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

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ClinicalTrials.gov Identifier: NCT03255057
Recruitment Status : Recruiting
First Posted : August 21, 2017
Last Update Posted : January 20, 2021
Sponsor:
Information provided by (Responsible Party):
Alung Technologies

Tracking Information
First Submitted Date  ICMJE August 9, 2017
First Posted Date  ICMJE August 21, 2017
Last Update Posted Date January 20, 2021
Actual Study Start Date  ICMJE February 18, 2018
Estimated Primary Completion Date December 2021   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: October 8, 2019)
The amount of time in the first five days following randomization that a patient is free of Invasive MV and alive [ Time Frame: 5 days ]
Statistically analyzed as Ventilator-Free Days during the 5 days from randomization (VFD-5)
Original Primary Outcome Measures  ICMJE
 (submitted: August 16, 2017)
VFD-60 [ Time Frame: 60 days ]
Ventilator-Free Days at Day 60 from randomization
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: October 8, 2019)
  • Physiologic benefit [ Time Frame: Time to extubation from first intubation up to 60 days from randomization ]
    Based on blood gases and concomitant ventilation parameters
  • Avoidance of intubation [ Time Frame: Within 60 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.
  • Ability to communicate by speaking [ Time Frame: Randomization to end of treatment or 14 days, whichever is sooner ]
    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
  • Ability to eat and drink orally [ Time Frame: Randomization to end of treatment or 14 days, whichever is sooner ]
    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
  • ICU Mobility [ Time Frame: Randomization to end of treatment or 14 days, whichever is sooner ]
    Ability of subject to mobilize in bed and out of bed while in Intensive Care as assessed using ICU Mobility Score (IMS)
  • Daily dose of sedatives, analgesics, and paralytics while in ICU [ Time Frame: From randomization to ICU discharge up to 60 days from randomization ]
    A qualify of life measure for subjects while in ICU measured by reported concomitant medications while in ICU.
  • Incidence of new tracheotomies [ Time Frame: Within 60 days from randomization ]
    Incidence of new tracheotomies
  • Adverse events [ Time Frame: Within 60 days from randomization ]
    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)
  • All-cause in-hospital mortality [ Time Frame: Within 60 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.
  • All-cause (health-related) mortality at 60 days from randomization [ Time Frame: Within 60 days from randomization ]
    Incidence of health-related deaths at 60 days from randomization, regardless of subject location at time of death.
  • Incidence of failed extubations [ Time Frame: Within 60 days from randomization ]
    Incidence of re-intubation within 48 hours of extubation for original exacerbation
Original Secondary Outcome Measures  ICMJE
 (submitted: August 16, 2017)
  • 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)
  • Use 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.
Current Other Pre-specified Outcome Measures
 (submitted: October 8, 2019)
  • Time to ICU discharge [ Time Frame: From ICU admission to discharge up to 60 days from randomization ]
    Time from ICU admission to ICU discharge for initial exacerbation for which the subject was enrolled for subjects surviving to discharge
  • Time to hospital discharge [ Time Frame: From hospital admission to discharge up to 60 days from randomization ]
    Time from hospital admission to hospital discharge for initial exacerbation for which the subject was enrolled for subjects surviving to discharge
  • Time on ventilatory support [ Time Frame: Randomization to end of Hemolung an Invasive MV for initial exacerbation up to 60 days from randomization ]
    Total time on Hemolung and/or Invasive MV support for initial exacerbation
  • VFD-30 [ Time Frame: Randomization to Day 30 ]
    Ventilator-free days from randomization to 30 days from randomization
  • SOFA Score [ Time Frame: From randomization to 24 hours after end of investigational treatment (Investigational Arm) or first extubation (Control Arm) up to a maximum of 14 days ]
    Sequential Organ Failure Assessment Score from randomization to 24 hours after end of treatment
  • Dyspnea [ Time Frame: From randomization to 24 hours after end of investigational treatment (Investigational Arm) or first extubation (Control Arm) up to a maximum of 14 days ]
    A quality of life measure for subjects while in ICU measured with a Visual Analog Score
  • ICU Delirium [ Time Frame: From randomization to 24 hours after end of investigational treatment (Investigational Arm) or first extubation (Control Arm) up to a maximum of 14 days ]
    A quality of life measure for subjects while in ICU measured with the Confusion Assessment Measure for ICU (CAM-ICU) score
  • Incidence of DNI/DNR/Comfort care requests post-randomization [ Time Frame: From randomization to 60 days from randomizaiton ]
    Incidence of DNI/DNR/Comfort care requests post-randomization
  • Incidence of hospital readmissions [ Time Frame: From randomization to 60 days from randomizaiton ]
    Number of new hospital admissions after hospital discharge for original exacerbation
Original Other Pre-specified Outcome Measures
 (submitted: August 16, 2017)
  • 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.
  • Ability to wean 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
  • Ability to wean 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 preferences 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.
 
Descriptive Information
Brief Title  ICMJE Extracorporeal CO2 Removal With the Hemolung RAS for Mechanical Ventilation Avoidance During Acute Exacerbation of COPD
Official Title  ICMJE 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
Brief Summary 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 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.
Study Type  ICMJE Interventional
Study Phase  ICMJE Not Applicable
Study Design  ICMJE 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
Condition  ICMJE Acute Exacerbation of COPD
Intervention  ICMJE
  • 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.
Study Arms  ICMJE
  • 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)
    Interventions:
    • Device: Hemolung Respiratory Assist System
    • Device: Invasive mechanical ventilation
  • Active Comparator: SOC IMV
    Standard-of-care (SOC) invasive mechanical ventilation (IMV) alone
    Intervention: Device: Invasive mechanical ventilation
Publications * Burki NK, Mani RK, Herth FJF, Schmidt W, Teschler H, Bonin F, Becker H, Randerath WJ, Stieglitz S, Hagmeyer L, Priegnitz C, Pfeifer M, Blaas SH, Putensen C, Theuerkauf N, Quintel M, Moerer O. A novel extracorporeal CO(2) removal system: results of a pilot study of hypercapnic respiratory failure in patients with COPD. Chest. 2013 Mar;143(3):678-686. doi: 10.1378/chest.12-0228.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: October 8, 2019)
180
Original Estimated Enrollment  ICMJE
 (submitted: August 16, 2017)
500
Estimated Study Completion Date  ICMJE December 2021
Estimated Primary Completion Date December 2021   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  1. Age ≥ 40 years
  2. Confirmed diagnosis of underlying COPD or ACOS (Asthma-COPD Overlap Syndrome)
  3. Experiencing acute hypercapnic respiratory failure
  4. Informed consent from patient or legally authorized representative
  5. Meets one of the three following criteria:

    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.

      *OR*

    3. 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:

  1. DNR/DNI order
  2. Hemodynamic instability (mean arterial pressure < 60 mmHg) despite infusion of vasoactive drugs
  3. Acute coronary syndrome
  4. Current presence of severe pulmonary edema due to Congestive Heart Failure
  5. PaO2/FiO2 < 120 mmHg on PEEP >/= 5 cmH2O
  6. Presence of bleeding diathesis or other contraindication to anticoagulation therapy
  7. Platelet count >= 100,000/mm3 not requiring daily transfusions to maintain platelet count above 100,000/mm3 at time of screening
  8. 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
  9. 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
  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.
  17. Fulminant liver failure
  18. Known vascular abnormality or condition which could complicate or prevent successful Hemolung Catheter insertion
  19. Terminal patients not expected to survive current hospitalization
  20. Requiring continuous home ventilation via a tracheostomyy
  21. 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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 40 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03255057
Other Study ID Numbers  ICMJE HL-CA-5000
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
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
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Alung Technologies
Study Sponsor  ICMJE Alung Technologies
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Nicholas Hill, MD Tufts University Medical Center
PRS Account Alung Technologies
Verification Date January 2021

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP