Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

Artificial Increase in Chest Wall Elastance as an Alternative to Prone Positioning in Moderate-to-severe ARDS. (ALTERPRONE)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03719937
Recruitment Status : Recruiting
First Posted : October 25, 2018
Last Update Posted : October 25, 2018
Sponsor:
Information provided by (Responsible Party):
Massimo Antonelli, Catholic University of the Sacred Heart

Tracking Information
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
 (submitted: October 24, 2018)
oxygenation [ Time Frame: 120 minutes after the intervention ]
PaO2/FiO2 ratio
Original Primary Outcome Measures  ICMJE Same as current
Change History No Changes Posted
Current Secondary Outcome Measures  ICMJE
 (submitted: October 24, 2018)
  • Alveolar recruitment [ Time Frame: 1 and 2 hours after the intervention ]
    Changes in End expiratory lung impedance (EELI), measured with electrical impedance tomography A ten-minute period EIT signals will be recorded and offline reviewed using a dedicated software. Image acquisition rate will be 30 Hz. Lungs will be divided into four regions (ventral, mid-ventral, mid-dorsal and dorsal): the % of impedance variation related to tidal volume and the % EELI in the four regions as compared to the absolute values will be calculated
  • tidal volume dsitribution [ Time Frame: 1 and 2 hours after the intervention ]
    Changes in Tidal volume distribution in 4 area of the lungs (Ventral, mid ventral, mid-dorsal, dorsal) A ten-minute period EIT signals will be recorded and offline reviewed using a dedicated software. Image acquisition rate will be 30 Hz. Lungs will be divided into four regions (ventral, mid-ventral, mid-dorsal and dorsal): the % of impedance variation related to tidal volume and the % EELI in the four regions as compared to the absolute values will be calculated
  • Lung stress [ Time Frame: 1 and 2 hours after the intervention ]
    Measured at the end of an end-inspiratory occlusion, as: airway pressure - esophageal pressure + esophageal pressure at atmospheric pressure Static and dynamic strain will be calculated according to the following formulas: Lung Stress= PplatAW-PplatESO-PEEPES,ZEEP Dynamic strain = VT/FRCPEEPset Static strain= Strain due to peep ([PEEPvolume-RecZEEP at PEEP/FRCPEEPset) Pressure-volume curves at PEEP0 AND set PEEP will be conducted to confirm the reliability of the previous calculations at the end of each of the study steps
  • Dynamic strain [ Time Frame: 1 and 2 hours after the intervention ]
    Computed as the ratio of tidal volume to functional residual capacit, with the latter measured with the nitrogen washin-washout technique Static and dynamic strain will be calculated according to the following formulas: Lung Stress= PplatAW-PplatESO-PEEPES,ZEEP Dynamic strain = VT/FRCPEEPset Static strain= Strain due to peep ([PEEPvolume-RecZEEP at PEEP/FRCPEEPset) Pressure-volume curves at PEEP0 AND set PEEP will be conducted to confirm the reliability of the previous calculations at the end of each of the study steps
  • Driving pressure [ Time Frame: 1 and 2 hours after the intervention ]
    Respiratory system elastic pressure, measured as plateau pressure-PEEP
  • Transpulmonary Driving pressure [ Time Frame: 1 and 2 hours after the intervention ]
    Lung elastic pressure, measured as transpulmonary plateau pressure- transpulmonary PEEP
  • Chest wall elastance [ Time Frame: 1 and 2 hours after the intervention ]
    Elastance of abdomen/chest wall, measured as tidal change in Pes/tidal volume
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
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
Brief Summary

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).

Detailed Description

Design: Prospective, pilot, physiological study Setting: 20-bed general ICU, 13 bed surgical ICU, 10 bed neurosurgical ICU, "A. Gemelli" University hospital, Rome, Italy.

Protocol

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.

Procedures

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:

  • 30-minute period in the supine position (T0);
  • 120-minute period in the supine position with a 100 g/kg soft and smooth weight (warm saline bags) placed and secured on each emithorax (T1);
  • 120-minute period in the supine position after the weight is removed (T2). Mechanical ventilation settings will be kept unchanged over the course of the entire study. In case of drops in the SpO2, an increase in the FiO2 will be allowed to achieve the previously described oxygenation target.

Measurements

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:

  1. baseline, T0: after the 30-minute period in the supine position (study enrolment, no weight);
  2. T1a: 60 minutes after weights are positioned on the thorax;
  3. T1b 120 minutes after weights are positioned on the thorax, end of T1;
  4. T2a 60 minutes after weights are removed;
  5. T2b 120 min after weights are removed, end of T2, end of the study;

At each timepoint the following data will be collected.

  • Adverse events, if any.
  • Respiratory rate, SpO2, pH, PCO2, PaO2, SaO2, PaO2/FiO2;
  • Heart Rate, arterial blood pressure, central venous pressure; dosage of vasoactive or inotrope agents.
  • End expiratory lung impedance (EELI) and tidal volume distribution. A ten-minute period EIT signals will be recorded and offline reviewed using a dedicated software (Swisstome EIT). Image acquisition rate will be 30 Hz. Lungs will be divided into four regions (ventral, mid-ventral, mid-dorsal and dorsal): the % of impedance variation related to tidal volume and the % EELI in the four regions as compared to the absolute values will be calculated (Appendix 3, Figures 4-5)(16).
  • Respiratory mechanics End-expiratory airway pressure (PEEPAW) and the end-expiratory esophageal pressure (PEEPES) will be recorded during an 8-second expiratory hold. End-inspiratory airway pressure (PplatAW) and end-inspiratory esophageal pressure (PplatES) will be measured during a 2-second end inspiratory hold. Tidal volume (VT) will be measured as the integration of the flow-time curve during expiration.

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 study
Masking: 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
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: October 24, 2018)
15
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

Inclusion Criteria:

  1. Patients with ARDS and moderate to severe oxygenation impairment (PaO2/FiO2≤150 mmHg while receiving controlled mechanical ventilation with PEEP=5 cmH2O) will be the studied population.

    Acute respiratory failure within 1 week of a known clinical insult or new or worsening respiratory symptoms;

    • Bilateral infiltrates at the chest x-ray or CT scan, not fully explained by effusions, lobar/lung collapse, or nodules;
    • Respiratory failure not fully explained by cardiac failure or fluid overload; objective assessment required to exclude hydrostatic edema if no risk factor present.
    • PaO2/FiO2 ratio<150 mmHg after 30 mins - 1 hour of mechanical ventilation with PEEP=5 cmH2O(14).
    • Written informed consent.
  2. Prone positioning deemed non-feasible by the attending clinician, or presence of at least one of the following absolute contraindications for prone positioning(5)

    • Serious facial trauma or facial surgery during the previous 15 days
    • Deep venous thrombosis treated for less than 2 days
    • Unstable spine, femur, or pelvic fractures
    • Pregnant women
    • Intracranial pressure >30 mm Hg or cerebral perfusion pressure <60 mm

Exclusion Criteria:

  • Chest trauma
  • Cardiothoracic surgery in the last 4/6 weeks
  • Cardiac PM inserted the last 2 days
  • Haemodynamic instability (MAP < 65 mmHg despite vasoactive/inotrope support)
  • Chest tube with air leaks
  • Presence of intrinsic PEEP > 1 cmH2O
  • BMI < 18
  • Height < 150 cm
  • More than 48 hours from endotracheal intubation to the time of randomization
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Roberta Barelli, MD +39 32860011430 robertabarelli@me.com
Contact: Domenico L Grieco, MD +39 3397681623 dlgrieco@outlook.it
Listed Location Countries  ICMJE Italy
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03719937
Other Study ID Numbers  ICMJE 1505
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: Undecided
Responsible Party Massimo Antonelli, Catholic University of the Sacred Heart
Study Sponsor  ICMJE Catholic University of the Sacred Heart
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Chair: Massimo Antonelli, MD Catholic University of the Sacred Heart
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