Study of New Catheter & Pressure Monitor System to Help Prevent Compartment Syndrome From Developing in the Injured Leg

Compartment Syndrome (CS) may occur in patients with a fracture or crushing injury to an
extremity. The current standard-of-care for patients at risk of developing CS is clinical by
watching for signs and symptoms of CS, and if needed, measuring the pressure within the
muscle compartment (intramuscular pressure, IMP). Currently, IMP measurements are made by
placing a percutaneous pressure sensor into the targeted muscle compartment, which is then
attached to a pressure monitor. Whenever the clinical exam and/or pressure measurements
suggest that CS is developing, fasciotomy is generally performed immediately.

Twin Star Medical has developed a novel Compartment Monitoring System (CMS) that consists of
a pressure monitoring module and two types of catheters. Both Twin Star Catheters remove
interstitial tissue fluid, which may contribute to a reduction in compartment pressure, and
which may be used for clinical analysis to determine if certain analyte indicators of muscle
injury (biomarkers) can be predictive of CS development. One type of catheter Pressure
Measurement/Fluid Collection, (PMFC), removes fluid and monitors pressure via a solid-state
fiber optic transducer at the tip of the catheter. The other type of catheter, Fluid
Collection (FC), only removes fluid and does not have a pressure transducer at the tip. The
monitoring module senses, displays and records pressure as measured by the PMFC catheter as
well as provides a vacuum source, which is required for the operation of the fluid removal
catheter. The Twin Star CMS Monitoring Module has been successfully tested to (1) ensure the
delivery of the specified functional performance requirements needed to reliably operate the
Twin Star Catheter, and (2) meet current electrical safety standards established for
clinical use. The first model of the Twin Star catheter and monitor was reviewed and
approved by the Food and Drug Administration (FDA) for the indications of pressure
measurement and the withdrawal of interstitial fluid. The devices being used for this
clinical study represent the newly designed catheter and monitor and are not FDA approved
and are therefore considered investigational. It is anticipated that the second-generation
model of the catheter and monitor will be submitted to the FDA for approval while this study
is being conducted.

The purpose of this Study is to determine if the removal of interstitial fluid by the Twin
Star Catheter can lower muscle compartment pressure and impact other measures of subject
clinical status, including possible reduction of the need for fasciotomy. The Study
population will be Subjects who have suffered an isolated tibial fracture (open or closed)
requiring surgical stabilization within 72 hours of injury. This Study will use an Adaptive
study design in which a total of up to 90 subjects will be enrolled. All Subjects will
receive the Twin Star catheters, which will be inserted at the end of the surgical procedure
to stabilize the tibia fracture and will be connected to the pressure monitor before leaving
the surgical room. The catheters will be used for the first 24-hours after surgical fixation
of the affected lower leg in order to (1) measure and record muscle compartment pressure,
and (2) remove accumulated interstitial fluid in the subset of subjects that are randomized
to the Treatment Group. The first 20 Subjects (Phase 1) will not be randomized; all will be
actively treated but with different combinations of catheters and vacuum levels. The purpose
of Phase I of the study is to optimize treatment parameters that will be used in the
remaining 70 subjects, which will constitute Phase II. All subjects will receive a total of
3 catheters placed in the anterior compartment. Subjects in Phase 1 will be enrolled into
two groups: 1) receiving constant vacuum (-150 mmHg) and fluid removal or, 2) receiving
intermittent vacuum (-50 mmHg) and fluid removal. Within the anterior compartment, there
will be one PMFC and 2 FC catheters inserted.

The first 10 subjects in Phase 1 will all be treated with single-fiber catheters, but with
one of two different vacuum levels (intermittent at -50 mmHg or constant at -150 mmHg).
After the first 10 subjects have completed the study, fluid removal results will be
analyzed. If results demonstrate that fluid in the anterior compartment is being withdrawn
at a rate of ≥ 0.5 mls/24 hours, the second group of 10 subjects will continue using the
same single fiber catheters. If the results of the first 10 subjects demonstrate fluid is
being withdrawn in the anterior compartment at < 0.5 mls/24 hours, the next 10 subjects will
instead receive treatment with two multi-fiber FC catheters plus the same PMFC catheter.

After the first 20 subjects have been enrolled in the study, the remaining subjects to be
enrolled in Phase 2 will be randomized to either a Treatment or Control group. Both groups
will receive treatment with whichever combination of catheter type (single or multi-fiber)
and vacuum (constant or intermittent) was most efficacious in terms of fluid removal in
Phase 1. The randomization will determine whether subjects will receive no vacuum at all
(Control Group: Monitoring alone) or the fluid removal mode that was shown to be best in the
first phase of the study (Treatment Group: Monitoring plus Fluid Removal).

The rationale for the adaptive study design is that we have developed second-generation
catheters whose fluid removal function has not been optimized in vivo in humans. Although
our first generation catheter used multi-fibers, animal study results have demonstrated that
single-fiber catheters remove the same amount of fluid in vivo as multi-fiber catheters, but
can be made much smaller than multi-fiber catheters.

The Subject's length of initial hospital stay will be determined by the attending physician
based on the subject's medical condition(s). The standard-of-care for routine clinical
compartment pressure monitoring will apply to both the vacuum and non-vacuum groups in this
Study with the catheters being left in place for 24 hours. Compartment syndrome is a
dignosis that depends on clinical assessment supplemented by pressure measurement.
Throughout the study, the treating physicians will monitor the subjects according to
standard clinical practice and will apply standard clinical judgment regarding the diagnosis
of compartment syndrome. Treating physicians may end the study and perform fasciotomy if
they feel it is necessary because of clinical suspicion that compartment syndrome is
developing. A two-week and a 3-month follow-up visit will be required post discharge,
coinciding with typical clinical follow-up visits. The purpose of the two-week visit will be
primarily to assess whether there have been any adverse consequences related to the
catheter. The purpose of the three-month assessment will be primarily to look for any
evidence of the sequelae of missed or untreated compartment syndrome, such as clawing of the
toes or persistent neurologic dysfunction. Functional outcomes will be measured during these
follow-up visits as well as the occurrence of any adverse events since discharge. Functional
outcomes will include an assessment of whether any loss of motor function resulted as part
of the primary injury.

Inclusion Criteria:

- Subject with a tibial shaft fracture requiring intramedullary nailing or bicondylar
tibial plateau fracture requiring application of a knee-spanning external fixator.

- Operative procedure (nailing or external fixation) performed within 72 hours of
injury.

- The Subject is between 18 and 60 years of age.

- Able to understand what he/she is being asked to do, willing/able to understand and
sign the Informed Consent to return for follow-up visits at 2 weeks and 3 months post
surgery.

Exclusion Criteria:

- Current evidence of CS prior to Study.

- Surgical stabilization will result in the presence of a bead pouch or wound vac or
other dressing that would interfere with placement of any of the three Catheters in
the anterior compartment.

- The Subject has a medical condition(s) that precludes use of Catheters, such as
dermatologic conditions, immunological deficits or traumatic skin lesions that
interfere with Catheter placement.

- The Subject has co-morbidities that may place the Subject at risk of hypotension
(e.g., significant blood loss, heart failure, significant chest or abdominal trauma,
septicemia, pelvic fractures, femur fractures or massive soft tissue trauma.)

- Likely problems, in the investigator's judgment, with maintaining follow-up
(including developmental delay, address greater than 2 hours drive from the treating
institution, substance abuse problems, intoxication, current or pending
incarceration, etc.).