Continuous Flow Ventilation With the Ventijet System in Acute Respiratory Distress Syndrome: a First-in-Human Feasibility and Non-Inferiority Trial

NCT ID: NCT07121257

Last Updated: 2025-08-13

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 14 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2021-06-08
• Study Completion Date: 2023-03-16

Brief Summary

This prospective, non-randomized, single-arm, proof-of-concept clinical trial evaluates the physiological performance and safety of the Ventijet System, a hybrid ventilation system based on continuous high-velocity gas flow. The system was conceived during the coronavirus disease 2019 (COVID-19) pandemic as a response to ventilator shortages, building upon a previously patented continuous-flow nozzle system developed by Dr. Lucas Picazo in the 1990s. The concept combines the physiological benefits of continuous flow ventilation (CFV) with the potential ease of design, monitoring, and scalability.

Patients with moderate acute respiratory distress syndrome (ARDS) - defined by a ratio of arterial partial pressure of oxygen to inspired oxygen fraction (PaO₂/FiO₂) between 150 and 200 mmHg - were first stabilized on a conventional mechanical ventilator (Puritan Bennett 840, PB840) using lung-protective settings. They were then transitioned to the Ventijet system following a structured protocol that included real-time monitoring and esophageal pressure measurements.

The primary endpoint was oxygenation, measured as the change in PaO₂ after one hour of ventilation with the Ventijet system compared to baseline values under conventional ventilation. The study was designed to demonstrate non-inferiority, with a predefined margin of ±20 mmHg in PaO₂.

Secondary outcomes included carbon dioxide clearance (PaCO₂), respiratory system mechanics, safety events, and feasibility in intensive care unit (ICU) conditions.

Detailed Description

This is a prospective, interventional, single-center clinical study conducted to evaluate the physiological effects and safety of a novel ventilation system-continuous flow ventilation with Ventijet-in adult patients diagnosed with moderate acute respiratory distress syndrome (ARDS). The objective was to compare gas exchange and pulmonary mechanics between conventional pressure-controlled ventilation and the Ventijet system, which delivers continuous flow through a high-velocity nozzle.

Ventijet is a prototype mechanical ventilator developed during the COVID-19 pandemic, motivated by the urgent need for scalable and physiologically effective ventilatory support. The system builds on the concept of continuous-flow extratracheal jet ventilation (VC-ET), originally described and patented by Dr. Lucas Picazo in the 1990s. It generates a high-speed continuous gas stream via a proximally placed nozzle (tobera), which creates an expiratory braking effect. This facilitates alveolar recruitment throughout the respiratory cycle while maintaining low airway pressures and small tidal volumes. Unlike classical jet systems, Ventijet integrates real-time safety monitoring and operates using time-cycled, volume-controlled settings, making it suitable for intensive care unit (ICU) use.

Inclusion and Exclusion Criteria

Patients were screened in the ICU and included if they met all of the following:

• Age ≥ 18 years
• Intubated and on invasive mechanical ventilation
• Diagnosis of moderate ARDS (PaO₂/FiO₂ ratio between 150-200 mmHg, Berlin definition)
• Richmond Agitation-Sedation Scale (RASS) score of -5 (deep sedation)
• Stable hemodynamic and ventilatory parameters

Exclusion criteria included:

• Obstructive pulmonary disease (e.g., chronic obstructive pulmonary disease [COPD], asthma)
• Known intracranial hypertension
• Pregnancy
• Morbid obesity (body mass index [BMI] ≥ 40 kg/m²)
• Contraindication to esophageal balloon catheter placement

Study Protocol and Ventilation Phases

All patients were first stabilized on a conventional ICU ventilator (Puritan Bennett™ 840) with lung-protective settings:

• Tidal volume ≤ 6 mL/kg predicted body weight (PBW)
• Positive end-expiratory pressure (PEEP) titrated to maintain an end-expiratory transpulmonary pressure (PLexp) between 0-2 cm H₂O
• Respiratory rate adjusted to maintain arterial pH > 7.30
• Fraction of inspired oxygen (FiO₂) adjusted to maintain oxygen saturation (SpO₂) > 92%

Once stability was confirmed, patients remained on these settings for 1 hour (Conventional-1h phase), after which a full dataset was collected, including:

• Arterial blood gas (ABG) analysis
• Respiratory and ventilatory parameters
• Hemodynamic variables
• Pulmonary mechanics

Patients were then transitioned to the Ventijet system using end-expiratory clamping to avoid alveolar derecruitment. Ventijet parameters were adjusted to approximate the previous conventional settings. After 1 hour on Ventijet (VJ-1h phase), the same dataset was recorded. This timepoint served as the primary comparison for non-inferiority analysis of oxygenation (PaO₂).

Patients who remained stable on Ventijet continued for up to 24 hours. Additional datasets were collected at 6, 12, and 24 hours (VJ-6h, VJ-12h, VJ-24h). Afterward, they were reconnected to the conventional ventilator (again using end-expiratory clamping), and evaluations were repeated at 1, 12, and 24 hours post-reconnection (Post-VJ-1h, Post-VJ-12h, Post-VJ-24h).

Monitoring and Data Collection Each study phase was supervised continuously by a trained investigator. A CARESCAPE™ B650 monitoring system (General Electric™) was used to capture ventilatory and hemodynamic parameters. Active humidification was maintained throughout. Deep sedation (RASS -5) was ensured during all Ventijet phases.

Variables collected at each phase included:

• Clinical and demographic data
• Age, sex, ICU admission diagnosis
• Comorbidities, corticosteroid use
• Neuromuscular blockers, vasoactive drugs
• Gas exchange
• Arterial partial pressures: oxygen (PaO₂), carbon dioxide (PaCO₂)
• pH, bicarbonate (HCO₃-), arterial oxygen saturation (SaO₂)
• Ventilatory variables
• Tidal volume (VT), respiratory rate (RR), PEEP
• FiO₂, inspiratory time, end-tidal CO₂ (EtCO₂), SpO₂
• Hemodynamics
• Mean arterial pressure (MAP), heart rate (HR)
• Pulmonary mechanics
• Esophageal pressure (Pes)
• Transpulmonary pressures (PLinsp, PLexp)
• Compliance of the respiratory system (Crs), lung (CL), and chest wall (Ccw)
• Driving pressures (airway and transpulmonary)

Outcomes

• Primary outcome: Change in PaO₂ between Conventional-1h and VJ-1h phases. The study was powered as a non-inferiority trial using a predefined margin of ±20 mmHg in PaO₂. Based on an estimated standard deviation of 30 mmHg, the required sample size was 14 patients (α=0.05, β=0.2).
• Secondary outcomes: Change in PaCO₂ across all phases.
• Other prespecified outcomes (collected and reported):
• Changes in respiratory mechanics (compliance, pressures)
• Duration of mechanical ventilation
• ICU and hospital length of stay
• Need for tracheostomy
• ICU, in-hospital, and 1-year mortality

Safety and Oversight

Adverse events were continuously monitored. Protocol mandated immediate reconnection to the conventional ventilator in case of:

• Hemodynamic instability
• Worsening gas exchange
• Equipment malfunction

The study was conducted in compliance with Good Clinical Practice (GCP) guidelines and was externally monitored by the Clinical Research Support Unit (SEIC) at Biocruces Bizkaia.

Conditions

ARDS; Mechanical Ventilation; Hypoxemic Respiratory Failure

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Continuous Flow Ventilation with VENTIJET

All patients were initially ventilated with a conventional mechanical ventilator (PB840) under lung-protective settings. After a 1-hour stabilization and baseline assessment period, patients were transitioned to continuous flow ventilation using the Ventijet system for up to 24 hours, followed by reconnection to the conventional ventilator for post-intervention follow-up.

Group Type: EXPERIMENTAL

VENTIJET system

Intervention Type: DEVICE

The Ventijet system is an investigational ventilation device delivering continuous high-velocity gas flow through a proximal nozzle. The system is designed to maintain alveolar recruitment with low driving pressures, acting as an expiratory brake. Patients received continuous flow ventilation using Ventijet for 1 to 24 hours after baseline assessment with conventional mechanical ventilation.

Interventions

VENTIJET system

The Ventijet system is an investigational ventilation device delivering continuous high-velocity gas flow through a proximal nozzle. The system is designed to maintain alveolar recruitment with low driving pressures, acting as an expiratory brake. Patients received continuous flow ventilation using Ventijet for 1 to 24 hours after baseline assessment with conventional mechanical ventilation.

Intervention Type: DEVICE

Other Intervention Names

Continuous Flow Ventilation

Eligibility Criteria

Inclusion Criteria

• Age ≥ 18 years.
• Invasive mechanical ventilation via endotracheal tube.
• Diagnosis of moderate ARDS according to the Berlin Definition (PaO₂/FiO₂ between 150 and 200 mmHg with PEEP ≥ 5 cmH₂O).
• Lung-protective ventilation strategy prior to inclusion (VT ≤ 6 mL/kg PBW, PEEP titrated to transpulmonary pressure 0-2 cmH₂O).
• Deep sedation with RASS score of -5 at the time of inclusion.
• Informed consent obtained from the patient's legal representative.

Exclusion Criteria

• Known obstructive pulmonary disease (e.g., COPD, asthma).
• Severe hemodynamic instability or uncontrolled shock.
• Pregnancy.
• Do-not-resuscitate (DNR) orders or limitations of life support.
• Anticipated need for ECMO in the next 24 hours.
• Presence of pneumothorax or bronchopleural fistula.
• Contraindications to esophageal pressure monitoring.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Hospital del Mar Research Institute (IMIM)

OTHER

Sponsor Role: collaborator

Hospital del Mar

OTHER

Sponsor Role: lead

Responsible Party

Lucía Picazo Moreno

Principal Investigator and Intensive Care Specialist at Hospital del Mar

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Lucía Picazo, MD

Role: PRINCIPAL_INVESTIGATOR

Intensive Care Department, Hospital del Mar

Locations

Hospital del Mar

Barcelona, Barcelona, Spain

Countries

Spain

Other Identifiers

2020/9238

Identifier Type: OTHER

Identifier Source: secondary_id

Ventijet01

Identifier Type: -

Identifier Source: org_study_id