EDICT: Ischemic Conditioning in STEMI Patients

Sponsor

Beth Israel Deaconess Medical Center (Other)

Overall Status

Unknown status

CT.gov ID

NCT03097419

Collaborator

(none)

300

Enrollment

Location

Arms

102.1

Anticipated Duration (Months)

2.9

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The purposes of the study are to 1) study alterations in the metabolomic profile of patients exposed to post-ischemic conditions and 2) study alterations in myocardial infarction size of patients exposed to post-ischemic conditioning.

Condition or Disease	Intervention/Treatment	Phase
Cardiac Arrest	Procedure: Remote post-ischemic conditioning	N/A

Detailed Description

Myocardial infarction is a common, morbid and mortal disease. This study will examine both the clinical effects of the treatment as well as the molecular mechanism. Evaluating patients in the emergency department (ED) is more than a daily occurrence for every practicing emergency physician in the country. Every year there are approximately 4.5 million visits to the ED for chest pain and over 1.5 million hospitalizations for acute coronary syndrome (ACS).2 Despite its prevalence, ACS is a difficult diagnosis to evaluate and manage; it involves taking a thorough history and performing a physical as well as performing an electrocardiogram (ECG) and biomarker analysis. The pathogenesis of unstable angina and non-ST segment elevation myocardial infarctions (NSTEMI) involves occlusive narrowing of a coronary artery, usually from an atherosclerotic plaque. The downstream effect of which is inadequate oxygen delivery to the myocardium, resulting in cell death.

Ischemic conditioning is the protective mechanism by which brief episodes of ischemia protect the heart from ischemia-reperfusion injury. There are two types of ischemic conditioning commonly referred to in the literature: pre-conditioning and post-conditioning. In the example of pre-operative coronary artery bypass graft (CABG) patients who may experience a degree of ischemia peri-operatively, ischemic conditioning can be performed before the surgery to prevent or limit myocardial injury. In the example of a patient with an ongoing STEMI who is going to the interventional cardiology suite for a percutaneous intervention, post-ischemic conditioning therapy may prevent or limit myocardial injury. A "remote" qualifier specifies that the therapy is implemented by inducing ischemia at a location that is not the heart itself.

The investigators propose to leverage the novel technique of metabolomics to better study the mechanisms behind ischemic post-conditioning. This study will pair clinical human data with molecular data. It is a novel theoretical concept in the field and the investigators believe that this methodology will be the basis for future research.

The investigators will utilize metabolomics as a tool to gain mechanistic insight into the potential mechanisms of action behind ischemic conditioning. Metabolomics is a burgeoning field of molecular biology that studies the metabolome, the catalogue of material and product of every biochemical reactions in the body occurring at that point in time. As such, the metabolome is ever changing and can reflect what the body is doing, not doing or responding to, and if so, by how much for each of the over 2,500 known human metabolites. Because there is such a large amount of data available by this technique, proper analysis requires the use of proprietary statistical software that can account for the effect of random chance in the data.

The particular innovation to this methodology compared to other studies to date is that we will pair biological as well as clinical data for analysis. This means that even if the investigators cannot find a difference in troponin levels between the treatment and control groups, the investigators will have some data on where to investigate next and be able to detect the biological response that remote post-ischemic conditioning induces. If this particular therapy does not develop any further, at least the investigators will know what appropriate mechanisms are at work and perhaps some of those could be targeted by pharmaceuticals in the future. Finally, if the investigators detect no differences at all, this will serve as an argument against the potential of ischemic post-conditioning in the NSTEMI population.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

300 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Intervention Model Description:

We will perform a prospective, randomized-controlled study of 300 patients presenting to the BIDMC ED with a suspected non-ST segment elevation myocardial infarction. After obtaining consent, the patients will be assigned to either the intervention or standard of care group via a computerized block 1:1 randomization process.We will perform a prospective, randomized-controlled study of 300 patients presenting to the BIDMC ED with a suspected non-ST segment elevation myocardial infarction. After obtaining consent, the patients will be assigned to either the intervention or standard of care group via a computerized block 1:1 randomization process.

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

The Effect of Remote Ischemic Conditioning on the Metabolomic Profile of NSTEMI Patients

Actual Study Start Date :

Nov 28, 2012

Anticipated Primary Completion Date :

Jun 1, 2021

Anticipated Study Completion Date :

Jun 1, 2021

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Intervention Remote post-ischemic conditioning	Procedure: Remote post-ischemic conditioning A manual sphygmomanometer will be inflated over the brachial artery of the participants' arm that does not have an intravenous catheter actively infusing medications. If both arms are in use, then the participant's non-dominant arm will be used. The sphygmomanometer will be inflated to a pressure at least 20 mmHg greater than the participants' last recorded systolic blood pressure. The sphygmomanometer will be inflated for 5 minutes then rapidly deflated for 5 minutes, thereby concluding one iteration. Five (5) total iterations constitute the treatment. The left arm will be preferentially used instead of the right arm, unless the left arm is receiving medication administration.
No Intervention: Control Standard medical care by the primary treatment team.

Arm

Intervention/Treatment

Experimental: Intervention

Remote post-ischemic conditioning

Procedure: Remote post-ischemic conditioning

A manual sphygmomanometer will be inflated over the brachial artery of the participants' arm that does not have an intravenous catheter actively infusing medications. If both arms are in use, then the participant's non-dominant arm will be used. The sphygmomanometer will be inflated to a pressure at least 20 mmHg greater than the participants' last recorded systolic blood pressure. The sphygmomanometer will be inflated for 5 minutes then rapidly deflated for 5 minutes, thereby concluding one iteration. Five (5) total iterations constitute the treatment. The left arm will be preferentially used instead of the right arm, unless the left arm is receiving medication administration.

No Intervention: Control

Standard medical care by the primary treatment team.

Outcome Measures

Primary Outcome Measures

Changes in the Metabolomic Profile [Time: 0 minutes (baseline), 60 minutes, 2 hours, 3 hours, 24 hours, and 72 hrs.]
The change in metabolic profiles as compared to a subject's baseline readout will be analyzed using both, an "untargeted" and a "targeted" approach. A comparison of the these changes will be made between the interventional and control groups.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Adult patient 18 ≥ years old in the BIDMC ED
Clinical suspicion of myocardial infarction
ECG without pathognomonic ST-segment elevation
At least one positive troponin-T (>0.10)

Exclusion Criteria:

Inability to consent to enrollment
Concurrent diagnosis of an emergent condition that may be antecedent to the NSTEMI
Presentation to the ED greater than 24 hours after onset of NSTEMI symptoms
Patients with a history of mastectomy or upper extremity arteriovenous fistula.
Patients with active medication administration in both arms will be excluded from the study.