To evaluate the efficacy and safety of preserved spontaneous breathing activity in the early phase of moderate to severe ARDS.
ID
Source
Brief title
Condition
- Lower respiratory tract disorders (excl obstruction and infection)
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Primary efficacy endpoints:
• All-cause mortality at study day 28 (D28)
• Number of ventilator free days (VFD) until D28
Secondary outcome
Key secondary endpoint(s):
• All-cause mortality at study day 90 (D90)
• Number of vasoactive drug free days until D28
• Number of renal support free days until D28
• Number of ICU free days until D28
• Sequential Organ Failure Assessment (SOFA) score during ICU stay
Background summary
The potential benefits of preserved early spontaneous breathing activity during
mechanical ventilation are an increased aeration of dependent lung regions,
less need for sedation, improved cardiac filling, and better matching of
pulmonary ventilation and perfusion and thus oxygenation. Two small randomized
controlled trials (RCTs) in patients with acute respiratory distress syndrome
(ARDS) reported less time on mechanical ventilation and in the intensive care
unit (ICU) with preserved early spontaneous breathing activity during Airway
Pressure Release Ventilation (APRV).
Debate exists over the net effects of preserved early spontaneous breathing
activity with regard to ventilator-associated lung injury (VALI). In fact, by
taking advantage of the potential improvement in oxygenation and recruitment at
lower inflation pressures associated with APRV, physicians could possibly
reduce potentially harmful levels of inspired oxygen, tidal volume, and
positive end-expiratory pressure (PEEP). However, spontaneous breathing during
mechanical ventilation has the potential to generate less positive pleural
pressures that may add to the alveolar stretch applied from the ventilator and
contribute to the risk of VALI. This has led to an ongoing controversy about
the question whether an initial period of controlled mechanical ventilation
with deep sedation and neuromuscular blockade or preserved early spontaneous
breathing activity during mechanical ventilation is advantageous with respect
to outcomes in ARDS patients. A RCT investigating the effects of early
spontaneous breathing activity on mortality in moderate to severe ARDS has been
highly recommended in the research agenda for intensive care medicine.
Study objective
To evaluate the efficacy and safety of preserved spontaneous breathing activity
in the early phase of moderate to severe ARDS.
Study design
Confirmatory, prospective, randomized, open controlled international
multi-centre trial.
Intervention
After inclusion, a lung-protective ventilator strategy will be applied (if this
has not yet been implemented) and patients will be randomized to:
Spontaneous Breathing Group
Spontaneous breathing activity will be allowed during APRV within one hour
after randomization throughout the first 48 hours.
Controlled Mechanical Ventilation Group
Pressure controlled mechanical ventilation will be applied throughout the first
48 hours.
After 48 hours, standard routine care should be provided in both groups,
although we suggest moderate sedation while spontaneous breathing is maintained
with APRV, pressure support ventilation (PSV), or other assisting ventilator
modes. Weaning off mechanical ventilation will be performed after 48 hours
according to a protocol using spontaneous breathing trials.
Study burden and risks
Two standard treatments are compared with similar risks and complications. Our
expectation is that there will be no difference.
Venusberg-Campus 1
Bonn 53127
DE
Venusberg-Campus 1
Bonn 53127
DE
Listed location countries
Age
Inclusion criteria
1. Moderate to severe ARDS for <= 48 hours according to the Berlin definition is
defined by acute onset of:
a. PaO2/FiO2 <= 200 mmHg (equivalent to <= 26.7 kPa) under invasive mechanical
ventilation with PEEP >= 5 cmH2O
b. Bilateral infiltrates documented by chest radiograph
c. Not fully explained by cardiac failure or fluid overload (e.g.
echocardiography)
2. Requirement for positive pressure ventilation via an endotracheal tube/
tracheotomy
3. Informed consent according to local regulations
4. Age >= 18 years
5. Expected duration of invasive mechanical ventilation > 48 hours at
randomization
Exclusion criteria
1. Need of extracorporeal lung support, high frequency oscillation and/or
inhaled vasodilators for severe hypoxemia at randomization
2. Woman known to be pregnant, lactating or having a positive or indeterminate
pregnancy test
3. Neuromuscular disease that impairs ability to ventilate spontaneously
4. Severe chronic respiratory disease (e.g. COPD, pulmonary fibrosis, and other
chronic diseases of the lung, chest wall or neuromuscular system) requiring
home oxygen therapy or mechanical ventilation (non-invasive ventilation or via
tracheotomy) except for Continuous Positive Airway Pressure (CPAP) or
non-invasive Biphasic Positive Airway Pressure (BiPAP) used solely for
sleep-disordered breathing
5. Chronic kidney disease stage V (requirement of dialysis) according to the
K/DOQI definition of chronic kidney disease
6. Massive diffuse alveolar haemorrhage
7. Recent lung transplant < 12 months
8. Morbid obesity defined as weight greater than 1 kg / cm
9. Burns > 70% total body surface
10. Suspected or known elevated intracranial pressure
11. Chronic liver disease (Child-Pugh grade C)
12. Ongoing chemotherapy and/or bone marrow transplantation within the last 3
months
13. Moribund patient not expected to survive 48 hours
14. Patients not expected to survive 90 days on the basis of the premorbid
15. Patient, surrogate, or physician not committed to full life support.
Design
Recruitment
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| ClinicalTrials.gov | NCT04228471 |
| CCMO | NL82657.015.22 |