Respiratory FailureNCT04521426
Ventilator-associated Injury (VAI) in Chronic Home Mechanical Ventilation
An observational study of Respiratory Failure and Long-term Non-invasive Ventilation, run by University Medical Center Groningen at 1 site in Netherlands.
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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Respiratory Failure, Long-term Non-invasive Ventilation
- Type of treatment
- Injection or infusion
- How many people
- 15 participants
- Where
- 1 siteNetherlands
- Study dates
- 1 Oct 2020to 1 Sep 2023
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Study population: see above
Who may be able to join
- RLD: probable or confirmed diagnosis of interstitial pulmonary fibrosis (IPF) or other fibrotic lung disease of unknown origin.
- COPD: GOLD stage III or IV
- Being listed for lung transplantation
Who cannot join
- Concomitant neuromuscular or systemic/collagen-vascular disease
- Prior lung surgery (except for lung biopsies) or lung volume reduction treatment
- Being unable to understand the patient information and consent for the study
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Ventilator-associated Injury (VAI) in Chronic Home Mechanical Ventilation: a Paradigm Switch in Order to Improve Ventilatory Support
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.
Read more
Objective: The aims of the study are to get insight in:
- 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.
Read the detailed 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:
- 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.
- Being tested
- No other than standard care
- Keywords
- COPD, Lung fibrosis, non-invasive ventilation, respiratory muscles, diaphragm, lung inflammation, ventilator-induced lung injury
- Medical subject headings
- Respiratory Insufficiency, Pulmonary Disease, Chronic Obstructive, Pulmonary Fibrosis, Pneumonia, Ventilator-Induced Lung Injury
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
No other than standard careOther
No other than standard care.
| Study group | Role | What they receive |
|---|---|---|
| Lung Fibrosis | 1. probable or confirmed diagnosis of interstitial pulmonary fibrosis (IPF) or other fibrotic lung disease of unknown origin.
2. being listed for lung transplantation Receives: Other: No other than standard care | |
| COPD standard therapy | 1. COPD: GOLD stage III or IV
2. being listed for lung transplantation
3. did not underwent LVR surgery or endoscopic LVR
4. not being treated with chronic NIV Receives: Other: No other than standard care | |
| COPD with long-term NIV | 1. COPD: GOLD stage III or IV
2. being listed for lung transplantation
3. did not underwent LVR surgery or endoscopic LVR
4. being treated with chronic NIV before lung transplantation (at least 1 months, at least 4 hours per day). Receives: Other: No other than standard care |
What is being measured
The primary outcome is the main question the study is designed to answer.
Respiratory muscle morphology and functioning
Biopsies of the diaphragm and intercostal muscles will be taken during surgery
Measured: during surgery
Ventilator-associated lung injury serum TNF-alfa
serum TNF-alfa
Measured: during surgery
Ventilator-associated lung injury serum IL-6
serum IL-6
Measured: during surgery
Ventilator-associated lung injury serum IL-1beta
serum IL-1beta
Measured: during surgery
Ventilator-associated lung injury serum IL-8
serum IL-8
Measured: during surgery
Ventilator-associated lung injury serum MIP-2
serum MIP-2
Measured: during surgery
Ventilator-associated lung injury serum sRAGE
serum sRAGE
Measured: during surgery
Ventilator-associated lung injury BAL TNF-alfa
BAL TNF-alfa
Measured: during surgery
Ventilator-associated lung injury BAL IL-6
BAL IL-6
Measured: during surgery
Ventilator-associated lung injury BAL IL-1beta
BAL IL-1beta
Measured: during surgery
Ventilator-associated lung injury BAL IL-8
BAL IL-8
Measured: during surgery
Ventilator-associated lung injury BAL MIP-2
BAL MIP-2
Measured: during surgery
Ventilator-associated lung injury BAL sRAGE
BAL sRAGE
Measured: during surgery
Ventilator-associated lung injury basal membrane
histopathological changes to the basal membrane
Measured: during surgery
Ventilator-associated lung injury alveolar cells
histopathological changes to type I alveolar cells
Measured: during surgery
Ventilator-associated lung injury edema
edema in the alveoli and interstitium
Measured: during surgery
Ventilator-associated lung injury fibrin
interstitial fibrin
Measured: during surgery
Ventilator-associated lung injury inflammatory cells
Inflammatory cells influx in the alveoli
Measured: during surgery
Ventilator-associated lung injury gene-expression
Gene-expression profiling of epithelial cells with regard to inflammatory factors
Measured: during surgery
Secondary outcomes (9)
Ventilatory use
Duration of usage (longitudinally and use per day)
Measured: during surgery
Ventilatory settings
Settings of the NIV
Measured: during surgery
Demographics_age
age
Measured: during surgery
Demographics_gender
gender
Measured: during surgery
Demographics_BMI
BMI
Measured: during surgery
Lung Function_FEV1
FEV1
Measured: during surgery
Lung Function_FVC
FVC
Measured: during surgery
Blood gasses_PaCO2
PaCO2
Measured: during surgery
Blood gasses_HCO3-
HCO3-
Measured: during surgery
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 Aug 2020
- Study start1 Oct 2020
- Primary completion1 Oct 2022
- Study completion1 Sep 2023
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Respiratory FailureStudies of the same condition, open and under way.
- More trials run by University Medical Center GroningenThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Case-control
- Time perspective
- Prospective
- Enrolment
- 15 participants (actual)
Sponsor and investigators
- Lead sponsor
- University Medical Center Groningen
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Marieke Duiverman, University Medical Center Groningen
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04521426
- Sponsor's protocol ID
- VAI-HMV
- Status last verified
- Nov 2023
- First submitted
- 29 Jul 2020
- Last updated
- 29 Nov 2023
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Study at a glance
From the registry record, last updated by the sponsor on 29 Nov 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Ventilator-associated Injury (VAI) in Chronic Home Mechanical Ventilation: a Paradigm Switch in Order to Improve Ventilatory Support
- ClinicalTrials.gov ID
- NCT04521426
- Acronym / sponsor ID
- VAI-HMV
- Keywords
- COPD, Lung fibrosis, non-invasive ventilation, respiratory muscles, diaphragm, lung inflammation, ventilator-induced lung injury
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 15 participants (actual)
- Lead sponsor
- University Medical Center GroningenUniversity, hospital or other
- Study start
- 1 Oct 2020 (actual)
- Primary completion
- 1 Oct 2022 (actual)
- Study completion
- 1 Sep 2023 (actual)
- First posted
- 20 Aug 2020 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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:
- 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.
Detailed 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:
- 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.
Study design
- Observational model
- Case-control
- Time perspective
- Prospective
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Lung Fibrosis | – | Other: No other than standard care1. probable or confirmed diagnosis of interstitial pulmonary fibrosis (IPF) or other fibrotic lung disease of unknown origin. 2. being listed for lung transplantation |
| COPD standard therapy | – | Other: No other than standard care1. COPD: GOLD stage III or IV 2. being listed for lung transplantation 3. did not underwent LVR surgery or endoscopic LVR 4. not being treated with chronic NIV |
| COPD with long-term NIV | – | Other: No other than standard care1. COPD: GOLD stage III or IV 2. being listed for lung transplantation 3. did not underwent LVR surgery or endoscopic LVR 4. being treated with chronic NIV before lung transplantation (at least 1 months, at least 4 hours per day). |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- see above
Key inclusion criteria (3 listed)
- RLD: probable or confirmed diagnosis of interstitial pulmonary fibrosis (IPF) or other fibrotic lung disease of unknown origin.
- COPD: GOLD stage III or IV
- Being listed for lung transplantation
Key exclusion criteria (3 listed)
- Concomitant neuromuscular or systemic/collagen-vascular disease
- Prior lung surgery (except for lung biopsies) or lung volume reduction treatment
- Being unable to understand the patient information and consent for the study
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| No other than standard careNo other than standard care. | Other | COPD standard therapy, COPD with long-term NIV, Lung Fibrosis |
Primary outcome
Respiratory muscle morphology and functioning
Time frame: during surgery
Biopsies of the diaphragm and intercostal muscles will be taken during surgery
Ventilator-associated lung injury serum TNF-alfa
Time frame: during surgery
serum TNF-alfa
Ventilator-associated lung injury serum IL-6
Time frame: during surgery
serum IL-6
Ventilator-associated lung injury serum IL-1beta
Time frame: during surgery
serum IL-1beta
Ventilator-associated lung injury serum IL-8
Time frame: during surgery
serum IL-8
Ventilator-associated lung injury serum MIP-2
Time frame: during surgery
serum MIP-2
Ventilator-associated lung injury serum sRAGE
Time frame: during surgery
serum sRAGE
Ventilator-associated lung injury BAL TNF-alfa
Time frame: during surgery
BAL TNF-alfa
Ventilator-associated lung injury BAL IL-6
Time frame: during surgery
BAL IL-6
Ventilator-associated lung injury BAL IL-1beta
Time frame: during surgery
BAL IL-1beta
Ventilator-associated lung injury BAL IL-8
Time frame: during surgery
BAL IL-8
Ventilator-associated lung injury BAL MIP-2
Time frame: during surgery
BAL MIP-2
Ventilator-associated lung injury BAL sRAGE
Time frame: during surgery
BAL sRAGE
Ventilator-associated lung injury basal membrane
Time frame: during surgery
histopathological changes to the basal membrane
Ventilator-associated lung injury alveolar cells
Time frame: during surgery
histopathological changes to type I alveolar cells
Ventilator-associated lung injury edema
Time frame: during surgery
edema in the alveoli and interstitium
Ventilator-associated lung injury fibrin
Time frame: during surgery
interstitial fibrin
Ventilator-associated lung injury inflammatory cells
Time frame: during surgery
Inflammatory cells influx in the alveoli
Ventilator-associated lung injury gene-expression
Time frame: during surgery
Gene-expression profiling of epithelial cells with regard to inflammatory factors
9 secondary outcomes
Ventilatory use
Time frame: during surgery
Ventilatory settings
Time frame: during surgery
Demographics_age
Time frame: during surgery
Demographics_gender
Time frame: during surgery
Demographics_BMI
Time frame: during surgery
Lung Function_FEV1
Time frame: during surgery
Lung Function_FVC
Time frame: during surgery
Blood gasses_PaCO2
Time frame: during surgery
Blood gasses_HCO3-
Time frame: during surgery
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 29 Nov 2023.
- Individual participant dataSharing planned: Undecided
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Respiratory Failure and Long-term Non-invasive Ventilation, run by University Medical Center Groningen at 1 site in Netherlands.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 3 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 29 Nov 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Netherlands. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Respiratory muscle morphology and functioning (time frame: during surgery). The study lists 19 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 29 Nov 2023.