Case Report FormCase Report Form

Start-up MeetingMarch 25, 2010Kingston, ON

FormatsFormats

Web-based Central Web-based Central Randomization System (CRS) Randomization System (CRS)

(Includes screening, pre-(Includes screening, pre-randomization and randomization)randomization and randomization)

Paper-Based Case Report Form Paper-Based Case Report Form (Includes baseline, daily data, (Includes baseline, daily data,

antibiotics, microbiology, study antibiotics, microbiology, study intervention, mechanical ventilation, intervention, mechanical ventilation, infection adjudication and outcomes)infection adjudication and outcomes)

Central Randomization Central Randomization SystemSystem

Logs all screened Logs all screened patientspatients

Randomizes Randomizes eligible, consented eligible, consented patientspatients

Pharmacy access Pharmacy access to prepare study to prepare study treatmenttreatment

Central Randomization Central Randomization ProcessProcess

SCREEN NEW PATIENT

Does NOT meet all Inclusion Criteria.

Will NOT be saved on CRS

Form 1 Inclusion Criteria

Form 2 Exclusion Criteria

Patient Eligible

Form 3 Pre-Randomization

Meets at least one exclusion criteria.

Data entry complete.

Consent NOT obtained. Enter reason why.

Data entry complete.

Form 4 Randomization

CRF pg. 4-5

CRF pg. 6-7

CRF pg. 8-9

Pre-Randomization—Consent = Yes

Pre-Randomization—Consent = No

RandomizationRandomization

CRF pg. 10-11

Paper-Based CRFPaper-Based CRF Once the patient has been Once the patient has been

randomized, all subsequent data randomized, all subsequent data collected should be entered onto the collected should be entered onto the paper-based CRFpaper-based CRF

Instructions Data Entry Page

CRF pg. 12-13

CRF pg. 14-15

To be collected within the first 24 hours of ICU

admission

To be collected from Study Day 1 until ICU discharge, death or 28 days post randomization.

Exception: Patient discharged to the ward < 14 days from randomization, continue until end of study day 14

CRF pg. 16-17

CRF pg. 18-19

To be collected from Study Day 1 until ICU discharge, death or 28 days post randomization.

Exception: Patient discharged to the ward < 14 days from randomization, continue until end of study day 14

To be collected from Study Day 1 until Day 14 (unless patient dies or is discharged from hospital.

CRF pg. 20-21

Protocol ViolationsProtocol Violations

Started open-label antifungal Started open-label antifungal therapytherapy

Dosing errorDosing error Accidental unblindingAccidental unblinding Dose missed Dose missed Partial dose received Partial dose received Other, please specify Other, please specify   

CRF pg. 22-23

To be collected from Study Day 1 until Day 14 (unless patient dies or

is discharged from hospital.

Should be reported to the Project Leader in “real

time.”

CRF pg. 24-25

To be collected on Study Days 1, 3, 8 &

14.

CRF pg. 26-27

To be collected if:

•Initiated within 7 days of randomization

•Started in the ICU and continued in the ICU

•Started in ICU and continue past ICU discharge

•For patients receiving study treatment on the ward, collect until Study Day 17

CRF pg. 28-29

Do NOT record cultures that are NO GROWTH or

CONTAMINANT

Do NOT record SWABS

To be collected if:

•Culture taken within 7 days of randomization

•Taken in the ICU

•For patients receiving study treatment on the ward, collect cultures taken until the end of Study Day 17

CRF pg. 30-31

If patient extubated < 48 hours, then mechanical ventilation is re-initiated, it is considered a continuation of previous ventilation.

CRF pg. 32-33

If patient discharged from ICU, then re-admitted within 48 hours, the re-admission is considered a continuation of the previous ICU stay.

Newly Acquired Hospital Newly Acquired Hospital Infection AdjudicationInfection Adjudication

Site Investigator to make determination of a newly Site Investigator to make determination of a newly acquired infection based on antibiotic and microbiology acquired infection based on antibiotic and microbiology datadata

No

Possible NO

Antibiotic Form

Was the antibiotic given for prophylaxis?

OR Was this antibiotic a

substitute for an antibiotic previously ordered for an

infection that occurred within the first 72 hours of

randomization?

Choose the appropriate Category of Infection AND Degree of Certainty

Definite YES Probable YES or Possible YES

Yes

If this is a suspicion that has been previously adjudicated, do not need to re-adjudicate.

This defines a Clinical Suspicion of an infection that requires adjudication by the Site

Investigator/MD delegate Go to Infection Adjudication Form

Probable NO

NO adjudication required

Complete microbiology and antibiotics forms

Yes

Yes infection

No infection

No

NO adjudication

required

Complete antibiotics

form

Yes To either question

Was a new antibiotic started OR was there a positive culture taken

> 72 hours from randomization?

Microbiology Form

Is this organism a

manifestation of an infection that occurred within the first 72 hours

of randomization?

NO adjudication

required

Complete microbiology

form

AlgorithAlgorithm for m for Newly Newly

Acquired Acquired Infection Infection AdjudicatAdjudicat

ionion

If antibiotics started > 72 hr from randomization,

2 questions will be asked to help determine suspicion of hospital acquired infection

Suspicion of Hospital Suspicion of Hospital Acquired InfectionAcquired Infection

1.1. Is this antibiotic prescribed for Is this antibiotic prescribed for prophylaxis?prophylaxis?

2.2. Is this a substitute for an antibiotic Is this a substitute for an antibiotic previously ordered for an infection previously ordered for an infection that occurred within 72 hrs of that occurred within 72 hrs of randomization? randomization? “NO” to both questions

CLINICAL SUSPICION OF INFECTION

Need Adjudication performed by Investigator or MD Delegate

If culture taken > 72 hr from randomization,

1 question will be asked to help determine suspicion of hospital acquired infection

Suspicion of Hospital Suspicion of Hospital Acquired InfectionAcquired Infection

1.1. Is this organism a manifestation Is this organism a manifestation of an infection that occurred of an infection that occurred within the first 72 hrs of within the first 72 hrs of randomization?randomization?

“NO” to question

CLINICAL SUSPICION OF INFECTION

Need Adjudication performed by Investigator or MD Delegate

CRF pg. 34-35

Infection AdjudicationInfection Adjudication

Needs to be done for every suspicion that is triggered by an antibiotic or organism

Categories of Infection & associated definitions found in Appendix 5

Is there an Infection?Is there an Infection?

CRF pg. 34

This suspicion has already been adjudicated. 5

YES to InfectionRefer to categories of infection

for definitions of Definite, Probable & Possible

0 1

NO to InfectionIndicate whether Probable or

Possible NO

YESYES to Infection to Infection

CRF Appendix 5

NO to Newly Acquired NO to Newly Acquired InfectionInfection

CRF pg. 36-37

CRF pg. 38-39

CRF pg. 40-41