Abdominal Compression Elastic Support (ACES)

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.