Safety and Performance Evaluation of Seraph 100 Microbind Affinity Blood Filter (Seraph 100) in the reduction of pathogen load from the blood in septic patients with suspected, life-threatening bloodstream infection.

Seraph 100 Microbind Affinity Blood Filter is used to reduce pathogen load
during bloodstream infection. Bacteremia or bloodstream infection, also called
BSI, occurs when a bacterial infection elsewhere in the body enters the
bloodstream. This clinical condition can quickly become life-threatening and
progress to sepsis. Sepsis is defined as life-threatening organ dysfunction
caused by a dysregulated host response to infection (Singer et al., 2016).When
sepsis occurs with extremely low blood pressure, it*s called septic shock.
Septic shock is fatal in many cases.
Sepsis can be triggered by many types of bacteremia although the exact source
of the infection often cannot be determined. Some of the most common infections
that lead to BSI are lung infections (i.e. pneumonia) and infections in the
abdominal area. Patients who are already in the hospital for something else,
such as a surgery, are at a higher risk of developing BSI. These infections are
even more dangerous when the bacteria are already resistant to antibiotics. The
National Institutes of Health (NIH) estimates that over 1 million Americans get
sepsis each year. Between 28 and 50 percent of these patients may die from the
condition.

The primary objectives are to demonstrate the safety and performance of the
Exthera Medical Seraph 100 Microbind Affinity Blood Filter in the reduction of
pathogen load from the blood in septic patients with suspected,
life-threatening bloodstream infection (BSI).

This is a prospective, open-label, randomized, controlled clinical
investigation designed to evaluate the safety and performance of Exthera
Medical Seraph 100 Microbind Affinity Blood Filter in the reduction of pathogen
load from the blood in septic patients with suspected, life-threatening
bloodstream infection (BSI).
The clinical investigation will be conducted at approximately 16 centers in
Europe. Subjects will be randomized to the treatment group (Seraph 100 +
antibiotic therapy) versus control group (antibiotic therapy only).
Subjects will be followed until the last subject completes their 3-months
follow-up phone call. Clinical Investigation follow-up will occur at Baseline
(confirmation of eligibility), Day 0 or Treatment, Follow-up visits at Day 1,
Day 2, Day 7 and Follow-up phone call at 3-months.

Index Procedure
Procedures Involved in the Use of the Device Under Investigation
Seraph 100 is intended for use with standard, commercially available bloodlines
compatible with the pump system used. Refer to the IFU for description on
specific instructions for use of the device under investigation, including any
necessary handling requirements, preparation for use, any pre-use checks of
safety and performance and any precautions to be taken after use.
Treatment Strategy or Treatment Procedures
If the subject is receiving supplemental IV iron during the treatments, the
delivery of IV iron must be stopped during the trial period (day of procedure +
7 days of follow-up).
Systemic heparinization during hemodialysis with concomitant filtration with
the Seraph 100 Filter is recommended with a 3-5-minute waiting period after the
initial heparin bolus before beginning dialysis. Refer to the IFU for
description on specific instructions.Treatment with Seraph 100 should be run at
250-350 mL/min for (4,5h ± 30 min. The treatment procedure will be in
accordance with the IFU, except that specific blood samples will be taken
before and after the Seraph 100 filter cartridge utilizing the bloodline sample
ports in the stand-alone or combination configuration set-up (see Figure 1).
Blood samples will be taken at different timepoints during Day 0 visit in order
to assess pathogen load (TTP):
• Treatment group: Day 0 will be considered as Treatment day being t=0 the
moment immediately before the treatment with Seraph 100 starts.
• Control group: Day 0 will be considered the day when the randomization occurs
and t=0 will be assessed as soon as the subject is randomized to control group,
no later than 24 hours after randomization.
The timepoints at which the blood samples will be taken are specified in the
following table. Blood samples at timepoint 5 minutes*, 45 minutes* and 2
hours* will not be taken for control group.

Anticipated Clinical Benefits
Benefits of the Seraph 100 Microbind Affinity Blood Filter may include
potential reduction in the duration of bacteremia and the incidence of
metastatic infections including, septic arthritis and osteomyelitis. As part of
early treatment of sepsis, Seraph 100 could also theoretically prevent the
development of multi-system organ dysfunction and lower mortality.

Risks associated with the specified device and procedure, together with their
likely incidence, are described in the IFU. There may be risks related to the
device under investigation that are unknown at present. Likewise, the exact
frequency of the risk may be unknown.

Multiple risks assessments for the Seraph 100 device that includes use, design,
and manufacturing have been conducted. The risks and mitigations have been
performed to reduce the risk to As Low As Possible (ALAP) levels. Outcomes of
this analysis has been shown that the potential benefit outweigh potential
patient risks. Further, additional risks are associated with the operator
error, damage during shipment, and not following the Clinical Trial Protocol.
Further residual risks will be assessed as part of the outcome of the clinical
trial.
Risks associated with the Seraph 100 Filter are similar to those associated
with other filters used during extracorporeal treatment. Known and unexpected
risks are relatively mitigated by working with an Investigator who is
experienced and skilled in hemofiltration procedure with patients who show
signs of sepsis. Additionally, the Investigator will be thoroughly trained on
proper device properties and operation. Risks will also be minimized under this
study protocol through adherence to the inclusion/exclusion criteria.
Complications that may occur may include the following, but are not limited to:
Potential Adverse Event

Hypotension
Cramps
Febrile reactions
Arrhythmia
Hemolysis
Hypoxemia
Thrombosis
Hematoma
Device failure/malfunction