Clinical trial NCT03255057: Extracorporeal CO2 Removal With the Hemolung RAS for Mechanical Ventilation Avoidance During Acute Exacerbation of COPD
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
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: NA
Conditions: Acute Exacerbation of COPD
Lead sponsor: Alung Technologies
Sponsor class: INDUSTRY
First posted: 2017-08-21
Enrollment: 113
Sex: ALL
Minimum age (years): 40
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Prospective, multi-center, randomized, controlled, two-arm, open-label, adaptive, two-strata, pivotal trial
Primary purpose: TREATMENT

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.

Eligibility 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

Primary outcomes:
measure: The amount of time in the first five days following randomization that a patient is free of Invasive MV and alive
timeFrame: 5 days
Secondary outcomes:
measure: Physiologic benefit
timeFrame: Time to extubation from first intubation up to 60 days from randomization
measure: Avoidance of intubation
timeFrame: Within 60 days from randomization
measure: Ability to communicate by speaking
timeFrame: Randomization to end of treatment or 14 days, whichever is sooner
measure: Ability to eat and drink orally
timeFrame: Randomization to end of treatment or 14 days, whichever is sooner
measure: ICU Mobility
timeFrame: Randomization to end of treatment or 14 days, whichever is sooner
measure: Daily dose of sedatives, analgesics, and paralytics while in ICU
timeFrame: From randomization to ICU discharge up to 60 days from randomization
measure: Incidence of new tracheotomies
timeFrame: Within 60 days from randomization
measure: Adverse events
timeFrame: Within 60 days from randomization
measure: All-cause in-hospital mortality
timeFrame: Within 60 days from randomization
measure: All-cause (health-related) mortality at 60 days from randomization
timeFrame: Within 60 days from randomization
measure: Incidence of failed extubations
timeFrame: Within 60 days from randomization
Other outcomes:
measure: Time to ICU discharge
timeFrame: From ICU admission to discharge up to 60 days from randomization
measure: Time to hospital discharge
timeFrame: From hospital admission to discharge up to 60 days from randomization
measure: Time on ventilatory support
timeFrame: Randomization to end of Hemolung an Invasive MV for initial exacerbation up to 60 days from randomization
measure: VFD-30
timeFrame: Randomization to Day 30
measure: SOFA Score
timeFrame: From randomization to 24 hours after end of investigational treatment (Investigational Arm) or first extubation (Control Arm) up to a maximum of 14 days
measure: Dyspnea
timeFrame: From randomization to 24 hours after end of investigational treatment (Investigational Arm) or first extubation (Control Arm) up to a maximum of 14 days
measure: ICU Delirium
timeFrame: From randomization to 24 hours after end of investigational treatment (Investigational Arm) or first extubation (Control Arm) up to a maximum of 14 days
measure: Incidence of DNI/DNR/Comfort care requests post-randomization
timeFrame: From randomization to 60 days from randomizaiton
measure: Incidence of hospital readmissions
timeFrame: From randomization to 60 days from randomizaiton
Locations:
city: Sacramento
country: United States
facility: UC Davis Medical Group
state: California
city: Denver
country: United States
facility: Denver Health Medical Center
state: Colorado
city: Newark
country: United States
facility: Christiana Care Health System
state: Delaware
city: Gainesville
country: United States
facility: University of Florida - Health Shands
state: Florida
city: Jacksonville
country: United States
facility: Mayo Clinic Jacksonville
state: Florida
city: Marietta
country: United States
facility: WellStar Kennestone Regional Medical Center
state: Georgia
city: Chicago
country: United States
facility: Northwestern Memorial Hospital
state: Illinois
city: Iowa City
country: United States
facility: University of Iowa
state: Iowa
city: Lexington
country: United States
facility: Lexington VA Healthcare
state: Kentucky
city: Louisville
country: United States
facility: University of Louisville
state: Kentucky
city: Shreveport
country: United States
facility: LSU Health Shreveport
state: Louisiana
city: Boston
country: United States
facility: Tufts Medical Center
state: Massachusetts
city: Grand Rapids
country: United States
facility: Spectrum Health Hospitals
state: Michigan
city: Minneapolis
country: United States
facility: Minneapolis Heart
state: Minnesota
city: New Brunswick
country: United States
facility: Rutgers-Robert Wood Johnson University Hospital
state: New Jersey
city: Albany
country: United States
facility: Albany Medical Center
state: New York
city: New Hyde Park
country: United States
facility: Northwell Health
state: New York
city: New York
country: United States
facility: New York Presbyterian Hospital/Columbia University Medical Center
state: New York
city: Durham
country: United States
facility: Duke University Medical Center
state: North Carolina
city: Cleveland
country: United States
facility: Cleveland Clinic
state: Ohio
city: Columbus
country: United States
facility: Ohio State University
state: Ohio
city: Allentown
country: United States
facility: Lehigh Valley Health Network
state: Pennsylvania
city: Philadelphia
country: United States
facility: Hospital of University of Pennsylvania
state: Pennsylvania
city: Philadelphia
country: United States
facility: Temple University
state: Pennsylvania
city: Pittsburgh
country: United States
facility: Allegheny General Hospital
state: Pennsylvania
city: Providence
country: United States
facility: Rhode Island Hospital
state: Rhode Island
city: Chattanooga
country: United States
facility: UT Erlanger
state: Tennessee
city: Memphis
country: United States
facility: Memphis VA Medical Center
state: Tennessee
city: Houston
country: United States
facility: UT McGovern Medical School Memorial Hermann
state: Texas
city: Temple
country: United States
facility: Baylor Scott and White Memorial Hospital
state: Texas
city: Charlottesville
country: United States
facility: University of Virginia Medical Center
state: Virginia
city: Falls Church
country: United States
facility: Inova Health Care Services
state: Virginia
Study officials:
affiliation: Tufts University Medical Center
name: Nicholas Hill, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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.