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Table 2 Schedule of procedures through treatment period

From: Inhaled sedation versus propofol in respiratory failure in the ICU (INSPiRE-ICU2): study protocol for a multicenter randomized controlled trial

 

Screening Period

   

Treatment Period

    
 

Screening/Randomization

  

Baseline

     

Hour, Day, or Month (± Window)

Initial Screening D -30 to Randomization

Complete Screening-24h to Randomization

Randomization

Randomization to Initiation of Study Drug (up to 6 hours)

Q2h (±0.5h)

Q4hnn (±0.5h)

Q8h (±2h)

Daily

EOT/Up to 48h (±6h)

Informed consentd

X

        

Inclusion/exclusion criteria

X

Xe

       

Demographic information

X

        

Medical/surgical history

X

Xe

       

Prior/concomitant relevant medicationsf

 

X

 

X

X

Weight and heightg

 

X

       

Physical examinationh

 

X

      

X

Clinical laboratory assessmentsi

 

X

     

X

 

Pregnancy testl

 

X

       

Physical function and outcomesm

Xkk

        

Cognitive function and outcomesn

Xkk

        

Reduction of SOC sedation and opioids to half

   

Xo

     

Discontinuation of SOC sedatives and opioids

   

Xll

     

Patient characteristicsp

 

X

       

Predicted time remaining on ventilatorq

 

X

       

Ventilator parametersr

   

X

  

Xs

  

Blood gasest

   

X

  

Xs

  

Organ function (SOFA)u

   

X

   

X

 

Randomizationv

  

X

      

Vital signsw

   

Xx

  

Xs

  

RASS

   

Xx

Xy

  

Xz

Xy

CPOT

   

Xx

Xy

    

Study drug administrationv

   

X

X

Isoflurane end-tidal concentration measurementaa

     

X

   

Sedaconda ACD-S device deficiencies

    

X

Adverse eventscc

    

X

Restraints

       

X

 

CAM-ICU-7ee

       

Xz

Xee

Wake-up testff

        

X

  1. ABG arterial blood gas, AE adverse event, BPI Brief Pain Inventory, CAM-ICU-7 7-point scale of the Confusion Assessment Method for the Intensive Care Unit, CPOT Critical Care Pain Observation Tool, D day, ECLS extracorporeal life support, Ecrf electronic case report form, EOT end of treatment, EtCO2 end-tidal carbon dioxide, EW early withdrawal, FAQ functional activities questionnaire, FiO2 fraction of inspired oxygen, h hour, ICU intensive care unit, IES‑R impact of event scale, IQCODE Informant Questionnaire on Cognitive Decline in the Elderly, Katz ADL Katz Index of Independence in Activity of Daily Living, LAR legally authorized representative, LTO Long-Term Outcomes, M month, P0.1 airway occlusion pressure, PC pressure assist/control, PEEP positive end‑expiratory pressure, PIP peak inspiratory pressure, PROMIS Patient-Reported Outcomes Measurement Information System, PS pressure support, Q every, RASS Richmond Agitation Sedation Scale, SAPS Simplified Acute Physiology Score, Sedaconda ACD‑S Sedaconda Anesthetic Conserving Device – S, SOC standard of care, SOFA sequential organ failure assessment, SpO2 peripheral capillary oxygen saturation, TICS Telephone Interview for Cognitive Status, UNS unscheduled, W week(s), WAIS Wechsler adult intelligence scale, WHODAS 2.0 World Health Organization Disability Assessment Schedule 2.0, WMS Wechsler memory scale
  2. aMajor ICU interventions, information on ICU care, and relevant concomitant medications are to be collected at Study Day 30 or at ICU discharge, whichever comes first. Level of care (can be collected retrospectively for the whole study period), duration of mechanical ventilation, late onset drug-induced liver injury, mortality, and follow-up of any unresolved AEs are to be performed through telephone call if not possible to retrieve information through medical records at Study Day 30 (regardless of ICU discharge status)
  3. bPatients will be followed-up via telephone call at 3 and 6 months (±4 weeks)
  4. cUnless consent is withdrawn, the patient should continue in the study for assessment and follow-up even if study drug is discontinued. If consent is withdrawn, patients will be encouraged to complete the EW visit, if possible
  5. dInformed consent must be obtained from patient or patient’s LAR before any study-related procedures are performed. If the patient is unable to consent at the time of Screening, informed consent may be obtained from the patient’s LAR; however, information about the study will be given to, and consent obtained from, the patient as soon as the patient’s condition allows
  6. eTo be assessed only if Initial Screening is performed more than 24 hours prior to the Complete Screening
  7. fAll relevant prior and concomitant medications are recorded from ICU admission or 24 hours prior to initiation of study drug treatment, whichever is shortest, until the end of the 24-hour post‑treatment monitoring period. After this, only receipt of specific sedative, antipsychotic, and analgesic medications and relevant concomitant medications associated with ongoing AEs will be collected from 24 hours after EOT until Study Day 30 or ICU discharge, whichever comes first. All administered opioids, including the mean opioid dose assessment at 60 minutes prior to randomization, are to be collected also during Screening
  8. gBody weight (lb) and height (inch) should be measured when possible or be estimated. Weight and height available in patient’s records can be used if measured within the last 7 days
  9. hPhysical examinations should be performed appropriately, per the patient’s condition. Any findings should be recorded on the physical examination eCRF
  10. iIncludes clinical chemistry, lipid profile, hematology, and coagulation. Screening/Baseline clinical laboratory tests, other than those pertaining to trial eligibility, may be collected at any time during the Complete Screening (-24 hours to 0 hour) or post-randomization period (0 hour to +6 hours) prior to initiation of study drug treatment
  11. jAssessment should be performed once during post-treatment monitoring period, if the patient is still in the ICU. Analyses performed per SOC with an 18-to-48-hour window after EOT can be used
  12. kOnly applicable if EW is during study drug treatment period
  13. lFemale patients of childbearing potential must have a negative (serum or urine) pregnancy test prior to randomization. A pregnancy test obtained previously as part of usual care during this hospital episode that is documented in the patient’s medical record will suffice. Female patients not of childbearing potential are defined as female patients who have been postmenopausal for at least 1 year, have been surgically sterilized, or are 60 years of age
  14. mPhysical outcomes assess activities of daily living by the Katz ADL and Pfeffer FAQ
  15. nCognitive baseline will be assessed by the IQCODE. LTO will be assessed by TICS, WAIS IV-Digit Span, Hayling Sentence Completion Test, Controlled Oral Word Association, WMS-IV – Immediate Memory (Adult/Older Adult), WMS-IV – Delayed Memory (Adult/Older Adult), and PROMIS Cognitive Function questionnaire
  16. oTo be performed within 30 minutes from randomization
  17. pSAPS III, reasons for ICU admission, ICU diagnosis criteria, hospital and ICU admission, time for intubation, and exposure of volatile anesthetics in the past 24 hours (and if yes, what drug [sevoflurane/isoflurane/desflurane]) to be assessed at Complete Screening
  18. qPredicted remaining time on the ventilator for each patient to be collected just shortly before randomization in order to monitor the proportion of patients with longer (>24 hours) versus shorter (12 to 24 hours) exposure times
  19. rVentilator parameters include ventilator mode, set tidal volume, observed tidal volume, set rate, observed rate, observed minute volume, set PEEP, PS above PEEP, PC above PEEP, PIP, plateau pressure (once daily only), mean airway pressure, FiO2, SpO2, EtCO2, ventilator trigger, P0.1, and ABG
  20. sThese assessments will be performed more frequently when clinically indicated (as patients will often be observed continuously or more frequently than every 8 hours in clinical practice)
  21. tOnly applicable when arterial line is available
  22. uOrgan function will be assessed by SOFA once daily at Baseline, during the study drug treatment period, the 24-hour post-treatment period, and until 7 days after EOT
  23. vAfter randomization, the study equipment will be set-up and study drug treatment shall be initiated as close to randomization as possible and no later than 6 hours after randomization
  24. wVital signs include systolic, diastolic, and mean arterial blood pressure, heart rate, SpO2, (measured by pulse oximetry; will not be assessed while patients are on ventilator support, as it will be captured as a ventilator parameter), respiratory rate (will not be recorded as part of vital sign assessments while patient is on ventilator support, as it will be captured in the ventilator parameter records as observed breathing rate), and body temperature
  25. xUnblinded baseline assessment for RASS and CPOT should be performed within 30 minutes prior to initiation of study drug administration. Vital signs should be performed within 60 minutes prior to initiation of study drug administration
  26. yAssessment will be performed in a blinded manner by a blinded assessor
  27. zCAM-ICU-7 and RASS will be performed daily (at a minimum) during the study drug treatment period and until 7 days after EOT or until hospital discharge, whichever comes first. However, more frequent assessments will be performed when clinically indicated. RASS
  28. aaA separate gas monitor will be readily available during the study drug treatment period for measurement of end-tidal isoflurane concentrations. Only applicable for isoflurane‑treated patients
  29. bbMajor ICU interventions through Study Day 30 or until ICU discharge, whichever comes first, include the following: renal replacement therapy, ECLS, tracheostomy, non‑invasive ventilation, and re-admission to the ICU
  30. ccRecording of AEs will start at the initiation of study drug administration and continue until Day 7 post EOT
  31. ddOnly AEs unresolved at D7 to be followed-u
  32. eeCAM-ICU-7 will be assessed 60 (±10) minutes after EOT in all patients by a blinded assessor. CAM-ICU-7 will not be required for patients reaching EOT due to treatment failure, patients transitioned to comfort care, or patients continued onto benzodiazepines or propofol sedation due to clinical need before 60 minutes after EOT
  33. ffWake-up test will be assessed through blinded RASS assessments
  34. ggTo be collected for patients who are extubated on study drug only
  35. hhOnly applicable if EW is after EOT
  36. iiMemory panorama from time in the ICU will be assessed by the ICU Memory Tool at the 3-month follow-up visit only
  37. jjPsychological outcomes will be assessed by the PROMIS Depression and Anxiety questionnaires and IES-R
  38. kkQuality of life will be assessed by the WHODAS 2.0 and BPI questionnaires
  39. llBaseline data can be collected until 48 hours after initiation of study drug treatment as the time period of interest is not synonymous with when data needs to be captured
  40. mmAs soon as the study drug treatment has been initiated, the SOC sedative should be stopped (ie, slow weaning will not be permitted) to limit the impact of residual SOC sedation
  41. nnFor isoflurane-treated patients only
  42. ooLTO assessments will be completed at 3 and 6 months. ICU Memory Tool will be assessed at 3 months follow-up only
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