Elective Percutaneous Coronary Intervention With or Without Supplemental OXYgen (EPOXY-IMR)

September 30, 2020 updated by: Nils Witt, Karolinska Institutet

Elective Percutaneous Coronary Intervention With or Without Supplemental OXYgen and Evaluation of Effects on Coronary Microcirculation Using the Index of Microcirculatory Resistance

Supplemental oxygen is frequently used in patients admitted to hospital due to ischemic heart disease. In the setting of suspected myocardial infarction, clinical practice guidelines advocate the use of supplementary oxygen even in patients with normal levels of peripheral oxygen saturation. The theoretical basis for this practice is that an increase in blood oxygen content may limit ischemia and final myocardial damage and subsequent infarct size. However, although some experimental laboratory data and small studies in humans have supported the use of supplemental oxygen in patients with coronary artery disease, contradicting evidence suggests possible harmful effects, mainly through mechanisms involving coronary vasoconstriction and reduction of myocardial perfusion (hyperoxemic coronary vasoconstriction).

In the EPOXY-IMR trial, the investigators aim to further explore possible detrimental effects from routine use of supplemental oxygen on the coronary circulation with special focus on the small vessels referred to as the coronary microcirculation.

Study Overview

Status

Status

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

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

Aim:

The aim of the EPOXY-IMR trial is to evaluate the effect of supplemental oxygen on coronary circulation in the setting of elective coronary angiography and percutaneous coronary intervention (PCI). To achieve this, different functional parameters such as the index of microcirculatory resistance (IMR), fractional flow reserve (FFR) and coronary flow reserve (CFR) will be obtained and serial biomarkers (cardiac troponin) will be analyzed.

Background:

Coronary artery disease (CAD) based on arteriosclerotic narrowing of the coronary blood vessels is the most common cause of death in the western world. To determine the severity of the disease in symptomatic patients and guide optimal therapy, coronary angiography is frequently performed. Simplified, three outcomes can be found:

  1. No or mild evidence of CAD leading to continuous medical therapy.
  2. Severe disease demanding revascularization therapy done by either percutaneous coronary intervention (PCI), where most commonly balloon dilatation followed by placement of a metal stent in the coronary vessel is performed, or coronary artery bypass grafting (CABG).
  3. In patients with moderate disease further functional testing is required to assess the gravity of the narrowing. This can be achieved by placing a pressure sensor equipped guide wire to the diseased artery comparing blood pressure proximal and distal to the stenosis during hyperemia, known as Fractional Flow Reserve (FFR). Although based on pressure recordings, FFR is a highly accurate measure of the flow limitation of a given stenosis. A common cut-off value of 0,8 is used where a lower value mandates therapy as in patients with severe disease.

Further information regarding the coronary circulation can be obtained by calculation of coronary flow reserve (CFR) and the index of microcirculatory resistance (IMR), the former representing a measure of the flow situation in the complete coronary arterial system, the latter more specifically the vascular resistance in the microcirculatory compartment. These indices are based on thermodilution measurements using a temperature sensor also located in the above mentioned pressure sensor equipped guide wire.

Supplemental oxygen is frequently used all over the world in patients hospitalized with suspected coronary artery disease (CAD) irrespective of oxygen levels in the blood. Scientifically, only experimental laboratory data and small studies in humans have supported this practice.

In contrast, mounting evidence suggests possible harmful effects of supplemental oxygen by causing a decrease in cardiac function, especially through mechanisms of narrowing of the coronary arteries due high oxygen levels in the blood (hyperoxemic coronary vasoconstriction). Clinically, epicardial coronary vasoconstriction mediated by oxygen therapy may result in underestimation of vessel size during percutaneous coronary intervention (PCI), possibly increasing the risk of subsequent complications such as stent thrombosis and in-stent restenosis. Furthermore, vasoconstriction in the microcirculatory compartment may result in increased periprocedural myocardial injury as a result of microvascular obstruction from plaque related and thrombotic material.

In the EPOXY-IMR trial, the investigators aim to analyze possible detrimental effects of supplemental oxygen in patients undergoing coronary angiography and intracoronary pressure/flow measurements due to angiographically intermediate coronary lesions and with special focus on the circulation of the small vessels (microvascular function).

Design:

EPOXY-IMR is a single centre, interventional, double-blinded, randomized, controlled trial aiming to recruit 40 patients in the treatment group (cohort A, patients in whom PCI is performed) and 25 patients in the non-intervention group (cohort B, patients in whom PCI is deferred on the basis of a non-significant FFR-value).

Materials and methods:

Patients with suspected coronary artery disease (CAD) scheduled for elective coronary angiography and normal oxygen saturation (≥90% on pulse oximeter) are asked to participate in the trial in good time prior to the exam. After written informed consent standard diagnostic coronary angiography is performed. If coronary stenosis of moderate degree is found in the larger arteries (40-90% diameter stenosis), further functional evaluation is mandated to determine if the stenosis impedes coronary blood flow significantly. According to clinical routine, this is achieved by placing a pressure wire in the diseased vessel passing the narrowed section, obtaining data on coronary blood pressure proximal and distal to the stenosis and inducing hyperemia with adenosine infusion for determination of FFR. Using thermodilution with intracoronary bolus injections of room temperature saline, data for calculation of the index of microcirculatory resistance (IMR) and coronary flow reserve (CFR) will be obtained.

Those patients with FFR <0,8 indicative of restricted blood flow to the heart muscle mandating further treatment by PCI, form cohort A. Patients with FFR >0,8 make up cohort B.

Thereafter, the patients are randomized in a double blinded fashion by a designated study nurse to either supplemental oxygen 6l/min delivered by an open face mask (Oxymask®) or ambient air (sham placement of Oxymask®).

Cohort A: After 10 minutes inhalation of oxygen/ambient air, FFR, CFR and IMR are re-measured followed by PCI according to clinical routine. Finally, post PCI measurements of IMR, FFR and CFR are performed. Troponin levels are obtained at baseline, 4 hours and 12-24 hours post PCI. An arterial blood gas sample is drawn just before PCI. During PCI, coronary pressure distal to the lesion is recorded during balloon inflation, allowing for recording of wedge pressure which is required for correct calculation of flow- and resistance indices in a significantly stenosed vessel.

Cohort B: After 10 minutes inhalation of oxygen/ambient air, FFR, CFR and IMR are re-measured

Hypothesis:

  • Supplemental oxygen reduces coronary blood flow and increases microcirculatory resistance
  • Supplemental oxygen increases microcirculatory resistance leading to increased procedure related myocardial damage

Primary endpoint is the effect of supplemental oxygen on IMR. Secondary endpoints will furthermore evaluate effects on CFR, FFR and serial cardiac troponin.

Conclusion:

To date, there is limited and conflicting evidence supporting the routine administration of supplemental oxygen in patients with coronary artery disease. The EPOXY-IMR trial is designed to explore the effects of supplemental oxygen on coronary blood flow and microvascular resistance as potential mediators of detrimental clinical effects.

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.
65

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 3

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

  • Sweden
      • Stockholm, Sweden, 11883
        • Stockholm South 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 and older (ADULT, OLDER_ADULT)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Adults ≥ 18 years of age, AND
  • Undergoing elective coronary angiography due to suspected stabile coronary artery disease
  • Evidence of moderate (40%-79%) stenosis, requiring further routine assessment with FFR.
  • Informed consent

Exclusion Criteria:

  • Acute coronary syndrome or myocardial infarction within 7 days
  • Hypoxia with oxygen saturation measured on pulse oximeter < 90% with the patient breathing air
  • Left ventricular hypertrophy on echocardiography (septum >13mm)
  • Asthma (not COPD)
  • Advanced AV-block without pacemaker in situ
  • Altered conscious state/inability to provide informed consent

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
  • Masking: TRIPLE

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: Supplemental oxygen
Inhalation of oxygen 6 L/min through an open face mask
Drug: Oxygen gas
The intervention is administered as previously described. The duration of intervention is 10 minutes.
SHAM_COMPARATOR: Ambient air
Breathing ambient air through an open face mask
Other: Ambient air
Administered similarly to treatment arm, via an open face mask and during 10 minutes

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
Index of Microcirculatory Resistance (IMR)
Time Frame: Change from baseline to 1 hour
Measure of microvascular resistance. Intracoronary pressure- and flow-based measurements derived from thermodilution recordings.
Change from baseline to 1 hour

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
Coronary Flow Reserve (CFR)
Time Frame: Change from baseline to 1 hour
Flow-related index based om thermodilution measurements
Change from baseline to 1 hour
High sensitive troponin
Time Frame: Measured at baseline, after 4, 12 and 24 hours.
Cardiac biomarker and a measure of periprocedural myocardial damage
Measured at baseline, after 4, 12 and 24 hours.

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.
Karolinska Institutet

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.
January 1, 2018

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.
May 1, 2019

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.
August 1, 2020

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).
November 28, 2017

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.
December 8, 2017

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.
December 11, 2017

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 5, 2020

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 30, 2020

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, 2020

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.
  • 2017-10.1

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

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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