Artificial Increase in Chest Wall Elastance as an Alternative to Prone Positioning in Moderate-to-severe ARDS. (ALTERPRONE)
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|ClinicalTrials.gov Identifier: NCT03719937|
Recruitment Status : Recruiting
First Posted : October 25, 2018
Last Update Posted : October 25, 2018
|First Submitted Date ICMJE||October 19, 2018|
|First Posted Date ICMJE||October 25, 2018|
|Last Update Posted Date||October 25, 2018|
|Actual Study Start Date ICMJE||October 1, 2018|
|Estimated Primary Completion Date||April 1, 2020 (Final data collection date for primary outcome measure)|
|Current Primary Outcome Measures ICMJE
||oxygenation [ Time Frame: 120 minutes after the intervention ]
|Original Primary Outcome Measures ICMJE||Same as current|
|Change History||No Changes Posted|
|Current Secondary Outcome Measures ICMJE
|Original Secondary Outcome Measures ICMJE||Same as current|
|Current Other Pre-specified Outcome Measures||Not Provided|
|Original Other Pre-specified Outcome Measures||Not Provided|
|Brief Title ICMJE||Artificial Increase in Chest Wall Elastance as an Alternative to Prone Positioning in Moderate-to-severe ARDS.|
|Official Title ICMJE||ArtificiaL Increase in chesT Wall Elastance as an alteRnative to PRONE Positioning in Moderate-to-severe ARDS: a Physiological Study The ALTERPRONE Study|
During moderate to severe ARDS, sessions of prone positioning lead to lung and chest wall mechanics changes that modify regional ventilation, with a final redistribution of tidal volume and PEEP towards dependent lung regions: this limits ventilator-induced lung injury, increases oxygenation and convincingly improves clinical outcome.
Physiological data indicate that the increase in chest wall elastance is crucial in determining the benefit by prone positioning on oxygenation. In some patients, however, prone positioning may not be feasible or safe due to particular comorbidities and/or technical issues.
In the present pilot-feasibility study enrolling 15 subjects with moderate to severe ARDS in whom prone positioning is contraindicated or unfeasible, we aim at assessing whether and to what extent an artificial increase in chest wall elastance while the patient is in the supine position may yield a significant benefit to oxygenation. The increase in chest wall elastance will be achieved placing 100g/kg weight on the anterior chest wall of the patient while he/she is in the supine position: this approach previoulsy appeared safe and effective in case reports and small case series. Patient's position will be standardized (30 degrees head-up, semi seated position).
This one-arm sequential study will evaluate the effects of the procedure on gas exchange, haemodynamics, lung and chest wall mechanics, alveolar recruitment (measured with the nitrogen washout-technique and multiple PV curves) and tidal volume and PEEP distribution (assessed with electrical impedance tomography).
Design: Prospective, pilot, physiological study Setting: 20-bed general ICU, 13 bed surgical ICU, 10 bed neurosurgical ICU, "A. Gemelli" University hospital, Rome, Italy.
Screening visit and oxygenation criterion validation Each patient meeting inclusion criteria will be evaluated for the presence of the oxygenation criterion. After endotracheal suctioning, eligible patients will be ventilated for 30 minutes with PEEP=5 cmH2O in the semi recumbent position and an ABG will be performed to compute PaO2/FiO2 ratio.
Patients showing PaO2/FiO2≤150 mmHg will be enrolled. Patients showing PaO2/FiO2<200 and >150 mmHg will be treated according to the standard clinical practice and reassessed for the presence of oxygenation criterion within 48 hours from the diagnosing of ARDS.
To limit the exposure to low PEEP of possibly derecruiting patient with severe oxygenation impairment, the ABG certifying the oxygenation criterion will be permitted at any time during the 30-minute monitoring period.
All patients will be sedated, paralysed with cisatracurium infusion and connected to a ventilator equipped with lung volume measurement module (Carescape R860 - GE Healthcare, USA) through a standard bi-tube low-resistance circuit with a low-dead space, low-resistance, high-efficiency heat and moisture exchanger. For the purpose of the study, the use of heated and humidified bi-tube circuits (Fisher and Paykel healthcare, humidification chamber temperature set at 37 °C, absolute humidity provided 44 mg H2O/L) will be reserved to patients that remain hypercapnic (ph<7.30 and PaCO2>50) despite all adequate ventilator settings provided by the study protocol.
Each patient will be ventilated in volume-control mode, in the semirecumbent position (or smaller head elevation for patients with spine/pelvis movement limitations), which will not be changed throughout the study.
Ventilation settings will be standardized as follows: VT = 6 mL/Kg (predicted body weight, PBW); inspiratory flow set at 60 l/min resulting in an end-inspiratory pause of 0.2-0.5 sec, I:E ratio 1:1 to 1:3, respiratory rate tailored to achieve 45 mmHg>PaCO2>35 mmHg, PEEP set according to the clinical judgment, FiO2 set to achieve a SpO2>88-95%. A Pplat < 30 cmH2O will be considered as a safety limit.
Predicted body weight will be calculate as:
Males: PBW (kg) = 50 + 0.91 (height in cm-152) Females PBW (kg) = 45.5 + 0.91 (height in cm-152) In case of hypercapnia with Ph<7.30 despite a respiratory rate=30-35, an increase in VT up to 8 ml/kg will be allowed.
A dedicated orogastric or nasogastric tube provided with an oesophageal balloon (Cooper esophageal catheter) to monitor oesophageal pressure, estimate pleural pressure and compute transpulmonary pressure will be placed in all enrolled patients after inclusion. The adequate positioning of the esophageal catheter will be certified by an occlusion test, as previously demonstrated(15).
The GE-dedicated pneumotacograph and differential pressure transducer will be connected to the respiratory circuit to record airway pressure (PAW) and flow. The oesophageal pressure (PES) will be measured using the previously inserted oesophageal catheter, that will be connected to the auxillary pressure port of the ventilator. All the three signals will be continuously acquired by the ventilator with an analog-digital converter at a sample rate of 25 Hz (GE healthcare). A dedicated laptop connected to the ventilator will acquire PAW, PES and Flow signals through a dedicated software over the entire course of the study (Ohmeda research tool, GE healthcare).
At study enrolment, an electrical impedance tomography (EIT) belt with 16 electrodes will be placed around the thorax between the 5th or 6th parasternal intercostal space and connected to a dedicated device to record electrical impedance signals of the thorax (Swisstom EIT, Switzerland).
After included in the study, each patient will be treated as follow:
Patient's demographics will be collected at study entry: initials, age, sex, height, weight, BMI, cause of hospital and ICU admission, SAPSII, Apache, SOFA score, date and time of ICU admission, date and time of enrolment, comorbidities, NYHA category before respiratory failure, body temperature, chest x-ray (jpeg images), chest CT scan (whether available).
During the study, each patient will undergo a standard ICU monitoring: ECG; Invasive blood pressure, SpO2, respiratory rate, diuresis.
All the relevant data follow described will be collected at prespecified timepoints.
The prespecified timepoints are:
At each timepoint the following data will be collected.
The following parameters will be calculated offline while reviewing signals:
Airway driving pressure (∆P)=PplatAW-PEEPAW Transpulmonary end-inspiratory pressure (PplatL)=PplatAW-PplatESO Transpulmonary end-expiratory pressure (PEEPL)=PEEPAW-PEEPES Lung driving pressure (∆PL)= PplatL-PEEPL Lung plateau pressure, elastance derived (PplatL,EL)=PplatAW X (∆PL/∆P) Static respiratory system compliance (CstRS)=VT/∆P Static Lung compliance (CstL)=VT/∆PL Static Chest-wall compliance=VT/(PplatES-PEEPES) Oxygenation stretch index=PaO2/(FiO2x∆P)
• Stress and strain (measured only at T0, T1b and T2b) End-Expiratory lung volume (EELV) at the set PEEP (PEEPSET) will be measured by nitrogen washin-washout technique with a 0.2 change in the FiO2 (0.1 change in the FiO2 only allowed in case of baseline FiO2=0.9-1).
A one-breath derecruitment maneuver from PEEPSET to PEEP 0 (ZEEP) will be conducted to assess baseline functional residual capacity (FRC), that will be measured as the difference between EELV at set PEEP and the lung volume increase above FRC, measured as the difference in expired tidal volume as PEEP is decreased from 0 cmH2O in one breath with respiratory rate set at 8-10 breaths per minute. In particular, the lung volume due to the presence of set PEEP (PEEPvolume) will be measured by subtracting the insufflated VT from the expired VT (i.e. the integration of the flow signal after 5s exhalation) during a 5-second exhalation just after PEEP is reduced from set PEEP to 0.
|Study Type ICMJE||Interventional|
|Study Phase ICMJE||Not Applicable|
|Study Design ICMJE||Intervention Model: Sequential Assignment
Intervention Model Description:
pilot-feasibility studyMasking: None (Open Label)
Primary Purpose: Treatment
|Condition ICMJE||Acute Respiratory Distress Syndrome|
|Intervention ICMJE||Device: weight on the anterior chest of the patient
The investigators aim at assessing whether and to what extent an artificial increase in chest wall elastance, while the patient is in the supine position, may yield a significant benefit to oxygenation. The increase in chest wall elastance will be will be achieved placing a 100 g/kg weight on the anterior chest wall of the patient while he/she is in the supine/semirecumbant position. The weights will be placed on the patients' chest for 120 minutes, and then removed. A number of measurements will be recorded before and after the procedure.
|Study Arms ICMJE||Experimental: anterior chest wall weight
moderate to severe ARDS patients in whom prone positioning is contraindicated. Patients will have a 100 g/kg weight placed on the anterior chest wall, while in the supine/semirecumbant position. The weights will be placed on the patients' chest for 120 minutes, and then removed. A number of measurements will be recorded before and after the procedure.
Intervention: Device: weight on the anterior chest of the patient
* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
|Recruitment Status ICMJE||Recruiting|
|Estimated Enrollment ICMJE
|Original Estimated Enrollment ICMJE||Same as current|
|Estimated Study Completion Date ICMJE||April 2020|
|Estimated Primary Completion Date||April 1, 2020 (Final data collection date for primary outcome measure)|
|Eligibility Criteria ICMJE||
|Ages ICMJE||18 Years and older (Adult, Older Adult)|
|Accepts Healthy Volunteers ICMJE||No|
|Listed Location Countries ICMJE||Italy|
|Removed Location Countries|
|NCT Number ICMJE||NCT03719937|
|Other Study ID Numbers ICMJE||1505|
|Has Data Monitoring Committee||No|
|U.S. FDA-regulated Product||
|IPD Sharing Statement ICMJE||
|Responsible Party||Massimo Antonelli, Catholic University of the Sacred Heart|
|Study Sponsor ICMJE||Catholic University of the Sacred Heart|
|Collaborators ICMJE||Not Provided|
|PRS Account||Catholic University of the Sacred Heart|
|Verification Date||October 2018|
ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP