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

Acute Exacerbation of COPD Clinical Trial

— VENT-AVOID  

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT03255057
• Other study ID #: HL-CA-5000
• Status: Terminated
• Phase: N/A
• Start date: February 18, 2018
• Est. completion date: August 17, 2022

Study information

• Verified date: October 2022
• Source: Alung Technologies
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 113
• Est. completion date: August 17, 2022
• Est. primary completion date: August 10, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 40 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Acute Exacerbation of COPD

Intervention

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.
• 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.

Locations

Country	Name	City	State
United States	Albany Medical Center	Albany	New York
United States	Lehigh Valley Health Network	Allentown	Pennsylvania
United States	Tufts Medical Center	Boston	Massachusetts
United States	University of Virginia Medical Center	Charlottesville	Virginia
United States	UT Erlanger	Chattanooga	Tennessee
United States	Northwestern Memorial Hospital	Chicago	Illinois
United States	Cleveland Clinic	Cleveland	Ohio
United States	Ohio State University	Columbus	Ohio
United States	Denver Health Medical Center	Denver	Colorado
United States	Duke University Medical Center	Durham	North Carolina
United States	Inova Health Care Services	Falls Church	Virginia
United States	University of Florida - Health Shands	Gainesville	Florida
United States	Spectrum Health Hospitals	Grand Rapids	Michigan
United States	UT McGovern Medical School Memorial Hermann	Houston	Texas
United States	University of Iowa	Iowa City	Iowa
United States	Mayo Clinic Jacksonville	Jacksonville	Florida
United States	Lexington VA Healthcare	Lexington	Kentucky
United States	University of Louisville	Louisville	Kentucky
United States	WellStar Kennestone Regional Medical Center	Marietta	Georgia
United States	Memphis VA Medical Center	Memphis	Tennessee
United States	Minneapolis Heart	Minneapolis	Minnesota
United States	Rutgers-Robert Wood Johnson University Hospital	New Brunswick	New Jersey
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	Christiana Care Health System	Newark	Delaware
United States	Hospital of University of Pennsylvania	Philadelphia	Pennsylvania
United States	Temple University	Philadelphia	Pennsylvania
United States	Allegheny General Hospital	Pittsburgh	Pennsylvania
United States	Rhode Island Hospital	Providence	Rhode Island
United States	UC Davis Medical Group	Sacramento	California
United States	LSU Health Shreveport	Shreveport	Louisiana
United States	Baylor Scott and White Memorial Hospital	Temple	Texas

Sponsors (1)

Lead Sponsor	Collaborator
Alung Technologies

Country where clinical trial is conducted

United States, 

References & Publications (1)

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	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
Other	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
Other	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
Other	VFD-30	Ventilator-free days from randomization to 30 days from randomization	Randomization to Day 30
Other	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
Other	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
Other	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
Other	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
Other	Incidence of hospital readmissions	Number of new hospital admissions after hospital discharge for original exacerbation	From randomization to 60 days from randomizaiton
Primary	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	Physiologic benefit	Based on blood gases and concomitant ventilation parameters	Time to extubation from first intubation up to 60 days from randomization
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	Incidence of new tracheotomies	Incidence of new tracheotomies	Within 60 days from randomization
Secondary	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
Secondary	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
Secondary	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
Secondary	Incidence of failed extubations	Incidence of re-intubation within 48 hours of extubation for original exacerbation	Within 60 days from randomization