative stress biomarkers. Subjects will be contacted by phone asking for health status and adverse events at 14 and 30 days after the IV infusion.
- Conditions
- Acute Myocardial Infarction, Ischemia-reperfusion Injury, Reperfusion Injury, Myocardial, Reperfusion Arrhythmias, Reperfusion Injury
- Being tested
- Antioxidant therapy, NaCl 0.9%
- Keywords
- antioxidants, acute myocardial infarction, reperfusion injury, randomized clinical trial, multi-target interventions
- Medical subject headings
- Reperfusion Injury, Myocardial Reperfusion Injury
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Antioxidant therapyDrug
Also called ascorbate, n-acetylcysteine, deferoxamine
Active therapy
NaCl 0.9%Drug
Also called saline solution
Placebo
| Study group | Role | What they receive |
|---|---|---|
| Combined antioxidant therapy (CAT) | Experimental | Intravenous administration of deferoxamine, n-acetylcysteine, and ascorbate over 90 minutes. Receives: Drug: Antioxidant therapy |
| Placebo | Placebo comparator | Intravenous administration of NaCl 0.9% over 90 minutes Receives: Drug: NaCl 0.9% |
What is being measured
The primary outcome is the main question the study is designed to answer.
Peak plasma concentration (Cmax) of each CAT component
Cmax of deferoxamine, n-acetylcysteine and ascorbate
Measured: 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
Measured: 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
Measured: 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
Measured: 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
Measured: 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
Measured: 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
Measured: 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
Number of serious and non-serious adverse events from day 0 to day 30 after the intervention, assessed by a phone interview on day 14 and day 30 after the infusion, using a standardized report form
Measured: 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
Number of patients with serious and non-severe adverse events from day 0 to day 30 after the intervention, assessed by a phone interview on day 14 and day 30 after the infusion, using a standardized report form
Measured: From day 0 to day 30 after the intervention
Plasma levels of oxidative stress biomarkers over the time
Plasma concentrations of the antioxidant defenses (ferric reducing ability of plasma assay), and lipid peroxidation (F2-isoprostanes) during the IV infusion and after 30 minutes
Measured: 0 (just before infusion onset) and 30, 90 and120 minutes after infusion onset.
Plasma concentrations over the time of each CAT component
Plasma concentrations of deferoxamine, n-acetylcysteine and ascorbate during the IV infusion and after 90 minutes, assessed by high performance liquid chromatography (HPLC)
Measured: 0 (just before infusion onset) and 30, 60, 90, 120 and 180 minutes after infusion onset.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted31 Jan 2022
- Study start9 Aug 2022
- Primary completion22 Nov 2022
- Study completion22 Dec 2022
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Acute Myocardial InfarctionStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Combined antioxidant therapy (CAT) and placebo
- Masking
- Triple blind
- Who is masked
- Participant, Investigator, Outcomes assessor
- Enrolment
- 18 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Chile
- Sponsor type
- University, hospital or other
- Collaborators
- Fondo Nacional de Desarrollo Científico y Tecnológico, Chile
- Responsible party
- Principal investigator, Ramon Rodrigo, University of Chile
- Investigators
- Ramón Rodrigo, Prof., Study director, Program of Pharmacology, ICBM, Faculty of Medicine, University of ChileAbraham IJ Gajardo, MD, PhD, Study chair, Intensive Care Unit, Hospital Clínico Universidad de Chile
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05215743
- Sponsor's protocol ID
- FONDECYT 1211850
- Status last verified
- Jan 2024
- First submitted
- 17 Jan 2022
- Last updated
- 12 Jan 2024
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Gajardo Cortez AIJ, Lillo-Moya J, San-Martin-Martinez D, Pozo-Martinez J, Morales P, Prieto JC, Aguayo R, Puentes A, Ramos C, Silva S, Catalan M, Ramos K, Olea-Azar C, Rodrigo R. Safety and Pharmacokinetics of a Combined Antioxidant Therapy against Myocardial Reperfusion Injury: A Phase 1 Randomized Clinical Trial in Healthy Humans. Clin Pharmacol Drug Dev. 2024 Sep;13(9):1051-1060. doi: 10.1002/cpdd.1443. Epub 2024 Jul 8.
PubMed 38973337
Study at a glance
From the registry record, last updated by the sponsor on 12 Jan 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Cardioprotection of Patients With Acute Myocardial Infarction Undergoing Percutaneous Coronary Angioplasty Through a Combined Antioxidant Therapy. A Phase I, Randomized Clinical Trial.
- ClinicalTrials.gov ID
- NCT05215743
- Acronym / sponsor ID
- FONDECYT 1211850
- 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
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 18 participants (actual)
- Lead sponsor
- University of ChileUniversity, hospital or other
- Collaborators
- Fondo Nacional de Desarrollo Científico y Tecnológico, Chile
- Study start
- 9 Aug 2022 (actual)
- Primary completion
- 22 Nov 2022 (actual)
- Study completion
- 22 Dec 2022 (actual)
- First posted
- 31 Jan 2022 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
In this single-blind trial, healthy subjects from 18-35 years old will be allocated to a placebo or an intravenous combined antioxidant therapy (CAT) following a fixed-dose scalation approach. Before the study onset, blood samples will be drawn from eligible subjects to measure a general health profile, and also a physician evaluation and medical exams will be scheduled to further confirm the healthy status two weeks after the CAT/placebo infusion.
Two different CAT formulations (named CAT1 and CAT2) will be tested, each one with a different dose of deferoxamine, N-acetylcysteine, and ascorbate. The infusions (CAT or placebo) will be administered at the "CREA" - Hospital Clínico Universidad de Chile. The first nine subjects will be randomized 1:2 to placebo (NaCl 0.9%) or CAT1, infused at two different rates (one in the first 30 min, and another one in the following 60 minutes). If the stopping rules are not observed (see below), then the next nine subjects will be randomized 1:2 to placebo or CAT2 to be infused I.V over 90 min at a constant rate. The protocol will be stopped at any time if more than 33% of the subjects in a group (2 volunteers) suffer a serious adverse event, following the international definitions (death, disability, life-threatening, medical admission).
Vital signs will be continuously assessed during the IV infusion and for the following 90 minutes after the infusion ends, together with adverse events assessment in this 180-minute observation period. Blood samples will be collected at 0, 15, 30, 60, 90, 120, and 180 minutes. Concentrations of ascorbate, deferoxamine, and N-acetylcysteine will be measured, as well as oxidative stress biomarkers. Subjects will be contacted by phone asking for health status and adverse events at 14 and 30 days after the IV infusion.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, investigator, outcomes assessor)
- Number of arms
- 2
- Model description
- Combined antioxidant therapy (CAT) and placebo
| Arm | Type | Receives |
|---|---|---|
| Combined antioxidant therapy (CAT) | Experimental | Drug: Antioxidant therapyIntravenous administration of deferoxamine, n-acetylcysteine, and ascorbate over 90 minutes. |
| Placebo | Placebo comparator | Drug: NaCl 0.9%Intravenous administration of NaCl 0.9% over 90 minutes |
Who may qualify
- Ages
- 18 to 35 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (2 listed)
- Healthy subjects from 18 to 35 years old
- Not obese (BMI 19-29.9 kg/m2)
Key exclusion criteria (6 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Antioxidant therapyAlso: ascorbate, n-acetylcysteine, deferoxamineActive therapy | Drug | Combined antioxidant therapy (CAT) |
| NaCl 0.9%Also: saline solutionPlacebo | Drug | Placebo |
Primary outcome
Peak plasma concentration (Cmax) of each CAT component
Time frame: 180 minutes (just before the infusion onset up to 90 minutes after infusion ending)
Cmax of deferoxamine, n-acetylcysteine and ascorbate
Half-life time (T1/2) of each CAT component
Time frame: 180 minutes (just before the infusion onset up to 90 minutes after infusion ending)
T1/2 of deferoxamine, n-acetylcysteine and ascorbate
Area under the plasma concentration versus time curve (AUC) of each CAT component
Time frame: 180 minutes (just before the infusion onset up to 90 minutes after infusion ending)
AUC of deferoxamine, n-acetylcysteine and ascorbate
Volume of distribution (Vd) of each CAT component
Time frame: 180 minutes (just before the infusion onset up to 90 minutes after infusion ending)
Vd of deferoxamine, n-acetylcysteine and ascorbate
Clearence (CL) of each CAT component
Time frame: 180 minutes (just before the infusion onset up to 90 minutes after infusion ending)
CL of deferoxamine, n-acetylcysteine and ascorbate
Elimination rate constant (Ke) of each CAT component
Time frame: 180 minutes (just before the infusion onset up to 90 minutes after infusion ending)
Ke of deferoxamine, n-acetylcysteine and ascorbate
Incidence of serious adverse events during combined antioxidant therapy infusion or along the 30-day follow-up
Time frame: From day 0 to day 30 after the intervention
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
4 secondary outcomes
Incidence of any adverse event (serious and non-serious) up to thirty days after infusion ending
Time frame: 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
Time frame: From day 0 to day 30 after the intervention
Plasma levels of oxidative stress biomarkers over the time
Time frame: 0 (just before infusion onset) and 30, 90 and120 minutes after infusion onset.
Plasma concentrations over the time of each CAT component
Time frame: 0 (just before infusion onset) and 30, 60, 90, 120 and 180 minutes after infusion onset.
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 12 Jan 2024.
- Derived from this study: PubMed 38973337Gajardo Cortez AIJ, Lillo-Moya J, San-Martin-Martinez D, Pozo-Martinez J, Morales P, Prieto JC, Aguayo R, Puentes A, Ramos C, Silva S, Catalan M, Ramos K, Olea-Azar C, Rodrigo R. Safety and Pharmacokinetics of a Combined Antioxidant Therapy against Myocardial Reperfusion Injury: A Phase 1 Randomized Clinical Trial in Healthy Humans. Clin Pharmacol Drug Dev. 2024 Sep;13(9):1051-1060. doi: 10.1002/cpdd.1443. Epub 2024 Jul 8.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Ramón Rodrigo, Prof. study director
Program of Pharmacology, ICBM, Faculty of Medicine, University of Chile
Abraham IJ Gajardo, MD, PhD study chair
Intensive Care Unit, Hospital Clínico Universidad de Chile
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Antioxidant therapy and NaCl 0.9% in people with Acute Myocardial Infarction and Ischemia-reperfusion Injury, run by University of Chile at 1 site in Chile.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 2 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 12 Jan 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Chile. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Peak plasma concentration (Cmax) of each CAT component (time frame: 180 minutes (just before the infusion onset up to 90 minutes after infusion ending)). The study lists 7 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT05215743, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 12 Jan 2024.