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Trial registered on ANZCTR


Registration number
ACTRN12615001244594
Ethics application status
Approved
Date submitted
11/09/2015
Date registered
12/11/2015
Date last updated
27/03/2017
Type of registration
Prospectively registered

Titles & IDs
Public title
Comparative physiological evaluation with diaphragmatic ultrasound of the application of two different oxygen-therapy techniques in patients recovering from severe exacerbation of chronic respiratory failure.
Scientific title
Comparative physiological evaluation with diaphragmatic ultrasound of the application of oxygen-therapy through a Venturi mask or a nasal high-flow device in patients recovering from severe exacerbation of chronic respiratory failure.
Secondary ID [1] 287460 0
nil
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Acute exacerbation of chronic respiratory failure 296183 0
Condition category
Condition code
Respiratory 296462 296462 0 0
Chronic obstructive pulmonary disease
Respiratory 296912 296912 0 0
Other respiratory disorders / diseases

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
After obtaining written informed consent, the patient will undergo to 5 consecutive 30-minute trials: 1) Non-Invasive Ventilation (NIV_1); 2) Venturi mask; 3) Non-Invasive Ventilation (NIV_2); 4) Optiflow; 5) Non-Invasive Ventilation (NIV_3).
The sequence of Venturi mask and Optiflow trials will be randomized, according to a sequence generated by a computer. During non-invasive ventilation (NIV) trials (NIV_1, NIV_2 and NIV_3), the inspiratory support will be given with a dedicated ventilator for NIV, in Pressure Support Ventilation mode, through a mask, as clinically indicated. The Optiflow will be initially set with the highest flow value between 50-60 L/min, according to the patient's tolerance. The nasal cannula size will be appropriately chosen. Moreover, the temperature of the heater will be set at 37 degrees
During all trials, FiO2 will be kept unchanged, in order to assure an arterial saturation in O2 > 94% (SpO2).
Intervention code [1] 292835 0
Treatment: Devices
Comparator / control treatment
The Optiflow will be compared with the application of simple Oxygen therapy delivered throughout a Venturi mask with a nominal FiO2 equal to those set during NIV and Optiflow trials. The L/min of Oxygen will be modified according to the nominal FiO2 required and to the Venturi kit used.
Control group
Active

Outcomes
Primary outcome [1] 296087 0
To evaluate if in patients recovering from SE-CRF, the respiratory effort varies between treatments, as assessed through the diaphragm ultrasonogaphy.
Timepoint [1] 296087 0
At the end of each trial, recording the diaphragm thickening fraction (TF) and displacement with the ultrasound.
Secondary outcome [1] 317460 0
Evaluation of gas exchanges as assessed by an arterial blood sample.
Timepoint [1] 317460 0
At the end of each trial.
Secondary outcome [2] 317461 0
Evaluation of patient's comfort as assessed through a 11-point Numeric Rating Scale (NRS). The patient will be ask to evaluate, after having received a proper explication of the NRS before the initiation of study protocol.
Timepoint [2] 317461 0
At the end of each trial.
Secondary outcome [3] 317462 0
Evaluation of patient's dyspnoea as assessed through a 11-point Numeric Rating Scale (NRS). The patient will be ask to evaluate, after having received a proper explication of the NRS before the initiation of study protocol.
Timepoint [3] 317462 0
At the end of each trial

Eligibility
Key inclusion criteria
All the patients meeting the following criteria will be eligible for the study: 1) age equal or greater than 18 years; 2) presence of consciousness; 3) previous NIV for at least 24 hours due to SE-CRF; 4) pH greater than 7.34; 5) respiratory rate (RR) less than or equal to 30 breaths/min.
Minimum age
18 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Patients will be excluded if they meet one or more of the following criteria:
1. refusal of patient's consent;
2. Hemodynamic instability, as defined by a systolic blood pressure < 90 mmHg despite volemic optimizationn, or use of vasoactive agents, i.e. vasopressin or epinephrine at any dosage, norepinephrine > 0.2 mcg/kg/min, dopamine or dobutamine > 5 mcg/kg/min;
3. major cardiac arrhythmia or electrographic signs of ischemia;
4. use of accessory muscles with dyspnoea;
5. pregnancy.

The protocol will be interrupted if:
1. agitation or mental status alteration
2. increase use of accessory muscles and/or dyspnoea
3. pH < 7.30
4. systolic blood pressure < 90 mmHg
5. onset of new cardiac arrhythmia

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Everyday all patients admitted in our intensive care unit will be screened for meeting inclusion criteria. The randomization sequence for the cross-over design is contained in sealed opaque envelopes, in the office of the director of the ICU. When the patient is enrolled, a nurse or a doctor not involved in the study is asked to take the envelopes and read to the investigator the randomization sequence for Venturi and Optiflow.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
We will use a computer-generated randomization sequence, which will be generated by an independent statistician who is not otherwise involved in the trial. The envelopes will be kept in the head nurses’ office. The nurses who open the envelopes will be those on shift and will be totally independent from the enrollment process. They will communicate the random treatment allocation to the physician responsible for the patient enrollment.
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Crossover
Other design features
Phase
Not Applicable
Type of endpoint(s)
Efficacy
Statistical methods / analysis
Due to the lack of previous data, it is not possible to compute an adequate sample size. However, we believe that a total of 30 patients could be sufficient for the purpose of the study.
The normal distribution will be evaluated with a Kolmogorov-Smirnov test. Data will be analyzed with the Analysis of Variance for repeated measure (ANOVA); when indicated, a Bonferroni post hoc test will be applied. P values <0.05 will be considered for statistical differences.

Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment outside Australia
Country [1] 7161 0
Italy
State/province [1] 7161 0
Vercelli
Country [2] 8261 0
Italy
State/province [2] 8261 0
Bari
Country [3] 8262 0
Italy
State/province [3] 8262 0
Bologna

Funding & Sponsors
Funding source category [1] 292032 0
Self funded/Unfunded
Name [1] 292032 0
Federico Longhini, MD
Address [1] 292032 0
Intensive Care Unit, ASL VC - Azienda Sanitaria Locale di Vercelli, C.so Mario Abbiate n. 21 - 13100 - Vercelli
Country [1] 292032 0
Italy
Primary sponsor type
Individual
Name
Federico Longhini, MD
Address
Intensive Care Unit, ASL VC - Azienda Sanitaria Locale di Vercelli, C.so Mario Abbiate n. 21 - 13100 - Vercelli
Country
Italy
Secondary sponsor category [1] 290702 0
None
Name [1] 290702 0
Address [1] 290702 0
Country [1] 290702 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 293518 0
Ethical Committee Alessandria
Ethics committee address [1] 293518 0
Via Venezia 16, 15121, Alessandria
Ethics committee country [1] 293518 0
Italy
Date submitted for ethics approval [1] 293518 0
20/05/2015
Approval date [1] 293518 0
16/07/2015
Ethics approval number [1] 293518 0
AslVC.Rian.15.01

Summary
Brief summary
In patients affected by severe exacerbation of chronic respiratory failure (SE-CRF), with worsened hypercapnia and respiratory acidosis, the sole oxygen therapy is not enough and a ventilatory assistance is required, most of the time through a mask or helmet, so call non-invasive ventilation. The advantage of NIV is to guarantee a ventilatory assistance, avoiding complications related to the presence of the endotracheal tube, such as ventilator associated pneumonia. Furthermore, it has been widely shown that, in patients with SE-CRF, NIV reduces the mortality rate, as opposed to invasive mechanical ventilation.
However, NIV is a "bridge-therapy", applied in the attempt to permit the pharmacological treatments (i.e. antibiotics and bronchodilators) solve the underlying reason of exacerbation; afterwards, patients can be weaned from NIV, and, whenever required, starts oxygen therapy.
Among devices for oxygen therapy, Venturi mask is frequently used in Intensive Care Unit (ICU), because it is possible to provide a nominal fraction of inspired oxygen (FiO2) between 24 and 60%. Recently a new device has become commercially available (Optiflow, Fisher & Paykel, New Zealand) able to provide high flow of heated and humidified gas through nasal cannula. The humidification of gas flow reduces the risk of mucosa dryness and airway muco-ciliar clearence. The use of high-flow of gas (up to 60L/min) permits to provide accurate FiO2 during all the inspiratory phase and to wash out the naso-pharyngeal dead space, in addition to the application of a minimal positive pressure. In patients with hypoxemic acute respiratory failures of mild to moderate degree, Optiflow has been shown to be better tolerated and to guarantee a better oxygenation, in comparison with Venturi mask. Moreover, in another study a high-flow oxygen-therapy system has been shown to reduce the respiratory rate in patients with CRF and the arterial partial pressure of carbon dioxide (PaCO2).
Basing on these data, the Optiflow system could potentially positively influence the inspiratory effort of patients experiencing SE-CRF, when compared to Venturi mask.
Though both commonly used in clinical practice, nowadays no study has compared Optiflow with Venturi mask at this regard.
We aim to evaluate if some differences in respiratory effort exists between Venturi mask and Optiflow, in patients recovering from SE-CRF, through a diaphragm ultrasonogaphy evaluation.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 60282 0
Dr Federico Longhini
Address 60282 0
Intensive Care Unit, ASL VC - Azienda Sanitaria Locale di Vercelli, C.so Mario Abbiate n. 21 - 13100 - Vercelli
Country 60282 0
Italy
Phone 60282 0
+393475395967
Fax 60282 0
Email 60282 0
longhini.federico@gmail.com
Contact person for public queries
Name 60283 0
Dr Federico Longhini
Address 60283 0
Intensive Care Unit, ASL VC - Azienda Sanitaria Locale di Vercelli, C.so Mario Abbiate n. 21 - 13100 - Vercelli
Country 60283 0
Italy
Phone 60283 0
+393475395967
Fax 60283 0
Email 60283 0
longhini.federico@gmail.com
Contact person for scientific queries
Name 60284 0
Dr Federico Longhini
Address 60284 0
Intensive Care Unit, ASL VC - Azienda Sanitaria Locale di Vercelli, C.so Mario Abbiate n. 21 - 13100 - Vercelli
Country 60284 0
Italy
Phone 60284 0
+393475395967
Fax 60284 0
Email 60284 0
longhini.federico@gmail.com

No information has been provided regarding IPD availability
Summary results
Have study results been published in a peer-reviewed journal?
Other publications
Have study results been made publicly available in another format?
Results – basic reporting
Results – plain English summary