Safety Study of External Counterpulsation as a Treatment for Acute Ischemic Stroke "CUFFS"

Completed

Phase 1 Results

Trial Description

The purpose of this study is to determine if external counterpulsation (ECP) is feasible to perform, tolerable, and safe as a treatment for patients with acute ischemic stroke (i.e., a blockage of one of the arteries supplying a part of the brain), and to assess what type of effect it might have on 1) the velocity of blood flow in the arteries supplying the brain and 2) stroke symptoms. The hypothesis of the study is that ECP will be feasible and safe to perform, and will be tolerable for patients with acute ischemic stroke at pressures that increase the velocity of arterial blood flow to the brain.

Detailed Description

A stroke is usually caused by a blockage of one of the arteries that carries blood to the brain. Sometimes with a stroke, there may be a small amount of blood flow that manages to get through or around the blockage, and it may be possible that the amount of damage from a stroke may be reduced by increasing this blood flow. External counterpulsation (ECP) is a procedure in which a machine uses electrical signals from the heart that are detectable on the surface of the body in order to time the inflation of cuffs (similar to a blood pressure cuff) that are wrapped around a patient's legs (calves, thighs and buttocks). Using a reading of the electrical activity from the patient's heart (an electrocardiogram, or ECG, monitor), the machine inflates the cuffs with air at just the right time during each heart beat, during diastole, in order to change the blood pressure in a way that has been shown to increase blood flow to the kidneys, skin, eyes, heart, and brain.
In this study, patients presenting within the first 48 hours of an acute ischemic stroke (i.e., a blockage of one of the arteries supplying a part of the brain) will be randomly assigned to either of (1) a 1-hour treatment of external counterpulsation (ECP) applied at a pressure that is typically therapeutic, or (2) a 1-hour treatment of ECP at a minimal pressure in a control group. ECP-induced changes in brain artery flow velocity will be assessed with an ultrasound prior to and then during ECP in each group, and an optimal pressure that results in an augmentation of flow velocity will be determined. A neurological exam will be performed prior to, during, and after ECP in each group, in order to assess any changes in stroke symptoms related to ECP. Patients will be followed to 30 days. The main goal of this trial is to evaluate if ECP is safe and feasible to use as a treatment for stroke. In addition, the trial will enable an assessment of whether or not ECP increases blood flow to the brain or affects the neurological symptoms of a patient with a stroke.

Conditions

Interventions

  • External counterpulsation (ECP) Procedure/Surgery
    Intervention Desc: a procedure in which a machine uses electrical signals from the heart that are detectable on the surface of the body in order to time the inflation of cuffs (similar to a blood pressure cuff) that are wrapped around a patient's legs (calves, thighs and buttocks). Using a reading of the electrical activity from the patient's heart (an electrocardiogram, or ECG, monitor), the machine inflates the cuffs with air at just the right time during each heart beat, during diastole, in order to change the blood pressure in a way that has been shown to increase blood flow to the kidneys, skin, eyes, heart, and brain.
  • External counterpulsation at a full pressure Device
    Other Names: External counterpulsation
    Intervention Desc: A one-hour treatment of ECP at full pressure, which will be applied in a tiered, dose-escalating manner, starting at 200mmHg and increasing up to 300mmHg based on assessments made.
    ARM 1: Kind: Experimental
    Label: Full-pressure ECP
    Description: Patients in the "Full-pressure ECP" arm receive a 1-hour treatment of ECP at full pressure, which will be applied in a tiered, dose-escalating manner up to 300mmHg, while assessments are made.
  • External counterpulsation at sham-pressure Device
    Other Names: External counterpulsation
    Intervention Desc: A one-hour treatment of ECP at an inactive pressure, which will be applied at 75mmHg and kept there for the hour while assessments are made.
    ARM 1: Kind: Experimental
    Label: Sham-pressure ECP
    Description: A 1-hour treatment of ECP at an inactive pressure (75mmHg)
  • Full-pressure ECP Device
    Other Names: External counterpulsation
    Intervention Desc: A one-hour treatment of ECP at full pressure, which will be applied in a tiered, dose-escalating manner, starting at 200mmHg and increasing up to 300mmHg based on assessments made.
    ARM 1: Kind: Experimental
    Label: Full-pressure ECP
    Description: Patients in the "Full-pressure ECP" arm receive a 1-hour treatment of ECP at full pressure, which will be applied in a tiered, dose-escalating manner up to 300mmHg, while assessments are made.
  • Sham-pressure ECP Device
    Other Names: External counterpulsation
    Intervention Desc: A one-hour treatment of ECP at an inactive pressure, which will be applied at 75mmHg and kept there for the hour while assessments are made.
    ARM 1: Kind: Experimental
    Label: Sham-pressure ECP
    Description: A 1-hour treatment of ECP at an inactive pressure (75mmHg)

Trial Design

  • Allocation: Randomized
  • Masking: Single Blind (Subject)
  • Purpose: Treatment
  • Endpoint: Safety Study
  • Intervention: Parallel Assignment

Patient Involvement

patients presenting within the first 48 hours of an acute ischemic stroke (i.e., a blockage of one of the arteries supplying a part of the brain) will be randomly assigned to either of (1) a 1-hour treatment of external counterpulsation (ECP) applied at a pressure that is typically therapeutic, or (2) a 1-hour treatment of ECP at a minimal pressure in a control group. ECP-induced changes in brain artery flow velocity will be assessed with an ultrasound prior to and then during ECP in each group, and an optimal pressure that results in an augmentation of flow velocity will be determined. A neurological exam will be performed prior to, during, and after ECP in each group, in order to assess any changes in stroke symptoms related to ECP. Patients will be followed to 30 days.

Outcomes

Type Measure Time Frame Safety Issue
Primary Feasibility and tolerability of external counterpulsation and safety (including endpoints such an increase NIHSS during or immediately after ECP, and acute hemorrhage on repeating imaging, serious adverse events related to ECP, mortality).
Secondary Acute change in NIHSS during or immediately after ECP, NIHSS at 7 days and 30 days post-randomization, and lesion size on day 30 head CT.
Primary Feasibility and tolerability of external counterpulsation During one hour of treatment No
Primary Safety (including endpoints such an increase NIHSS during or immediately after ECP, and acute hemorrhage on repeating imaging, serious adverse events related to ECP, mortality) 30 days Yes
Secondary Acute change in NIHSS during or immediately after ECP Within the 1 hour treatment period and immediately after treatment No
Secondary NIHSS at 7 days and 30 days post-randomization 30 days No
Secondary Lesion size on day 30 head CT 30 days No
Primary Safety (Including Endpoints Such an Increase NIHSS During or Immediately After ECP, and Acute Hemorrhage on Repeating Imaging, Serious Adverse Events Related to ECP, Mortality) 30 days Yes

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