Extracorporeal CO2 Removal for Acute Decompensation of COPD

NCT04582799 | Withdrawn DMC

• 1 other identifier: ORION
• Study Type: interventional
• Target: N/A
• Locations: 0 countries
• Sites: N/A

Brief Summary

Chronic obstructive pulmonary disease (COPD) is the third leading cause of death worldwide, resulting in a social and economic burden that is substantial and increasing. Exacerbations affect the prognosis and quality of life of patients with COPD. Hospital mortality of patients admitted for a hypercapnic exacerbation of COPD is approximately 10% and the long-term outcome is poor. In addition, hypercapnic exacerbation of COPD have serious negative impacts on patient quality of life, lung function and costs. Thus, prompt treatment of exacerbations may impact the clinical progression of COPD by ameliorating quality of life and prognosis. Standard of care for patients with COPD exacerbation that need ICU admission for management of acute hypercapnic respiratory failure and severe respiratory acidosis is non-invasive ventilation (NIV). When NIV fails (arterial pH remains \< 7.30), invasive ventilation through endotracheal intubation is initiated to restore adequate gas-exchange. Extracorporeal circuits designed to remove CO2 (ECCO2R) may enhance the efficacy of NIV to remove CO2 and avoid the worsening of respiratory acidosis. A recent matched cohort study with historical control, showed that: (a) the hazard of being intubated was three times higher in patients treated with "NIV-only" than in patients treated with "NIV-plus-ECCO2R"; (b) hospital mortality was significantly lower in "NIV plus ECCO2R" than in "NIV-only" \[8% (95% CI 1.0-26.0%) vs. 33% (95% CI 18.0-57.5%), respectively\]. However, ECCO2R-related complications were observed in almost half of the patients. The consistency of the above discussed data, and the observation of the continuous increase use of ECCO2R despite the lack of solid evidence confirm that the equipoise regarding the use of ECCO2R may justify a randomized clinical trial to evaluate whether patients with respiratory acidosis refractory to NIV should be intubated and take the risks associated with invasive mechanical ventilation, or should be connected to ECCO2R to avoid intubation, but run the risk of the potentially serious ECCO2R-related complication The main objective of this randomized multicenter clinical trial is to test the hypothesis that in patients with acute life-threatening exacerbation of COPD, use of ECCO2R could increase event-free survival as compared to standard of care.

Conditions

Pulmonary Disease, Chronic Obstructive

Keywords

COPD; ECCO2R

Outcome Measures

Primary Outcomes (1)

• Combined 28-day mortality or surrogate events

  Incidence of death, prolonged mechanical ventilation, development of septic shock, development of severe hypoxemia, second episode of COPD exacerbation

  28 days after enrollment

Secondary Outcomes (5)

• Endotracheal intubation

  28 days after enrollment

• Tracheostomy

  28 days after enrollment

• Hospital length-of-stay

  Whole hospital stay

• ICU length-of-stay

  Whole ICU stay

• 90-day mortality

  90 days after enrollment

Study Arms (2)

Standard of Care (NIV)

ACTIVE COMPARATOR

Patients in the control group will be treated with non-invasive ventilation only.

Device: NIV

Extracorporeal CO2 Removal (NIV+ECCO2R)

EXPERIMENTAL

Patients in the treatment group will be treated with non-invasive ventilation combined with Extracorporeal CO2 Removal.

Device: ECCO2R; Device: NIV

Interventions

ECCO2R DEVICE

Extracorporeal CO2 Removal

Extracorporeal CO2 Removal (NIV+ECCO2R)

NIV DEVICE

Non-invasive ventilation

Extracorporeal CO2 Removal (NIV+ECCO2R); Standard of Care (NIV)

Eligibility Criteria

• Age: 18 Years - 90 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients older than 18 and younger than 90 years
• Documented clinical history of COPD
• ICU admission for exacerbation of COPD requiring non-invasive ventilatory support After two hours of NIV at least two of the following criteria must be fulfilled
• arterial pH ≤ 7.25
• respiratory rate ≥30 breaths/min
• use of accessory muscles or paradoxical abdominal movements

You may not qualify if:

• mean arterial pressure \<60 mmHg despite infusion of fluids and vasoactive drugs
• ratio of arterial-to-inspired oxygen O2 fraction (PaO2/FiO2) ≤ 150 with FiO2 of less than 0.6 and PEEP of at least 5 cm H2O
• contraindications to anticoagulation (i.e. any of the following: platelet count \<50,000/mm3; prothrombin time-international normalized ratio (INR) \>1.5; stroke or severe head trauma or intracranial arterio-venous malformation, or cerebral aneurysm, or central nervous system mass lesion within the previous 3 months; epidural catheter in place or expected to be positioned during the study; history of congenital bleeding diatheses; gastrointestinal bleeding within the 6 weeks prior to study entry; esophageal varices, chronic jaundice, cirrhosis, or chronic ascites; trauma);
• heparin-induced thrombocytopenia;
• body weight \>120 Kg;
• contraindication to continuation of active treatment;
• failure to obtain consent
• catheter access to femoral vein or jugular vein impossible
• pneumothorax
• patient moribund
• severe liver insufficiency (Child-Pugh scores \> 7) or fulminant hepatic failure
• diagnosed with acute or chronic neuromuscular disease
• required chronic mechanical ventilation prior to hospital admission

Sponsors & Collaborators

• University of Bologna: lead
• University of Milan: collaborator
• University of Turin, Italy: collaborator
• University of Roma La Sapienza: collaborator

Related Publications (1)

• Tonetti T, Pisani L, Cavalli I, Vega ML, Maietti E, Filippini C, Nava S, Ranieri VM. Extracorporeal carbon dioxide removal for treatment of exacerbated chronic obstructive pulmonary disease (ORION): study protocol for a randomised controlled trial. Trials. 2021 Oct 19;22(1):718. doi: 10.1186/s13063-021-05692-w.

  PMID: 34666820 DERIVED

MeSH Terms

Conditions

Pulmonary Disease, Chronic Obstructive

Condition Hierarchy (Ancestors)

Lung Diseases, Obstructive; Lung Diseases; Respiratory Tract Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• V. Marco Ranieri, M.D.

  University of Bologna

  STUDY CHAIR

• Stefano Nava, M.D.

  University of Bologna

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Full Professor

Study Record Dates

• First Submitted: October 3, 2020
• First Posted: October 12, 2020
• Study Start: August 1, 2024
• Primary Completion: August 1, 2024
• Study Completion: August 1, 2024
• Last Updated: April 1, 2025

Record last verified: 2025-03

Data Sharing

• IPD Sharing: Will not share