Recruitment Assessment in Patients With Acute Respiratory Distress Syndrome and Covid-19

• ClinicalTrials.gov Identifier: NCT05248243
• Recruitment Status: Recruiting
• First Posted: February 21, 2022
• Last Update Posted: March 10, 2023
• Sponsor: Ramos Mejía Hospital
• Information provided by (Responsible Party): Roberto Santa Cruz, Ramos Mejía Hospital

Tracking Information

• First Submitted Date: February 15, 2022
• First Posted Date: February 21, 2022
• Last Update Posted Date: March 10, 2023
• Actual Study Start Date: March 7, 2022
• Actual Primary Completion Date: March 7, 2023 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: February 17, 2022)

Potential recruitment of patients with ARDS and ARDS-Covid-19 [ Time Frame: First 7 days of the patient on mechanical ventilation (MV) ]

To determine the Recruitment Index (R/I) of patients with ARDS and ARDS-Covid-19. Tidal volume and pressure will be combined to report the Recruitment Index (R/I) in mL/cmH2O. A threshold of 0.5 will be used to define high recruitability (R/I ratio >= 0.5 ml/cmH2O) and low recruitability (R/I ratio < 0.5 ml/cmH2O).

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: February 17, 2022)

• To compare the potential recruitment in the supine position (SD) and in the prone position (PD). [ Time Frame: First 7 days of the patient on mechanical ventilation (MV) ]
  To compare the R/I (ml/cmH2O) in patients with ARDS and ARDS-Covid-19 in the supine position (SD) and in the prone position (PD). Tidal volume and pressure will be combined to report the Recruitment Index (R/I) in mL/cmH2O. A threshold of 0.5 will be used to define high recruitability (R/I ratio >= 0.5 ml/cmH2O) and low recruitability (R/I ratio < 0.5 ml/cmH2O).
• Correlation between recruitment index (RI) and recruitment assessed by hysteresis ratio. [ Time Frame: First 7 days of the patient on mechanical ventilation (MV) ]
  Assess the correlation between recruitment index (RI) and recruitment assessed by the hysteresis ratio (hysteresis and the product of the pressure span and the maximum volume reached (maximum hysteresis) in ml/cmH2O Tidal volume and pressure will be combined to report the Recruitment Index (R/I) in mL/cmH2O. Tidal volume and pressure will be combined to report the hysteresis ratio in mL/cmH2O.
• Assess the relationship between potential recruitment with respiratory parameters. [ Time Frame: First 7 days of the patient on mechanical ventilation (MV) ]
  Assess the correlation between IR and respiratory parameters

  • Oxygenation: PaO2/FiO2 (ratio between arterial oxygen pressure and inspired fraction of oxygen).
  • Static compliance (cmH2O)
  • Plateau pressure (cmH2O)
  • ∆P (ml/cmH2O)

  Tidal volume and pressure will be combined to report the Recruitment Index (R/I) in mL/cmH2O.
• Assess the relationship between potential recruitment and clinical parameters. [ Time Frame: First 7 days of the patient on mechanical ventilation (MV) ]
  Assess the correlation between IR and clinical parameters:

  • Symptom onset date (FIS) (in case of ARDS-Covid-19)
  • APACHE II (Acute Physiology And Chronic Health Evaluation) score
  • SOFA (Sequential Organ Failure Assessment Score) score
  • Ventilator free days (in days)

  Tidal volume and pressure will be combined to report the Recruitment Index (R/I) in mL/cmH2O.

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Recruitment Assessment in Patients With Acute Respiratory Distress Syndrome and Covid-19
• Official Title: Recruitment Assessment in Patients With Acute Respiratory Distress Syndrome and Covid-19
• Brief Summary: Respiratory failure associated with Covid-19 can be expressed as acute respiratory distress syndrome (ARDS), which is an acute inflammatory lung injury,which generally requires the use of invasive mechanical ventilation (MV). There are inconclusive results regarding the potential lung recruitment in ARDS. Recently, a new index based on lung compliance has been described to directly quantify the potential for lung recruitment, called the recruitment-inflation index (R/I index). The objective of this study is to prospectively evaluate the recruitment capacity in patients with ARDS and ARDS-Covid-19.

Detailed Description

During the first 7 days of the patient on mechanical ventilation (MV), measurements will be taken. For this, the patient will be in the supine position (DS) or the prone position (DP). The patient will be on a dose of analgesics, under sedation and muscle relaxation and will not present any respiratory stimulus.

Data from MV will also be recorded (prior to recruitment assessment): tidal volume (TV) in milliliters (ml), respiratory rate (RR) in a minute, fraction of inspired oxygen (FiO2), positive end-expiratory pressure (PEEP), in centimeters of water (cmH2O), plateau pressure (Pplat, measured after an end-inspiratory pause, cmH2O), mean airway pressure (PM, cmH2O), minute volume (calculated as the product of RR and TV) in milliliters per minute, ∆P (calculated as Pplat minus PEEP, cmH2O), static compliance (calculated as TV divided by ∆P, ml/cmH2O). Arterial blood gases will also be considered. The proposed recruitment assessment (R/I index) will be compared with another already validated method to evaluate recruitment, such as the measurement of pulmonary hysteresis ratio.For measurements, a ventilator (Neumovent GraphNet Advance-TS, Córdoba Argentina) will be used. Additionally, a dedicated software connected to a computer will be used to perform the measurements.

The following will be assessed: presence of autoPEEP, preset inspiratory tidal volume (TVi), TV exhaled by the ventilator (TVexh) and TV exhaled from high to low PEEP (difference of 10 cm of H2O),during a single maneuver (TVeHL). The measurement will be performed with a high level of PEEP (PEEPH), with values between 15 and 18 cmH2O and a low level of PEEP (PEEPL) with values between 5 and 8 cmH2O. Pplat in PEEPL will also be measured. Additionally, an attempt will be made to determine if there is complete airway closure (a confounder for measurement of alveolar pressure). This is because there are patients who have complete airway closure. In this case, the lungs required an airway opening pressure (AOP) to reopen airways before initiating lung inflation. When AOP is higher than PEEPL, the AOP will be considered as the lower pressure value (instead of PEEPL).

The recruitment index (R/I index) will be as follows:

R/I = (TVexHL - TVexH)/TVi X (Ppl - PEEPL/PEEPH - PEEPL) - 1

TVexH: TV exhaled with PEEPH.

In case of airway closure PEEPL will be replaced by AOP.

A threshold of 0.5 was used to define high recruitability (R/I ratio >= 0.5) and low recruitability (R/I ratio < 0.5).

The evaluation of pressure in relation to volume will also be carried out, through the pressure/volume curve (PV curve), available in the respirator. A low-flow inflation and deflation PV curve from 0 up to 40 cm H2O and from 40 down to 0 cm H2O will be performed using the automatic tool on the ventilator (P/V tool; Neumovent GraphNet Advance-ts, Córdoba Argentina). The P-V curve can be visualized immediately on the screen of the mechanical ventilator and will be taken as a reference method to assess lung recruitment through the hysteresis-like behavior of the respiratory system. Inflation and deflation volume data will be corrected for changes in oxygen consumption.

Ratio hysteresis of the respiratory system will be measured by planimetry using SigmaPlot 12.0 software. There, through a cursor, for the measurement of hysteresis, the place where the volume was greater was drawn and the coincident pressure value was considered. Subsequently the ratio hysteresis was calculated as the ratio between hysteresis and the product of the pressure span and the maximum volume reached (maximum hysteresis). Recruitment potential will be considered if this relationship presents a value > 28%.

Data Analysis. Categorical variables will be presented as number and percentage, while continuous variables will be presented as mean and standard deviation or median and interquartile range, as appropriate. The Chi2 test or Fisher's exact test will be used for qualitative variables and the Student test or the Mann-Whitney U test for quantitative variables. To evaluate correlation, the Pearson or Spearman test will be used, according to the distribution of the evaluated variables. A p ≤ 0.05 will be used.

• Study Type: Observational
• Study Design: Observational Model: Cohort; Time Perspective: Prospective
• Target Follow-Up Duration: Not Provided
• Biospecimen: Not Provided
• Sampling Method: Non-Probability Sample
• Study Population: Patients 15 years of age or older who have been receiving MV in the first 7 days and have been defined as ARDS and ARDS-Covid-19 (with a positive polymerase chain reaction in nasopharyngeal swab samples) according to the clinical criteria of the Berlin definition.

Condition

• Acute Respiratory Distress Syndrome
• COVID-19 Pneumonia
• Recruitment

Intervention

Procedure: Recruitment assessment

TV exhaled from high to low PEEP (difference of 10 cm of H2O),during a single maneuver (TVeHL). The measurement will be performed with a high level of PEEP (PEEPH), with values between 15 and 18 cmH2O and a low level of PEEP (PEEPL) with values between 5 and 8 cmH2O. Pplat in PEEPL will also be measured.

• Study Groups/Cohorts: Not Provided

Publications *

• ARDS Definition Task Force; Ranieri VM, Rubenfeld GD, Thompson BT, Ferguson ND, Caldwell E, Fan E, Camporota L, Slutsky AS. Acute respiratory distress syndrome: the Berlin Definition. JAMA. 2012 Jun 20;307(23):2526-33. doi: 10.1001/jama.2012.5669.
• Ziehr DR, Alladina J, Petri CR, Maley JH, Moskowitz A, Medoff BD, Hibbert KA, Thompson BT, Hardin CC. Respiratory Pathophysiology of Mechanically Ventilated Patients with COVID-19: A Cohort Study. Am J Respir Crit Care Med. 2020 Jun 15;201(12):1560-1564. doi: 10.1164/rccm.202004-1163LE. No abstract available.
• Gattinoni L, Caironi P, Cressoni M, Chiumello D, Ranieri VM, Quintel M, Russo S, Patroniti N, Cornejo R, Bugedo G. Lung recruitment in patients with the acute respiratory distress syndrome. N Engl J Med. 2006 Apr 27;354(17):1775-86. doi: 10.1056/NEJMoa052052.
• Marini JJ, Gattinoni L. Management of COVID-19 Respiratory Distress. JAMA. 2020 Jun 9;323(22):2329-2330. doi: 10.1001/jama.2020.6825. No abstract available.
• Chen L, Del Sorbo L, Grieco DL, Junhasavasdikul D, Rittayamai N, Soliman I, Sklar MC, Rauseo M, Ferguson ND, Fan E, Richard JM, Brochard L. Potential for Lung Recruitment Estimated by the Recruitment-to-Inflation Ratio in Acute Respiratory Distress Syndrome. A Clinical Trial. Am J Respir Crit Care Med. 2020 Jan 15;201(2):178-187. doi: 10.1164/rccm.201902-0334OC.
• Chiumello D, Arnal JM, Umbrello M, Cammaroto A, Formenti P, Mistraletti G, Bolgiaghi L, Gotti M, Novotni D, Reidt S, Froio S, Coppola S. Hysteresis and Lung Recruitment in Acute Respiratory Distress Syndrome Patients: A CT Scan Study. Crit Care Med. 2020 Oct;48(10):1494-1502. doi: 10.1097/CCM.0000000000004518. Erratum In: Crit Care Med. 2022 Mar 1;50(3):e339.
• Demory D, Arnal JM, Wysocki M, Donati S, Granier I, Corno G, Durand-Gasselin J. Recruitability of the lung estimated by the pressure volume curve hysteresis in ARDS patients. Intensive Care Med. 2008 Nov;34(11):2019-25. doi: 10.1007/s00134-008-1167-8. Epub 2008 Jun 25.
• Pan C, Chen L, Lu C, Zhang W, Xia JA, Sklar MC, Du B, Brochard L, Qiu H. Lung Recruitability in COVID-19-associated Acute Respiratory Distress Syndrome: A Single-Center Observational Study. Am J Respir Crit Care Med. 2020 May 15;201(10):1294-1297. doi: 10.1164/rccm.202003-0527LE. No abstract available.
• Chen L, Del Sorbo L, Grieco DL, Shklar O, Junhasavasdikul D, Telias I, Fan E, Brochard L. Airway Closure in Acute Respiratory Distress Syndrome: An Underestimated and Misinterpreted Phenomenon. Am J Respir Crit Care Med. 2018 Jan 1;197(1):132-136. doi: 10.1164/rccm.201702-0388LE. No abstract available.
• Knaus WA, Draper EA, Wagner DP, Zimmerman JE. APACHE II: a severity of disease classification system. Crit Care Med. 1985 Oct;13(10):818-29.
• Vincent JL, de Mendonca A, Cantraine F, Moreno R, Takala J, Suter PM, Sprung CL, Colardyn F, Blecher S. Use of the SOFA score to assess the incidence of organ dysfunction/failure in intensive care units: results of a multicenter, prospective study. Working group on "sepsis-related problems" of the European Society of Intensive Care Medicine. Crit Care Med. 1998 Nov;26(11):1793-800. doi: 10.1097/00003246-199811000-00016.
• Schoenfeld DA, Bernard GR; ARDS Network. Statistical evaluation of ventilator-free days as an efficacy measure in clinical trials of treatments for acute respiratory distress syndrome. Crit Care Med. 2002 Aug;30(8):1772-7. doi: 10.1097/00003246-200208000-00016.
• Hohmann F, Wedekind L, Grundeis F, Dickel S, Frank J, Golinski M, Griesel M, Grimm C, Herchenhahn C, Kramer A, Metzendorf MI, Moerer O, Olbrich N, Thieme V, Vieler A, Fichtner F, Burns J, Laudi S. Early spontaneous breathing for acute respiratory distress syndrome in individuals with COVID-19. Cochrane Database Syst Rev. 2022 Jun 29;6(6):CD015077. doi: 10.1002/14651858.CD015077.

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: February 17, 2022): 41
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: March 1, 2025
• Actual Primary Completion Date: March 7, 2023 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

- Patients who have been receiving MV with diagnosis of ARDS (Berlin definition) and ARDS-Covid-19.

Exclusion Criteria:

• Patients with chronic pulmonary disease
• Patients with a high risk of death within 3 months for reasons other than ARDS-Covid-19
• Patients having made the decision to withhold life-sustaining treatment.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 15 Years and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No

Contacts

Contact: Roberto Santa Cruz, Dr.; +5492966559019; resc.hrrg@gmail.com

• Listed Location Countries: Argentina

Administrative Information

• NCT Number: NCT05248243
• Other Study ID Numbers: Hospital General Ramos Mejía
• 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

• Plan to Share IPD: No

• Current Responsible Party: Roberto Santa Cruz, Ramos Mejía Hospital
• Original Responsible Party: Same as current
• Current Study Sponsor: Ramos Mejía Hospital
• Original Study Sponsor: Same as current
• Collaborators: Not Provided
• Investigators: Not Provided
• PRS Account: Ramos Mejía Hospital
• Verification Date: March 2023