Comparison of Gas Exchange Between Two Invasive Mechanical Ventilation Modes in Children

Study Overview
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Brief Summary
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This study assesses the feasibility of digital data collection for a randomized controlled trial in a quaternary pediatric intensive care unit and the effect of two commonly used mechanical ventilation modes on gas exchange (CO2) in children over 2 days after randomization. This is a single-center, open-labelled, randomized controlled trial with two parallel 1:1 treatment arms: pressure controlled (PC) vs pressure-regulated volume controlled (PRVC) mechanical ventilation modes. Use to routine digital data is essential to enable health learning systems and to provide rapid clinical trials readiness, as the pandemic has demonstrated. Despite availability of data to perform digital trials in PICU settings, these are yet scarcely done.

Official Title
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Comparison of Carbon Dioxide Control During Pressure Controlled (PC) Versus Pressure Regulated Volume Control (PRVC) Ventilation in Children (CoCO2): A Digital, Randomized Controlled Trial

Conditions
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Respiratory Failure

Intervention / Treatment
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* Other: Respiratory support a
* Other: Respiratory support b


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Informed consent provided by the participant or the participant's parents or legal guardians. In case of an emergency situation, a physician who is independent of the research project must be consulted prior to inclusion in order to safeguard the interests of the test subject. Admission to PICU at the University Children's Hospital Zurich Need for mechanical ventilation for >60 min during PICU hospitalization. Need for mechanical ventilation will be based on clinical decision of the treating physician. Need for an arterial line during PICU hospitalization. Need for an arterial line will be based on clinical decision of the treating physician. Age <18 years Weight >2 Kg Exclusion Criteria: Substantial air leaks around the endotracheal tube (>30%) Cyanotic shunt lesions Intracranial hypertension (i.e. traumatic brain injury or patients admitted after neurosurgery) Pulmonary hypertension under treatment (i.e sildenafil or inhaled nitric oxide) Time from start of invasive mechanical ventilation until time of screening is > 24 hours Previous enrolment in the study in the past 30 days Inability of the parents or legal guardians to understand the study due to linguistic or cognitive reasons

Ages Eligible for Study
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Minimum Age: 0 Years
Maximum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Supportive Care
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: This is a single center, open labelled, randomized controlled trial with one to one allocation to two invasive mechanical ventilation modes used in clinical care as intervention arms
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Pressure control (PC)<br>In PC physicians set the inspiratory pressure and time, the respiratory rate and the PEEP while the ventilator measures tidal volume and the actual respiratory rate | Other: Respiratory support b<br>* Invasive mechanical ventilation mode<br>|
| Active Comparator: Pressure regulated volume control (PRVC)<br>In PRVC physicians set a target tidal volume and the respiratory rate. An algorithm delivers pressure using a decelerating flow pattern to reach the target tidal volume based on the lung compliance measured during previous breaths. | Other: Respiratory support a<br>* Invasive mechanical ventilation mode<br>* Other names: Target Vent is the brand name of the PRVC ventilation mode in the Bellavista ventilator;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Adherence to the allocated ventilation mode among randomized/enrolled participants | Main feasibility outcome | From time of randomization until 48 hours, extubation, discharge or death, whichever comes first (assessed up to 48 hours) | 
| Proportion of time spent within the target range of carbon dioxide (normocarbia, defined as carbon dioxide ≥ 35 mmHg or 4.5 kPa and ≤ 45 mmHg or 6 kPa) measured using end-tidal carbon dioxide recorded every minute by the ventilation device | Main physiological outcome | From time of randomization until 48 hours, extubation, discharge or death, whichever comes first (assessed up to 48 hours) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of patients who were screened, were missed, gave consent and were randomized/enrolled per month | Secondary feasibility outcome 1 | From date of recruitment start until date of recruitment end (assessed when n=60, anticipated through 6 months of recruitment period) | 
| Reasons for protocol violations | Other feasibility outcome 2a | From time of randomization until 48 hours, extubation, discharge or death, whichever comes first (assessed up to 48 hours since randomization) | 
| Time from randomization to protocol violation | Other feasibility outcome 2b | From time of randomization until time of protocol violation (assessed up to 48 hours) | 
| Proportion of enrolled participants with complete primary and secondary outcome data extracted from the electronic patient records | Other feasibility outcome 3 | From date of recruitment start until date of study end (assessed when n=60 and data has been extracted for all participants, anticipated through 8 months) | 
| Time from ventilation start until screening | Other feasibility outcome 4a | From time of ventilation start until time of screening (assessed up to 48 hours) | 
| Time from ventilation start until randomization | Other feasibility outcome 4b | From time of ventilation start until time of randomization (assessed up to 48 hours) | 
| Time from consent until randomization | Other feasibility outcome 5 | From time of consent signed until time of randomization (assessed up to 48 hours) | 
| Time weighted average of hypocarbia (carbon dioxide < 35 mmHg or 4.5 kPa), measured using continuous end-tidal carbon dioxide | Secondary physiological outcome 1a | From time of randomization until 48 hours, extubation, discharge or death, whichever comes first (assessed up to 48 hours) | 
| Time weighted average of hypocarbia (carbon dioxide < 35 mmHg or 4.5 kPa) measured using intermittent arterial blood measurements | Other physiological outcome 1b | From time of randomization until 48 hours, extubation, discharge or death, whichever comes first (assessed up to 48 hours) | 
| Time weighted average of hypocarbia (carbon dioxide < 35 mmHg or 4.5 kPa) measured using continuous transcutaneous carbon dioxide measurements calibrated with results of arterial blood gas analysis | Other physiological outcome 1c | From time of randomization until 48 hours, extubation, discharge or death, whichever comes first (assessed up to 48 hours) | 
| Time weighted average of hypercarbia (carbon dioxide > 45 mmHg or 6 kPa) measured using continuous end-tidal carbon dioxide | Other physiological outcome 2a | From time of randomization until 48 hours, extubation, discharge or death, whichever comes first (assessed up to 48 hours) | 
| Time weighted average of hypercarbia (carbon dioxide >45 mmHg or 6 kPa) measured using intermittent arterial blood measurements | Other physiological outcome 2b | From time of randomization until 48 hours, extubation, discharge or death, whichever comes first (assessed up to 48 hours) | 
| Time weighted average of hypercarbia (carbon dioxide > 45 mmHg or 6 kPa) measured using continuous transcutaneous carbon dioxide measurements calibrated with results of arterial blood gas analysis | Other physiological outcome 2c | From time of randomization until 48 hours, extubation, discharge or death, whichever comes first (assessed up to 48 hours) | 
| Time weighted average of hypo- and hypercarbia (i.e. outside normocarbia, carbon dioxide < 35 mmHg or 4.5 kPa; or carbon dioxide >45 mmHg or 6 kPa) measured using continuous end-tidal carbon dioxide | Other physiological outcome 3a | From time of randomization until 48 hours, extubation, discharge or death, whichever comes first (assessed up to 48 hours) | 
| Time weighted average of hypo- and hypercarbia (i.e. outside normocarbia, carbon dioxide < 35 mmHg or 4.5 kPa; or carbon dioxide >45 mmHg or 6 kPa) measured using intermittent arterial blood measurements | Other physiological outcome 3b | From time of randomization until 48 hours, extubation, discharge or death, whichever comes first (assessed up to 48 hours) | 
| Time weighted average of hypo- and hypercarbia (i.e. carbon dioxide < 35 mmHg or 4.5 kPa; or >45 mmHg or 6 kPa) measured using continuous transcutaneous carbon dioxide measurements calibrated with results of arterial blood gas analysis | Other physiological outcome 3c | From time of randomization until 48 hours, extubation, discharge or death, whichever comes first (assessed up to 48 hours) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Pediatrics, Child, Infant, Mechanical ventilation, Pressure control, Pressure regulated volume control, Randomized controlled trial