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Background
• Commissioned call NIHR HTA
• Objective: To determine if invasive ventilation using protocolised weaning that includes non-invasive ventilation (NIV) as an intermediate step is clinically and cost effective compared to protocolised weaning without NIV
Study summary
• Design: Pragmatic, open label, RCT• Population: Adults, ventilated > 48 hr, fail SBT• Intervention: Weaning using NIV• Comparator: Protocolised invasive weaning• Outcome: Time to liberation from ventilation• Sample size: 920 over 30 months
Study Timeline
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 23 24 25 26 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48
Jan Feb Mar Apr May Jun Jul Aug Sep Oct Nov Dec Jan Feb Mar Apr Nov Dec Jan Feb Jun Jul Aug Sep Oct Nov Dec Jan Feb Mar Apr May Jun Jul Aug Sep Oct Nov DecNOTES:48 Months (4 years)
TASK:Trial Set UpSite Set UpPatient Recruitment3 Month Follow-up6 Month Follow-UpData AnalysisReporting
2013 2014 2015 2016
Timeline
Recruitment PlanTarget for sites 1.5 patients per month
Outcomes
Primary clinical outcome:
Time from randomisation to liberation from ventilation
Secondary clinical outcomes• 30, 90 and 180 day all cause mortality• Duration of invasive mechanical ventilation and total
ventilator days • Time to meeting ICU discharge criteria• Hospital length of stay• Antibiotic use• Re-intubation, tracheostomy; adverse events• Health related quality of life
Inclusion criteria
• Is the patient age 16 years or older?• Has the patient received invasive mechanical
ventilation for respiratory failure for greater than 48 hours?
• Is the patient ready for weaning?
Exclusion criteria
• Patient known to be pregnant• Presence of tracheostomy• Profound neurological deficit • Any absolute contraindication to NIV • Home ventilation prior to ICU admission • Decision not to re-intubate / withdrawal • Further surgery / procedure requiring sedation planned in
next 48 hours • Previous participation in the Breathe study
Daily ScreeningAll ventilated patients will be assessed each morning for eligibility by ICU nursing / medical staff. Patients will be identified as potentially eligible if they fulfil the following criteria:
• anticipated or actual requirement for invasive ventilation for > 24 hours• at least partial reversal of the condition precipitating invasive
ventilation• stabilisation of "other" organ system failures (i.e. no worsening) • arterial oxygen saturation measured using pulse oximetry (SpO2) ≥ 90%
with fractional concentration inspired oxygen (FiO2) ≤ 0.70 • PEEP ≤ 10 cmH2O• the absence of trial exclusion criteria (above)
A screening log will be maintained at each site which will include the reasons for non-enrolment.
Obtain consent
Spontaneous Breathing Trial
Record baseline characteristics
ExcludedPASS
Daily screening for eligibility and assess for readiness to wean
RANDOMISE
Protocolised NIV
weaning arm
Protocolised Invasive
weaning arm
FAIL
* England, Wales, NI
CONSENT PROCESS
Cooperative and pain freeGood cough
PaO2 : FiO2 ratio >24 kPaPEEP <10 cmH2O
Hb >7 g dL-1 Temperature 36 - 38.5°CVasoactive drugs stable
Spont respiratory rate >6 min-1
Readiness to wean
Walsh BJA 2004
Record baseline characteristics
• Exhaled minute volume• Total respiratory rate• PEEP• Plateau pressure• Heart rate• Systolic blood pressure• Arterial blood gases
SBTTo be performed in accordance with local unit practices
30 mins duration
• T-piece• Psupp 5cm H2O• CPAP
Pass – ExtubateFail - Randomise
Ely N Engl J Med 1996
Standardised protocols
• Ventilator care bundle– head up position; oral decontamination;
sedation hold; peptic ulcer prophylaxis • Tracheostomy–More than 7 days IMV; inability to protect
airway; persistent inability to remove respiratory secretions
• Re-intubation– Protocolised and clinical endpoints
Data collection
Baseline variables• Patient identifiers • Inclusion and exclusion criteria • APACHE II (at admission) • Admission diagnosis • Presence of COPD • Height and weight• Duration of ventilation prior to randomisation • CAM-ICU
Daily data• Ventilation status
(IMV, NIV, self-ventilating)
• Organ support requirements
• Level of critical care• Antibiotic use for
respiratory and non-respiratory infection
• Adverse events • Sedation usage • Weaning and
ventilator bundle compliance
Study endpoints
• Liberation from ventilation– Add definition from CRF
• Death• Tracheostomy• Re-intubation
– Actual– Protocolised
• ICU discharge data
Discontinuation of intervention
• NIV arm – re-intubation• IPPV arm – tracheostomy• Withdrawal of consent
• Need to continue data collection after discontinuation of intervention until ICU / hospital discharge
Endpoints
After dischargeBefore hospital discharge
(on site)
• Consent• Antibiotic use if
started within ICU • Acute hospital
discharge date and status
• HRQoL
After hospital discharge(WCTU)
• Survival to 180 days• EQ-5D and SF-12• Healthcare resource
use questionnaire
Serious Adverse EventsA serious adverse event is an AE that fulfils one or more of the following criteria:• Results in death• Is immediately life-threatening• Requires hospitalisation or prolongation of existing
hospitalisation• Results in persistent or significant disability or incapacity• Is a congenital abnormality or birth defect• Is an important medical condition.
The causality of SAEs (i.e. relationship to trial treatment) will be assessed by the investigator(s) and recorded on the SAE form.**Do not report death, pneumonia, organ failure as SAE**
Safety Reporting
All suspected SAE’s report to Warwick Clinical Trials Unit within 24 hours
(Tel: 02476 575849 Fax: 02476 150549)
Patient Follow-up
Health-related quality of life: EQ-5D, SF12 at baseline (estimated)
Patient follow-up: 3 and 6 months EQ-5D and SF12
Study team
Chief Investigator: Prof Gavin PerkinsProject Manager: Sarah DugganTrial Coordinator: Bev HoddellTrainee Trial Coordinator: Jess SmithResearch Facilitator: Laura BlairResearch Nurse: Vikki Gordon
Pilot Study Sites
Hospital PIResearch Nurse
HEFT – Heartlands Prof Fang Gao-SmithPeter Sutton
UHCW Chris BassfordMarie McCauley
Guys & St Thomas’ Nick Hart & Luigi Camporota Katie Lei/John SmithQEHB Catherine Snelson
Arlo WhitehouseBristol RI Tim Gould & Sanjoy Shah
Katie SweetRVH Belfast Danny McAuleyJR Oxford Duncan Young
Questions?Contact: Bev Hoddell, Trial Coordinator. Tel No: 02476-575849 Email: [email protected] Address: Warwick Clinical Trials Unit, University of Warwick, Gibbet Hill Road, Coventry CV4 7AL