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Trial registered on ANZCTR


Registration number
ACTRN12616001321437
Ethics application status
Approved
Date submitted
8/09/2016
Date registered
21/09/2016
Date last updated
5/09/2018
Type of registration
Prospectively registered

Titles & IDs
Public title
Study of the diaphragmatic function in patients with respiratory failure treated by standard oxygenotherapy, high-flow nasal oxygenotherapy, and noninvasive ventilation
Scientific title
Diaphragmatic ultrasound to assess respiratory workload during standard oxygenotherapy, high-flow nasal oxygenotherapy, noninvasive ventilation in respiratory failure
Secondary ID [1] 290090 0
None
Universal Trial Number (UTN)
U1111-1187-2058
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Acute Respiratory failure 300179 0
Condition category
Condition code
Respiratory 300063 300063 0 0
Other respiratory disorders / diseases

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Three different modes of non-invasive ventilation will be applied to the included patients:
High-flow nasal oxygenotherapy (HFNO): HFNO will be performed using the Optiflow'Trademark' system (Fisher & Paykel Healthcare, Auckland, NZ) with gas flow = 50L/min and inspired FiO2 to target SpO2 between 93 and 97%. Because HFNO is our respiratory failure first-line treatment, baseline PaO2/FiO2 ratio and the first diaphragmatic ultrasound examination will be recorded with this respiratory support mode.
Standard oxygenotherapy (SO): SO will be then delivered using a reservoir facemask with O2 flow between 9 and 15 L/min ( FiO2 approximatively 55 to 80%) to get equal SpO2 as baseline. To avoid potential recruitement effects of the NIV, and because patients will move from one mode to another, without washout period, SO diaphragmatic thickness fraction (DTF) measurements will be performed before BIPAP (second measurement).
Noninvasive ventilation (NIV): NIV will be delivered as Bilevel positive airway pressure (BiPAP). BIPAP will be applied with BIPAP Vision or Respironics V60 ventilators (Philips Healthcare, Andover, MA, USA) according to availability, with an oronasal mask. Standard BIPAP settings will be: pressure support (PS) = 4 cmH2O, PEEP = 4 cmH2O (BIPAP 4/4), and inspired FiO2 equal to previously set FIO2 with HNFO. Recordings will be required during two extra BIPAP periods if DTF is above 10%, to assess the specific effects of PS and PEEP level (fourth measurement: PS =8 cmH2O and PEEP = 4 cmH2O [BIPAP 8/4]; fifth measurement: PS = 4 cmH2O and PEEP = 8 cmH2O [BIPAP 4/8]). The inspired FiO2 will be kept constant during the three BIPAP measurement periods. If DTF is inferior to 10% with BIPAP 4/4, we will consider increasing PS or PEEP futile, and will not record the 4th and 5th measures.
Ultrasound examination:
The diaphragmatic ultrasound examinations will be performed after at least 5 minutes of stable and constant breathing with each technique. Every measurement will last 5 to 10 minutes, giving a total of 10 to 15 minute in each ventilation mode. Ultrasound examinations will be performed by a single operator, experienced in diaphragmatic ultrasound examination. Available echographs were Vivid 6 (GE Healthcare, Little Chalfont, UK) or CX50 POC (Philips Healthcare, Andover, MA, USA), with high frequency probes. Measurements were performed in the semi-recumbent position. The right side was the first choice for ultrasound examination because of generally easier visualization compared to the left hemidiaphragm. However, the latter was chosen in case of poor visualization of the right hemidiaphragm (chest drains, surgical wound, pneumothorax, dressings), to limit the high risk of multiple protocol exclusions in our thoracic surgery patients. The diaphragm was located at its zone of apposition to the thorax, by placing the probe in the 9th intercostal space in the midaxillary line with the ultrasound beam in the cephalocaudal direction. The diaphragm will be identified between the two hyperechogenic parallel lines of the pleura and the peritoneum. Measurements were then performed in 2D mode according to the leading-edge method in order to minimize the ultrasound overestimation of the peritoneal membrane thickness. The measurements will include diaphragmatic end-inspiratory thickness (eIT) and end-expiratory thickness (eET). eET was recorded just before the thickening start and eIT at maximal thickening. The diaphragmatic thickening fraction (DTF) was calculated as follows: DTF = (eIT - eET)/eET.
Intervention code [1] 295828 0
Diagnosis / Prognosis
Comparator / control treatment
It is a cross-over study. This study compares DTF between three modes of ventilation.
Control group
Active

Outcomes
Primary outcome [1] 299530 0
Diaphragmatic thickening fraction assessed by ultrasound examination
Timepoint [1] 299530 0
The diaphragmatic ultrasound examinations will be performed after at least 5 minutes of stable and constant breathing with each technique
Secondary outcome [1] 327461 0
Respiratory rate measured on the patient's monitoring screen, using the EKG électrodes.
Timepoint [1] 327461 0
The secondary outcome will be recorded after at least 5 minutes of stable and constant breathing with each technique
Secondary outcome [2] 327462 0
Proportion of intubated patients during the 72 hours following measurements. This outcome will be assessed using patients' medical records.
Timepoint [2] 327462 0
The secondary outcome will be recorded once, at the 72th hour after ultrasound examination

Eligibility
Key inclusion criteria
Every patient older than 18 years who underwent acute respiratory failure, including acute hypoxemia (PaO2 < 75 mmHg under 6 L/min oxygen therapy, or PaO2/FiO2 ratio under 300 mmHg), hypercapnia (PaCO2 > 45 mmHg), and clinical signs of acute respiratory failure, was treated with HFNO and subsequently included in the study.
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Exclusion criteria were mechanical ventilation or need for immediate intubation, tracheostomy, therapeutic limitations, cardiogenic pulmonary edema, acute exacerbation of chronic obstructive pulmonary disease, poor visualization of both hemidiaphragms, , or contraindication to BIPAP or HFNO.

Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Who is / are masked / blinded?



Intervention assignment
Other design features
Phase
Type of endpoint/s
Statistical methods / analysis
We will express continuous variables as the mean +/- standard deviation (SD). Normality of the distribution of data will be assessed by the Kolmogorov-Smirnov test. In order to evidence a 10% difference in DTF between HFNO and SB, with a SD of 12%, observed on a 10-patients previous test sample, we estimated the minimum size of the population at 50 patients, with a 5% a-risk and a 80% power. Changes in DTF between first to third measures were analysed using repeated measures ANOVA followed by the Scheffe test, as appropriate. Changes in DTF between the three BIPAP stings (measures 3 to 5) were compared with the Friedman test with Wilcoxon paired tests if necessary. Significativity threshold was set to 0.05.

Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
5/09/2017
Actual
5/04/2017
Date of last participant enrolment
Anticipated
30/11/2017
Actual
18/12/2017
Date of last data collection
Anticipated
22/12/2017
Actual
29/12/2017
Sample size
Target
50
Accrual to date
Final
51
Recruitment outside Australia
Country [1] 8188 0
France
State/province [1] 8188 0
Ile de France

Funding & Sponsors
Funding source category [1] 294459 0
Hospital
Name [1] 294459 0
Hopital Marie Lannelongue
Country [1] 294459 0
France
Primary sponsor type
Hospital
Name
Hopital marie Lannelongue
Address
133 avenue de la Resistance
92350 Le Plessis Robinson
Country
France
Secondary sponsor category [1] 293325 0
None
Name [1] 293325 0
Address [1] 293325 0
Country [1] 293325 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 295932 0
Comite de Protection des Personnes Ile de France VII
Ethics committee address [1] 295932 0
78 rue du General LECLERC
94270 LE KREMLIN BICETRE
Ethics committee country [1] 295932 0
France
Date submitted for ethics approval [1] 295932 0
30/09/2016
Approval date [1] 295932 0
09/11/2016
Ethics approval number [1] 295932 0
ID-RCB 2016-00156229

Summary
Brief summary
Although high flow nasal oxygenation (HFNO) demonstrated benefits in survival in acute hypoxemic failure, few are known about mechanisms leading to this improved outcome.
Diaphragm ultrasonography with measure of the diaphragmatic thickening fraction (DTF) is now recognized as a simple, non invasive and reproductible method to assess respiratory workload in acutely ill patients.
We hypothesized that HFNO decreases respiratory workload, and then DTF, versus standard oxygenation. Thus, we will compare DTF during HFNO, standard facemask oxygenation, and non invasive ventilation, with standardized levels of pressure support and PEEP, in 50 cardiothoracic ICU patients with acute respiratory failure.
Inclusion criteria are age > 18 years, acute respiratory failure, including acute hypoxemia (PaO2 < 75 mmHg under 6 L/min oxygen therapy, or PaO2/FiO2 ratio under 300 mmHg), hypercapnia (PaCO2 > 45 mmHg), and clinical signs of acute respiratory failure.
Exclusion criteria are mechanical ventilation or need for immediate intubation, tracheostomy, therapeutic limitations, cardiogenic pulmonary edema, acute exacerbation of chronic obstructive pulmonary disease, poor visualization of both hemidiaphragms, bilateral absence of diaphragmatic thickening, or contraindication to BIPAP or HFNC.
We expect the duration of inclusion period lower than 3 months.
Trial website
Trial related presentations / publications
Public notes
Attachments [1] 2088 2088 0 0
/AnzctrAttachments/371441-CPP Florent.pdf (Ethics approval)

Contacts
Principal investigator
Name 68822 0
Prof STEPHAN
Address 68822 0
Hopital Marie LANNELONGUE
133 avenue de la resistance
92350 LE PLESSIS ROBINSON
Country 68822 0
France
Phone 68822 0
+33140948590
Fax 68822 0
Email 68822 0
f.stephan@ccml.fr
Contact person for public queries
Name 68823 0
STEPHAN
Address 68823 0
Hopital Marie LANNELONGUE
133 avenue de la resistance
92350 LE PLESSIS ROBINSON
Country 68823 0
France
Phone 68823 0
+33140948590
Fax 68823 0
Email 68823 0
f.stephan@ccml.fr
Contact person for scientific queries
Name 68824 0
LAVERDURE
Address 68824 0
Hopital Marie LANNELONGUE
133 avenue de la resistance
92350 LE PLESSIS ROBINSON
Country 68824 0
France
Phone 68824 0
+33140948590
Fax 68824 0
Email 68824 0
f.laverdure@ccml.fr

No information has been provided regarding IPD availability


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

Documents added manually
No documents have been uploaded by study researchers.

Documents added automatically
SourceTitleYear of PublicationDOI
EmbaseUltrasound Assessment of Respiratory Workload With High-Flow Nasal Oxygen Versus Other Noninvasive Methods After Chest Surgery.2019https://dx.doi.org/10.1053/j.jvca.2019.05.020
N.B. These documents automatically identified may not have been verified by the study sponsor.