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Extracorporeal CO2 Removal With the Hemolung RAS for Mechanical Ventilation Avoidance During Acute Exacerbation of COPD (VENT-AVOID)

This study is not yet open for participant recruitment.
Verified October 2017 by Alung Technologies
Sponsor:
ClinicalTrials.gov Identifier:
NCT03255057
First Posted: August 21, 2017
Last Update Posted: October 24, 2017
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
Information provided by (Responsible Party):
Alung Technologies
  Purpose
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.

Condition Intervention
Acute Exacerbation of COPD Device: Hemolung Respiratory Assist System Device: Invasive mechanical ventilation

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description:
Prospective, multi-center, randomized, controlled, two-arm, open-label, adaptive, two-strata, pivotal trial
Masking: Single (Outcomes Assessor)
Masking Description:
Due to the nature of the interventional device and treatment, the study participants, care providers, and investigators will not be masked. However, an independent Clinical Endpoint Committee will be masked for adjudication of the primary endpoint and serious adverse events. An independent Data and Safety Monitoring Board will make study continuation recommendations based on the statistical analysis plan and the overall safety and efficacy endpoints without masking.
Primary Purpose: Treatment
Official Title: 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

Further study details as provided by Alung Technologies:

Primary Outcome Measures:
  • VFD-60 [ Time Frame: 60 days ]
    Ventilator-Free Days at Day 60 from randomization


Secondary Outcome Measures:
  • All-cause in-hospital mortality [ Time Frame: Within 90 days from randomization ]
    Subject death from any cause while still admitted to hospital for the acute exacerbation for which they were enrolled in the study.

  • Total and individual incidence of pre-identified critical care safety endpoints (representing primary complication risks of the investigational treatment, the active control treatment, and the severity of illness) [ Time Frame: Within 90 days from randomization ]
    The complication risks of the investigational therapy are different in nature to the complication risks of the active control therapy and are, therefore, difficult to compare. The Critical Safety Events are a set of key complication risks that will be used to compare the overall safety profile of the investigational treatment compared to standard of care. These include: 1) Severe cardiac events, 2) Disabling stroke or neurologic event, 3) Ventilator associated events, 4) Sepsis, 5) Multiple organ failure, 6) Pulmonary thromboembolism, 7) Pneumothorax, pneumomediastinum, or pneumoperitoneum, 8) Major hemorrhage/bleeding, 9) Disseminated intravascular coagulation, 10) Infection caused by catheter, endotracheal tube, or tracheostomy, 11) Vascular injury or obstruction caused by cannulation, 12) Tracheostomy, 13) Airway injury caused by intubation/tracheotomy, 14) Hemolysis

  • All Serious Adverse Events [ Time Frame: Within 90 days from randomization ]
    All Serious Adverse Events (SAE) adjudicated by the Clinical Endpoints Committee (CEC)

  • Incidence of failed extubations [ Time Frame: Within 90 days from randomization ]
    Failed extubations are defined is re-intubation within 72 hours of extubation.

  • Inability to wean from invasive MV at 90 days from randomization [ Time Frame: Within 90 days from randomization ]
    Incidence of patients becoming ventilator dependent, defined as those receiving uninterrupted ventilatory support at Day 90 from randomization through either an endotracheal tube or tracheotomy (if subjects are extubated for less than 72 hours, that time will not be counted as time weaned).

  • All-cause (health-related) mortality at 90 days from randomization [ Time Frame: Within 90 days from randomization ]
    Incidence of health-related deaths at 90 days from randomization, regardless of subject location at time of death.

  • Avoidance of intubation [ Time Frame: Within 90 days from randomization ]
    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.

  • Time on invasive MV [ Time Frame: Time to extubation from first intubation up to 90 days from randomization ]
    Total time receiving positive pressure mechanical ventilation through either an endotracheal tube or tracheotomy.

  • Incidence of Ventilator-Associated Events [ Time Frame: Within 90 days from randomization ]
    Incidence of ventilator-associated events (VAE) as defined by the Center for Disease Control (CDC).

  • Number of days in ICU [ Time Frame: Time to ICU discharge up to 90 days from randomization ]
    Time in ICU for initial exacerbation for which the subject was enrolled in the study (subjects readmitted to ICU within 72 hours of discharge will not be considered as discharged).

  • Number of days to hospital discharge (to baseline environment) [ Time Frame: Time to hospital discharge up to 90 days from randomization ]
    Number of days to hospital discharge for the admission of the acute exacerbation for which the subject was enrolled in the study. Subjects discharged to a long-term care facility will not be counted as discharged unless the subject was already in such a facility prior to being admitted for the acute exacerbation for which the subject was enrolled in the study.

  • Time in ICU that subject is able to eat, drink, and speak orally [ Time Frame: Time to ICU discharge up to 90 days from randomization ]
    Quality of Life Measure while in ICU

  • Device performance: CO2 removal rate greater than 50 mL/min (at sweep gas flows > 8 L/min) [ Time Frame: During investigational device treatment from randomization to a maximum of 14 days ]
    A measure of the ability of the Hemolung device to perform its intended function

  • Device performance: Blood flow ≥ 350 mL/min [ Time Frame: During investigational device treatment from randomization to a maximum of 14 days ]
    A measure of the ability of the Hemolung device to operate as intended.

  • Device performance: Demonstrated decrease in PaCO2 in patients on noninvasive ventilation [ Time Frame: During investigational device treatment from randomization to a maximum of 14 days ]
    A measure of the ability of low-flow ECCO2R with the Hemolung to have a physiologic impact of removing basal metabolic carbon dioxide demonstrated by a reduction in the partial pressure of carbon dioxide in arterial blood (PaCO2) over time in patients with acute hypercapnia due to failure of noninvasive ventilation (NIV).

  • Dyspnea in ICU [ Time Frame: During investigational device treatment from randomization to a maximum of 14 days ]
    A quality of life measure for subjects while in ICU measured with a Visual Analog Score

  • ICU mobility [ Time Frame: During investigational device treatment from randomization to a maximum of 14 days ]
    A quality of life measure for subjects while in ICU measured with the ICU mobility score.

  • ICU delirium [ Time Frame: From randomization to ICU discharge up to 90 days from randomization ]
    A quality of life measure for subjects while in ICU measured with the Confusion Assessment Measure for ICU (CAM-ICU) score.

  • ICU-Acquired Weakness [ Time Frame: From randomization to ICU discharge up to 90 days from randomization ]
    A quality of life measure for subjects while in ICU measured with the Medical Research Council Sum Score (MRC-SS)

  • Daily dose of sedatives, analgesics, and paralytics while in ICU [ Time Frame: From randomization to ICU discharge up to 90 days from randomization ]
    A qualify of life measure for subjects while in ICU measured by reported concomitant medications while in ICU.


Other Outcome Measures:
  • Changes to ventilator plateau pressure while on Hemolung RAS [ Time Frame: During investigational device treatment from randomization to a maximum of 14 days ]
    This is an exploratory endpoint to measure the impact of ECCO2R on the ability to reduce the plateau pressure used by the mechanical ventilator.

  • Changes to ventilator respiratory rate while on Hemolung RAS [ Time Frame: During investigational device treatment from randomization to a maximum of 14 days ]
    This is an exploratory endpoint to measure the impact of ECCO2R on the ability to reduce the forced respiratory rate of the mechanical ventilator.

  • Changes to ventilator tidal volume while on Hemolung RAS [ Time Frame: During investigational device treatment from randomization to a maximum of 14 days ]
    This is an exploratory endpoint to measure the impact of ECCO2R on the ability to reduce the tidal volume of the mechanical ventilator.

  • Changes to ventilator driving pressure while on Hemolung RAS [ Time Frame: During investigational device treatment from randomization to a maximum of 14 days ]
    This is an exploratory endpoint to measure the impact of ECCO2R on the ability to reduce the driving pressure (plateau pressure minus positive end expiratory pressure) of the mechanical ventilator.

  • Anticoagulation trends (ACT or aPTT) with impact on bleeding complications and thrombosis-related events [ Time Frame: During investigational device treatment from randomization to a maximum of 14 days ]
    An exploratory endpoint to capture real-world anticoagulation trends and their correlation to adverse events of bleeding or thrombosis.

  • Incidence of readmission after discharge [ Time Frame: Within 90 days from randomization ]
    A measure of new acute exacerbations requiring hospital admission within 90 days of the admission for the acute exacerbation for which the subject was enrolled in the study.

  • Incidence of new intubation for invasive MV [ Time Frame: Within 90 days from randomization ]
    A measure of new acute exacerbations requiring hospital admission and invasive mechanical ventilation within 90 days of the admission for the acute exacerbation for which the subject was enrolled in the study.

  • Incidence of weaning pre-Hemolung pulmonary support (NIV or MV) while on Hemolung support [ Time Frame: Within 14 days from randomization ]
    Ability to wean pre-Hemolung pulmonary support (NIV or MV) while on Hemolung support

  • Incidence of weaning from Hemolung support within 14 days [ Time Frame: Within 14 days from randomization ]
    Ability to durably wean from Hemolung support (i.e. no reinstitution of NIV or MV after Hemolung is weaned)

  • Patient preference questionnaire collected at discharge or 90-day follow-up [ Time Frame: Within 90 days from randomization ]
    An exploratory endpoint of patient preferences regarding their ICU experience at the time of ICU discharge.


Estimated Enrollment: 500
Anticipated Study Start Date: December 2017
Estimated Study Completion Date: December 2020
Estimated Primary Completion Date: December 2019 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Hemolung plus SOC IMV
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
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.
Other Names:
  • Low-flow extracorporeal carbon dioxide removal
  • ECCO2R
  • Hemolung RAS
  • Hemolung
  • Respiratory dialysis
  • Lung dialysis
Device: Invasive mechanical ventilation
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.
Active Comparator: SOC IMV
Standard-of-care (SOC) invasive mechanical ventilation (IMV) alone
Device: Invasive mechanical ventilation
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.

Detailed Description:
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.
  Eligibility

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Ages Eligible for Study:   22 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Age ≥ 22 years
  • Confirmed diagnosis of underlying COPD (based on prior spirometry or approved screening procedure )
  • Diagnosed as experiencing an acute exacerbation of COPD
  • Subject has been receiving standard of care treatment for an acute exacerbation of COPD, including treatment with bronchodilators, corticosteroids, antibiotics, and controlled oxygen therapy.
  • Able to generate adequate cough and control of secretions
  • Minimum platelet count of 100,000/mm3 (and not requiring daily transfusions to maintain platelet count above 100,000/mm3 at time of screening)
  • 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)
  • Informed consent from patient or legally authorized representative
  • 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:

  • DNR) order
  • Presence of acute, uncontrolled arrhythmia
  • Hemodynamic instability (mean arterial pressure < 60 mmHg) despite infusion of vasoactive drugs
  • Acute coronary syndrome
  • Acute exacerbation is due primarily to congestive heart failure
  • Diagnosis of obesity hypoventilation syndrome
  • Severely hypoxemic, potentially indicating ARDS or severe pneumonia: PaO2/FiO2 < 150 mmHg on PEEP > 5 cmH2O
  • Was extubated within the previous 48 hours following intubation and invasive MV due to any cause (i.e. a failed extubation)
  • Presence of bleeding diathesis or other contraindication to anticoagulation therapy
  • Significant weakness or paralysis of respiratory muscles due to causes unrelated to acute exacerbation of COPD
  • Recent (< 7 days) prolonged (> 24 hrs) use of muscle paralyzing agents
  • Cerebrovascular accident, intracranial bleed, head injury or other neurologic disorder likely to affect ventilation
  • Hypersensitivity to heparin or history of previous heparin-induced thrombocytopenia (HIT Type II)
  • Presence of a significant pneumothorax or bronchopleural fistula
  • History of uncontrolled, major psychiatric disorder
  • Current participation in any other interventional clinical study
  • Pregnant women (women of child bearing potential require a pregnancy test)
  • Known to have AIDS defined illness
  • Received chemotherapy or radiation within the previous 45 days and still under treatment for the underlying cancer
  • Received or currently receiving immunosuppressive therapy, excluding corticosteroids, within the last 3 months
  • Presence of severe (acute or chronic) renal failure defined as requiring any form of dialysis (including CRRT and CVVH) and/or having a serum creatinine > 2.5 mg/dL and urine clearance < 20 mL/hr
  • Severe liver insufficiency (Child-Pugh scores >7) or INR > 1.6 suspected to be related to liver disease (liver associated coagulopathy)
  • Diagnosis of acute pulmonary embolism during current ICU admission
  • Known vascular abnormality or unavailable vascular access which could complicate or prevent successful Hemolung Catheter insertion
  • Inability to have an arterial catheter placed for blood gas sampling and blood pressure monitoring
  • Terminal patients not expected to survive current hospitalization
  • Presence or history of clinically significant disease or other foreseeable risk that outweighs the potential
  Contacts and Locations
Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03255057


Sponsors and Collaborators
Alung Technologies
Investigators
Principal Investigator: Nicholas Hill, MD Tufts University Medical Center
  More Information

Publications:
Responsible Party: Alung Technologies
ClinicalTrials.gov Identifier: NCT03255057     History of Changes
Other Study ID Numbers: HL-CA-5000
First Submitted: August 9, 2017
First Posted: August 21, 2017
Last Update Posted: October 24, 2017
Last Verified: October 2017

Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: Yes
Device Product Not Approved or Cleared by U.S. FDA: Yes
Pediatric Postmarket Surveillance of a Device Product: No