Clinical trial NCT02243449: Screening Elderly Patients for Weaning
Official title: Screening Elderly PatieNts For InclusiOn in a Weaning Trial: The SENIOR Trial
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Critically Ill
Keywords: mechanical ventilation
weaning
elderly
critically ill
screening
spontaneous breathing trial
invasive ventilation
Lead sponsor: Unity Health Toronto
Sponsor class: OTHER
First posted: 2014-09-18
Enrollment: 102
Sex: ALL
Minimum age (years): 65
Standard ages: OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: SCREENING

Brief summary: During weaning the work of breathing is transferred from the ventilator back to the patient. Approximately 40% of the time on ventilators is spent weaning. Studies support the use of screening protocols and tests of patient's ability to breathe spontaneously (SBTs) to identify weaning candidates. The investigators work demonstrates that once daily screening is the current standard of care. The conduct of daily ward rounds and once daily screening in ICUs is poorly aligned with the rapidly changing clinical status of critically ill patients. With respiratory therapists (RTs) in Canadian intensive care units (ICUs), a significant opportunity exists to screen patients more often, conduct more SBTs, and reduce the time spent on ventilators and in the ICU. Only one mechanical ventilation trial has focused on the elderly and no trial has evaluated weaning outcomes in the elderly and very elderly which may be influenced by the presence of comorbidities, frailty, malnutrition and treatment limitations.

The investigators propose to conduct a pilot randomized trial in 100 elderly (\>/= 65 years) critically ill adults comparing 'once daily' screening to 'at least twice daily' screening in 8 adult ICUs. In the proposed trial, the investigators will (i) evaluate their ability to recruit elderly (\>/= 65 years) critically ill patients into a weaning trial and (ii) assess whether protocols can be adhered to similarly between elderly (65 to 80 years) and very elderly (\>80 years) trial participants. Moreover, they will also address generalizability issues in the conduct of mechanical ventilation research by evaluating potential biases associated with exclusion criteria and consent between elderly and very elderly patients and obtain preliminary estimates of differences in important clinical outcomes between elderly and very elderly participants.

Detailed description: In the context of a multicentre, pilot trial in 100 elderly (\>/= 65 years) critically ill adults comparing two strategies to identify weaning candidates ('once daily' vs. 'at least twice daily' screening) in 8 ICUs across Canada, we propose to assess feasibility metrics that reflect our ability to consent, enroll and recruit elderly and very elderly invasively ventilated patients and evaluate adherence to the study protocols in preparation for launching a large scale screening RCT.

1. Primary Research Question (i) Can we recruit invasively ventilated elderly (age \>/= 65 years) critically ill adults into a weaning trial comparing alternative screening strategies?
2. Secondary Research Questions (ii) Can clinicians adhere to the assigned screening protocols in both study arms?
3. Tertiary Research Questions

   (ii) What are the proportions of enrolled elderly and very elderly trial participants? (iii) Are the proportions of consents obtained and declined for trial participation similar between eligible elderly and very elderly trial participants? (iv) What are the rates and reasons for trial exclusion based between eligible elderly and very elderly patients? (v) What effect, in preliminary estimates, do the alternative screening strategies have on clinically important outcomes\[e.g., time to first Spontaneous Breathing Trial (SBT) and first successful SBT, time to first extubation and successful extubation, total duration of mechanical ventilation, intensive care unit (ICU) and hospital length of stay, ICU and hospital mortality, use of noninvasive ventilation (NIV) following extubation, complications (self-extubation, tracheostomy, reintubation, proportion requiring prolonged mechanical ventilation) and adverse events\] between elderly and very elderly trial participants.
4. Quaternary Research Questions

(i) Can we assess and quantify current practices related to sedation, analgesia an delirium management and mobilization before conducting 'once daily' or 'at least twice daily screening' assessments of weaning readiness with the goal of quantifying factors that may lead to performance bias in the future, planned, large scale weaning trial.

(ii) Can we identify barriers (clinician and institutional) to recruitment into this study? (iii) Can we classify trial participants as requiring (i) simple, (ii) difficult or (iii) prolonged weaning using the 'Task Force on Weaning' definitions.

Hypotheses

We hypothesize that we will achieve our feasibility metrics, specifically, that:

1. We will recruit at least 2 elderly critically ill patients, on average, per month per ICU.
2. Compliance rates will be at least 80% in both study arms and contamination in the once daily screening arm will be \< 10%.
3. We expect that we will enroll similar proportions of elderly than very elderly trial participants.
4. We anticipate that the proportion of consents obtained will be similar between eligible elderly and very elderly participants, the rate of declined consents will be higher in very elderly trial participants.
5. We anticipate that rates of exclusion will be greater for very elderly trial participants due to increased prevalence of comorbid illnesses and treatment limitations.
6. We expect that preliminary estimates of the impact of the alternative screening strategies on clinically important outcomes will be similar between elderly and very elderly trial participants.
7. Practices in sedation, analgesia, delirium and mobilization will be recorded at least 80% of the time.
8. We will identify potentially modifiable clinician and institutional barriers to recruitment.
9. Proportions of critically ill adults requiring simple, difficult or prolonged weaning in Canadian ICUs will be similar to those reported in the world literature.

Eligibility criteria: Inclusion Criteria:

The investigators will include:

1. elderly (age \>/= 65 years) critically ill adults
2. receiving invasive mechanical ventilation for at least 24 hours who can breathe spontaneously on Pressure Support (PS) or trigger breaths on volume or pressure Assist Control (AC), volume or pressure Synchronized Intermittent Mandatory Ventilation (SIMV) ± PS, Pressure Regulated Volume Control (PRVC) or Airway Pressure Release Ventilation (APRV).
3. patients must be receiving \</= 70% inspired oxygen
4. and a positive end-expiratory pressure of \</= 12 cm H2O (Table 2). .

Exclusion Criteria:

The investigators will exclude patients who have already undergone extubation or an SBT, are unlikely to benefit (e.g. moribund, expected brain death), on automated weaning modes, participating in studies with a weaning protocol, and those who can not be optimized with regard to sedation and mobilization.

Specifically, we will exclude patients:

1. admitted after cardiopulmonary arrest or with brain death or expected brain death,
2. who have evidence of myocardial ischemia in the 24 hour period before enrollment,
3. who have received continuous invasive mechanical ventilation for \>/= 2 weeks,
4. who have a tracheostomy in situ at the time of screening,
5. who are receiving sedative infusions for seizures or alcohol withdrawal,
6. who require escalating doses of sedative agents,
7. who are receiving neuromuscular blockers or who have known quadriplegia, paraplegia or 4 limb weakness or paralysis preventing active mobilization (e.g., active range of motion, exercises in bed, sitting at edge of bed, transferring from bed to chair, standing, marching in place, ambulating),
8. who are moribund (e.g., at imminent risk for death) or who have limitations of treatment (e.g., withdrawal of support, do not reintubate order, however, do not resuscitate orders will be permitted),
9. who have profound neurologic deficits (e.g. large intracranial stroke or bleed) or Glasgow Coma Scale (GCS) \</= 6,
10. who are using modes that automate SBT conduct,
11. who are current enrolled in a confounding study that includes a weaning protocol,
12. who were previously enrolled in this trial,
13. patients who have already undergone an SBT or
14. patients who have already undergone extubation \[planned, unplanned (e.g. self, accidental)\] during the same ICU admission.

Primary outcomes:
measure: Recruit, on average, 2 elderly invasively ventilated, critically ill patients per ICU per month.
timeFrame: 12 months
Secondary outcomes:
measure: Adhere to the assigned screening protocols in both study arms.
timeFrame: 12 months
Other outcomes:
measure: Proportion of enrolled elderly and very elderly trial participants
timeFrame: 12 months
measure: Proportion of consents obtained and declined for trial participation
timeFrame: 12 months
measure: Rates and reasons for trial exclusion
timeFrame: 12 months
measure: Effect of the alternative screening strategies on clinically important outcomes (see below) between elderly and very elderly trial participants?
timeFrame: 12 months + 2 months follow up
Locations:
city: Vancouver
country: Canada
facility: St. Paul's Hospital
state: British Columbia
city: Hamilton
country: Canada
facility: Hamilton General Hospital
state: Ontario
city: Hamilton
country: Canada
facility: St Joseph's Hospital
state: Ontario
city: Ottawa
country: Canada
facility: Ottawa General Hospital
state: Ontario
city: Toronto
country: Canada
facility: Mount Sinai Hospital
state: Ontario
city: Toronto
country: Canada
facility: St. Michael's Hospital
state: Ontario
city: Montréal
country: Canada
facility: Hôpital Saint-Luc
state: Quebec
city: Sherbrooke
country: Canada
facility: Universite Hopitalier de Sherbrooke
state: Quebec
Study officials:
affiliation: St. Michael's Hospital (Toronto, Canada)
name: Karen E. A. Burns, MD, FRCPC
role: PRINCIPAL_INVESTIGATOR
References:
citation: Burns KEA, Wong JTY, Dodek P, Cook DJ, Lamontagne F, Cohen A, Mehta S, Kho ME, Hebert PC, Aslanian P, Friedrich JO, Brochard L, Rizvi L, Hand L, Meade MO, Amaral AC, Seely AJ; Canadian Critical Care Trials Group. Frequency of Screening for Weaning From Mechanical Ventilation: Two Contemporaneous Proof-of-Principle Randomized Controlled Trials. Crit Care Med. 2019 Jun;47(6):817-825. doi: 10.1097/CCM.0000000000003722.