Mechanical Insufflation-Exsufflation (Cough Assist) in Critically Ill Adults (ACACIA)

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ClinicalTrials.gov Identifier: NCT06027008

Recruitment Status : Recruiting

First Posted : September 7, 2023

Last Update Posted : January 31, 2024

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Sponsor:

Information provided by (Responsible Party):

Prof. Dr. Marcus J. Schultz, Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)

Study Description

Brief Summary:

The goal of this randomized feasibility trial is to evaluate the feasibility of Mechanical Insufflation-Exsufflation (MI-E) in invasively ventilated critically ill patients.

The main question[s] it aims to answer are:

Is MI-E feasible?
Is MI-E safe?

Participants in the intervention group will receive:

MI-E
Airway secretions will be removed by endotracheal suctioning, as part of routine airway care.
Manual hyperinflation will only be used when necessary in an emergency situation. Patients in the control group will receive endotracheal suctioning and manual hyperinflation when clinically indicated.

The primary outcome is the proportion of delivered MI-E sessions (2 times per calendar day a MI-E session of 3 x 3 cycles of an in- and exsufflation) per patient according to study protocol (feasibility). Secondary outcomes are the total number of serious adverse events in relation to MI-E (safety) and preliminary exploratory data on the need for airway care interventions and clinical outcomes including duration of invasive ventilation, length of stay in ICU and mortality (efficacy).

Condition or disease	Intervention/treatment	Phase
Critically Ill	Device: Mechanical Insufflation-Exsufflation	Not Applicable

Detailed Description:

Bedside nurses, trained in using the MI-E device, will apply MI-E sessions at two moments per calendar day (morning and afternoon) for a maximum of 7 days while a patient is invasively ventilated.

MI-E settings are a 2-second insufflation and an immediate 2-second exsufflation. The cycles of the MI-E session will be performed with a positive and negative pressure of 40 cmH2O. The program is set up with the possibility of auto-triggering by the patient.

Study Design

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Study Type :	Interventional (Clinical Trial)
Estimated Enrollment :	50 participants
Allocation:	Randomized
Intervention Model:	Parallel Assignment
Intervention Model Description:	Randomized feasibility trial
Masking:	None (Open Label)
Masking Description:	Due to the nature of the intervention, blinding of healthcare professionals and any research personnel involved in the delivery of the intervention is not possible.
Primary Purpose:	Treatment
Official Title:	Mechanical Insufflation-Exsufflation (Cough Assist) in Critically Ill Adults (ACACIA)-a Randomized Clinical Feasibility Trial
Actual Study Start Date :	October 30, 2023
Estimated Primary Completion Date :	May 2025
Estimated Study Completion Date :	June 2025

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Cough

U.S. FDA Resources

Arms and Interventions

Arm	Intervention/treatment
Experimental: Mechanical Insufflation-Exsufflation Invasively ventilated patients will receive MI-E until successful extubation or for a maximum of 7 days. MI-E will be given in the morning and afternoon each calendar day. Patients will be pre-oxygenated with FiO2 100% prior to disconnection from the ventilator; additional 15 litres oxygen can be added; A pre-set program is used: three times three cycles with a 2-second insufflation and an immediate 2-second exsufflation. The cycles of the MI-E session will be performed with a positive and negative pressure of 40 cmH2O. The program is set up with the possibility of auto-triggering by the patient.	Device: Mechanical Insufflation-Exsufflation MI-E will be applied twice a day in invasively ventilated patients. Since the severity of illness can change in the ICU, each day the attending nurse will check for clinical reasons to not apply MI-E with regard to safety. The following clinical criteria are predefined as a reason to refrain from MI-E at that day: severe ventilator instability (requiring > 12 cm H2O PEEP and dependency of > 60% FiO2); severe hemodynamic instability (a need for large and sustained increase in continuous administration of intravenous vasopressive medication that are adjusted on a frequent basis in each nursing shift); extra corporal membrane oxygenation (ECMO); and deeply sedated patient (RASS score ≤ -4). Other Name: Cough assist
No Intervention: Standard airway care Patients in the control group will receive usual airway care which includes endotracheal suctioning and manual hyperinflation used when indicated based on clinical signs as part of regular airway care. Care protocols for endotracheal suctioning and manual hyperinflation are predefined. As with the intervention arm, there will be no use of saline instillation during suctioning. Manual hyperinflation technique is described in the care protocol of the intensive care unit and ICU nurses are trained to perform this technique.

Arm

Intervention/treatment

Experimental: Mechanical Insufflation-Exsufflation

Invasively ventilated patients will receive MI-E until successful extubation or for a maximum of 7 days. MI-E will be given in the morning and afternoon each calendar day. Patients will be pre-oxygenated with FiO2 100% prior to disconnection from the ventilator; additional 15 litres oxygen can be added; A pre-set program is used: three times three cycles with a 2-second insufflation and an immediate 2-second exsufflation. The cycles of the MI-E session will be performed with a positive and negative pressure of 40 cmH2O. The program is set up with the possibility of auto-triggering by the patient.

Device: Mechanical Insufflation-Exsufflation

MI-E will be applied twice a day in invasively ventilated patients. Since the severity of illness can change in the ICU, each day the attending nurse will check for clinical reasons to not apply MI-E with regard to safety. The following clinical criteria are predefined as a reason to refrain from MI-E at that day:

severe ventilator instability (requiring > 12 cm H2O PEEP and dependency of > 60% FiO2);
severe hemodynamic instability (a need for large and sustained increase in continuous administration of intravenous vasopressive medication that are adjusted on a frequent basis in each nursing shift);
extra corporal membrane oxygenation (ECMO); and
deeply sedated patient (RASS score ≤ -4).

Other Name: Cough assist

No Intervention: Standard airway care

Patients in the control group will receive usual airway care which includes endotracheal suctioning and manual hyperinflation used when indicated based on clinical signs as part of regular airway care. Care protocols for endotracheal suctioning and manual hyperinflation are predefined. As with the intervention arm, there will be no use of saline instillation during suctioning. Manual hyperinflation technique is described in the care protocol of the intensive care unit and ICU nurses are trained to perform this technique.

Outcome Measures

Primary Outcome Measures :

intervention delivery [ Time Frame: max. 7 days ]
the proportion of complete sessions of MI-E every calender day (i.e. two MI-E sessions with 3 x 3 cycles of an in- and exsufflation) for all patients with a maximum of seven days of invasive ventilation

Secondary Outcome Measures :

incidence of pneumothorax (safety) [ Time Frame: max 7 days ]
incidence of pneumothorax for which drainage is needed attributed to MI-E or to routine airway care procedures (i.e., manual hyperinflation)
incidence of endotracheal tube obstruction (safety) [ Time Frame: max 7 days ]
incidence of endotracheal tube obstruction due to mucus plugging attributed to MI-E or regular airway care
incidence of severe hypoxemia (safety) [ Time Frame: max 7 days ]
incidence of severe hypoxemia
incidence of severe hypotension (safety) [ Time Frame: max 7 days ]
incidence of severe hypotension
incidence of severe hypertension (safety) [ Time Frame: max 7 days ]
incidence of severe hypertension
Acceptability of Intervention Measure (AIM) [ Time Frame: through study completion, estimated one year ]
1 = Completely disagree, 2 = Disagree, 3 = Neither agree nor disagree, 4 = Agree, 5 = Response scale 1 (completely disagree) - 5 (completely agree)
Intervention Appropriateness Measure (IAM) [ Time Frame: through study completion, estimated one year ]
1 = Completely disagree, 2 = Disagree, 3 = Neither agree nor disagree, 4 = Agree, 5 = Response scale 1 (completely disagree) - 5 (completely agree)
Feasibility of Intervention Measure (FIM) [ Time Frame: through study completion, estimated one year ]
1 = Completely disagree, 2 = Disagree, 3 = Neither agree nor disagree, 4 = Agree, 5 = Response scale 1 (completely disagree) - 5 (completely agree)
amount of time needed for MI-E (feasibility) [ Time Frame: maximum of 1 hour per session ]
time needed to deliver the MI-E intervention
endotracheal suctioning (feasibility) [ Time Frame: max. 7 days ]
frequency of endotracheal suctioning per ventilation day
MH (feasibility of MI-E) [ Time Frame: max. 7 days ]
frequency of manual hyperinflation
VAP (efficacy MI-E sample size calculation) [ Time Frame: 28 days after inclusion ]
incidence of ventilator associated pneumonia (VAP)
duration MV (efficacy MI-E sample size calculation) [ Time Frame: 28 days after inclusion ]
duration of invasive ventilation
Mortality day 28 (efficacy MI-E sample size calculation) [ Time Frame: up to day 28 from ICU admission ]
mortality at day 28
VFD-28 (efficacy MI-E sample size calculation) [ Time Frame: 28 days after inclusion ]
ventilator-free days at day 28
ICU mortality (efficacy MI-E sample size calculation) [ Time Frame: 28 days after inclusion ]
ICU mortality
hospital mortality (efficacy MI-E sample size calculation) [ Time Frame: 28 days after inclusion ]
hospital mortality
supplemental oxygen (efficacy MI-E sample size calculation) [ Time Frame: 28 days after inclusion ]
use of supplemental oxygen on ICU delivery after detubation
LOS ICU (efficacy MI-E sample size calculation) [ Time Frame: 28 days after inclusion ]
length of stay in ICU
LOS hospital (efficacy MI-E sample size calculation) [ Time Frame: 28 days after inclusion ]
length of stay in hospital

Eligibility Criteria

Information from the National Library of Medicine

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Ages Eligible for Study:	18 Years and older (Adult, Older Adult)
Sexes Eligible for Study:	All
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

admission to one of the participating ICUs;
receiving invasive mechanical ventilation via an endotracheal tube; and
expected to need invasive ventilation for more than 48 hours from consideration for inclusion.

Exclusion Criteria:

use of MI-E before hospital admission, i.e., at home;
known presence of bullous emphysema;
known bronchopleural fistula;
known pneumothorax or pneumomediastinum;
known rib fractures;
known barotrauma;
known unstable spinal fractures;
unsecured subarachnoidal haemorrhage;
uncontrollable intracranial pressures; and
any infection, or colonization with pathogens that requires strict aerogenic isolation. With an exception for patients in cohort isolation due to COVID-19.

Contacts and Locations

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT06027008

Contacts

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Contact: Frederique Paulus, RN, PHD	+31-20-5669111	f.paulus@amsterdamumc.nl
Contact: Willemke Stilma, RN, MSc, LLM	+31-20-5669111	w.stilma@amsterdamumc.nl

Locations

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Netherlands
Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)	Recruiting
Amsterdam, Netherlands
Contact: Willemke Stilma, RN, MSc, LLM +31-20-5669111 w.stilma@amsterdamumc.nl
Contact: Frederique Paulus, PHD +31-20-5669111 f.paulus@amsterdamumc.nl
Principal Investigator: Marcus J Schultz, MD, PHD
Principal Investigator: Frederique Paulus, RN, PHD

Sponsors and Collaborators

Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)

Investigators

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Principal Investigator:	Frederique Paulus, RN, PHD	Amsterdam UMC - intensive care

More Information

Publications:

Stilma W, Verweij L, Spek B, Scholte Op Reimer WJM, Schultz MJ, Paulus F, Rose L. Mechanical insufflation-exsufflation for invasively ventilated critically ill patients-A focus group study. Nurs Crit Care. 2023 Nov;28(6):923-930. doi: 10.1111/nicc.12858. Epub 2022 Dec 4.

Swingwood EL, Stilma W, Tume LN, Cramp F, Voss S, Bewley J, Ntoumenopoulos G, Schultz MJ, Scholte Op Reimer W, Paulus F, Rose L. The Use of Mechanical Insufflation-Exsufflation in Invasively Ventilated Critically Ill Adults. Respir Care. 2022 Aug;67(8):1043-1057. doi: 10.4187/respcare.09704. Epub 2022 May 24.

Rose L, Adhikari NK, Leasa D, Fergusson DA, McKim D. Cough augmentation techniques for extubation or weaning critically ill patients from mechanical ventilation. Cochrane Database Syst Rev. 2017 Jan 11;1(1):CD011833. doi: 10.1002/14651858.CD011833.pub2.

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Responsible Party:	Prof. Dr. Marcus J. Schultz, Prof. dr., Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
ClinicalTrials.gov Identifier:	NCT06027008
Other Study ID Numbers:	ACACIA
First Posted:	September 7, 2023 Key Record Dates
Last Update Posted:	January 31, 2024
Last Verified:	January 2024
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD:	No
Plan Description:	Currently, there is no decision on a data sharing plan

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Studies a U.S. FDA-regulated Drug Product:	No
Studies a U.S. FDA-regulated Device Product:	No

Keywords provided by Prof. Dr. Marcus J. Schultz, Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA):


Mechanical insufflation-exsufflation Cough Assist

Additional relevant MeSH terms:

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Critical Illness Disease Attributes Pathologic Processes

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