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

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

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.

Study Overview

• Status: Terminated
• Conditions: Acute Exacerbation of COPD
• Intervention / Treatment: Device: Hemolung Respiratory Assist System; Device: Invasive mechanical ventilation

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: Interventional
• Enrollment (Actual): 113
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • California
    • Sacramento, California, United States, 95817
      • UC Davis Medical Group
  • Colorado
    • Denver, Colorado, United States, 80204
      • Denver Health Medical Center
  • Delaware
    • Newark, Delaware, United States, 19718
      • Christiana Care Health System
  • Florida
    • Gainesville, Florida, United States, 32610
      • University of Florida - Health Shands
    • Jacksonville, Florida, United States, 32224
      • Mayo Clinic Jacksonville
  • Georgia
    • Marietta, Georgia, United States, 30060
      • WellStar Kennestone Regional Medical Center
  • Illinois
    • Chicago, Illinois, United States, 60611
      • Northwestern Memorial Hospital
  • Iowa
    • Iowa City, Iowa, United States, 52242
      • University of Iowa
  • Kentucky
    • Lexington, Kentucky, United States, 40502
      • Lexington VA Healthcare
    • Louisville, Kentucky, United States, 40202
      • University of Louisville
  • Louisiana
    • Shreveport, Louisiana, United States, 71103
      • LSU Health Shreveport
  • Massachusetts
    • Boston, Massachusetts, United States, 02111
      • Tufts Medical Center
  • Michigan
    • Grand Rapids, Michigan, United States, 49504
      • Spectrum Health Hospitals
  • Minnesota
    • Minneapolis, Minnesota, United States, 55407
      • Minneapolis Heart
  • New Jersey
    • New Brunswick, New Jersey, United States, 08902
      • Rutgers-Robert Wood Johnson University Hospital
  • New York
    • Albany, New York, United States, 12208-3412
      • Albany Medical Center
    • New Hyde Park, New York, United States, 11040
      • Northwell Health
    • New York, New York, United States, 10032
      • New York Presbyterian Hospital/Columbia University Medical Center
  • North Carolina
    • Durham, North Carolina, United States, 27710
      • Duke University Medical Center
  • Ohio
    • Cleveland, Ohio, United States, 44195
      • Cleveland Clinic
    • Columbus, Ohio, United States, 43210
      • Ohio State University
  • Pennsylvania
    • Allentown, Pennsylvania, United States, 18103
      • Lehigh Valley Health Network
    • Philadelphia, Pennsylvania, United States, 19140
      • Temple University
    • Philadelphia, Pennsylvania, United States, 19104
      • Hospital of University of Pennsylvania
    • Pittsburgh, Pennsylvania, United States, 15212
      • Allegheny General Hospital
  • Rhode Island
    • Providence, Rhode Island, United States, 02903
      • Rhode Island Hospital
  • Tennessee
    • Chattanooga, Tennessee, United States, 37403
      • UT Erlanger
    • Memphis, Tennessee, United States, 38104
      • Memphis VA Medical Center
  • Texas
    • Houston, Texas, United States, 77030
      • UT McGovern Medical School Memorial Hermann
    • Temple, Texas, United States, 76508
      • Baylor Scott and White Memorial Hospital
  • Virginia
    • Charlottesville, Virginia, United States, 22903
      • University of Virginia Medical Center
    • Falls Church, Virginia, United States, 22042
      • Inova Health Care Services

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 38 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
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.

What is the study measuring?

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
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
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
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

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time to ICU discharge	Time from ICU admission to ICU discharge for initial exacerbation for which the subject was enrolled for subjects surviving to discharge	From ICU admission to discharge up to 60 days from randomization
Time to hospital discharge	Time from hospital admission to hospital discharge for initial exacerbation for which the subject was enrolled for subjects surviving to discharge	From hospital admission to discharge up to 60 days from randomization
Time on ventilatory support	Total time on Hemolung and/or Invasive MV support for initial exacerbation	Randomization to end of Hemolung an Invasive MV for initial exacerbation up to 60 days from randomization
VFD-30	Ventilator-free days from randomization to 30 days from randomization	Randomization to Day 30
SOFA Score	Sequential Organ Failure Assessment Score from randomization to 24 hours after end of treatment	From randomization to 24 hours after end of investigational treatment (Investigational Arm) or first extubation (Control Arm) up to a maximum of 14 days
Dyspnea	A quality of life measure for subjects while in ICU measured with a Visual Analog Score	From randomization to 24 hours after end of investigational treatment (Investigational Arm) or first extubation (Control Arm) up to a maximum of 14 days
ICU Delirium	A quality of life measure for subjects while in ICU measured with the Confusion Assessment Measure for ICU (CAM-ICU) score	From randomization to 24 hours after end of investigational treatment (Investigational Arm) or first extubation (Control Arm) up to a maximum of 14 days
Incidence of DNI/DNR/Comfort care requests post-randomization	Incidence of DNI/DNR/Comfort care requests post-randomization	From randomization to 60 days from randomizaiton
Incidence of hospital readmissions	Number of new hospital admissions after hospital discharge for original exacerbation	From randomization to 60 days from randomizaiton

Collaborators and Investigators

• Sponsor: Alung Technologies
• Investigators: Principal Investigator: Nicholas Hill, MD, Tufts University Medical Center

Publications and helpful links

General 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.
• Stokes JW, Gannon WD, Rice TW. Extracorporeal Carbon Dioxide Removal or Extracorporeal Membrane Oxygenation: Why Should We Care? Crit Care Med. 2021 May 1;49(5):e546-e547. doi: 10.1097/CCM.0000000000004844. No abstract available.

Study record dates

Study Major Dates

• Study Start (Actual): February 18, 2018
• Primary Completion (Actual): August 10, 2022
• Study Completion (Actual): August 17, 2022

Study Registration Dates

• First Submitted: August 9, 2017
• First Submitted That Met QC Criteria: August 16, 2017
• First Posted (Actual): August 21, 2017

Study Record Updates

• Last Update Posted (Actual): October 14, 2022
• Last Update Submitted That Met QC Criteria: October 13, 2022
• Last Verified: October 1, 2022

More Information

Terms related to this study

• Other Study ID Numbers: HL-CA-5000

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: Yes