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

Not Applicable

Terminated

• Conditions: Acute Exacerbation of COPD
• Interventions: Device: Hemolung Respiratory Assist System; Device: Invasive mechanical ventilation

• Registration Number: NCT03255057
• Lead Sponsor: Alung Technologies

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 Timeline

• Study First Submitted: 2017-08-09
• Study First Submitted QC: 2017-08-16
• Study First Posted: 2017-08-21
• Study Start: 2018-02-18
• Primary Completion: 2022-08-10
• Study Completion: 2022-08-17
• Status Verified: 2022-10
• Last Update Submitted: 2022-10-13
• Last Update Posted: 2022-10-14

Recruitment & Eligibility

• Status: TERMINATED
• Sex: All
• Target Recruitment: 113

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Hemolung plus SOC IMV	Hemolung Respiratory Assist System	Low-flow ECCO2R with the Hemolung Respiratory Assist System as an alternative or adjunct to standard-of-care (SOC) invasive mechanical ventilation (IMV)
Hemolung plus SOC IMV	Invasive mechanical ventilation	Low-flow ECCO2R with the Hemolung Respiratory Assist System as an alternative or adjunct to standard-of-care (SOC) invasive mechanical ventilation (IMV)
SOC IMV	Invasive mechanical ventilation	Standard-of-care (SOC) invasive mechanical ventilation (IMV) alone

Primary Outcome Measures

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

Secondary Outcome Measures

Name	Time	Method
Physiologic benefit	Time to extubation from first intubation up to 60 days from randomization	Based on blood gases and concomitant ventilation parameters
Daily dose of sedatives, analgesics, and paralytics while in ICU	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.
All-cause (health-related) mortality at 60 days from randomization	Within 60 days from randomization	Incidence of health-related deaths at 60 days from randomization, regardless of subject location at time of death.
Avoidance of intubation	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	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
Adverse events	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)
Ability to eat and drink orally	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	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)
Incidence of new tracheotomies	Within 60 days from randomization	Incidence of new tracheotomies
All-cause in-hospital mortality	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.
Incidence of failed extubations	Within 60 days from randomization	Incidence of re-intubation within 48 hours of extubation for original exacerbation

Trial Locations

Locations (32)

Rutgers-Robert Wood Johnson University Hospital; 🇺🇸 New Brunswick, New Jersey, United States

Northwestern Memorial Hospital; 🇺🇸 Chicago, Illinois, United States

Cleveland Clinic; 🇺🇸 Cleveland, Ohio, United States

Christiana Care Health System; 🇺🇸 Newark, Delaware, United States

Mayo Clinic Jacksonville; 🇺🇸 Jacksonville, Florida, United States

WellStar Kennestone Regional Medical Center; 🇺🇸 Marietta, Georgia, United States

University of Iowa; 🇺🇸 Iowa City, Iowa, United States

LSU Health Shreveport; 🇺🇸 Shreveport, Louisiana, United States

Tufts Medical Center; 🇺🇸 Boston, Massachusetts, United States

Spectrum Health Hospitals; 🇺🇸 Grand Rapids, Michigan, United States

Albany Medical Center; 🇺🇸 Albany, New York, United States

Northwell Health; 🇺🇸 New Hyde Park, New York, United States

New York Presbyterian Hospital/Columbia University Medical Center; 🇺🇸 New York, New York, United States

Ohio State University; 🇺🇸 Columbus, Ohio, United States

Lehigh Valley Health Network; 🇺🇸 Allentown, Pennsylvania, United States

Hospital of University of Pennsylvania; 🇺🇸 Philadelphia, Pennsylvania, United States

Temple University; 🇺🇸 Philadelphia, Pennsylvania, United States

Memphis VA Medical Center; 🇺🇸 Memphis, Tennessee, United States

UT Erlanger; 🇺🇸 Chattanooga, Tennessee, United States

Allegheny General Hospital; 🇺🇸 Pittsburgh, Pennsylvania, United States

Baylor Scott and White Memorial Hospital; 🇺🇸 Temple, Texas, United States

University of Virginia Medical Center; 🇺🇸 Charlottesville, Virginia, United States

Inova Health Care Services; 🇺🇸 Falls Church, Virginia, United States

Minneapolis Heart; 🇺🇸 Minneapolis, Minnesota, United States

Duke University Medical Center; 🇺🇸 Durham, North Carolina, United States

UT McGovern Medical School Memorial Hermann; 🇺🇸 Houston, Texas, United States

Denver Health Medical Center; 🇺🇸 Denver, Colorado, United States

UC Davis Medical Group; 🇺🇸 Sacramento, California, United States

University of Florida - Health Shands; 🇺🇸 Gainesville, Florida, United States

Lexington VA Healthcare; 🇺🇸 Lexington, Kentucky, United States

University of Louisville; 🇺🇸 Louisville, Kentucky, United States

Rhode Island Hospital; 🇺🇸 Providence, Rhode Island, United States