Clinical trial NCT05899894: NAVA in Infants With Acute Viral Bronchiolitis: A Feasibility Study
Official title: Neurally Adjusted Ventilatory Assist (NAVA) Use in Infants With Acute Viral Bronchiolitis: a Randomised, Crossover Feasibility Study
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Acute Viral Bronchiolitis
Lead sponsor: Guy's and St Thomas' NHS Foundation Trust
Sponsor class: OTHER
First posted: 2023-06-12
Enrollment: 16
Sex: ALL
Minimum age (years): 1
Maximum age (years): 1
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Intervention model description: Patients will act as their own control. They will be randomised on day 1 to receive either standard dose or low dose morphine and on day two they will receive the alternate dose. Ventilation levels will be titrated as per a titration protocol.
Primary purpose: OTHER

Brief summary: This exploratory intervention feasibility study aims to evaluate the use of a novel mode of ventilation known as Neurally adjusted ventilatory assist (NAVA) in infants with acute viral bronchiolitis.

The main aims are:

1. To determine whether an optimal combination of NAVA support level and Positive End Expiratory Pressure (PEEP) exists that can:

   1. maximise aspects of respiratory muscle unloading and
   2. minimize air trapping
2. To evaluate the impact of two morphine infusion doses on comfort levels and respiratory drive (standard = 20mcg/kg/hr, low = 5mcg/kg/hr) during ventilation titration.

Patients will act as their own control and will be randomly allocated to receive either standard or low dose morphine. They will receive the alternate dose on day 2. During each period of morphine dosing ventilation levels will be titrated and vital signs, respiratory parameters and comfort b scales will be recorded.

Detailed description: This study is a Randomised, non-blinded, crossover (morphine dose), mode of ventilation feasibility study to evaluate the use of NAVA in infants with acute viral bronchiolitis.

Background and study aims:

This study aims to evaluate a novel mode of mechanical ventilation (breathing machine), Neurally Adjusted Ventilatory Assist (NAVA), in infants admitted to the paediatric intensive care unit (PICU) with acute viral bronchiolitis. This respiratory illness accounts for 12% of PICU admissions nationally. Current modes of ventilation are inefficient, often requiring prolonged use of sedative drugs for comfort and to improve ease of ventilation (synchronicity). Consequences of prolonged sedative use are muscle wastage including the respiratory muscles, increased risk of developing secondary infections and the potential for withdrawal from medication symptoms.

NAVA is a mode of ventilation that is delivered using our current ventilators (breathing machines). However, it differs from current modes by providing respiratory support in proportion to the signal from the brain to move the diaphragm, this is achieved via measurement of electrical activity of the diaphragm (the main muscle used to initiate a breath). This is measured by using a modified version of the patients' feeding tube (which is used in PICU to feed patients whilst on a ventilator).

Research in children to date has demonstrated that NAVA, compared to other ventilatory modes, allows for improved ventilator synchrony, reduced work of breathing and potentially less sedative use. This is consistent with our clinical impression (we have been using NAVA in an ad hoc way for \>5 years). Although some of these studies included infants with bronchiolitis, the findings were not specific to this patient group. Of note, we do not yet know how to optimise NAVA settings in bronchiolitis, and whether current common sedative drugs (e.g. morphine) affect this, by decreasing respiratory drive excessively (potentially compromising NAVA utility).

We will evaluate how to optimise NAVA settings when compared to conventional ventilation in infants with acute viral bronchiolitis admitted to PICU. A range of NAVA settings will be systematically evaluated over two periods on consecutive days (maximum 4 hours per period per day). Observation of the effects of different levels of NAVA support on synchronicity, work of breathing and changes in physiological parameters will take place. Patients will also receive 2 different adjustments to their morphine infusions in random order on the consecutive days: standard dose morphine (20mcg/kg/hr) and low dose morphine (5mcg/kg/hr). Both morphine doses are within the range currently used clinically. Patient comfort will be assessed frequently throughout, and the effects of morphine on diaphragmatic neural activity will be recorded.

Who can participate:

* Infants aged \> 36 weeks corrected gestation and \< 1 year of age
* Admitted to PICU with acute viral bronchiolitis within 48 hours of admission
* Likely to require mechanical ventilation for \> 24 hours after enrolment
* Able to pass a nasogastric tube

What does the study involve:

Within 48 hours parents/carers of patients admitted with a primary diagnosis of acute viral bronchiolitis who meet the inclusion criteria will be approached by a member of the direct healthcare team and invited to take part in the study. The pre-existing feeding tubes will be replaced with NAVA catheters by the bedside nurse or research team. Ventilation modes will be titrated on 2 consecutive days accompanied by two different Morphine doses delivered to the participant in random order. Participants will be randomised to receive either standard dose morphine (20mcg/kg/hr) or low dose morphine (5 mcg/kg/hr). These doses have been chosen to reflect current clinical practice and also using knowledge of morphine kinetics/dynamics on infant respiratory drive.

Ventilation titration involves changes in NAVA level which increase over time and changes in PEEP which decrease over time to assess the ventilator setting that the patient responds to in terms of the outcome measures. This will enable identification of the optimum ventilation strategy for that participant. Titration will occur over time on 2 consecutive days as outlined above. There will be a wash in period of 5-10 minutes for each change in ventilator setting and a period of 5 minutes when the recordings of the outcome measures will take place.

Baseline recordings will be taken for current ventilator settings, vital signs and respiratory measures and COMFORT-behavioral scale (comfort/pain scale). Study procedures will be timed to accommodate routine care such as daily physiotherapy sessions.

Benefits and risks:

Due to changes in ventilation settings during the two NAVA/PEEP titration periods (one per day) there is the potential for the child to experience changes in their comfort levels and/or physiological parameters. These will be continuously monitored by the researchers and the clinical bedside team. If the patient experiences discomfort during the study period as expressed by a COMFORT-b the patient will be returned to the previous ventilator settings and the reasons for discomfort will be assessed. Pain and sedation guidance will be adhered to as per usual care.

Eligibility criteria: Inclusion Criteria:

* Infants aged \> 36 weeks corrected gestation and \< 1 year of age
* Admitted to PICU with acute viral bronchiolitis within 48 hours of admission
* Likely to require mechanical ventilation for \> 24 hours after enrolment
* Able to pass a nasogastric tube

Exclusion Criteria:

* Apnoea as a primary reason for ventilation in the absence of respiratory symptoms
* History of gastro-intestinal bleeds in previous 30 days or significant coagulopathy
* Facial trauma or surgery
* Known neuro-muscular disease or diaphragmatic palsy
* Haemodynamic instability (requiring inotropes)

Primary outcomes:
measure: Changes to neuroventilatory efficiency when ventilation parameters are titrated
timeFrame: Measures will be recorded during the intervention
measure: Changes to neuromuscular efficiency when ventilation parameters are titrated.
timeFrame: Measures will be recorded during the intervention
measure: Changes to air trapping when ventilation parameters are titrated
timeFrame: Measures will be recorded immediately after each intervention
measure: Change in Electrical activity of the diaphragm (Edi) when ventilator parameters are titrated
timeFrame: Measures will be recorded immediately after each intervention
measure: Maintenance of patient comfort
timeFrame: Measures will be recorded immediately after each intervention
measure: Changes in blood pressure
timeFrame: Measures will be recorded immediately after each intervention
measure: Changes in heart rate
timeFrame: Measures will be recorded immediately after each intervention
measure: changes in respiratory rate
timeFrame: Measures will be recorded immediately after each intervention
measure: Stabilisation of vital signs
timeFrame: Measures will be recorded immediately after each intervention
Secondary outcomes:
measure: To assess recruitment rate
timeFrame: On study completion up to 1 year
measure: To assess retention rates
timeFrame: On study completion up to 1 year
measure: To assess time to recruit participants
timeFrame: On study completion up to 1 year
measure: To record the incidence of adverse events
timeFrame: On study completion up to 1 year
measure: To assess the willingness of clinicians to recruit participants
timeFrame: On study completion up to 1 year
Other outcomes:
Locations:
city: London
country: United Kingdom
facility: Guys and St Thomas' NHS Foundation Trust
Study officials:
affiliation: Guy's and St Thomas' NHS Foundation Trust
name: Shane Tibby
role: PRINCIPAL_INVESTIGATOR
References: