Weaning Algorithm for Mechanical VEntilation (WAVE)

• ClinicalTrials.gov Identifier: NCT03697785
• Recruitment Status: Unknown
• First Posted: October 5, 2018
• Last Update Posted: October 5, 2018
• Sponsor: Royal Brompton & Harefield NHS Foundation Trust
• Collaborators: Mermaid Care A/S; Aalborg University; Imperial College London
• Information provided by (Responsible Party): Royal Brompton & Harefield NHS Foundation Trust

Study Description

Brief Summary:

To compare the duration of mechanical ventilation and the weaning period between two groups of patients managed with either Standard Care or with mechanical ventilation adjusted according to the Beacon Caresystem, in patients receiving mechanical ventilation for more than 24 hours

Condition or disease	Intervention/treatment	Phase
Respiration, Artificial; Critical Care; Respiratory Insufficiency; Intensive Care (ICU) Myopathy; Mechanical Ventilation Complication	Device: Beacon Care System	Not Applicable

Detailed Description:

Patients admitted to the intensive care unit typically receive invasive mechanical ventilatory support when they are critically ill. Whilst mechanical ventilation is a life-saving intervention, it can also lead to deleterious consequences and cause lung damage (known as ventilator-associated lung injury) if not implemented carefully. Hence, reducing the duration of mechanical ventilation should reduce complications such as ventilator-associated lung injury, ventilator-acquired pneumonia, respiratory and skeletal muscle wasting, and patient discomfort, leading to decreasing mortality and economic costs etc. Importantly, prolonged weaning perpetuates these complications which further increase the duration of mechanical ventilation thereby creating a viscous cycle leading to greater morbidity and mortality.

The availability and education of intensive care unit (ICU) staff are important considerations in minimizing the duration of mechanical ventilation through weaning protocols. It is common practice that the attending physician decides upon patient's therapy and ventilatory management according to recommendations. This usually occurs as part of medical rounds. In addition, nurses often manage the weaning of patients from mechanical ventilation either by following attending physicians' instructions or local guidelines protocols. Such protocol-directed, nurse-driven weaning has been shown to reduce the duration of mechanical ventilation. However, it has been shown that the quantity and quality of nursing are important factors if duration is to be reduced.

Several decision support systems have been developed to help select optimal mechanical ventilator strategies. Those finding their way into routine clinical practice have typically been based on clinical guidelines or rules rather than detailed physiological description of the individual patient. A recent Cochrane review of weaning trials with these systems concluded that use of these systems may reduce duration of weaning, but pointed out that many of these trials are based on patients that are 'simple to wean'. Such patients are usually less complex, without lung pathology, and ventilated for less than 48 hours. However, there is a need to develop and validate protocolised systems that utilize a more detailed physiological description of individual patients to aid in the management of complex patients ventilated for longer durations.

The Beacon Caresystem is a model-based decision support system using mathematical models tuned to the individual patient's physiology to advise on appropriate ventilator settings. Personalised approaches using individual patient description may be particularly advantageous in complex patients, including those who are difficult to mechanically ventilate and wean; precisely those where previous systems have not been sufficiently evaluated. The Beacon Caresystem is a commercial version of the system previously known as INVENT, which has been retrospectively evaluated in post-operative cardiac patients and patients with severe lung disease, and prospectively evaluated in advising on the correct level of inspiratory oxygen. Furthermore, studies are near completion showing that the system provides safe and appropriate advice on inspired oxygen, respiratory frequency, tidal volume, pressure support/control and positive end expiratory pressure (PEEP) in a wide variety of patients ranging from patients with severe respiratory failure to patients close to extubation (unpublished data). However, previous and ongoing studies with the Beacon Caresystem have focused on safety and efficacy of advice under limited time periods, and have not focused on weaning from mechanical ventilation.

The core of the Beacon Caresystem is a set of physiological models including pulmonary gas exchange, acid-base chemistry, lung mechanics, and respiratory drive. The Beacon Caresystem tunes these models to the individual patient such that they describe accurately current measurements. Once tuned, the models are used by the system to simulate the effects of changing ventilator settings. The results of these simulations are then used to calculate the clinical benefit of changing ventilator settings by balancing the competing goals of mechanical ventilation. For example, an increased inspiratory volume will reduce an acidosis of the blood while detrimentally increasing lung pressure. Appropriate ventilator settings therefore imply a balance between the preferred value of pH weighted against the preferred value of lung pressure. A number of these balances exist, and the system weighs these, calculating a total score for the patient for any possible ventilation strategy. The system then calculates advice as to changes in ventilator settings so to as improve this score. The Beacon Caresystem functions as an "open loop" system. This means that the advice provided by the system is presented to the clinician. The ventilator settings are then changed by the clinician, and the patient's physiological response to these changes is automatically used by the system to re-tune the models and repeat the process of generating new advice.

In calculating appropriate advice, selecting the correct level of positive end expiratory pressure (PEEP) is particularly challenging. The nature of the challenge is however, very different depending upon the presence or type of lung abnormality, and the function of the heart. Patients with severe lung abnormalities such as acute respiratory distress syndrome (ARDS), which often result in small, stiff lungs, are often in control ventilation mode with little or no spontaneous breathing. For these patients, PEEP is often increased to try to recruit units of the lung which are collapsed. This can be difficult, as increasing PEEP may result in elevated lung pressure and hence an increased the risk of lung injury, incomplete expiration and air trapping, and haemodynamic compromise, especially in those with heart failure.

Patients in support ventilation modes have some degree of spontaneous breathing, and the correct selection of PEEP therefore includes different criteria. It is important that these patients be weaned as quickly as possible, and PEEP is reduced as part of that process. If the setting of PEEP is too low, there is a risk of increased resistance to airflow with added respiratory work and consequent risk of respiratory muscle fatigue. If the patient has intrinsic PEEP due to dynamic hyperinflation, reducing PEEP below the level of intrinsic PEEP would also cause increased inspiratory threshold load on the respiratory muscles, and potential muscle fatigue. If PEEP is too high the respiratory muscle fibres may be shortened reducing their pressure generating capacity and endurance thus increasing the risk of respiratory muscle fatigue. Changing pressure support may help to work against an additional workload, as in cases of increased resistance or autoPEEP, whilst correct PEEP may counter the additional load.

The above factors are taken into account by the physiological models of the Beacon Caresystem, and patient specific advice is also provided on PEEP. In addition to providing advice on changing individual ventilator settings, the system also advises on when measurement of arterial blood gas is necessary, when it is important to change ventilator mode, and when a spontaneous breathing test is passed, and as such extubation should be considered.

However, previous and ongoing studies with the Beacon Caresystem have focused on safety and efficacy of advice under limited time periods, and have not focused on weaning from mechanical ventilation. A current study is underway in a French hospital (Clinical Trials number: NCT02842944), and at a UK hospital (IRAS 226610), to assess the benefit of the Beacon Caresystem in general medical intensive care patients. However, as mechanical ventilation therapy can vary with different patient populations it is important that investigation of the effects of use of the Beacon system be studied in numerous different clinical situations. In contrast to other studies, this study will investigate the effects of the Beacon Caresystem in ICU patients with primary cardio-thoracic disease, with these patients representing a substantial sub group of all ICU patients worldwide.

The purpose of this study is to compare mechanical ventilation following advice from the Beacon Caresystem to that of routine care in cardio-thoracic ICU patients from the start of requiring invasive mechanical ventilation until ICU discharge or death. The Beacon Caresystem will be compared to routine care to investigate whether use of the system results in similar care or reduced time for weaning from mechanical ventilation.

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 286 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Single (Outcomes Assessor)
• Primary Purpose: Supportive Care
• Official Title: Weaning Algorithm for Mechanical VEntilation (WAVE Study): A Randomised Control Trial Comparing an Open-loop Decision Support System Versus Routine Care for Weaning From Mechanical Ventilation in the Cardiothoracic Intensive Care Unit
• Actual Study Start Date: September 24, 2018
• Estimated Primary Completion Date: October 1, 2021
• Estimated Study Completion Date: October 1, 2021

Arms and Interventions

Arm	Intervention/treatment
Experimental: Beacon Caresystem with weaning advice; Beacon care system set up to give weaning advice and options to accept or reject advice.	Device: Beacon Care System; Beacon has been developed by Mermaid Care in Denmark. BEACON is a critical care ventilation assist system (http://beaconcaresystem.com/beacon-5/), which potentially enables better ventilation strategies and a more efficient patient care workflow. As an add-on to standard ventilation systems it provides ventilation recommendations 24/7 based on non-stop, personalised monitoring/diagnostics of patients. Based on unique mathematical algorithms and physiological models, it recommends changes in ventilation settings, supporting the critical decision-making processes.
Beacon Caresystem for monitoring only; Beacon care system attached but only for data collection purposes. No advice will be given.	Device: Beacon Care System; Beacon has been developed by Mermaid Care in Denmark. BEACON is a critical care ventilation assist system (http://beaconcaresystem.com/beacon-5/), which potentially enables better ventilation strategies and a more efficient patient care workflow. As an add-on to standard ventilation systems it provides ventilation recommendations 24/7 based on non-stop, personalised monitoring/diagnostics of patients. Based on unique mathematical algorithms and physiological models, it recommends changes in ventilation settings, supporting the critical decision-making processes.

Outcome Measures

Primary Outcome Measures :

1. Duration of mechanical ventilation [ Time Frame: Until the date of discharge from ICU, up to 12 months. ]
   Defined as the time from the start of mechanical ventilation, defined as either the time of intubation in the ICU (or the time of admission to the ICU following previous intubation for surgery) and until successful extubation, with successful extubation defined as ≥48 hours of unassisted spontaneous breathing after extubation.

Secondary Outcome Measures :

1. Duration of mechanical ventilation following randomisation [ Time Frame: Until the date of discharge from ICU, up to 12 months. ]
   Defined as the time from randomisation and until successful extubation, with successful extubation defined as ≥48 hours of unassisted spontaneous breathing after extubation.
2. Time from control mode to support mode [ Time Frame: Until the date of discharge from ICU, up to 12 months. ]
   Defined as the time following randomisation, from initiation of control modes of ventilation and until initiation of support modes of ventilation.
3. Time from support mode to successful extubation [ Time Frame: Until the date of discharge from ICU, up to 12 months. ]
   Defined as the time following randomisation, from initiation of support modes of ventilation and until successful extubation.
4. Number of changes in ventilator settings per day [ Time Frame: Until the date of discharge from ICU, up to 12 months. ]
   Defined as the daily registered number of changes to ventilator settings from patient randomization until successful extubation.
5. Time to first spontaneous breathing test (SBT) [ Time Frame: Until the date of discharge from ICU, up to 12 months. ]
   Defined as the time from randomization to the first performed SBT.
6. Time to first successful SBT [ Time Frame: Until the date of discharge from ICU, up to 12 months. ]
   Defined as the time from randomization to the first successful SBT.
7. Time to first extubation [ Time Frame: Until the date of discharge from ICU, up to 12 months. ]
   Defined as the time from randomization to the first extubation attempt.
8. % of time in control mode ventilation [ Time Frame: Until the date of discharge from ICU, up to 12 months. ]
   Defined as the time from randomization spent in controlled modes of mechanical ventilation in percent of duration of mechanical ventilation
9. % of time in support mode ventilation [ Time Frame: Until the date of discharge from ICU, up to 12 months. ]
   Defined as the time from randomisation which is spent in support modes of mechanical ventilation in percent of duration of mechanical ventilation
10. Time to first period trachemask [ Time Frame: Until the date of discharge from ICU, up to 12 months. ]
    Defined as the time of randomisation to the point of trachemask initiation.
11. Use of neuromuscular blockading agents [ Time Frame: Until the date of discharge from ICU, up to 12 months. ]
    Defined as the cumulative use of neuromuscular blockading agents from randomization until successful extubation.
12. Use of sedatives [ Time Frame: Until the date of discharge from ICU, up to 12 months. ]
    Defined as the cumulative use of sedative drugs from randomization until successful extubation.
13. Number of intubation free days [ Time Frame: Until the date of discharge from ICU, up to 12 months. ]
    Defined as the number of days without intubation from randomization until successful extubation.
14. Number of reintubations [ Time Frame: Until the date of discharge from ICU, up to 12 months. ]
    Defined as the number of reintubations following extubation from randomization until successful extubation.
15. Number of tracheostomies [ Time Frame: Until the date of discharge from ICU, up to 12 months. ]
    Defined as the number of patients having tracheostomy performed from randomization until successful extubation or protocol end.
16. Number of patients on prolonged mechanical ventilation [ Time Frame: Until the date of discharge from ICU, up to 12 months. ]
    Defined as the number of patients on mechanical ventilation ongoing for more than 21 days after initial intubation.
17. Number and types of adverse events related to mechanical ventilation [ Time Frame: Until the date of discharge from ICU, up to 12 months. ]
    Defined as the incidence of adverse events directly related to mechanical ventilation
18. Frequency of accepting Beacon care system advice [ Time Frame: Until the date of discharge from ICU, up to 12 months. ]
    Number of times and the reasons the advice from the Beacon system is overridden and not accepted by a treating clinician.
19. ICU mortality [ Time Frame: Until the date of discharge from ICU, up to 12 months. ]
    defined as the mortality from randomization and until death or ICU discharge.
20. Hospital mortality [ Time Frame: Until the date of discharge from ICU, up to 12 months. ]
    defined as the mortality from randomization and until death or hospital discharge.
21. Length of ICU stay [ Time Frame: Until the date of discharge from ICU, up to 12 months. ]
    defined as the duration of ICU admission from randomization to ICU discharge
22. Length of hospital stay [ Time Frame: Until the date of discharge from hospital, up to 12 months. ]
    defined as the duration of hospital admission from randomization to hospital discharge
23. Time to first mobilization [ Time Frame: Until the date of discharge from ICU, up to 12 months. ]
    Defined as the time from randomisation until first mobilization, e.g. sitting on the edge of the bed, standing up and marching on the spot
24. Time to independent mobilization [ Time Frame: Until the date of discharge from ICU, up to 12 months. ]
    Defined as the time from randomisation until regaining independency, e.g. able to drink/eat or comb hair.
25. Daily patient physiological blood gas status [ Time Frame: Until the date of discharge from ICU, up to 12 months. ]
    Defined as daily PaO2/FiO2 from randomization until successful extubation.
26. Changes in Oxygenation Index [ Time Frame: Until the date of discharge from ICU, up to 12 months. ]
    defined as daily averages of oxygenation index (Oxygen Index (OI) = (FiO2 x Mean Alveaolr Pressure x 100) / PaO2
27. Changes in anatomical dead space volume [ Time Frame: Until the date of discharge from ICU, up to 12 months. ]
    defined as daily changes in dead space volume as continuously measured by the Beacon system.
28. Changes in pulmonary shunt fraction [ Time Frame: Until the date of discharge from ICU, up to 12 months. ]
    defined as daily changes in pulmonary shunt fraction as continuously measured by the Beacon system.
29. Changes in end-tidal end-tidal CO2 fraction (FE'CO2) [ Time Frame: Until the date of discharge from ICU, up to 12 months. ]
    defined as daily changes in end-tidal CO2 fraction as continuously measured by the Beacon system.
30. Changes in pulmonary mechanics [ Time Frame: Until the date of discharge from ICU, up to 12 months. ]
    defined as daily changes in respiratory system compliance as continuously measured by the Beacon system.
31. Changes in metabolism [ Time Frame: Until the date of discharge from ICU, up to 12 months. ]
    defined as daily changes in resting energy expenditure as continuously measured by the Beacon system.
32. ICU/hospital lung imaging in relation to prolonged ventilation [ Time Frame: Until the date of discharge from hospital, up to 12 months. ]
    e.g. chest CT injury indices.
33. Timed-up-and-go at day 10 (or first mobilisation) and ICU/Hospital Discharge [ Time Frame: Until the date of discharge from hospital, up to 12 months. ]
    Timed-up-and-go at day 10 (or first mobilisation) and ICU/Hospital Discharge
34. Sit to stand at day 10 (or first mobilisation) and ICU/Hospital Discharge [ Time Frame: Until the date of discharge from hospital, up to 12 months. ]
    Sit to stand at day 10 (or first mobilisation) and ICU/Hospital Discharge
35. Chelsea Critical Care Physiotherapy Assessment score (CPAx) trajectory [ Time Frame: Until the date of discharge from hospital, up to 12 months. ]
    Chelsea Critical Care Physiotherapy Assessment score (CPAx) trajectory (performed every 72 hours)
36. Barthel index at hospital discharge [ Time Frame: Until the date of discharge from hospital, up to 12 months. ]
    Barthel index at hospital discharge
37. 6-minute walk test at hospital discharge [ Time Frame: Until the date of discharge from hospital, up to 12 months. ]
    6-minute walk test at hospital discharge
38. 3-month +/- 6-month +/- 1-year ICU follow-up lung imaging and function in relation to prolonged ventilation [ Time Frame: Until the date of discharge from hospital, up to 24 months. ]
    ICU follow-up lung imaging and function in relation to prolonged ventilation (as per current clinical protocol i.e. if clinically indicated, which may include pulmonary function tests, CT imaging).
39. Sf-36 Health Related Quality of life (patient and carers) [ Time Frame: Until one year after hospital discharge, up to 24 months. ]
    -Sf-36 Health Related Quality of life (patient and carers)
40. EQ-5D-5L [ Time Frame: Until one year after hospital discharge, up to 24 months. ]
    EQ-5D-5L
41. St George's Respiratory Questionnaire [ Time Frame: Until one year after hospital discharge, up to 24 months. ]
    St George's Respiratory Questionnaire
42. mini Mental State examination [ Time Frame: Until one year after hospital discharge, up to 24 months. ]
    mini Mental State examination
43. PTSS-14 [ Time Frame: Until one year after hospital discharge, up to 24 months. ]
    PTSS-14
44. Hospital Anxiety and Depression Scale (HADS) [ Time Frame: Until one year after hospital discharge, up to 24 months. ]
    Hospital Anxiety and Depression Scale (HADS)
45. Return to work rates e.g. W&SAS (patient and carers) [ Time Frame: Until one year after hospital discharge, up to 24 months. ]
    Return to work rates e.g. W&SAS (patient and carers)
46. Primary and Secondary care utilisation [ Time Frame: Until one year after hospital discharge, up to 36 months. ]
    Primary and Secondary care utilisation
47. 6-minute walk test [ Time Frame: Until one year after hospital discharge, up to 24 months. ]
    6-minute walk test

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion criteria:

• Patient remains on mechanical ventilation at 24 hours following intubation.
• Age > 18 years
• Patient consent or, in the case that the patient is unable, advice from the next of kin or treating physician following understanding and acceptance of oral and written information describing the study.

Exclusion criteria:

• The absence of an arterial catheter for blood sampling at study start.
• Mechanical ventilation initiated for more than 48 hours.
• Medical history of home mechanical ventilation which may lead to prolonged stay in the ICU, including long term oxygen therapy and non-invasive ventilation not associated with sleep apnoea.
• Patients mechanically ventilated in a ventilator mode, and by a ventilator not supported by the Beacon Caresystem on screening.
• Respiratory failure likely requiring extracorporeal support.
• Severe cardiogenic shock likely requiring extracorporeal support.
• Severe isolated right heart failure.
• Head trauma or other conditions where intra-cranial pressure may be elevated and tight regulation of arterial CO2 level is paramount.
• Primary (non-overdose related) neurological patients (Glasgow coma score <10, neurologic damage with limited prognosis, stroke hemiplegia).
• End stage liver disease.
• Repeated ICU admission within same hospital admission and/or likely to have prolonged ICU stay with mechanical ventilation (>21 days)
• Pregnancy.

Contacts and Locations

Contacts

Contact: Brijesh V Patel, MBBS MRCP FRCA FFICM PhD; +44 (0)20 7352 8121; brijesh.patel@imperial.ac.uk

Contact: Cliff Morgan, MBBS FRCA; +44 (0)20 7352 8121; c.morgan@rbht.nhs.uk

Locations

United Kingdom

Royal Brompton Hospital; Recruiting

London, United Kingdom, SW3 6NP

Contact: Brijesh V Patel, FRCA PhD +44 (0)20 7352 8121 b.patel4@rbht.nhs.uk

Principal Investigator: Cliff Morgan, MBBS FRCA

Harefield Hospital; Recruiting

Uxbridge, United Kingdom, UB9 6JH

Contact: Brijesh Patel

Sub-Investigator: Alex Rosenberg

Sponsors and Collaborators

Royal Brompton & Harefield NHS Foundation Trust

Mermaid Care A/S

Aalborg University

Imperial College London

Investigators

• Principal Investigator: Brijesh Patel, MBBS PhD; Royal Brompton & Harefield NHS Foundation Trust

More Information

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• Responsible Party: Royal Brompton & Harefield NHS Foundation Trust
• ClinicalTrials.gov Identifier: NCT03697785
• Other Study ID Numbers: REC Reference: 18/LO/0282; 239144 ( Other Identifier: IRAS Project ID )
• First Posted: October 5, 2018
• Last Update Posted: October 5, 2018
• Last Verified: October 2018

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Undecided

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Royal Brompton & Harefield NHS Foundation Trust:

weaning; cardiothoracic; mechanical ventilation; intensive care; critical care; beacon caresystem

Additional relevant MeSH terms:

Respiratory Insufficiency; Pulmonary Valve Insufficiency; Respiration Disorders; Respiratory Tract Diseases; Heart Valve Diseases; Heart Diseases; Cardiovascular Diseases