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

Mechanical Insufflation-Exsufflation (Cough Assist) in Critically Ill Adults (ACACIA)-a Randomized Clinical Feasibility Trial

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).

Study Overview

• Status: Recruiting
• Conditions: Critically Ill
• Intervention / Treatment: Device: Mechanical Insufflation-Exsufflation

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 Type: Interventional
• Enrollment (Estimated): 50
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Frederique Paulus, RN, PHD; Phone Number: +31-20-5669111; Email: f.paulus@amsterdamumc.nl
• Study Contact Backup: Name: Willemke Stilma, RN, MSc, LLM; Phone Number: +31-20-5669111; Email: w.stilma@amsterdamumc.nl

Study Locations

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

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / 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 Names: 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
intervention delivery	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	max. 7 days

Secondary Outcome Measures

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

Collaborators and Investigators

• Sponsor: Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
• Investigators: Principal Investigator: Frederique Paulus, RN, PHD, Amsterdam UMC - intensive care

Publications and helpful links

General Publications

• 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.
• 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.
• 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.

Study record dates

Study Major Dates

• Study Start (Actual): October 30, 2023
• Primary Completion (Estimated): May 1, 2025
• Study Completion (Estimated): June 1, 2025

Study Registration Dates

• First Submitted: February 6, 2023
• First Submitted That Met QC Criteria: August 30, 2023
• First Posted (Actual): September 7, 2023

Study Record Updates

• Last Update Posted (Estimated): January 31, 2024
• Last Update Submitted That Met QC Criteria: January 30, 2024
• Last Verified: January 1, 2024

More Information

Terms related to this study

• Keywords: Cough Assist; Mechanical insufflation-exsufflation
• Additional Relevant MeSH Terms: Pathologic Processes; Disease Attributes; Critical Illness
• Other Study ID Numbers: ACACIA

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: Currently, there is no decision on a data sharing plan

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No