Clinical trial NCT02086084: ECCO2R as an Adjunct to NIV in AECOPD
Official title: Extra-corporeal CO2 Removal as an Adjunct to Non-Invasive Ventilation in Acute Severe Exacerbations of COPD
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Chronic Obstructive Pulmonary Disease
Keywords: Acute Exacerbation Chronic Obstructive Pulmonary Disease
AECOPD
Non invasive ventilation
NIV
Extracorporeal carbon dioxide removal
ECCO2R
Lead sponsor: Guy's and St Thomas' NHS Foundation Trust
Sponsor class: OTHER
Collaborators: name: Alung Technologies
First posted: 2014-03-13
Enrollment: 21
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: SUPPORTIVE_CARE

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.


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

Primary outcomes:
measure: Time to cessation NIV
timeFrame: participants will be followed for the duration of ICU stay, an expected average of 4 days
Secondary outcomes:
measure: Mortality
timeFrame: at 90 days
measure: Time to event analysis
timeFrame: initial phase of study, an expected average of 3 hours
measure: Health-related quality of life (HRQoL)
timeFrame: 90 days
measure: Cannulation-related outcomes
timeFrame: participants will be followed for the duration of ICU stay, an expected average of 4 days
measure: haemolysis related to the intervention
timeFrame: participants will be followed for the duration of ICU stay, an expected average of 4 days
measure: work of breathing
timeFrame: participants will be followed for the duration of ICU stay, an expected average of 4 days
measure: Time to cessation ECCO2R
timeFrame: participants will be followed for the duration of ICU stay, an expected average of 4 days
measure: Time to normalisation of pH
timeFrame: participants will be followed for the duration of ICU stay, an expected average of 4 days
measure: Hospital Length of stay
timeFrame: participants will be followed for the duration of hospital stay, an expected average of 10 days
measure: Intubation rate
timeFrame: participants will be followed for the duration of ICU stay, an expected average of 4 days
measure: Incidence of tracheostomy
timeFrame: participants will be followed for the duration of ICU stay, an expected average of 4 days
measure: length of ICU stay
timeFrame: participants will be followed for the duration of ICU stay, an expected average of 4 days
measure: Tolerance of therapy
timeFrame: participants will be followed for the duration of ICU stay, an expected average of 4 days
measure: subjective dyspnoea
timeFrame: participants will be followed for the duration of ICU stay, an expected average of 4 days
measure: nutrition
timeFrame: participants will be followed for the duration of ICU stay, an expected average of 4 days
measure: Mobilisation
timeFrame: participants will be followed for the duration of ICU stay, an expected average of 4 days
measure: thrombotic complications
timeFrame: participants will be followed for the duration of ICU stay, an expected average of 4 days
measure: respiratory mechanics
timeFrame: participants will be followed for the duration of ICU stay, an expected average of 4 days
Other outcomes:
Locations:
city: London
country: United Kingdom
facility: Guy's and St Thomas' NHS Foundation Trust
Study officials:
affiliation: Guy's and St Thomas' NHS Foundation Trust
name: Nicholas Barrett, FCICM
role: PRINCIPAL_INVESTIGATOR
affiliation: Guy's and St Thomas' NHS Foundation Trust
name: Luigi Camporota, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Guy's and St Thomas' NHS Foundation Trust
name: Nicholas Hart, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Barrett NA, Hart N, Daly KJR, Marotti M, Kostakou E, Carlin C, Lua S, Singh S, Bentley A, Douiri A, Camporota L. A randomised controlled trial of non-invasive ventilation compared with extracorporeal carbon dioxide removal for acute hypercapnic exacerbations of chronic obstructive pulmonary disease. Ann Intensive Care. 2022 Apr 21;12(1):36. doi: 10.1186/s13613-022-01006-8.
citation: Barrett NA, Hart N, Camporota L. In vivo carbon dioxide clearance of a low-flow extracorporeal carbon dioxide removal circuit in patients with acute exacerbations of chronic obstructive pulmonary disease. Perfusion. 2020 Jul;35(5):436-441. doi: 10.1177/0267659119896531. Epub 2020 Jan 11.
citation: Barrett NA, Kostakou E, Hart N, Douiri A, Camporota L. Extracorporeal carbon dioxide removal for acute hypercapnic exacerbations of chronic obstructive pulmonary disease: study protocol for a randomised controlled trial. Trials. 2019 Jul 30;20(1):465. doi: 10.1186/s13063-019-3548-4.