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

• ClinicalTrials.gov Identifier: NCT03255057
• Recruitment Status: Terminated
• First Posted: August 21, 2017
• Last Update Posted: October 14, 2022
• Sponsor: Alung Technologies
• Information provided by (Responsible Party): Alung Technologies

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Acute Exacerbation of COPD	Device: Hemolung Respiratory Assist System; Device: Invasive mechanical ventilation	Not Applicable

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 Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 113 participants
• 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
• Actual Study Start Date: February 18, 2018
• Actual Primary Completion Date: August 10, 2022
• Actual Study Completion Date: August 17, 2022

Arms and Interventions

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.

Outcome Measures

Primary Outcome Measures :

1. 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)

Secondary Outcome Measures :

1. Physiologic benefit [ Time Frame: Time to extubation from first intubation up to 60 days from randomization ]
   Based on blood gases and concomitant ventilation parameters
2. 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.
3. 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
4. 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
5. 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)
6. 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.
7. Incidence of new tracheotomies [ Time Frame: Within 60 days from randomization ]
   Incidence of new tracheotomies
8. 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)
9. 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.
10. 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.
11. Incidence of failed extubations [ Time Frame: Within 60 days from randomization ]
    Incidence of re-intubation within 48 hours of extubation for original exacerbation

Other Outcome Measures:

1. 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
2. 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
3. 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
4. VFD-30 [ Time Frame: Randomization to Day 30 ]
   Ventilator-free days from randomization to 30 days from randomization
5. 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
6. 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
7. 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
8. 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
9. Incidence of hospital readmissions [ Time Frame: From randomization to 60 days from randomizaiton ]
   Number of new hospital admissions after hospital discharge for original exacerbation

Eligibility Criteria

• Ages Eligible for Study: 40 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

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

Contacts and Locations

Locations

United States, California

UC Davis Medical Group

Sacramento, California, United States, 95817

United States, Colorado

Denver Health Medical Center

Denver, Colorado, United States, 80204

United States, Delaware

Christiana Care Health System

Newark, Delaware, United States, 19718

United States, Florida

University of Florida - Health Shands

Gainesville, Florida, United States, 32610

Mayo Clinic Jacksonville

Jacksonville, Florida, United States, 32224

United States, Georgia

WellStar Kennestone Regional Medical Center

Marietta, Georgia, United States, 30060

United States, Illinois

Northwestern Memorial Hospital

Chicago, Illinois, United States, 60611

United States, Iowa

University of Iowa

Iowa City, Iowa, United States, 52242

United States, Kentucky

Lexington VA Healthcare

Lexington, Kentucky, United States, 40502

University of Louisville

Louisville, Kentucky, United States, 40202

United States, Louisiana

LSU Health Shreveport

Shreveport, Louisiana, United States, 71103

United States, Massachusetts

Tufts Medical Center

Boston, Massachusetts, United States, 02111

United States, Michigan

Spectrum Health Hospitals

Grand Rapids, Michigan, United States, 49504

United States, Minnesota

Minneapolis Heart

Minneapolis, Minnesota, United States, 55407

United States, New Jersey

Rutgers-Robert Wood Johnson University Hospital

New Brunswick, New Jersey, United States, 08902

United States, New York

Albany Medical Center

Albany, New York, United States, 12208-3412

Northwell Health

New Hyde Park, New York, United States, 11040

New York Presbyterian Hospital/Columbia University Medical Center

New York, New York, United States, 10032

United States, North Carolina

Duke University Medical Center

Durham, North Carolina, United States, 27710

United States, Ohio

Cleveland Clinic

Cleveland, Ohio, United States, 44195

Ohio State University

Columbus, Ohio, United States, 43210

United States, Pennsylvania

Lehigh Valley Health Network

Allentown, Pennsylvania, United States, 18103

Hospital of University of Pennsylvania

Philadelphia, Pennsylvania, United States, 19104

Temple University

Philadelphia, Pennsylvania, United States, 19140

Allegheny General Hospital

Pittsburgh, Pennsylvania, United States, 15212

United States, Rhode Island

Rhode Island Hospital

Providence, Rhode Island, United States, 02903

United States, Tennessee

UT Erlanger

Chattanooga, Tennessee, United States, 37403

Memphis VA Medical Center

Memphis, Tennessee, United States, 38104

United States, Texas

UT McGovern Medical School Memorial Hermann

Houston, Texas, United States, 77030

Baylor Scott and White Memorial Hospital

Temple, Texas, United States, 76508

United States, Virginia

University of Virginia Medical Center

Charlottesville, Virginia, United States, 22903

Inova Health Care Services

Falls Church, Virginia, United States, 22042

Sponsors and Collaborators

Alung Technologies

Investigators

• Principal Investigator: Nicholas Hill, MD; Tufts University Medical Center

More Information

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.

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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.

• Responsible Party: Alung Technologies
• ClinicalTrials.gov Identifier: NCT03255057
• Other Study ID Numbers: HL-CA-5000
• First Posted: August 21, 2017
• Last Update Posted: October 14, 2022
• Last Verified: October 2022

• 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