Ventilator-associated Injury (VAI) in Chronic Home Mechanical Ventilation

Respiratory Failure Clinical Trial

Official title:

Ventilator-associated Injury (VAI) in Chronic Home Mechanical Ventilation: a Paradigm Switch in Order to Improve Ventilatory Support

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04521426
• Other study ID #: VAI-HMV
• Status: Completed
• Start date: October 1, 2020
• Est. completion date: September 1, 2023

Study information

• Verified date: November 2023
• Source: University Medical Center Groningen
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

Rationale:

The pathophysiological changes in respiratory muscle morphology and functioning in patients with end-stage pulmonary disease are not very well known. Furthermore, in COPD, long-term high-intensity NIV is applied without knowing the exact consequences on the lungs and respiratory muscles.

Objective: The aims of the study are to get insight in:

A. changes respiratory muscles in end-stage respiratory disease, comparing COPD with restrictive lung disease (RLD) due to pulmonary fibrosis B. the effects of long-term HI-NIV in severe COPD patients on the respiratory muscles and the lungs; by comparing COPD patients that had been treated with long-term NIV to COPD patients that were not treated with long-term NIV.

Study design: In order to investigate this, the investigators will include in a small pilot cohort study patients being lung transplanted. In these patients there is lung tissue available and respiratory muscle biopsies will be performed during lung-transplant surgery.

Study population: Patients that are listed for lung transplantation for an underlying diagnosis of COPD or RLD will be asked to participate. Three groups will be included: patients with a RLD due to pulmonary fibrosis, COPD patients that had been treated with long-term NIV prior to being lung transplanted and COPD patients that were not treated with long-term NIV. Patients will be included definitely once being lung transplanted.

Main study parameters/endpoints: The study is an exploratory pilot study. Both contractile strength and the structure of single diaphragm and intercostal muscle fibres as well as lung injury; i.e. alveolar structure and damage and inflammation in the alveoli, will be investigated.

Description:

Rationale:

Chronic Obstructive Pulmonary Disease (COPD) is a progressive inflammatory disease characterised by airway and lung parenchyma damage. At end-stage disease patients may develop chronic hypercapnic respiratory failure, a disease characteristic that is however not uniformly seen in other end-stage lung diseases, such as in patients with pulmonary fibrosis. The underlying process for the development of chronic hypercapnic respiratory failure is incompletely understood and the role of respiratory muscle alterations is unclear.

Home noninvasive ventilation with high-intensity ventilatory settings (HI-NIV) has been shown to be effective in these severe COPD patients. However, in patients being mechanically ventilated on the intensive care unit for diverse reasons, high-intensity ventilation, especially high tidal volumes, has been shown to result in ventilator associated lung and diaphragm injury. Whether this occurs in home high-intensity NIV, is however completely unknown.

Objective: The aims of the study are to get insight in:

A. changes respiratory muscles in end-stage respiratory disease, comparing COPD with restrictive lung disease (RLD) due to pulmonary fibrosis B. the effects of long-term HI-NIV in severe COPD patients on the respiratory muscles; i.e. the contractile strength and the structure of single diaphragm and intercostal muscle fibres and the lungs; i.e. alveolar structure and damage and inflammation, by comparing COPD patients that had been treated with long-term NIV to COPD patients that were not treated with long-term NIV.

Study design: In order to investigate this, the investigators will include in a small pilot cohort study patients being lung transplanted. In these patients there is lung tissue available and respiratory muscle biopsies will be performed during lung-transplant surgery.

Study population: Patients that are listed for lung transplantation for an underlying diagnosis of COPD or RLD will be asked to participate. Three groups will be included: patients with a RLD due to pulmonary fibrosis, COPD patients that had been treated with long-term NIV prior to being lung transplanted and COPD patients that were not treated with long-term NIV. Patients will be included definitely once being lung transplanted.

Main study parameters/endpoints: The study is an exploratory pilot study. The study aims to get data on respiratory muscle and lung and airway pathology in order to, if important results are observed, set up a larger prospective trial investigating both clinical outcomes and pathology of the respiratory muscles/lungs. Both contractile strength and the structure of single diaphragm and intercostal muscle fibres as well as lung injury; i.e. alveolar structure and damage and inflammation in the alveoli, will be investigated.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 15
• Est. completion date: September 1, 2023
• Est. primary completion date: October 1, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

1. RLD: probable or confirmed diagnosis of interstitial pulmonary fibrosis (IPF) or other fibrotic lung disease of unknown origin.

2. COPD: GOLD stage III or IV

3. Being listed for lung transplantation

Exclusion Criteria:

1. Concomitant neuromuscular or systemic/collagen-vascular disease

2. Prior lung surgery (except for lung biopsies) or lung volume reduction treatment

3. Being unable to understand the patient information and consent for the study

Related Conditions & MeSH terms

• Long-term Non-invasive Ventilation
• Respiratory Failure
• Respiratory Insufficiency

Intervention

Other:
• No other than standard care
No other than standard care.

Locations

Country	Name	City	State
Netherlands	University Medical Center Groningen	Groningen

Sponsors (1)

Lead Sponsor	Collaborator
University Medical Center Groningen

Country where clinical trial is conducted

Netherlands, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Respiratory muscle morphology and functioning	Biopsies of the diaphragm and intercostal muscles will be taken during surgery	during surgery
Primary	Ventilator-associated lung injury serum TNF-alfa	serum TNF-alfa	during surgery
Primary	Ventilator-associated lung injury serum IL-6	serum IL-6	during surgery
Primary	Ventilator-associated lung injury serum IL-1beta	serum IL-1beta	during surgery
Primary	Ventilator-associated lung injury serum IL-8	serum IL-8	during surgery
Primary	Ventilator-associated lung injury serum MIP-2	serum MIP-2	during surgery
Primary	Ventilator-associated lung injury serum sRAGE	serum sRAGE	during surgery
Primary	Ventilator-associated lung injury BAL TNF-alfa	BAL TNF-alfa	during surgery
Primary	Ventilator-associated lung injury BAL IL-6	BAL IL-6	during surgery
Primary	Ventilator-associated lung injury BAL IL-1beta	BAL IL-1beta	during surgery
Primary	Ventilator-associated lung injury BAL IL-8	BAL IL-8	during surgery
Primary	Ventilator-associated lung injury BAL MIP-2	BAL MIP-2	during surgery
Primary	Ventilator-associated lung injury BAL sRAGE	BAL sRAGE	during surgery
Primary	Ventilator-associated lung injury basal membrane	histopathological changes to the basal membrane	during surgery
Primary	Ventilator-associated lung injury alveolar cells	histopathological changes to type I alveolar cells	during surgery
Primary	Ventilator-associated lung injury edema	edema in the alveoli and interstitium	during surgery
Primary	Ventilator-associated lung injury fibrin	interstitial fibrin	during surgery
Primary	Ventilator-associated lung injury inflammatory cells	Inflammatory cells influx in the alveoli	during surgery
Primary	Ventilator-associated lung injury gene-expression	Gene-expression profiling of epithelial cells with regard to inflammatory factors	during surgery
Secondary	Ventilatory use	Duration of usage (longitudinally and use per day)	during surgery
Secondary	Ventilatory settings	Settings of the NIV	during surgery
Secondary	Demographics_age	age	during surgery
Secondary	Demographics_gender	gender	during surgery
Secondary	Demographics_BMI	BMI	during surgery
Secondary	Lung Function_FEV1	FEV1	during surgery
Secondary	Lung Function_FVC	FVC	during surgery
Secondary	Blood gasses_PaCO2	PaCO2	during surgery
Secondary	Blood gasses_HCO3-	HCO3-	during surgery