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

• Sponsor: Alung Technologies (Industry)
• Overall Status: Recruiting
• CT.gov ID: NCT03255057
• Collaborator: (none)
• Enrollment: 180
• Locations: 40
• Arms: 2
• Anticipated Duration (Months): 45.4
• Patients Per Site: 4.5
• Patients Per Site Per Month: 0.1

Study Details

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	N/A

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
• Anticipated Enrollment: 180 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Intervention Model Description: Prospective, multi-center, randomized, controlled, two-arm, open-label, adaptive, two-strata, pivotal trialProspective, 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: Feb 18, 2018
• Anticipated Primary Completion Date: Dec 1, 2021
• Anticipated Study Completion Date: Dec 1, 2021

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 [5 days]

   Statistically analyzed as Ventilator-Free Days during the 5 days from randomization (VFD-5)

Secondary Outcome Measures

1. Physiologic benefit [Time to extubation from first intubation up to 60 days from randomization]

   Based on blood gases and concomitant ventilation parameters

2. 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.

3. 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

4. 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

5. 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)

6. 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.

7. Incidence of new tracheotomies [Within 60 days from randomization]

   Incidence of new tracheotomies

8. 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)

9. 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.

10. 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.

11. Incidence of failed extubations [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 [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 [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 [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 [Randomization to Day 30]

   Ventilator-free days from randomization to 30 days from randomization

5. SOFA 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]

   Sequential Organ Failure Assessment Score from randomization to 24 hours after end of treatment

6. Dyspnea [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 [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 [From randomization to 60 days from randomizaiton]

   Incidence of DNI/DNR/Comfort care requests post-randomization

9. Incidence of hospital readmissions [From randomization to 60 days from randomizaiton]

   Number of new hospital admissions after hospital discharge for original exacerbation

Eligibility Criteria

Criteria

• Ages Eligible for Study: 40 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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:

6. 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

1. 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

1. 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

	Site	City	State	Country	Postal Code
1	UC Davis Medical Group	Sacramento	California	United States	95817
2	Denver Health Medical Center	Denver	Colorado	United States	80204
3	Christiana Care Health System	Newark	Delaware	United States	19718
4	University of Florida - Health Shands	Gainesville	Florida	United States	32610
5	Memorial Regional Hospital	Hollywood	Florida	United States	33021
6	Mayo Clinic Jacksonville	Jacksonville	Florida	United States	32224
7	Emory University Hospital	Atlanta	Georgia	United States	30322
8	Atlanta VA Medical Center	Decatur	Georgia	United States	30033
9	WellStar Kennestone Regional Medical Center	Marietta	Georgia	United States	30060
10	Northwestern Memorial Hospital	Chicago	Illinois	United States	60611
11	Rush Presbyterian St. Lukes	Chicago	Illinois	United States	60612
12	Indiana University Methodist Hospita	Indianapolis	Indiana	United States	46202
13	University of Iowa	Iowa City	Iowa	United States	52242
14	Lexington VA Healthcare	Lexington	Kentucky	United States	40502
15	University of Louisville	Louisville	Kentucky	United States	40202
16	LSU Health Shreveport	Shreveport	Louisiana	United States	71103
17	Tufts Medical Center	Boston	Massachusetts	United States	02111
18	Brigham and Women's Hospital	Boston	Massachusetts	United States	02115
19	Spectrum Health Hospitals	Grand Rapids	Michigan	United States	49504
20	Minneapolis Heart	Minneapolis	Minnesota	United States	55407
21	St. Louis University	Saint Louis	Missouri	United States	63110
22	Rutgers-Robert Wood Johnson University Hospital	New Brunswick	New Jersey	United States	08902
23	Albany Medical Center	Albany	New York	United States	12208-3412
24	Northwell Health	New Hyde Park	New York	United States	11040
25	New York Presbyterian Hospital/Columbia University Medical Center	New York	New York	United States	10032
26	Duke University Medical Center	Durham	North Carolina	United States	27710
27	Cleveland Clinic	Cleveland	Ohio	United States	44195
28	Ohio State University	Columbus	Ohio	United States	43210
29	Lehigh Valley Health Network	Allentown	Pennsylvania	United States	18103
30	Hospital of University of Pennsylvania	Philadelphia	Pennsylvania	United States	19104
31	Temple University	Philadelphia	Pennsylvania	United States	19140
32	Allegheny General Hospital	Pittsburgh	Pennsylvania	United States	15212
33	Rhode Island Hospital	Providence	Rhode Island	United States	02903
34	UT Erlanger	Chattanooga	Tennessee	United States	37403
35	Memphis VA Medical Center	Memphis	Tennessee	United States	38104
36	University of Texas Southwestern Medical Center	Dallas	Texas	United States	75390
37	UT McGovern Medical School Memorial Hermann	Houston	Texas	United States	77030
38	Baylor Scott and White Memorial Hospital	Temple	Texas	United States	76508
39	University of Virginia Medical Center	Charlottesville	Virginia	United States	22903
40	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

Study Documents (Full-Text)

None provided.

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.

• Responsible Party: Alung Technologies
• ClinicalTrials.gov Identifier: NCT03255057
• Other Study ID Numbers: HL-CA-5000
• First Posted: Aug 21, 2017
• Last Update Posted: Jan 20, 2021
• Last Verified: Jan 1, 2021

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: Yes

Study Results

No Results Posted as of Jan 20, 2021