Clinical Trial Details
— Status: Completed
Administrative data
| NCT number |
NCT04708457 |
| Other study ID # |
ANZIC-RC/AB V3.1 |
| Secondary ID |
|
| Status |
Completed |
| Phase |
N/A
|
| First received |
|
| Last updated |
|
| Start date |
March 1, 2021 |
| Est. completion date |
December 31, 2022 |
Study information
| Verified date |
October 2023 |
| Source |
Australian and New Zealand Intensive Care Research Centre |
| Contact |
n/a |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Interventional
|
Clinical Trial Summary
Patients who are critically ill in intensive care with moderate to severe acute respiratory
infection often require mechanical ventilation. Prolonged ventilation increases the risk of
lung damage and other side effects as a result of long term use of sedation medications.
Extracorporeal membrane oxygenation therapy (ECMO), is a relatively new technology that uses
a pump to remove blood from the body and return it back to the body after adding oxygen and
removing carbon dioxide. ECMO can be used on patients who require mechanical ventilation and
can function without the need for ongoing mechanical ventilation, thus reducing risk of side
effects. Participants will be randomised into either the early ECMO therapy group or will
continue standard treatment involving mechanical ventilation.
This pilot study aims to determine if a phase 3 Randomised Control Trial (RCT) is feasible
for the use of early ECMO therapy to treat patients with Severe Acute Respiratory Infection
(SARI). The success of the study will be determined by the successful recruitment of adult
patients, that there is a difference between ECMO utilisation between groups and that there
are no safety issues.
Description:
Prolonged mechanical ventilation is standard care for SARI and is associated with long term
functional complications: Current guidelines recommend that mechanical ventilation, including
protective lung strategies such as low tidal volumes, low peak pressures and titrated peak
end expiratory pressure (PEEP), should form the mainstay of treatment for severe respiratory
failure. While these strategies have been shown to reduce mortality, the application of
invasive mechanical ventilation in the setting of SARIs may in fact propagate ongoing lung
injury. Ventilator induced lung injury (VILI) results from the high pressures, over
distension, and shear injury used by the ventilator to maintain gas exchange. Invasive
ventilation can lead to secondary bacterial infection from poor clearance of sputum by
sedated patients. And "air hunger" - the rapid and deep injurious breathing pattern by
patients with severe lung injury - can lead to patient self-induced lung injury (P-SILI).
Taken together, these factors can lead to a vicious cycle - the VILI Vortex - where lung
damage leads to shrinkage of the functional lung unit, reduced compliance, higher
transpulmonary pressures, worsening inflammation, further shrinkage, and ultimately even more
severe lung damage and gas exchange failure.
Current strategies to facilitate mechanical ventilation include prolonged heavy sedation to
assist patient-ventilator synchronization, and neuromuscular blockade (to prevent any
spontaneous respiratory effort), often for weeks at a time. These interventions, plus the
underlying lung damage, contribute to significant long term complications, including
immobility and ICU myopathy, delirium, respiratory muscle weakness and tracheostomy, leading
to significant delays in ICU and hospital discharge, rehabilitation, and return to home.
Survivors of prolonged mechanical ventilation have been shown to have high rates of
functional disability, immobility, psychological injury, and reduced health related quality
of life - and these outcomes can persist for up to 5 years.
Thus, conventional treatment with mechanical ventilation, deep sedation, and/or neuromuscular
paralysis is likely to adversely impact long term functional outcomes in patients with SARI.
There is a clear unmet need for novel strategies that facilitate safe lung ventilation, while
also limiting the intensity and duration of these interventions and complications.
ECMO is an external machine that oxygenates the blood in addition to a mechanical ventilator.
Venous cannulae drain blood out of the body and return it back after an oxygenator adds
oxygen and removes carbon dioxide. Venovenous (VV) ECMO supports patients with respiratory
failure, by providing the body with sufficient oxygen and by removing all the carbon dioxide
(CO2) in the blood (causing a respiratory alkalosis), which reduces the drive to breathe and
permits "lung rest". Resting the lungs avoids VILI, reduces pulmonary and systemic
inflammation, and reduces extra-pulmonary organ dysfunction. Traditionally, ECMO was employed
very late in the course of the disease as a "rescue therapy", when patients already had
severely damaged lungs, due to fears of complications such as bleeding that would worsen the
patients multi organ failure. However advances in modern ECMO technology mean it is
associated with a lower complication rate (<10% cannula site bleeding) and its use has
doubled over the last five years. ECMO now offers the ideal platform to prevent
ventilator-induced lung damage in patients that are less severely unwell, and earlier in the
disease process, while also reducing the need for heavy sedation and/or neuromuscular
blockade. It facilitates safe de-sedation without VILI as well as extubation, and
physiotherapy-which is difficult to carry out adequately when a patient is sedated and
ventilated. All these factors have been associated with improved long term health outcomes
for patients.
This study aims to determine if a large RCT looking at use of early ECMO to treat patients
with SARI is feasible.
