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

Study Overview
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Brief Summary
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This study evaluates the safety and efficacy of using the Hemolung RAS to provide low-flow extracorporeal carbon dioxide removal (ECCO2R) as an alternative or adjunct to invasive mechanical ventilation for patients who require respiratory support due to an acute exacerbation of Chronic Obstructive Pulmonary Disease (COPD). It is hypothesized that the Hemolung RAS can be safely used to avoid or reduce time on invasive mechanical ventilation compared to COPD patients treated with standard-of-care mechanical ventilation alone. Eligible patients will be randomized to receive lung support with either the Hemolung RAS plus standard-of-care mechanical ventilation, or standard-of-care mechanical ventilation alone.

Detailed Description
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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.

Official Title
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A Prospective, Multi-Center, Randomized, Controlled, Pivotal Trial to Validate the Safety and Efficacy of the Hemolung® Respiratory Assist System for COPD Patients Experiencing an Acute Exacerbation Requiring Ventilatory Support

Conditions
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Acute Exacerbation of COPD

Intervention / Treatment
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* Device: Hemolung Respiratory Assist System
* Device: Invasive mechanical ventilation


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age ≥ 40 years Confirmed diagnosis of underlying COPD or ACOS (Asthma-COPD Overlap Syndrome) Experiencing acute hypercapnic respiratory failure Informed consent from patient or legally authorized representative Meets one of the three following criteria: 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* 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. *OR* Currently intubated and receiving Invasive MV, meeting both of the following: Intubated for ≤ 5 days (from intubation to time of consent), AND Has failed a spontaneous breathing trial OR is deemed not suitable for a spontaneous breathing trial (SBT) OR is deemed not suitable for extubation Exclusion Criteria: DNR/DNI order Hemodynamic instability (mean arterial pressure < 60 mmHg) despite infusion of vasoactive drugs Acute coronary syndrome Current presence of severe pulmonary edema due to Congestive Heart Failure PaO2/FiO2 < 120 mmHg on PEEP >/= 5 cmH2O Presence of bleeding diathesis or other contraindication to anticoagulation therapy Platelet count >= 100,000/mm3 not requiring daily transfusions to maintain platelet count above 100,000/mm3 at time of screening Hemoglobin >= 7.0 gm% not requiring daily transfusions to maintain hemoglobin count above 7.0 gm% at time of screening, and no active major bleeding Unable to protect airway (e.g. unable to generate cough or clear secretions) or significant weakness or paralysis of respiratory muscles due to causes unrelated to acute exacerbation of COPD Cerebrovascular accident, intracranial bleed, head injury or other neurological disorder likely to adversely affect ventilation or airway protection. Hypersensitivity to heparin or history of previous heparin-induced thrombocytopenia (HIT Type II) Presence of a significant pneumothorax or bronchopleural fistula Current uncontrolled, major psychiatric disorder Current participation in any other interventional clinical study Pregnant women (women of child bearing potential require a pregnancy test) 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. Fulminant liver failure Known vascular abnormality or condition which could complicate or prevent successful Hemolung Catheter insertion Terminal patients not expected to survive current hospitalization Requiring continuous home ventilation via a tracheostomyy Any disease or condition that, in the judgment of the investigator, either places the subject at undue risk of complications from the Hemolung RAS device, or may reduce the subject's likelihood of benefitting from therapy with the Hemolung RASr

Ages Eligible for Study
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Minimum Age: 40 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Prospective, multi-center, randomized, controlled, two-arm, open-label, adaptive, two-strata, pivotal trial
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Hemolung plus SOC IMV<br>Low-flow ECCO2R with the Hemolung Respiratory Assist System as an alternative or adjunct to standard-of-care (SOC) invasive mechanical ventilation (IMV) | Device: Hemolung Respiratory Assist System<br>* Treatment with a medical device called the Hemolung RAS. The Hemolung RAS includes three components: the Hemolung Controller, the Hemolung Cartridge, and the Hemolung Catheter. The intervention is use of the Hemolung RAS to provide partial lung support for acute hypercapnic lung failure by filtering carbon dioxide from venous blood using a central venous catheter through which venous blood is pumped at flows of 350-550 milliliters per minute to and from an external circuit containing a hollow fiber membrane blood gas exchanger (with heparin-coated fibers) integrated with a centrifugal pump.<br>* Other names: Lung dialysis;Device: Invasive mechanical ventilation<br>* Lung support for acute lung failure applied with a mechanical ventilation device that uses positive pressure to mechanically inflate the lungs and facilitate exhalation via an endotracheal tube or tracheotomy.<br>|
| Active Comparator: SOC IMV<br>Standard-of-care (SOC) invasive mechanical ventilation (IMV) alone | Device: Invasive mechanical ventilation<br>* Lung support for acute lung failure applied with a mechanical ventilation device that uses positive pressure to mechanically inflate the lungs and facilitate exhalation via an endotracheal tube or tracheotomy.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The amount of time in the first five days following randomization that a patient is free of Invasive MV and alive | Statistically analyzed as Ventilator-Free Days during the 5 days from randomization (VFD-5) | 5 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Physiologic benefit | Based on blood gases and concomitant ventilation parameters | Time to extubation from first intubation up to 60 days from randomization | 
| Avoidance of intubation | Incidence of subjects who did not require intubation at any time during their primary hospital admission for the exacerbation for which they were enrolled in the study. | Within 60 days from randomization | 
| Ability to communicate by speaking | Number of days from randomization to end of treatment (end of Invasive MV in Control Arm and end of Hemolung treatment in Investigational Arm) subject is able to communicate by speaking | Randomization to end of treatment or 14 days, whichever is sooner | 
| Ability to eat and drink orally | Number of days from randomization to end of treatment (end of Invasive MV in Control Arm and end of Hemolung treatment in Investigational Arm) subject is able to eat and drink orally | Randomization to end of treatment or 14 days, whichever is sooner | 
| ICU Mobility | Ability of subject to mobilize in bed and out of bed while in Intensive Care as assessed using ICU Mobility Score (IMS) | Randomization to end of treatment or 14 days, whichever is sooner | 
| Daily dose of sedatives, analgesics, and paralytics while in ICU | A qualify of life measure for subjects while in ICU measured by reported concomitant medications while in ICU. | From randomization to ICU discharge up to 60 days from randomization | 
| Incidence of new tracheotomies | Incidence of new tracheotomies | Within 60 days from randomization | 
| Adverse events | All Serious Adverse Events (SAE) from randomization to 60 days and non-serious adverse events from randomization to ICU discharge or 30 days, whichever is sooner (adjudicated by the Clincal Events Committee) | Within 60 days from randomization | 
| All-cause in-hospital mortality | Subject death from any cause while still admitted to hospital for the acute exacerbation for which they were enrolled in the study. | Within 60 days from randomization | 
| All-cause (health-related) mortality at 60 days from randomization | Incidence of health-related deaths at 60 days from randomization, regardless of subject location at time of death. | Within 60 days from randomization | 
| Incidence of failed extubations | Incidence of re-intubation within 48 hours of extubation for original exacerbation | Within 60 days from randomization |