Principles across all domains Open label Prescribe using usual processes Dispense from ICUs own stock No separate supply of study drug No placebo for no intervention do not prescribe ID: 921064
Download Presentation The PPT/PDF document "Delivery of Interventions" is the property of its rightful owner. Permission is granted to download and print the materials on this web site for personal, non-commercial use only, and to display it on your personal computer provided you do not modify the materials and that you retain all copyright notices contained in the materials. By downloading content from our website, you accept the terms of this agreement.
Slide1
Delivery of Interventions
Slide2Principles across all domains
Open label
Prescribe using usual processesDispense from ICU’s own stockNo separate supply of ‘study drug’No placebo (for ‘no intervention’ do not prescribe)Allocated treatment can be modified if it is in the best interests of the patientIf discharged from ICU before the end of the specific treatment course, required duration should be prescribed to continue after ICU discharge (not a protocol violation if ceased by ward team)All other concomitant care as per treating clinician
Principles
Slide3ICH/GCP:
4.6.1 Responsibility for investigational product(s) accountability at the trial site(s) rests with the investigator/institution
4.6.2 Where allowed/required, the investigator/institution may/should assign some or all of the investigator's/institution’s duties for investigational product(s) accountability at the trial site(s) to an appropriate pharmacist or another appropriate individual who is under the supervision of the investigator/institution. 4.6.3 The investigator/institution and/or a pharmacist who is designated by the investigator/institution, should maintain records of product delivery, inventory onsite, use by subject and return or disposition of unused products. Drug accountability
Slide4Antibiotic Domain
IV Ceftriaxone plus macrolide
IV Piperacillin-tazobactam plus macrolideIV Amoxicillin-clavulanate plus macrolideIV Moxifloxacin (or Levofloxacin)IV Ceftaroline plus macrolide (included in approved protocol but not available at all sites)
Slide5Antibiotic Domain
Is at the discretion of the treating clinician
What you or local guidelines would recommendAdjust for weight and clearance as you would normally doRecommended doses in protocol, including adjustment for renal function provided
Intervention dose and frequency
Slide6Recommended antibiotic dose and frequency
R
Slide7Antibiotic Domain
If allocated to any of beta-lactam arms
must also receive a macrolideSite's preferred macrolideIV (at least initially) preferred over enteralAzithromycin, preferred over others, erythromycin is permitted but excludes from macrolide domainMacrolide administration within the Antibiotic Domain
Slide8Macrolide Preference
IV azithromycin
IV clarithromycinEnteral azithromycinEnteral azithromycin or roxithromycinIV or enteral erythromycinAntibiotic Domain
Slide9Duration of therapy & IV-oral switch
As determined by treating clinician
Change to any antibiotic if microbiological diagnosis madeSwitch to enteral / oral when clinically appropriateCease antibiotics if alternative diagnosis madeCease antibiotics when sufficient clinical response has occurredAntibiotic Domain
Slide10Changes to empiric antibiotic therapy
Treating clinicians need to document (in the patient’s medical record) the reason for
ANY change to antibiotic therapy while the patient was in the ICU. Antibiotic Domain
Slide11Permitted additional antibiotics
If suspected MRSA, add vancomycin, linezolid or other antibacterial active against MRSA (but not ceftaroline)
Other beta-lactams, carbapenems, monobactams or quinolones not permitted (unless based on results of microbiological tests)If allocated to moxifloxacin or levofloxacin, addition of macrolide, beta-lactam, carbapenem, or monobactam not permittedAdditional aminoglycoside, clindamycin, cotrimoxazole all permittedIf immune-suppressed should have been excluded from domain If site has resistance pattern for CAP organisms that is not appropriate for at least two antibiotic interventions, site should not participate in the domainAntibiotic Domain
Slide12Macrolide Duration Domain
Short course macrolide discontinued after 3 days unless there is confirmed or strongly suspected microbiological indication for prolonged administration (e.g. confirmed Legionella)
Extended course macrolide prescribed for 14 days or hospital discharge, whichever occurs first
Slide13Macrolide Preference
IV azithromycin
IV clarithromycinEnteral azithromycinEnteral azithromycin or roxithromycinIV to enteral switch can occur when clinically appropriate, at least 2 does of IV macrolide recommendedMacrolide Domain
Slide14Dose of Macrolide
Dose and frequency at discretion of treating clinician
Protocol provides recommended dosesIV and enteral doses the sameNo adjustment for renal function or renal replacement therapy neededMacrolide Duration Domain
Slide15Workflow
Patient will have been
randomised to Macrolide Duration Domain Commence macrolide (as per site preference) Macrolide Duration Domain
Slide16Workflow
Short Duration
Review microbiological results after day 3If no results indicate Legionella or other atypical organism (e.g. Chlaymidohila), cease macrolideIf Legionella (or other atypical organism) identified, then effective treatment for ‘atypical’ organisms must be continued, e.g. Prolonged macrolide (of choice)Quinolone (of choice)Macrolide Duration Domain
Slide17Workflow
Extended Duration
Prescribe macrolide for 14 daysIV to enteral switch permitted Prescribe to continue on ward if discharged from ICU before 14 days (not a protocol violation if ceased by ward staff)Macrolide Duration Domain
Slide18Early cessation of macrolide
Cease if patient experiences SAE thought to be related to macrolide (e.g. ventricular tachycardia)
Consider QT interval at time of cessation of continuous ECG monitoringMacrolide Duration Domain
Slide19Concomitant care
Low dose erythromycin
(for gastric emptying) is permitted (but discouraged)Duration of macrolide therapy not affected by macrolide susceptibility of infecting organismMacrolide Duration Domain
Slide20CAP versus shock literature
In shock: ADRENAL and APROCCHSS
No effect on mortality, but maybe…In pneumoniaFew ICU patientsOutcomes (and doses) differCorticosteroid Domain
Slide21Interventions
IV Hydrocortisone, 50 mg 6 hourly for 7 days
No corticosteroidCorticosteroid Domain
Slide22Allocated to hydrocortisone
Prescribe hydrocortisone IV 50 mg 6 hourly
Commence immediately after randomisationCease after 7 days or hospital discharge, whichever occurs firstPrescribe to continue on ward if discharged from ICU before 7 days (not a protocol violation if ceased by ward staff)Corticosteroid Domain
Slide233 arms:
No hydrocortisone
Hydrocortisone for 7 days or ICU dischargeHydrocortisone while on “significant” vasopressor support in ICUCorticosteroid Domain
Slide24Antiviral domain
3 arms
No antiviral agents (no placebo) 5 days of oseltamivir 10 days of oseltamivir
Slide25Temporary unavailability of intervention
If known that intervention is temporarily not available
Inform Research Staff, who can remove (and restore) interventions from that sites Eligibility eCRF (Antibiotic Domain)If not known that intervention is unavailable and allocated to that interventionProvide appropriate alternative and commence allocated intervention, if still clinically appropriate, as soon as possibleDocument what has occurred as a Domain-Specific Protocol DeviationPatient will be analysed on intention-to-treat basis
If know that intervention is not available but not able to contact Research Staff
Indicate that not all interventions are appropriate for that patient during completion of eligibility CRF (Patient Interest Statement)