Study Procedures & Operational Issues

Study Procedures & Study Procedures & Operational Operational

IssuesIssuesStart-up MeetingMarch 25, 2010Kingston, ON

CERU ContactsCERU Contacts

SponsorSponsor Dr. Daren Heyland

Cell: 613-484-5573Cell: 613-484-5573

dkh2@queensu.cadkh2@queensu.ca

Project Project LeaderLeader

Janet Overvelde

613.549.6666 x6241613.549.6666 x6241

overvelj@kgh.kari.netovervelj@kgh.kari.net

Data ManagerData Manager Jennifer Korol

613.549.6666 x6051613.549.6666 x6051

korolj@kgh.kari.netkorolj@kgh.kari.net

Role of Study Role of Study CoordinatorCoordinator

Regulatory

Screening & Randomization

Pharmacy Communication

Blood Sample Draws

Data Collection

Monitoring Study Intervention Administration

Monitoring & Identifying SAEs

Protocol Violation Reporting

Core Lab

•LPS Stimulation

•Blood Processing

•Shipping to central lab in Ohio, USA

Pharmacy

•Checking treatment allocation

•IP preparation & dispensing

•Dose adjustments for renal disease

•IP Accountability

Site Investigator

•Confirm patient eligibility

•Infection adjudication

•SAE Reporting

CANTREAT CANTREAT TeamworkTeamwork

Research

Coordinator

Micro Lab

•Identify yeast

•Confirm presence of Candida in qualifying respiratory samples

•Sending respiratory samples to OPHL

Pre-Study Pre-Study ActivitiesActivities

Required DocumentationRequired Documentation REB ApprovalREB Approval REB Approved ConsentREB Approved Consent Fully-Executed Site AgreementFully-Executed Site Agreement Team QualificationsTeam Qualifications

CVs & LicensesCVs & Licenses Delegation of AuthorityDelegation of Authority

OverallOverall PharmacyPharmacy Local LaboratoryLocal Laboratory

Laboratory Accreditation & Reference RangesLaboratory Accreditation & Reference Ranges CRS Access LogsCRS Access Logs

Study CoordinatorsStudy Coordinators PharmacyPharmacy

Implementation Manual pg. 9

Delegation of AuthorityDelegation of Authority

Must be kept up to date throughout

the duration of the study.

Implementation Manual pg. 9

TrainingTraining

All study related training should be All study related training should be documented.documented.

Any study related training initiated Any study related training initiated at the site should be documented at the site should be documented and a copy sent to CERU PLand a copy sent to CERU PL

CRS Access LogCRS Access Log

Implementation Manual pg. 10

Screening & Screening & RandomizationRandomization

Inclusion Inclusion CriteriaCriteria

Implementation Manual pg. 14

Entering screening data Entering screening data for a new patient: for a new patient:

Drop-down

Drop-down

Check boxes

ExclusiExclusion on

CriteriaCriteria

Implementation Manual pg. 18

Eligibility ConfirmationEligibility Confirmation Should have documented Should have documented

confirmation from MD regarding confirmation from MD regarding patient eligibilitypatient eligibility

Patient enrolled in CANTREAT study. Patient randomized to the study at hrs.

Patient met all the inclusion criteria and none of the exclusion criteria.

Eligibility confirmed with Dr. ______________. Consent obtained from _____________ (relationship to pt) on dd/mmm/yyyy at hrs.

All questions & concerns addressed with SDM at this time. Copy of consent given to SDM.

Date/time of entry: ____________ Signature of writer: ____________

Consent = Consent = NONO

Indicate the reason why consent was NOT obtained

Obtaining Informed Obtaining Informed ConsentConsent

Timing: When?Timing: When?Consent Consent mustmust be obtained within 96 hrs be obtained within 96 hrs

of the Candida +ve respiratory of the Candida +ve respiratory specimen sample timespecimen sample time

Who obtains consent?Who obtains consent? Site Investigator or delegate i.e. sub Site Investigator or delegate i.e. sub

investigator or research nurseinvestigator or research nurse MustMust be specified on the Delegation of be specified on the Delegation of

Authority LogAuthority LogImplementation Manual pg. 21

Whom to Get Consent Whom to Get Consent from?from?

Patients are often incapable given Patients are often incapable given acuity of illnessacuity of illness

Substitute decision maker (SDM) or Substitute decision maker (SDM) or patient’s patient’s legally acceptable legally acceptable representativerepresentative

Explain the Study Explain the Study ProceduresProcedures

Explain VAP and treatment of identified Explain VAP and treatment of identified bacterial organism as standard of carebacterial organism as standard of care

Presence of Presence of CandidaCandida “yeast” in the “yeast” in the sputum, usually NOT treatedsputum, usually NOT treated

Purpose of the study is to Purpose of the study is to determine if determine if treating treating CandidaCandida, with antibiotics , with antibiotics effective against effective against CandidaCandida, in addition to , in addition to the usual antibiotics administered for the usual antibiotics administered for lung infections will improve the lung infections will improve the outcome of these infections.outcome of these infections.

Explain Study Explain Study ProceduresProcedures

Study Treatment:Study Treatment: GROUP 1: GROUP 1: Standard ICU Care + antibiotic Standard ICU Care + antibiotic

forfor Candida Candida GROUP 2: GROUP 2: Standard ICU Care + Placebo Standard ICU Care + Placebo

(placebo oral solution or a bag of salt water (placebo oral solution or a bag of salt water intravenously)intravenously)

Risks & benefitsRisks & benefits Blood will be taken on days 1, 3, 8 & 14 Blood will be taken on days 1, 3, 8 & 14

to help us understand howto help us understand how Follow up at 90 days to check on Follow up at 90 days to check on

patients statuspatients status

If Consent Obtained, If Consent Obtained, Remember to:Remember to:

Ensure SDM has signed and dated the Ensure SDM has signed and dated the ICFICF

Place original in study files, copy to Place original in study files, copy to medical chart & copy to SDMmedical chart & copy to SDM

Write a note in the medical chart stating: Write a note in the medical chart stating: Name of SDM who provided consent, Name of SDM who provided consent,

relation to patientrelation to patient Date and time that consent was received Date and time that consent was received Time that patient was randomizedTime that patient was randomized

Telephone ConsentTelephone Consent

Document in the medical chart that Document in the medical chart that consent was obtained via telephone consent was obtained via telephone before the patient was randomizedbefore the patient was randomized

Follow up with the SDM to see that Follow up with the SDM to see that the ICF is signed as soon as possible.the ICF is signed as soon as possible.

Consent ToolsConsent Tools

Consent templateConsent template ICF Essential Elements ChecklistICF Essential Elements Checklist Sample Medical Chart entrySample Medical Chart entry

Consent = Consent = YESYES

We are interested in knowing any academic studies the patient is co-enrolled in.

Study ProceduresStudy Procedures

Study Procedures Manual

MD MD OrdersOrders

Implementation Manual pg. 26

Study InterventionStudy Intervention

Antifungal Therapy(anidulafungin and fluconazole)

OR

Placebo

Study Study Intervention: Intervention: Active Active Treatment ArmTreatment Arm

Generic name: Generic name: anidulafungin Trade anidulafungin Trade name: Eraxisname: Eraxis™™

Products provided by Pfizer

Generic name: Generic name: fluconazole Trade fluconazole Trade name: Diflucanname: Diflucan

IV administration Oral administration

Study Intervention: Study Intervention: Placebo armPlacebo arm

Normal saline OR Normal saline OR D5WD5W

IV AdministrationIV Administration

Infusion solution Infusion solution mustmust be be administered within 24 hoursadministered within 24 hours

Should be stored at room Should be stored at room temperaturetemperature

To be infused over 2-4 hours, as per To be infused over 2-4 hours, as per pharmacy instructionspharmacy instructions

Oral AdministrationOral Administration

Via NG tube or orallyVia NG tube or orally Administer 40mL ODAdminister 40mL OD Should be stored at room Should be stored at room

temperaturetemperature

Duration of Study Duration of Study TreatmentTreatment

Administered once dailyAdministered once daily Routes of administration: IV or PORoutes of administration: IV or PO Total of 14 daysTotal of 14 days Continue if discharged to the wardContinue if discharged to the ward

Exception: patients discharged from Exception: patients discharged from hospital before 14 days of study hospital before 14 days of study treatment completed, discharge day = treatment completed, discharge day = last day of study treatment last day of study treatment

Implementation Manual pg. 27-29

Initiating Study Initiating Study TreatmentTreatment

1.1. Following randomization, notify the Following randomization, notify the PharmacyPharmacy

2.2. Pharmacist will determine treatment Pharmacist will determine treatment code by logging into CRS code by logging into CRS (UNBLINDED)(UNBLINDED)

3.3. Pharmacy prepares study treatmentPharmacy prepares study treatment

4.4. Administration of study treatment Administration of study treatment should start should start within 2 hourswithin 2 hours of of randomizationrandomization

Things to consider once Things to consider once patient starts to receive IP:patient starts to receive IP:

Study Treatment ComplianceStudy Treatment Compliance Presence of renal disease or changes Presence of renal disease or changes

in renal function during the in renal function during the treatment periodtreatment period

Open-label antifungal useOpen-label antifungal use

Patient Randomized

IP initiated within 2 hours

IP administration initiated:

Anidulafungin (Eraxis) OR Placebo

IP administered via IV route minimum of 72 hrs

Compatible with normal saline and DW5

Speciation and susceptibility results from OPHL, sent to Pharmacy to adjust IP per

protocol

“Active” treatment arm will be switched to fluconazole if organism is susceptible

If gastro-intestinal tract functional, can switch IP

to oral route

If patient switched to fluconazole following switch to oral form, fluconazole loading dose should be IV route, then can proceed with oral

Dose adjustments for renal disease. SC reports any changes is renal

function to Pharmacy

Anidulafungin = NO changes required

Fluconazole = changes required

Last day of IP administration is Study

Day 14 (including patients discharged to the ward

Open-label antifungals clinically indicated, STOP IP & report

Protocol Violation

Protocol ViolationsProtocol Violations

Used to report deviations in Used to report deviations in compliance with IPcompliance with IP

Should be reported to CERU in “real Should be reported to CERU in “real time”time”

Blood DrawsBlood Draws

Type of samplesType of samples Sampling scheduleSampling schedule Local Lab ProceduresLocal Lab Procedures Central LabCentral Lab

Implementation Manual pg. 30

Sample TypesSample Types

Vacutainer tubes will be provided to Vacutainer tubes will be provided to the sitesthe sites

Sampling ScheduleSampling Schedule

Lab ResponsibilitiesLab Responsibilities

LocalLocal LPS StimulationLPS Stimulation Blood ProcessingBlood Processing Storing Frozen Storing Frozen

samplessamples Shipping samples Shipping samples

to Central Lab in to Central Lab in OhioOhio

CentralCentral Provide sites with Provide sites with

LPS stimulation LPS stimulation mediamedia

Provide sites with Provide sites with suppliessupplies

Provide sites with Provide sites with shipping containersshipping containers

Analyze samples Analyze samples received from sitesreceived from sites

Data CollectionData Collection

More on Paper CRFsMore on Paper CRFs

2-part NCR paper2-part NCR paper Top copies of CRFs will be sent to Top copies of CRFs will be sent to

CERU CERU Bottom copies to remain at the siteBottom copies to remain at the site

Study DaysStudy Days

Study days defined according to the Study days defined according to the ICU flow sheet:ICU flow sheet:

Study Day 1 = Randomization DayStudy Day 1 = Randomization Day

Study Day 2 = Next ICU flow sheetStudy Day 2 = Next ICU flow sheet

Study Day 3 = Next ICU flow sheetStudy Day 3 = Next ICU flow sheet

Study Day 4 = etc…Study Day 4 = etc…

ICU flow sheet from ICU flow sheet from 0700-06590700-0659

Implementation Manual pg. 35

Source DocumentationSource Documentation

Required DocumentsRequired Documents Patient FoldersPatient Folders Worksheets & Worksheets &

other data other data collection tools collection tools

Health Canada requires study documentation be retained for 25 years

Study ToolsStudy Tools

Patients FoldersPatients Folders Laminated reference cardsLaminated reference cards WorksheetsWorksheets

Patient ID ListPatient ID List

To be kept confidentialTo be kept confidential Enables identification of CANTREAT Enables identification of CANTREAT

study patiaents at the sitestudy patiaents at the site Required as per Health Canada and Required as per Health Canada and

ICH GCPICH GCP

Study ResourcesStudy Resources

www.zapthevap.comwww.zapthevap.com Project LeaderProject Leader