## Protocol Section
### Identification Module
**NCT ID:** NCT06438198

**Acronym:** SWITCH-SAFE

**Brief Title:** Early Switch From Controlled to Assisted Ventilation

**Official Title:** Unraveling the (Patho)Physiological Mechanisms and Potential Clinical Benefits of an Early Switch From Controlled to Assisted Ventilation

#### Organization Study ID Info
**ID:** MEC-2024-0011
#### Organization
**Class:** OTHER
**Full Name:** Erasmus Medical Center
### Status Module
#### Completion Date
**Date:** 2026-05

**Type:** ESTIMATED

#### Expanded Access Info
#### Last Update Post Date
**Date:** 2024-05-31

**Type:** ESTIMATED

**Last Update Submit Date:** 2024-05-29

**Overall Status:** NOT_YET_RECRUITING

#### Primary Completion Date
**Date:** 2026-04

**Type:** ESTIMATED

#### Start Date
**Date:** 2024-05

**Type:** ESTIMATED

**Status Verified Date:** 2024-05

#### Study First Post Date
**Date:** 2024-05-31
**Type:** ESTIMATED
**Study First Submit Date:** 2024-05-14
**Study First Submit QC Date:** 2024-05-29
### Sponsor Collaborators Module

#### Lead Sponsor

**Class:** OTHER

**Name:** Erasmus Medical Center

#### Responsible Party

**Investigator Affiliation:** Erasmus Medical Center

**Investigator Full Name:** Annemijn Jonkman

**Investigator Title:** Assistant Professor

**Type:** PRINCIPAL_INVESTIGATOR

### Oversight Module

**Is FDA Regulated Device:** False

**Is FDA Regulated Drug:** False

**Oversight Has DMC:** False

### Description Module

**Brief Summary:** The goal of this physiological intervention study is to unravel the (patho)physiological mechanisms and potential clinical benefits of a pre-specified early switch from controlled to assisted ventilation in mechanically ventilated adult patients with acute hypoxemic respiratory failure (PaO2/FiO2 ratio \< 200 mmHg).

The intervention is that participants will be switched from controlled to assisted ventilation when PaO2/FiO2 ratio \> 200 mmHg.

The primary endpoint is the change in regional lung stress (as derived by electrical impedance tomography) when switching from controlled to assisted ventilation and until a successful or failed switch.

**Detailed Description:** A crucial milestone in the trajectory of the mechanically ventilated patient is the switch from fully controlled mechanical ventilation to assisted ventilation. This switch should be made as early as feasible and safe, to limit the detrimental effects from prolonged controlled ventilation and sedation. However, there is also indirect evidence that excessive breathing effort during assisted ventilation may worsen lung injury (P-SILI). There are no guidelines that address this important switch moment.

Therefore, the overall aim of this physiological intervention study is to unravel the (patho)physiological mechanisms and potential clinical benefits of a pre-specified early switch from controlled to assisted ventilation in mechanically ventilated adult patients with acute hypoxemic respiratory failure (PaO2/FiO2 ratio \< 200 mmHg).

Participants will be switched from controlled to assisted ventilation switch when PaO2/FiO2 ratio \> 200 mmHg and will be monitored continuously using electrical impedance tomography, and oesophageal and gastric pressure until 4 hours post-switch and twice daily for 72 hours or until switch failure (switch back to controlled ventilation within 72 hours).

The primary endpoint is the change in regional lung stress (as derived by electrical impedance tomography) when switching from controlled to assisted ventilation and until a successful or failed switch.

### Conditions Module

**Conditions:**

- Acute Hypoxemic Respiratory Failure

- Mechanical Ventilation

**Keywords:**

- Electrical Impedance Tomography

- Esophageal manometry

- Controlled Mechanical Ventilation

- Assisted Mechanical Ventilation

- Respiratory Monitoring

### Design Module

#### Design Info

**Allocation:** NA

**Intervention Model:** SINGLE_GROUP

##### Masking Info

**Masking:** NONE

**Primary Purpose:** BASIC_SCIENCE

#### Enrollment Info

**Count:** 20

**Type:** ESTIMATED

**Phases:**

- NA

**Study Type:** INTERVENTIONAL

### Arms Interventions Module

#### Arm Group 1

**Description:** Switch from controlled to assisted mechanical ventilation when PaO2/FiO2-ratio \> 200 mmHg.

Before switch (on controlled ventilation) participants will undergo an electrical impedance tomography (EIT) perfusion measurement as well as a photon-counting CT (PCCT) scan to assess lung perfusion and ventilation/perfusion mismatch. From 15 minutes before until 4 hours after switch and 30 minutes twice daily for 72 hours or until switch failure participants will be monitored continuously using EIT, esophageal pressure and gastric pressure.

**Intervention Names:**

- Other: Pre-specified switch from controlled to assisted ventilation when PaO2/FiO2-ratio > 200 mmHg

**Label:** Mechanically ventilated adults

**Type:** EXPERIMENTAL

### Interventions

#### Intervention 1

**Arm Group Labels:**

- Mechanically ventilated adults

**Description:** A pre-specified switch from controlled to assisted ventilation will be initiated when PaO2/FiO2-ratio \> 200 mmHg. The moment of switch is pre-specified but patient management and ventilator settings are up to the clinical team. Switch is complete when the patient triggers all breaths spontaneously. Switch success is defined if patient reaches 72 hours on assisted ventilation. Switch failure is defined if patient switches back to controlled ventilation for more than 2 hours before 72 hours.

**Name:** Pre-specified switch from controlled to assisted ventilation when PaO2/FiO2-ratio > 200 mmHg

**Type:** OTHER

### Outcomes Module

#### Primary Outcomes

**Description:** The change in regional lung stress as derived from EIT recordings by computing the regional ventilation distribution (ventral-to-dorsal ratio).

**Measure:** Regional lung stress

**Time Frame:** 72 hours

#### Secondary Outcomes

**Description:** Change in EIT parameters after transition from controlled to assisted ventilation (%)

**Measure:** Electrical Impedance Tomography (EIT) parameters

**Time Frame:** 72 hours

**Description:** Ventilation/perfusion mismatch during controlled ventilation measured with photon-counting CT scan

**Measure:** Photon-Counting Computed Tomography (PCCT)-derived ventilation/perfusion mismatch

**Time Frame:** 30 minutes

**Description:** Ventilation/perfusion mismatch during controlled ventilation measured with EIT

**Measure:** Electrical Impedance Tomography (EIT)-derived ventilation/perfusion mismatch

**Time Frame:** 30 minutes

**Description:** Change in respiratory mechanics after transition from controlled to assisted ventilation (cmH2O)

**Measure:** Respiratory mechanics

**Time Frame:** 72 hours

**Description:** Time-course of breathing effort during assisted ventilation as measured with esophageal manometry (cmH2O).

**Measure:** Breathing effort

**Time Frame:** 72 hours

**Description:** Percentage of asynchronous breaths during assisted ventilation

**Measure:** Patient-ventilator asynchrony

**Time Frame:** 72 hours

**Description:** Change in gas exchange after transition from controlled to assisted ventilation (%)

**Measure:** Gas exchange

**Time Frame:** 72 hours

**Description:** Change in hemodynamics after transition from controlled to assisted ventilation (%)

**Measure:** Hemodynamics

**Time Frame:** 72 hours

**Description:** Blood biomarkers concentrations including cytokines and chemokines (i.e., interleukins, TNF-alpha, MCP-1 and MIP-1beta, CD14) measured as the difference between baseline vs. 72h (%)

**Measure:** Blood inflammatory biomarkers

**Time Frame:** 72 hours

**Description:** Swivel-derived exhaled-breath condensate biomarkers concentrations including cytokines and chemokines (i.e., interleukins, TNF-alpha, MCP-1 and MIP-1beta, CD14) measured as the difference between baseline vs. 72h (%)

**Measure:** Breath condensate inflammatory biomarkers

**Time Frame:** 72 hours

**Description:** Ventilator-free days at day 28

**Measure:** Ventilator-free days

**Time Frame:** 28 days

### Eligibility Module

**Eligibility Criteria:** Inclusion Criteria:

* 18 years old
* Written informed consent from a legal representative
* Mechanical ventilation via an endotracheal tube
* Acute hypoxemic respiratory failure with PaO2/FiO2 ratio \< 200 mmHg
* Under continuous sedation with or without paralysis

Exclusion Criteria:

* Expected mechanical ventilation duration of \<48 hours
* Pure chronic obstructive pulmonary disease exacerbation
* Pre-existent respiratory muscle disease
* Contraindication to EIT monitoring (as per clinical protocol, e.g. pacemaker, burns or thoracic wounds limiting electrode placement)
* Contra-indications to oesophageal manometry (as per clinical protocol, e.g., recent oesophageal surgery, oesophageal varices, severe bleeding disorders)
* Known pregnancy
* Anticipating withdrawal of life support and/or shift to palliation as the goal of care

**Minimum Age:** 18 Years

**Sex:** ALL

**Standard Ages:**

- ADULT

- OLDER_ADULT

### Contacts Locations Module

#### Central Contacts

**Contact 1:**

**Email:** a.jonkman@erasmusmc.nl

**Name:** Annemijn Jonkman, PhD

**Phone:** +3110-7035142

**Role:** CONTACT

#### Overall Officials

**Official 1:**

**Affiliation:** Erasmus Medical Center

**Name:** Annemijn Jonkman, PhD

**Role:** PRINCIPAL_INVESTIGATOR

### IPD Sharing Statement Module

**IPD Sharing:** NO

## Derived Section

### Condition Browse Module - Ancestors

- ID: D000012120

- Term: Respiration Disorders

- ID: D000012140

- Term: Respiratory Tract Diseases

### Condition Browse Module - Browse Branches

- Abbrev: BC08

- Name: Respiratory Tract (Lung and Bronchial) Diseases

- Abbrev: All

- Name: All Conditions

- Abbrev: Rare

- Name: Rare Diseases

### Condition Browse Module - Browse Leaves

- ID: M14968

- Name: Respiratory Insufficiency

- Relevance: HIGH

- As Found: Acute Hypoxemic Respiratory Failure

- ID: M14957

- Name: Respiration Disorders

- Relevance: LOW

- As Found: Unknown

- ID: M14977

- Name: Respiratory Tract Diseases

- Relevance: LOW

- As Found: Unknown

- ID: T170

- Name: Acute Graft Versus Host Disease

- Relevance: LOW

- As Found: Unknown

### Condition Browse Module - Meshes

- ID: D000012131

- Term: Respiratory Insufficiency

### Misc Info Module

- Version Holder: 2024-05-31
