Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12616000529448
Ethics application status
Approved
Date submitted
3/03/2016
Date registered
22/04/2016
Date last updated
21/10/2016
Type of registration
Prospectively registered

Titles & IDs
Public title
Effects of patient's inspiratory effort, as assessed by esophageal pressure, on Pulse Pressure Variation assessment of fluid responsiveness in patients undergoing mechanical ventilation.
Scientific title
Inspiratory effort and assessment of fluid responsiveness in mechanically ventilated patients.
Secondary ID [1] 288660 0
None
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Critical illness 297844 0
Hemodynamic status 297845 0
Fluid responsiveness 297846 0
Condition category
Condition code
Cardiovascular 298019 298019 0 0
Other cardiovascular diseases

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Patients will be monitored with a monitor for hemodynamic assessment (Most Care, Vytech Health, Padova, Italy), which uses a Pressure Recording Analytical Method (PRAM).
PRAM is a method designed for arterial pressure-derived continuous Cardiac Output and it is the only methodology that does not need any starting calibration, central venous catheterization, or any adjustments based on experimental data. As a consequence, PRAM needs only an arterial line (radial, brachial, femoral) for working.
Furthermore, we will position a catheter able to measure the esophageal pressure to properly assess the respiratory effort during the study protocol. The catheter will be connected to a dedicated pressure transducer and a recording system. In order to ascertain its correct positioning, an end-expiratory occlusion test will be performed.
This test is used in spontaneously breathing patients, to validate the correct position of
esophageal balloon; it is performed during an end-expiratory occlusion maneuver with the simultaneous measurement of the changes in airway and esophageal pressure during an inspiratory effort (i.e., no air flow) (Baydur’s occlusion test). The position of the esophageal catheter is considered acceptable when the ratio between the changes in two pressures is close to unity. In healthy subjects with or without anesthesia, when the esophageal catheter was correctly positioned, it has been found that the difference between the changes in esophageal and airway pressure was lower than 15 %.
When the patient has been monitored with Most Care device, baseline data will be acquired for 2 minutes during Pressure Support Ventilation (PSV) without modification of the clinical settings. Afterwards, the patients will undergo to the following different ventilator settings lasting 5 minutes each according to computer generated random sequence: 1) PSV with a 50% increment of the baseline pressure support; 2) PSV with a 50% reduction of the baseline pressure support; 3) Assist/Controlled Ventilation with a tidal volume equal to 6 ml/kg of ideal body weight; 4) Assist/Controlled Ventilation with a tidal volume equal to 8 ml/kg of ideal body weight; 5) Assist/Controlled Ventilation with a tidal volume equal to 10 ml/kg of ideal body weight. Between each single trial of incremental pressures, a return to baseline conditions will be guarantee for 15 minutes, to avoid carry-over effects.
In the end, after all the trials mentioned above, a single fluid challenge of 500 ml of normal saline will be infused in 5 minutes and the hemodynamic response will be evaluated to define if the patient is fluid responsive or not (i.e. if the cardiac index incremented of 15% at least, or not). All the conditions will be tested in one session and the entire study protocol will be conducted by one of the physicians involved in the research.
Intervention code [1] 294073 0
Diagnosis / Prognosis
Intervention code [2] 294304 0
Treatment: Devices
Comparator / control treatment
The control treatment is the baseline measurement during Pressure Support Ventilation delivered with the clinical settings decided by the treating physician. Moreover, every patient will be a self control. In fact, patients will be defined as fluid-responsive or not according to the modifications of the Cardiac Index after the fluid challenge. Therefore, the data obtained during the positive airway pressure applications will be classified and analyzed accordingly.
Control group
Active

Outcomes
Primary outcome [1] 297533 0
To assess the effects of patient's inspiratory effort, as assessed by the esophageal pressure, on Pulse Pressure Variation ability to predict fluid responsiveness, as defined by an increment of the cardiac index > 15% after a fluid challenge, in patients undergoing partial ventilatory assistance at different levels of inspiratory support and different administered tidal volumes,
Timepoint [1] 297533 0
Record and analysis of the Pulse Pressure Variation and Esophageal Pressure values at each protocol trial. The definition of the patient as fluid responder will be given according to the modifications of the cardiac index after a 500ml of fluid challenge, after the trials of different ventilation settings.
Secondary outcome [1] 321342 0
To assess end-expiratory occlusion test reliability in predicting fluidresponsiveness, as defined by an increment of the cardiac index > 15% after a fluid challenge, in patients undergoing partial ventilatory assistance,
Timepoint [1] 321342 0
The End-expiratory occlusion test will be performed soon after esophageal catheter placement, (to assess its correct positioning). The values of Pulse Pressure Variation and Esophageal Pressure will be recorded at the end of each 5-minute trial and offline analyzed through a dedicated acquisition system.

Eligibility
Key inclusion criteria
All patients 18 years/old or older undergoing invasive mechanical ventilation in Pressure Support mode (with a positive end-expiratory pressure between 4 and 6 cmH2O and a Pressure Support between 8 and 12 cmH2O), with a clinical need for fluid infusion, i.e. systolic arterial blood pressure < 90 mmHg or 50 mmHg reduction of values in patients with chronic hypertension, oliguria as defined by a diuresis < 0.5 ml/kg/h in the 2 previous hours, need for inotropes (dopamine >5mcg*kg/min or norepinephrine), lactate > 2 mmol/L.
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Patients will be excluded if meeting one or more off the following criteria: 1) cardiac arrhythmia; 2) atrial fibrillation or flutter; 3) patients undergoing any form of renal replacement therapy; 4) valvular defects of moderate to severe grade; 5) history of congestive cardiac failure; 6) previous or presence of pneumothorax or emphysema; 7) patients with Chronic Obstructive Pulmonary Disease (COPD); 8) patients with kyphoscoliosis; 9) use of expiratory muscles and 10) arterial partial pressure to inspired fraction of oxygen (PaO2/FiO2) ratio < 200.

Study design
Purpose of the study
Diagnosis
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Everyday physicians responsible for patients recruitment will screen all the patients in the Intensive Care Unit to check those meeting inclusion criteria. Allocation will be concealed since it will be done through sealed opaque envelopes.
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 enrolment process. They will communicate the random sequence of the application of the incremental positive pressures to the physician responsible for the patient enrolment.
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

Recruitment
Recruitment status
Recruiting
Date of first participant enrolment
Anticipated
Actual
15/05/2016
Date of last participant enrolment
Anticipated
31/12/2016
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
20
Accrual to date
Final
Recruitment outside Australia
Country [1] 7633 0
Italy
State/province [1] 7633 0
Novara

Funding & Sponsors
Funding source category [1] 293017 0
Self funded/Unfunded
Name [1] 293017 0
Federico Longhini, MD
Country [1] 293017 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] 291793 0
None
Name [1] 291793 0
Address [1] 291793 0
Country [1] 291793 0
Other collaborator category [1] 278858 0
Individual
Name [1] 278858 0
Antonio Messina, MD
Address [1] 278858 0
Corso Mazzini 19, Intensive Care Unit, "Maggiore della Carita" Universitary Hospital, 28100, Novara
Country [1] 278858 0
Italy

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 294527 0
Comitato Etico Interaziendale Novara
Ethics committee address [1] 294527 0
Ethics committee country [1] 294527 0
Italy
Date submitted for ethics approval [1] 294527 0
23/09/2014
Approval date [1] 294527 0
16/01/2015
Ethics approval number [1] 294527 0
CE 149/14

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 64018 0
Dr Antonio Messina
Address 64018 0
Intensive Care Unit, "Maggiore della Carita" Hospital, Corso Mazzini 18, 28100, Novara
Country 64018 0
Italy
Phone 64018 0
+3903213733380
Fax 64018 0
Email 64018 0
[email protected]
Contact person for public queries
Name 64019 0
Federico Longhini
Address 64019 0
Intensive Care Unit, ASL VC - Azienda Sanitaria Locale di Vercelli, C.so Mario Abbiate n. 21 - 13100 - Vercelli
Country 64019 0
Italy
Phone 64019 0
+393475395967
Fax 64019 0
Email 64019 0
[email protected]
Contact person for scientific queries
Name 64020 0
Federico Longhini
Address 64020 0
Intensive Care Unit, ASL VC - Azienda Sanitaria Locale di Vercelli, C.so Mario Abbiate n. 21 - 13100 - Vercelli
Country 64020 0
Italy
Phone 64020 0
+393475395967
Fax 64020 0
Email 64020 0
[email protected]

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
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Documents added automatically
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