Comparison of Gas Exchange Between Two Invasive Mechanical Ventilation Modes in Children (CoCO2)

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

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.

Study Overview

• Status: Completed
• Conditions: Respiratory Failure
• Intervention / Treatment: Other: Respiratory support b; Other: Respiratory support a

• Study Type: Interventional
• Enrollment (Actual): 59
• Phase: Phase 4

Contacts and Locations

Study Locations

• Switzerland
  • Zürich, Switzerland, 8032
    • University Children's Hospital Zurich

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Supportive Care
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Pressure control (PC); 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; Invasive mechanical ventilation mode
Active Comparator: Pressure regulated volume control (PRVC); 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; Invasive mechanical ventilation mode; Other Names: "Target Vent" is the brand name of the PRVC ventilation mode in the Bellavista ventilator

What is the study measuring?

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)

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Oxygenation index measured using peripheral oxygen saturation index	Other physiological outcome 4a (Peripheral oxygen saturation index = MAP * FiO2 *100 / SpO2; where MAP is mean airway pressure, FiO2 is fraction of inspired oxygen, SpO2 is peripheral oxygen saturation)	From time of randomization until 48 hours, extubation, discharge or death, whichever comes first (assessed up to 48 hours)
Oxygenation index measured using arterial oxygenation index	Other physiological outcome 4b (Arterial oxygenation index = MAP * FiO2 *100 / PaO2 ; where MAP is mean airway pressure, FiO2 is fraction of inspired oxygen, PaO2 is partial pressure of oxygen in arterial blood)	From time of randomization until 48 hours, extubation, discharge or death, whichever comes first (assessed up to 48 hours)

Collaborators and Investigators

• Sponsor: University Children's Hospital, Zurich
• Investigators: Principal Investigator: Rebeca Mozun, MD PhD, University Children's Hospital, Zurich

Study record dates

Study Major Dates

• Study Start (Actual): January 15, 2024
• Primary Completion (Actual): September 20, 2024
• Study Completion (Actual): September 20, 2024

Study Registration Dates

• First Submitted: January 24, 2023
• First Submitted That Met QC Criteria: April 24, 2023
• First Posted (Actual): May 6, 2023

Study Record Updates

• Last Update Posted (Estimated): December 13, 2024
• Last Update Submitted That Met QC Criteria: December 9, 2024
• Last Verified: December 1, 2024

More Information

Terms related to this study

• Keywords: Child; Randomized controlled trial; Pediatrics; Infant; Mechanical ventilation; Pressure control; Pressure regulated volume control
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Respiration Disorders; Respiratory Insufficiency
• Other Study ID Numbers: CoCO2

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED
• IPD Plan Description: The research team will have access to the dataset of this study. Anonymized data could be available upon reasonable request after approval from the research committee and sponsoring institution.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No