ECCO2R as an Adjunct to NIV in AECOPD

Study Overview
=================
Brief Summary
-----------------
Chronic obstructive pulmonary disease (COPD) is one of the UKs commonest chronic diseases and is responsible for a significant number of acute hospital admissions. COPD is characterised by progressive destruction in the elastic tissue within the lung, causing respiratory failure. The clinical course of COPD is characterised by recurrent acute exacerbations (AECOPD), causing considerable morbidity and mortality. Patients with moderate to severe acute exacerbations present with increased work of breathing and hypercapnia. The standard for respiratory support in this setting is non-invasive ventilation (NIV), a management strategy underpinned by a considerable evidence base. However despite NIV, up to 30% of patients with AECOPD will 'fail' and require intubation and mechanical ventilation. The mortality rate for patients requiring NIV is approximately 4%, if conversion to mechanical ventilation occurs the mortality is 29%. The last decade has seen an increasing interest in the provision of extracorporeal support for respiratory failure. The key element that has underpinned improving survival has been technological advancement. This has resulted in pumps causing less blood trauma and inflammatory response, better percutaneous cannulation techniques and coated circuits with reduced heparin requirements. Overall this has significantly reduced the complications associated with the provision of extracorporeal support. One variation of this technique (extra-corporeal CO2 removal ECCO2R) allows CO2 clearance from the blood. This approach has been the subject of a number of animal experiments and uncontrolled human case series demonstrating improved arterial CO2 and reduced work of breathing. Our own unpublished series demonstrates the same physiological changes. However to date the benefits of this approach have not been tested in a randomised controlled trial. The hypothesis is that the addition of ECCO2R to NIV will shorten the duration of NIV and reduce likelihood of intubation.

Official Title
-----------------
Extra-corporeal CO2 Removal as an Adjunct to Non-Invasive Ventilation in Acute Severe Exacerbations of COPD

Conditions
-----------------
Chronic Obstructive Pulmonary Disease

Intervention / Treatment
-----------------
* Device: NIV
* Device: ECCO2R


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion criteria Known COPD with an acute exacerbation. An acute exacerbation is defined as per the GOLD criteria as an increase in dyspnoea, cough and/or sputum over the patient's normal symptoms. A severe exacerbation is defined as one requiring hospital admission. Patients with a persistent arterial pH<7.30 due primarily to hypercapnic respiratory failure after standard medical therapy and at least 1 hour of NIV. Age over 18 Exclusion Criteria Haemodynamic instability after ensuring euvolaemia Acute multiple organ failure requiring other organ supportive therapy, including indication for intubation and mechanical ventilation Known allergy/intolerance of heparin including known heparin induced thrombosis and thrombocytopaenia Acute uncontrolled haemorrhage Intracerebral haemorrhage Recent (<6 months) ischaemic cerebrovascular accident Organ transplant recipient Expected to die within 24 hours Venous abnormality or body habitus precluding cannulation Contraindication to NIV (as per British Thoracic Society recommendation) Facial burns/trauma/recent facial or upper airway surgery Vomiting Fixed upper airway obstruction Undrained pneumothorax Recent upper gastrointestinal surgery Inability to protect the airway Life threatening hypoxaemia (PaO2/FiO2 <20kPa) Bowel obstruction Patient refusal Pregnancy Severe hepatic failure (ascites, hepatic encephalopathy or bilirubin >100umol/L) Severe chronic cardiac failure (NYHA class III or IV) Bleeding diathesis (INR>1.5, platelets <80,000) in the absence of anticoagulation therapy

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Supportive Care
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: NIV<br>Standard application of NIV in hypercapnic respiratory failure as per usual standard of care | Device: NIV<br>* Standard care<br>|
| Experimental: ECCO2R<br>Addition of ECCO2R to NIV in AECOPD | Device: NIV<br>* Standard care<br>Device: ECCO2R<br>* Application of ECCO2R in addition to NIV<br>* Other names: Haemolung;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to cessation NIV | Time to cessation of NIV is defined as from NIV commencement to 6 hours without NIV. | participants will be followed for the duration of ICU stay, an expected average of 4 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mortality |  | at 90 days | 
| Time to event analysis | This is a composite endpoint to assess the ability to complete the required elements of the study from screening to commencement of ECCO2R in a clinically relevant timeframe | initial phase of study, an expected average of 3 hours | 
| Health-related quality of life (HRQoL) |  | 90 days | 
| Cannulation-related outcomes | composite outcome of cannulation related complications | participants will be followed for the duration of ICU stay, an expected average of 4 days | 
| haemolysis related to the intervention |  | participants will be followed for the duration of ICU stay, an expected average of 4 days | 
| work of breathing |  | participants will be followed for the duration of ICU stay, an expected average of 4 days | 
| Time to cessation ECCO2R | Defined as from the commencement of ECCO2R to 6 hours following cessation of CO2 removal | participants will be followed for the duration of ICU stay, an expected average of 4 days | 
| Time to normalisation of pH |  | participants will be followed for the duration of ICU stay, an expected average of 4 days | 
| Hospital Length of stay |  | participants will be followed for the duration of hospital stay, an expected average of 10 days | 
| Intubation rate |  | participants will be followed for the duration of ICU stay, an expected average of 4 days | 
| Incidence of tracheostomy |  | participants will be followed for the duration of ICU stay, an expected average of 4 days | 
| length of ICU stay |  | participants will be followed for the duration of ICU stay, an expected average of 4 days | 
| Tolerance of therapy |  | participants will be followed for the duration of ICU stay, an expected average of 4 days | 
| subjective dyspnoea |  | participants will be followed for the duration of ICU stay, an expected average of 4 days | 
| nutrition | total caloric intake during interventional period | participants will be followed for the duration of ICU stay, an expected average of 4 days | 
| Mobilisation | mobilisation from bed during the study period | participants will be followed for the duration of ICU stay, an expected average of 4 days | 
| thrombotic complications | measurement of thrombotic complications in the patient related to the device | participants will be followed for the duration of ICU stay, an expected average of 4 days | 
| respiratory mechanics |  | participants will be followed for the duration of ICU stay, an expected average of 4 days | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Acute Exacerbation Chronic Obstructive Pulmonary Disease, AECOPD, Non invasive ventilation, NIV, Extracorporeal carbon dioxide removal, ECCO2R