Abdominal Compression Elastic Support (ACES)
Abdominal Compression Elastic Support (ACES)
Hemodialysis (HD) patients with end stage renal disease (ESRD) experience higher rates of
 cardiovascular (CV) morbidity and mortality than do the general population and many
 populations with other chronic diseases. This exceptional risk is explained in part by known
 risk factors, such as diabetes, hypertension, and other uremia-related factors, including
 vascular calcification and stiffness, autonomic dysfunction, and a high burden of circulating
 inflammatory mediators. Recent studies suggest that blood pressure variability, especially
 intra-dialytic hypotension (IDH) is the most significant risk factor for these CV events.
 Studies have also shown that the use of IAB is capable of improving cardiovascular function
 for avoiding or minimizing the development of an orthostatic hypotensive episode (OHE) in
 patients with autonomic dysfunction, orthostatic hypotension (OH) in diabetes patients and
 children with orthostatic intolerance, and post-dialytic orthostatic hypotension (PDOH).

 The investigators propose a study to examine the use of an abdominal compression elastic
 support (ACES) to prevent the development of IDH in patients who are known to be prone to
 these episodes. The ultimate goal is to facilitate more effective and safer dialysis therapy.
 The ACES has a configuration that is similar to a back-support work belt or an inflatable
 abdominal band (IAB). All of these devices are wrapped around to compress the abdomen at the
 waist.
I. Study Design: Biomedical

 1. Controls will be used. For the safety of ACES five healthy subjects will be used as
 controls to assess the safety and tolerability of the device. The regular HD treatments
 of each study patient will serve as their own control in assessing the effect of ACES
 use on their HD treatments. The control data are derived from the treatment logs of four
 to eight HD regular treatments taken by the patient.

 2. The study design is an open trial.

 3. No placebo is involved

 4. This is a single center study to be done only at the Medical Center of University of
 Virginia (UVa).

 II. Human Participants Ages: 18 or older Sex: Male and Female Race: All

 Subjects or Patients:

 1. 5 healthy subjects and 20 dialysis patients to complete protocol.

 2. There could be a 50% drop out rate for the dialysis patients.

 3. 30 (Up to 5 healthy subjects and Up to 35 dialysis patients) will be enrolled at all
 sites

 4. All 30 subjects and patients will sign a consent form under this protocol.

 5. The estimated time line for the study is 100% enrollment within 10 months III.
 Statistical Considerations

 1. Is stratification/randomization involved? No

 2. What are the statistical considerations for the protocol? In analyzing the data, if the
 systolic blood pressure (SBP) of a given patient compared with the first blood pressure
 reading after initiating dialysis is larger than the threshold 20 mmHg (condition A) or
 the decrease in mean arterial pressure is larger than 10 mmHg and the development of
 hypotensive symptoms (condition B), this session (hour) will be identified as an IDH
 session (hour). The data may be divided into two groups (one under condition A and one
 under condition B) for further analysis on the impact of the conditions on the
 effectiveness of ACES.

 In our study design, the countermeasure implemented in each "control" session may be
 different. Our study can lead to an answer on whether the use of ACES is more effective
 in alleviating IDH than the "control" countermeasure.

 The researchers will only handle the quantitative data and the analysis of enumeration
 and quantitative data. To assure integrity in and correctness of data analysis, all data
 will be forwarded to a statistician who is not physically involved with the study for an
 independent evaluation.

 3. Provide a justification for the sample size used in this protocol.

 A. On the safety issue: Due to the low compression pressure and no adverse effects seen
 in the use of IAB, we expect that the investigators should not see the development of
 any adverse effect in the current clinical trial. When the investigators carry out 40
 ACES session in Phase II and show no adverse effect, then the likely hood for an adverse
 effect to develop will be at most 2.5%. Even if the occurrence frequency were at 25%, a
 sample size of 16 sessions will be more than adequate to demonstrate the safety
 hypothesis with a confidence better than 99% (i.e. P<0.01).

 B. On the reduction in occurrence frequency. The patients participated in the study will
 have at least 2 episodes in a month. It can add up to an occurrence frequency of 25%.
 This is to say that 20 out of the 80 control sessions will have IDH developed. If the
 occurrence frequency is reduced to 12.5% (i.e. 12 sessions with IDH out of the 80 ACES
 sessions), the data of 80 ACES session will be adequate to show a confidence level of
 99% by the chi square test (P<0.01) that the use of ACES is effective in reducing the
 occurrence frequency. On the other hand, if the frequency estimated from the data of
 Phase II is reduced to 18% (instead of 12.5%), then the data of 80 ACES sessions in
 Phase II will yield a χ2 of about 2.0. With data of 80 more ACES sessions in Phase II,
 the value of χ2 for the same decrease in occurrence frequency may increase to 4 to
 indicate that the reduction in occurrence frequency has a confidence level of 95%
 (P<0.05).

 The above computation analysis has been expanded to examine how test size and the values
 of occurrence rate affect the value of χ2 and subsequently whether the occurrence rate
 is significantly reduced with the use of ACES. The investigators find that the three
 test sizes (80 tests mentioned here, 160 tests and 480 periods mentioned later) set for
 use in the protocol are adequate to carry out the statistical determination.

 Currently the investigators do not have a certain way to predict when IDH will develop.
 Thus, the investigators consider each HD session done on the same patient as
 independent.

 4. The investigators have worked with a retired statistician in designing this protocol.

 IV. Biomedical Research

 1. Healthy subjects:

 In order to fulfill the study statistical requirements, up to five (5) healthy subjects
 will be tested for safety and tolerability of wearing ACES for 3 hours. Each healthy
 individual will then wear the ACES for three consecutive hours in a supine or seated
 position, except for use of the restroom if needed, and assess the measured parameters.

 If no major concerns are identified with this healthy population the use of ACES device
 will be offered for use in dialysis patients who have three or more episodes of IDH in
 the 4 weeks leading up to recruitment.

 2. Dialysis Patients

 Hemodialysis patients at the University of Virginia Kidney Center have their
 hemodialysis done in a seated position (30° to 90°). The investigators will be using the
 ACES device on these patients in a seated position.

 In order to fulfill the study statistical requirements, up to ten (10) ESRD patients on
 HD will be tested for safety and tolerability of wearing ACES during their dialysis
 sessions.

 Screening trial session for Dialysis Patients After the patient reads and signs the
 consent form and passes the inclusion and exclusion criteria, the investigators will
 have him or her to undergo a trial session of ACES. This trial session can be done on
 the same day as the consent form or it can be done on another day that the patient is
 coming for a regular dialysis session. This trial session is designed to find out
 whether the patient can tolerate the compression of the ACES and whether his/her SBP and
 heart rate can be significantly altered by the compression. Over the course of this
 screening trial, the patient will be advised that he can request removal of the ACES
 whenever he/she wishes.

 3. Control & ACES Sessions:

 The patients will undergo a HD treatment as prescribed by their attending nephrologists.
 The investigators expect that the characteristics of these treatments will have the
 following general features:

 • The HD setting can lead to a Kt/V larger than 1.2

 • A procedure or countermeasure will have been prescribed and set up as standard of care
 to deal with the development of IDH.

 -  The measurement of blood pressure and heart rate will be performed by the usual
 dialysis machine for a given patient, providing internal equipment standardization

 -  The blood pressure cuff will be applied to bare skin on the patient's arm

 -  The data obtained for eight regular HD treatments without wearing the ACES will be
 identified as the control data. For each patient, four HD treatment sessions will
 be conducted with the use of ACES in Phase II and four more will be done in Phase
 III if the data of Phase II calls for.

 Preparation to start the hemodialysis with ACES

 • Before the screening test of the patient, the investigators will get the waist
 circumference of the patient. The size of the ACES is chosen from this specification:
 22"~27" (56~68cm)-Small, 28"~33" (71~84cm)-Medium, 34"~40" (86~101cm)-Large, 41"~47"
 (104~119cm)-Extra-Large, 48"~54" (122~137cm)-Extra-Extra-Large 55"~61" (140~155cm).

 • Put on the ACES with its band tips already aligned with the white marking. At this "no
 load" marking, the compression pressure imposed by the ACES is less than 2 mmHg. This
 step is done before the patient is seated and attached to the blood lines.

 • The HD treatment will start as usual.

 During HD Control and ACES session if the patient experiences IDH or SBP drop If the
 study investigators deem that the patient is experiencing symptoms of IDH or sees that
 the SBP drops 20 mm Hg, then a charted course will be used on what countermeasures are
 to be employed.

 Post-dialytic care and data collection • Post dialytic procedure and care will include:

 o Removal of the ACES and one more BP and pulse measurement,

 o Discharge of the patient who is diagnosed as having no PDOH,

 o Whether the patient is asked to come back for another HD treatment the next day,

 o If the patient is classified as one with PDOH, the procedure to discharge the patient
 as prescribed by the physician will be followed. If it is prescribed to take a standing
 up test, it will be done with the ACES on. If the patient is to be sent home, then the
 ACES will be taken off the patient and another standing up test be done. If the patient
 is to be sent to an emergency center, then the physician will make a decision on whether
 to send the patient with the ACES on or with it off.

 4. Events calling for decompression of the ACES.

 If the following complications develop while the ACES is in use the device will be removed •
 A decrease in toe O2 saturation below 90%, • An increase in leg circumference by more than
 10% to indicate leg edema,

 • Pain or cramping in the abdominal area and/or lower extremities being more severe than the
 norm

 -  Vomiting more severe than the norm

 -  Any other threatening complication

 -  The patient requests removal of the device (reason for request will be recorded)

 The study team will investigate whether the complications result from abdominal compression
 imposed by the ACES. If ACES is deemed as the cause, then the ACES will be decompressed. When
 the level of aspartate aminotransferase (AST) alanine aminotransferase (ALT) become available
 to Global Monitor, Inc. and is found to be higher than the norm, then a retrospective
 analysis will be made to determine whether the level increase relates to the use of ACES.

 V. Data and Safety Monitoring Plan An adverse event will be considered any undesirable sign,
 symptom or medical or psychological condition even if the event is not considered to be
 related to the investigational drug/device/intervention. Medical condition/diseases present
 before starting the investigational drug/intervention will be considered adverse events only
 if they worsen after starting study treatment/intervention. An adverse event is also any
 undesirable and unintended effect of research occurring in human patients as a result of the
 collection of identifiable private information under the research. Adverse events also
 include any problems associated with the use of an investigational device that adversely
 affects the rights, safety or welfare of patients.

 The symptoms or disease developments described as the exclusion criteria (i.e. beyond the
 first six) will be considered as adverse effect. The symptoms or excessive decrease in SBP,
 for example, that are normally associated with hypotension development and are found to be
 common in HD patients of UVa clinics will be reported but not considered as adverse event and
 not used as a trigger to discontinue the ACES session.

 The adverse event will be reported to FDA in a case report form.
Inclusion Criteria:

 -  Must be able to give informed consent for participation in this study

 -  Age ≥ 18 years

 -  A body weight > 100 lb or a body mass index > 18.5.

 -  End-stage renal disease with hemodialysis in-center three times per week

 -  Not missing any treatments in the preceding two weeks and in compliance with
 instructions from the health care provider.

 -  In the last month had at least two episodes of IDH (defined as having hypotensive
 symptoms such as dizziness, fainting, headache, nausea, vomiting, cramping, weakness,
 blurry vision and/or a decrease in systolic blood pressure (SBP) of more than 20
 mmHg).

 -  Hemoglobin greater than or equal to 9.0 g/dL (hematocrit 27%) to hemoglobin of 15.0
 g/dL (hematocrit 45%).

 Exclusion Criteria:

 -  • Pregnancy (self-reported)

 -  Allergic to nylon, polyesters and latex.

 -  Not able to understand the English language

 -  Not able to disengage the ACES from compression

 -  Having an excessively low systolic blood pressure (SBP which is less than 90 mmHg)

 -  Hemoglobin less than 9.0 g/dL or greater than 15 g/dL

 -  Excessive intra-abdominal fluid pressure

 -  Respiratory distress

 -  Bleeding in the chest and abdomen

 -  Bleeding dyscrasia causing serious coagulation problem

 -  Raised intra-abdominal pressure

 -  Having the following cardiovascular, pulmonary and abdominal complications:

 -  Systolic congestive heart failure, defined as a systolic ejection fraction of
 less than 25%

 -  Coronary artery disease defined as having a history of myocardial infarction or
 hemo-dynamically significant stenosis on cardiac catheterization or acute or
 chronic angina

 -  Circulatory shock

 -  Head trauma and/or abdominal trauma in the past three months

 -  Mesenteric ischemia

 -  Active foot ulcer

 -  Pulmonary edema

 -  Uncontrolled Hypertension (defined as systolic pressure of 180 mm Hg or a
 diastolic pressure of 110 mm Hg or higher) - using the average blood pressures
 obtained at one prior recent dialysis session and the average blood pressures
 obtained at the screening trial session for ACES.

 -  Liver disease as defined as an elevated ALT, AST, and Alkaline Phosphatase 2.5
 times the upper limit of normal on a prior lab from medical records.

 -  INR > 1.5 or use of coumadin

 -  Platelets < 100

 -  Active infection

 -  The need to use anti-hypotensive drugs on the days the ACES belt is applied.

 -  If the average systolic blood pressure with anti-hypotensive drugs or without and
 made before hemodialysis treatment is less than 90 mmHg, then the ACES session
 will be postponed to the next treatment. If similar hypotension situation occurs
 in the next ACES/hemodialysis treatment, then the subject will be taken out of
 the ACES trial and be considered a screen fail.