Extracorporeal CO2 Removal With the Hemolung RAS for Mechanical Ventilation Avoidance During Acute Exacerbation of COPD

The Hemolung RAS provides low-flow ECCO2R using a single, 15.5 French dual-lumen catheter
inserted percutaneously in the femoral or jugular vein. Low-flow ECCO2R offers an alternative
or supplement to invasive mechanical ventilation (MV) for patients suffering from acute,
reversible, hypercapnic respiratory failure. In contrast to invasive MV, low-flow ECCO2R
provides partial ventilatory support independently of the lungs. The rationale for this study
is that low-flow ECCO2R with the Hemolung RAS can be used to provide supplemental CO2 removal
in COPD patients experiencing acute hypercapnic respiratory failure to either avoid or reduce
time on invasive MV. In this patient population, avoidance or reduced time on invasive MV may
have significant clinical benefit in reducing the many complications associated with invasive
MV. The major complication risks of low-flow ECCO2R are associated with central venous
catheterization and the need for anticoagulation during treatment. This study is designed to
evaluate the safety and efficacy of Hemolung RAS plus standard-of-care as compared to
standard-of-care alone.

Inclusion Criteria:

1. Age ≥ 22 years

2. Confirmed diagnosis of underlying COPD (based on prior spirometry or approved
screening procedure) or ACOS (Asthma-COPD Overlap Syndrome) based on prior spirometry
or approved screening procedure.

3. Diagnosed as experiencing an acute exacerbation of COPD

4. Subject has been receiving standard of care treatment for an acute exacerbation of
COPD, including treatment with bronchodilators, corticosteroids, antibiotics, and
controlled oxygen therapy.

5. Able to generate adequate cough and control of secretions

6. Minimum platelet count of 100,000/mm3 (and not requiring daily transfusions to
maintain platelet count above 100,000/mm3) at time of screening.

7. Minimum hemoglobin of 7.0 gm %, no active major bleeding (and not requiring daily
transfusions to maintain hemoglobin count above 7.0 gm%) at time of screening.

8. Informed consent from patient or legally authorized representative

9. Meets one of the 2 following sets of population stratification criteria:

1. (Stratum 1) Has required noninvasive ventilation (NIV) for ≤ 4 days, and

1. Is at high risk of requiring intubation and invasive mechanical ventilation (MV) after
at least one hour on NIV due to one or more of the following:

-Respiratory acidosis (arterial pH < 7.25) despite NIV

-Worsening hypercapnia or respiratory acidosis relative to baseline blood gases

-No improvement in PaCO2 relative to baseline blood gases and presence of moderate or
severe dyspnea

-Presence of tachypnea > 30 breaths per minute

- Intolerance of NIV with failure to improve or worsening acidosis, dyspnea or work
of breathing

*OR*

2. After starting NIV with a baseline arterial pH ≤ 7.25, shows signs of progressive
clinical decompensation manifested by decreased mental capacity, inability to tolerate
NIV, or increased or decreased respiratory rate in setting of worsened or unchanged
acidosis.

2. (Stratum 2) Meets ALL of the following criteria:

-Has required intubation and invasive MV due to acute respiratory failure for ≤ 4
days, either immediately upon presentation or after having failed NIV

-PaCO2 ≥ 50 mmHg prior to intubation

- Has met criteria for weaning readiness

- Has failed first spontaneous breathing trial due to increased dyspnea, rate of
breathing, work of breathing, and/or dynamic hyperinflation (i.e. reasons
associated with hypercapnia)

- Able to protect airway

Exclusion Criteria:

1. DNR/DNI order

2. Presence of acute, uncontrolled arrhythmia

3. Hemodynamic instability (mean arterial pressure < 60 mmHg) despite infusion of
vasoactive drugs

4. Acute coronary syndrome

5. Acute exacerbation is due primarily to congestive heart failure

6. PaO2/FiO2 < 120 mmHg on PEEP >/= 5 cmH2O

7. Current intubation (Stratum 2), or likelihood of intubation (Stratum 1), or will
occur, greater than 24 hours but less than 72 hours after prior extubation

8. Presence of bleeding diathesis or other contraindication to anticoagulation
therapy

9. Significant weakness or paralysis of respiratory muscles due to causes unrelated
to acute exacerbation of COPD

10. Cerebrovascular accident, intracranial bleed, head injury or other neurological
disorder likely to adversely affect ventilation or airway protection.

11. Hypersensitivity to heparin or history of previous heparin-induced
thrombocytopenia (HIT Type II)

12. Presence of a significant pneumothorax or bronchopleural fistula

13. Current uncontrolled, major psychiatric disorder

14. Current participation in any other interventional clinical study

15. Pregnant women (women of child bearing potential require a pregnancy test)

16. Neutropenic (absolute neutrophil count < 1,00mm3, not transient) related to the
presence or treatment of a malignancy; recent bone marrow transplant (within
prior 8 months); current, uncontrolled AIDS; or receiving long-term (>3 months)
high dose immunosuppressants within the last 6 months.

17. Presence of severe (acute or chronic) renal failure defined as requiring any form
of dialysis.

18. Severe liver insufficiency (Child-Pugh scores >7) or INR > 1.6 suspected to be
related to liver disease (liver associated coagulopathy)

19. Diagnosis of acute pulmonary embolism during current ICU admission

20. Known vascular abnormality or unavailable vascular access which could complicate
or prevent successful Hemolung Catheter insertion

21. Terminal patients not expected to survive current hospitalization

22. Ventilated via tracheotomy

23. Presence or history of clinically significant disease or other foreseeable risk
that outweighs the potential, in the judgement of the investigator