Clinical trial NCT04147104: ecco2R to facilitatE earLy libEration From mechanicAl Ventilation inpatientS With Copd Acute Exacerbation
Official title: ecco2R to facilitatE earLy libEration From mechanicAl Ventilation inpatientS With Copd Acute Exacerbation
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
Conditions: Acute Exacerbation of COPD
Lead sponsor: Hospital Quiron Sagrado Corazon
Sponsor class: OTHER
First posted: 2019-10-31
Enrollment: 90
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: A pragmatic randomised controlled trial to determine whether early Veno-Venous Extracorporeal Carbon Dioxide Removal (VV-ECCO2R) in mechanically ventilated patients with acute exacerbated Chronic Obstructive Pulmonary Disease decreases the days of invasive mechanical ventilation.

Detailed description: Chronic obstructive pulmonary disease (COPD) is a major worldwide health burden. Currently, it is the fourth leading cause of death worldwide, and is the only leading cause of death that is rising, and will likely become the third cause of death by 2020. COPD is characterized by progressive destruction in the elastic tissue within the lung, causing respiratory failure.

Patients with COPD may experience acute exacerbations with severe hypercapnic respiratory failure. Hypercapnia results from acute worsening of expiratory flow limitation caused by the increased small airway resistance with consequent development of dynamic alveolar hyperinflation and intrinsic positive end-expiratory pressure (PEEP). In the most severe cases, these may be refractory to conventional therapies and mechanical ventilation, becoming life-threatening.

Extracorporeal carbon dioxide removal (ECCO2R) represents an attractive approach in this setting. The last decade has seen an increasing interest in the provision of extracorporeal support for respiratory failure, as demonstrated by the progressively increasing number of scientific publications on this topic. In particular, remarkable interest has been focused on extracorporeal carbon dioxide removal (ECCO2R), due to the relative ease and efficiency in blood CO2 clearance granted by extracorporeal gas exchangers as compared to oxygen delivery.

In recent years, a new generation of ECCO2R devices has been developed. More efficient veno-venous (VV)-ECCO2R devices have become available and have replaced the arterio-venous approach, having the advantage of not requiring arterial puncture.

The new VV-ECCO2R devices offer lower resistance to blood flow, have smaller priming volumes, and provide a much more efficient gas exchange with relatively low extracorporeal blood flows (0.4-1 L/min). The technology of these devices is now comparable to that of renal dialysis and has been experimented in several animal and human studies, demonstrating a significant reduction in arterial CO2 and improvement in the work of breathing.

In summary, minimally invasive ECCO2R appears very promising for patients with acute exacerbation of obstructive diseases refractory to conventional treatment, but systematic evaluation is needed to prove its clinical efficacy.

Eligibility criteria: Inclusion Criteria:

* Inclusion criteria

  * Age ≥ 18
  * Known or suspected aeCOPD that failed NIV that requires invasive mechanical ventilation
  * Failed treatment with NIV defined as:
* NIV for at least 2 hours and no more than 24 hours with signs of respiratory distress (respiratory rate \> 30 breaths/min and use of accessory muscles or paradoxical abdominal movements) AND
* PaCO2\> 55 mmHg and pH \< 7.25 or pH \< 7.30 and PaCO2 \> 55 mmHg, with PaCO2 decrease \< 20% from baseline

  • Known or suspected aeCOPD patients where NIV is contraindicated and need immediate invasive mechanical ventilation due to:
* Respiratory arrest
* Inability to protect the airway (impaired cough or swallowing or massive aspiration or respiratory pauses with loss of consciousness or gasping of air)
* Inability to clear secretions
* Agitated and confused patients
* Facial deformities or conditions that prevent mask from fitting
* Uncooperative or unmotivated patients

Exclusion Criteria:

* Participation in other interventional studies
* Patients already included in this study that need a new readmission because of a new aeCOPD episode
* aeCOPD intubated \> 12 hours
* Extubation within the previous 48 hours following intubation and invasive mechanical ventilation due to any cause
* Anatomical abnormalities or vascular diseases preventing the correct insertion of the ECCO2R cannula
* PaO2 to FiO2 ratio \< 150 on PEEP ≥ 5 cmH2O
* Known or suspected pregnancy (women of childbearing potential require a pregnancy test)
* Hemodynamic instability defined as

  * MAP \< 60 mmHg despite the infusion of fluids or vasoactive drugs OR
  * Failure to increase systolic blood pressure above 80-90 mmHg OR
  * Need for inotropic drugs to maintain systolic blood pressure\> 85 mmHg OR
  * ECG evidence of ischemia or significant uncontrolled ventricular arrhythmia
* Acute multiple organ failure defined as more than two organ failures assessed by SOFA score. Organ dysfunction can be identified as an acute change in total SOFA score \> 2 points
* Decompensated heart failure defined as an exacerbation of symptoms or signs after a period of relative stability such as dyspnea, fatigue or edema in the setting of previously established myocardial dysfunction (systolic or diastolic)32 and B-natriuretic peptide more than100 ng/L.
* Tracheostomized patients
* Untreated pulmonary embolism, pleural effusion, pneumothorax or bronchopleural fistula as the primary cause of acute respiratory failure
* Hemoglobin \< 7 gr/dL that require daily transfusion to maintain hemoglobin above 7 gr/dL at the time of screening
* Active major bleeding defined as35:

  * Fatal bleeding
  * Bleeding that is symptomatic and occurs in a critical area or organ, such as intracranial, intraspinal, intraocular, retroperitoneal, pericardial, in a non-operated joint, or intramuscular with compartment syndrome, assessed in consultation with the MD
  * Extrasurgical site bleeding causing a fall in hemoglobin level of 2 gr/dL or more or leading to transfusion of two or more units of whole blood or red cells, with temporal association within 24-48 hours to the bleeding
* Recent major surgery in the last 2 weeks
* Platelet count \< 50 000/mm3
* Prothrombin time-international normalized ratio (INR) \> 1.5 in the absence of anticoagulation therapy
* Heparin-induced thrombocytopenia (HIT) or known paradoxical/allergic reactions to heparin
* History within the previous 3 months of stroke or severe head trauma or intracranial arterio-venous malformation, or cerebral aneurysm, or central nervous mass lesion or intracranial bleeding
* Epidural catheter in place or plan to insert an epidural catheter during the study
* Gastrointestinal bleeding within the 6 weeks prior to study entry
* Severe liver insufficiency (Child-Pugh scores \>7) or INR \> 1.6 suspected to be related to liver disease (liver associated coagulopathy)
* Presence of severe (acute or chronic) renal failure defined as requiring any form of dialysis (including CRRT and CVVH) and/or having a serum creatinine \> 2.5 mg/dL and urine clearance \< 20 mL/hour
* Inability to receive blood products
* History of complications from extracorporeal support
* Permanent home ventilation except for sleep-disordered breathing
* Significant weakness or paralysis of respiratory muscles due to causes unrelated to aeCOPD
* Recent (\< 7 days) prolonged (\> 24 hours) use of muscle paralyzing agents
* Immunocompromised state defined as

  * Received chemotherapy or radiation within the previous 45 days and still under treatment for the underlying cancer
  * Received or currently receiving immunosuppressive therapy, excluding corticosteroids, within the last 3 months
  * Known to have AIDS defined illness
* Patients not expected to survive 6 months on the basis of premorbid health status
* History of uncontrolled, major psychiatric disorder
* Therapeutic restriction (DNR), moribund patient or not expected to survive current hospitalization
* Consent declined

Primary outcomes:
measure: The amount of time in the first 28 days following randomization that a patient is free of ventilatory support including non-invasive ventilation
timeFrame: 28 days
Secondary outcomes:
measure: All-cause (health-related) mortality at 28 and 90 days from randomization
timeFrame: 28 and 90 days
measure: Health-related quality of life (HRQoL)
timeFrame: 90 days after randomization
measure: Catheter-related complications
timeFrame: Participants will be followed for the duration of ICU stay, an expected average of 30 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 ECCO2R cessation
timeFrame: Participants will be followed for the duration of ICU stay, an expected average of 4 days
measure: Length of ECCO2R in situ
timeFrame: 7 days
measure: Time to normalization of pH and PaCO2
timeFrame: 3 hours
measure: Length of ICU stay
timeFrame: 4 days
measure: Hospital Length of stay
timeFrame: 10 days
measure: Incidence of new tracheostomies
timeFrame: Within 28 days from randomization
measure: Tolerance of ECCO2R therapy
timeFrame: 4 days
measure: Dyspnea
timeFrame: 4 days
measure: ICU Mobility
timeFrame: Randomization to end of treatment or 14 days, whichever is sooner
measure: Incidence of failed extubations
timeFrame: Within 28 days from randomization
measure: Frailty Index Score
timeFrame: 90 days after randomization
Other outcomes:
Locations:
Study officials:
affiliation: Hospital Universitari Sagrat Cor, Grupo Quironsalud
name: Antonio Artigas, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Del Sorbo L, Pisani L, Filippini C, Fanelli V, Fasano L, Terragni P, Dell'Amore A, Urbino R, Mascia L, Evangelista A, Antro C, D'Amato R, Sucre MJ, Simonetti U, Persico P, Nava S, Ranieri VM. Extracorporeal Co2 removal in hypercapnic patients at risk of noninvasive ventilation failure: a matched cohort study with historical control. Crit Care Med. 2015 Jan;43(1):120-7. doi: 10.1097/CCM.0000000000000607.
citation: 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.