Clinical Trial Details
— Status: Not yet recruiting
Administrative data
| NCT number |
NCT04582799 |
| Other study ID # |
ORION |
| Secondary ID |
|
| Status |
Not yet recruiting |
| Phase |
N/A
|
| First received |
|
| Last updated |
|
| Start date |
June 1, 2024 |
| Est. completion date |
June 1, 2027 |
Study information
| Verified date |
November 2023 |
| Source |
University of Bologna |
| Contact |
Lara Pisani, M.D. |
| Phone |
+39-051-2143253 |
| Email |
lara.pisani[@]unibo.it |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Interventional
|
Clinical Trial 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.
Description:
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.
The pathophysiological hallmarks of COPD patients include expiratory flow limitation and
small airway closure. Under these circumstances, a prolonged expiratory time is the
compensatory mechanism patients adopt to maintain a stable tidal breathing. COPD
exacerbations result in higher respiratory rates and reduced expiratory time, leading to
dynamic hyperinflation, elevated intrathoracic pressures, and excessive work of breathing.
Alteration of the balance between (a) the decreased capacity of the respiratory muscles to
generate pressure, and (b) the increased mechanical respiratory load due to expiratory flow
limitation and small airway closure leads to CO2 retention. The consequent reduction of
alveolar ventilation leads to a further worsening of CO2 retention and increased work of
breathing. This vicious circle is the underlying mechanisms responsible of acute respiratory
failure requiring admission in the intensive care unit (ICU) for ventilatory support.
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) have been used in patients with acute
hypercapnic respiratory failure since ECCO2R may enhance the efficacy of NIV to remove CO2
and avoid the worsening of respiratory acidosis. Although available studies are limited to
case series, several ECCO2R devices have been developed and proposed for the clinical use in
patients with COPD. These systems often represent modifications of renal replacement therapy
circuits, and are characterized by:
1. veno-venous by-pass systems
2. extracorporeal blood flow of 0.3-0.5 litres/min
3. 13 Fr bore catheters or a single co-axial catheter
4. very low doses or no heparin
5. minimal volumes for "priming"
This technological implementation of ECCO2-R is therefore closer to device for renal
replacement therapy than full ECMO. CO2 is removed through a double-lumen catheter and
constantly propelled, by a non-occlusive rotating pump, though an artificial membrane lung (a
filter adding oxygen and removing carbon dioxide) connected to a source of 100% O2 (flow 6-8
liters/min). These systems are able to reduce PaCO2 by 20-25%.
A recent matched cohort study with historical control, compared "NIV-plus-ECCO2R" and
"NIV-only" in patients at risk of NIV failure, and 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. A recent
systematic review evaluated the efficacy and safety of ECCO2R in patients with hypercapnic
respiratory failure across 12 studies and showed that the majority of patients were either
successfully weaned from mechanical ventilation or sustained on NIV, avoiding intubation.
However, this high success rates, was associated with a high frequency of potentially severe
complications.
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
Objectives:
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. Event free survival is defined
as survival at day 28 free of any of the followings: (a) development of sepsis; (b)
occurrence of a second episode of COPD exacerbation requiring or not mechanical ventilation;
(c) occurrence of severe hypoxemia; (d) prolonged mechanical ventilation (e) death.
