Acute Hypoxemic Respiratory Failure, Acute Respiratory Distress Syndrome (ARDS)
Conditions
Keywords
Acute respiratory distress syndrome, Acute hypoxemic respiratory failure, Mechanical ventilation, assisted ventilation, controlled ventilation, feasibility trial, randomised clinical trial
Brief summary
Acute hypoxemic respiratory failure may progress to acute respiratory distress syndrome, a life-threatening condition that often requires mechanical ventilation. The optimal ventilation strategy in this patient population remains uncertain. The SVALBARD trial is a feasibility and pilot study designed to compare spontaneous versus controlled mechanical ventilation in patients with acute hypoxemia respiratory failure. The primary objective is to assess the feasibility of the study procedures and interventions, while also collecting descriptive data on key clinical variables to inform the design of a future randomized controlled trial.
Detailed description
Acute hypoxemic respiratory failure is a condition that can progress to acute respiratory distress syndrome (ARDS), requiring invasive mechanical ventilation to support gas exchange and limit lung injury. ARDS guidelines recommend lung-protective ventilation strategies-specifically low tidal volumes and limited airway pressures-to reduce ventilator-induced lung injury. Observational studies, including the global LUNG SAFE project, have described the epidemiology and management of acute hypoxemic respiratory failure and ARDS. These studies report high mortality rates (global hospital mortality, 38.6%) associated with the severity of lung injury rather than strict fulfilment of ARDS criteria. They also reveal variability in the application of evidence-based ventilation strategies across institutions. This inconsistency highlights a barrier to progress: the lack of conclusive evidence guiding ventilation management in patients with acute hypoxemic respiratory failure. One unresolved issue is the role of spontaneous breathing during mechanical ventilation. Observational studies suggest that allowing spontaneous effort may reduce need for sedation and increase ventilator-free days. In contrast, preclinical models indicate that spontaneous breathing in severe lung injury may worsen outcomes through mechanisms such as patient-ventilator asynchrony and regional overdistension. This contrast underscores the need to balance potential benefits against physiological risks in the absence of adequate trial data. ARDS guidelines do not provide clear recommendations on this issue due to limited evidence. Only one large RCT has compared controlled ventilation to spontaneous breathing modes, finding no difference in short-term outcomes and not assessing long-term endpoints such as cognitive impairment or quality of life.As a result, clinicians must choose between guideline-based controlled ventilation and approaches that incorporate spontaneous breathing, within the context of evolving sedation practices and recovery goals. Given the variability of acute hypoxemic respiratory failure and the current evidence gap, genuine uncertainty ('clinical equipoise') exists regarding the optimal ventilation strategy. This supports the need for well-designed RCTs to determine whether spontaneous ventilation offers clinical benefit or harm. A recent survey of Nordic clinicians showed support for such a trial in patients with moderately severe acute hypoxemic respiratory failure, underscoring the relevance of this research. The SVALBARD study is a feasibility and pilot trial comparing spontaneous and controlled mechanical ventilation in patients with acute hypoxemic respiratory failure. The study will evaluate whether it is possible to recruit patients, apply the assigned ventilation strategies, and collect the required data in a reliable way. In addition, the study will collect descriptive clinical data to better understand patient characteristics and outcomes. The results will be used to improve the design and planning of a future randomized controlled trial. The trial will accrue 80 patients from eight different intensive care units, four in Norway and four in Denmark.
Interventions
PROCEDURESpontaneous Ventilation Strategy
Invasive mechanical ventilation strategy allowing spontaneous breathing while receiving ventilatory support from a standard ICU mechanical ventilator.
PROCEDUREControlled Ventilation Strategy
Invasive mechanical ventilation strategy in which spontaneous respiratory effort is suppressed and breaths are fully delivered by a standard ICU mechanical ventilator.
Sponsors
Oslo University Hospital
Rigshospitalet, Denmark
Aalborg University Hospital
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
SINGLE (Outcomes Assessor)
Intervention model description
The SVALBARD feasibility study is designed as an international, multicentre, randomised, parallel-group pilot trial comparing two invasive mechanical ventilation strategies in adult intensive care unit (ICU) patients with moderately severe acute hypoxaemic respiratory failure. Eligible patients are randomised in a 1:1 ratio to either a spontaneous (assisted) ventilation strategy or a controlled ventilation strategy, with randomisation stratified by country of enrolment and biological sex, using concealed block randomisation.
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
We will include patients who fulfil all the following criteria: * Acutely admitted to the ICU * AND age ≥ 18 years * AND invasive mechanical ventilation via endotracheal tube or tracheostomy for less than 24 hours * AND moderate acute hypoxemic respiratory failure, defined as a PaO₂-FiO₂ ratio between 13.3-26.6 kPa (100-200 mmHg) with PEEP ≥ 5 cm H2O, based on arterial blood gas analysis obtained within 2 hours before randomisation. * AND new pulmonary infiltrate (uni- or bilateral) on chest x-ray or CT-scan obtained no more than 24 hours before randomisation.
Exclusion criteria
* Previously randomised into the SVALBARD trial. * Informed consent following inclusion expected to be unobtainable * Patient under coercive measures * Withdrawal from active therapy or brain death deemed imminent. * Chronic hypercapnic respiratory failure defined as PaCO2 \> 8 kPa (60 mm Hg) in the outpatient setting. * Listed for lung transplant. * Acute heart failure / acute myocardial infarction / cardiac arrest during or causing index ICU admission. * Use of home oxygen. * Chronic mechanical ventilation for any reason except for non-invasive mechanical ventilation (CPAP/BIPAP) used solely for sleep apnoea disorder. * Currently receiving ECMO therapy. * Burns \>70 % total body surface. * Acute brain injury or stroke (any, including subarachnoid haemorrhage, SAH). * Intracranial hypertension. * Patients with planned repeat surgical interventions during current stay in ICU.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Recruitment Rate | 1 year from trial initiation | Proportion of eligible patients who are enrolled in the trial (primary feasibility outcome). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Consent Rate | 1 year from trial initiation | Proportion of eligible patients who provide informed consent to participate in the trial. |
| Randomisation Rate | 1 year from trial initiation | Proportion of consented participants who are randomised. |
| Protocol Adherence | 1 year from trial initiation | Proportion of study procedures completed according to protocol requirements. |
| Major Protocol Violations | 1 year from trial initiation | Proportion of enrolled participants with at least one major protocol deviation. |
| Retention Rate | 1 year from trial initiation | Proportion of randomised participants who complete study follow-up. |
| Time to Completion of Feasibility Study | Up to 1 year | Time from trial initiation to completion of feasibility study recruitment and follow-up. |
| Proportion of Participants Achieving Therapeutic Target at 48 Hours | 48 hours from randomisation | Proportion of randomised participants achieving the predefined therapeutic target within 48 hours after randomisation. |
| Between-Group Difference in Therapeutic Target Attainment at 48 Hours | 48 hours | Difference between study groups in the proportion of participants achieving the predefined therapeutic target at 48 hours. |
| Proportion of Missing Therapeutic Target Data at 48 Hours | 48 hours from randomisation | Proportion of randomised participants with missing data for the predefined therapeutic target assessed 48 hours after randomisation. |
| Clinical: All-Cause Mortality at 30 Days | 30 days | Proportion of enrolled participants who have died from any cause by 30 days. |
| Clinical: All-Cause Mortality at 90 Days | 90 days | Proportion of enrolled participants who have died from any cause by 90 days. |
| Clinical: All-Cause Mortality at 180 Days | 180 days | Proportion of enrolled participants who have died from any cause by 180 days. |
| Clinical: Clinical: Days Alive and Free of Life Support at 90 Days | 90 days | Number of days alive and free of life support (invasive mechanical ventilation, renal replacement therapy, or vasoactive drug support) from randomisation through day 90. Life support-free days are calculated as the number of calendar days alive and free of all listed life support modalities during the 90-day period. Participants who die before day 90 will be assigned 0 days. |
| Clinical: Days Alive and Out of Hospital at 90 Days | 90 days | Number of days alive and out of hospital from randomisation through day 90. Participants who die before day 90 will be assigned 0 days. |
| Clinical: Health-related quality of life (EQ-5D-5L Index Score) | 180 days | Health-related quality of life measured using the EuroQol 5-Dimension 5-Level (EQ-5D-5L) index score. The index value ranges from less than 0 (health state worse than death) to 1 (best health), with higher scores indicating better health. Participants who die before assessment will be assigned a value of 0. |
| Clinical: Health-Related Quality of Life (EQ-5D Visual Analogue Scale Score) | 180 days | Health-related quality of life measured using the EQ-5D Visual Analogue Scale (VAS), ranging from 0 (worst imaginable health) to 100 (best imaginable health). Higher scores indicate better health. Participants who die before assessment will be assigned a value of 0. |
| Clinical: Montreal Cognitive Assessment (MoCA) Score at 180 Days | 180 days | Cognitive function assessed using the Montreal Cognitive Assessment (MoCA) Version 2.1 (telephone version). Scores range from 0 to 15, with higher scores indicating better cognitive function. Participants who die before assessment will be assigned a score of 0. |
| Clinical: Impact of Event Scale-6 (IES-6) Score at 180 Days | 180 days | Post-traumatic stress symptoms assessed using the Impact of Event Scale-6 (IES-6). The scale consists of six items rated from 0 (not at all) to 4 (extremely). The mean score ranges from 0 to 4, with higher scores indicating more severe post-traumatic stress symptoms. |
| Clinical: Modified Medical Research Council (mMRC) Dyspnea Scale Score at 180 Days | 180 days | Dyspnea assessed using the Modified Medical Research Council (mMRC) Dyspnea Scale. Scores range from 0 (breathless only with strenuous exercise) to 4 (too breathless to leave the house or while dressing/undressing), with higher scores indicating worse dyspnea. |
| Clinical: Chalder Fatigue Questionnaire (CFQ) Score at 180 Days | 180 days | Fatigue assessed using the Chalder Fatigue Questionnaire (CFQ), consisting of 11 items scored from 0 to 3. Total scores range from 0 to 33, with higher scores indicating greater fatigue. |
Contacts
CONTACTJon Henrik Laake, MD, PHD
CONTACTTayyba Naz Aslam, MD
Outcome results
None listed