Stroke Hyperglycemia Insulin Network Effort (SHINE) Trial

1
Stroke Hyperglycemia Insulin Network Effort
(SHINE) Trial

• Protocol Training

NIH-NINDS U01 NSO69498
2
The Problem

• Over 750,000 strokes/ year (80 ischemic)
• 30-50 hyperglycemic on admission
• Hyperglycemia associated w/ worse clinical
  outcome
• Hypoglycemia bad for ischemic brain
• Unknown if Rx of hyperglycemia improves outcome
• Unknown if risks of aggressive Rx outweigh
  benefit
• Stroke community deals with hyperglycemic acute
  stroke patients every day without evidence on
  what is best

3
Specific Aims

• Specific Aim 1
• To determine the efficacy of tight glucose
  control to a target range of 80-130 mg/dL with IV
  insulin infusion in hyperglycemic acute ischemic
  stroke patients within 12 hours of symptom onset
  as measured by mRS at 90 days after stroke.
• Specific Aim 2
• To determine the safety of tight glucose control
  with IV insulin infusion in hyperglycemic acute
  ischemic stroke patients treated for up to 72 hrs.

4
Study Design

• Phase III, randomized, blinded, controlled trial
• 60 sites, 1400 patients
• Single blind double blind outcome assessment
• 12 hrs from symptom onset (rec 3 hrs door to Rx)
• Treatment Groups
• Insulin drip target 80-130 mg/dL
• Control -SQ insulin target lt180 mg/dL
• Up to 72 hours treatment
• 90 day outcome mRS (sliding dichotomy)
• 80 power to detect 7 absolute improvement in
  favorable outcome (mRS)

5
Study Innovation

• Response Adaptive Randomization (RAR)
• GlucoStabilizer electronic decision support
  tool
• Responder Analysis (sliding dichotomy)
• successful outcome based on enrollment stroke
  severity
• allows consideration of expected outcome to be
  considered in determination of favorable outcome

6
Identifying Patients

• Usually emergency room
• Could be arrival to ward upon direct transfer
  from OSH or in-house stroke
• Screen all acute ischemic stroke pts with onset
  within 12 hours and blood glucose gt 110
• Define plan for alerting screening team/
  enrolling team

7
Consent General Concepts

• Use standard consent procedures per local
  regulatory requirements
• Written informed consent with process documented
• No emergency exemption
• Randomization recommended but not required to
  occur w/in 3 hours of arrival to enrolling ED
  (hospital)

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Inclusion Criteria

• Age 18 years or older
• Diagnosis of ischemic stroke defined as acute
  neurological deficit occurring in one or more
  cerebral vascular territories. Neuroimaging must
  exclude ICH.
• Treatment must begin w/in 12 hrs of stroke
  symptom onset and is recommended w/in 3 hrs of
  hospital arrival
• Known history of type 2 diabetes glucose gt110
  mg/dL OR blood glucose 150 mg/dL in pts w/o
  known diabetes
• Baseline NIHSS 3-22
• Pre-stroke mRS of 0 if NIHSS of 3-7 OR pre-stroke
  mRS of 0 or 1 if NIHSS of 8-22
• Able to provide a valid informed consent

9
Exclusion Criteria

• Known history of type 1 diabetes
• Substantial neurological or psychiatric illness
  that would confound neurological or outcome
  assessment
• Received experimental therapy for enrollment
  stroke. IV tPA (up to 4.5 hrs), IA tPA IA
  therapies including FDA cleared devices allowed.
  Non FDA cleared devices excluded.
• Pregnant or breast-feeding
• Other serious conditions that make pt unlikely to
  survive 90 days
• Inability to follow protocol or return for 90 day
  f/u
• Renal dialysis

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Randomization General Concepts

• WebDCU-based randomization
• Randomization time is start of treatment time
• Must be randomized within 12 hours of symptom
  onset (recommended but not required within 3
  hours of arrival to enrolling hospital)
• RAR Response Adaptive Randomization
• Start out 11 (flip of coin)
• RAR higher chance of being enrolled in
  treatment group that has better outcomes

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Treatment Groups - General Concepts Control Group

• BG target 80-179 mg/dL
• SQ insulin (regular human) per sliding scale
• IV saline drip (to mimic IV insulin drip to
  maintain blind)
• Q1 hr glucose checks for first four hours
• Q3 hr glucose checks after 1st 4 hrs but insulin
  given only at 0600, 1200, 1800 and 2400 if
  indicated
• Basal insulin only for Level 3 indicated

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Treatment Groups - General Concepts Intervention
Group

• BG target 80-130 mg/dL
• Glucose checks and IV insulin (regular human)
  drip adjustments per GlucoStabilizer (computer
  decision support tool)
• For pts who are PO or on bolus tube feeds, SQ
  meal insulin (rapid acting analog) per meal
  carbohydrate diet
• For pts who are NPO or on continuous tube feeds,
  SQ saline administered (to mimic SQ insulin to
  maintain blind)

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Control Group
14
Control GroupInitiation of Treatment

• Enter orders/notify pharmacy
• Start SHINE laptop and select Control Group
• Re-check glucose when IV saline is ready
• Start IV saline infusion per protocol (displayed
  on control treatment screen) adjust as needed
  w/ EACH glucose check
• Check glucose once to start and then q1hr x4 hrs,
  then q3hr (0300, 0600, 0900, 1200, 1500,
  1800, 2100 and 2400)
• Give insulin per sliding scale ONLY at
  0600, 1200, 1800 and 2400

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Getting Started
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Control Group Computer Screen
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Control Group Documenting
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Control GroupContinuation of Treatment

• Check glucose per study sliding scale schedule
• Give SQ insulin only at the designated times if
  indicated by the sliding scale (180 mg/dL)
• All patients start at Level 1 for first 24 hrs
  (opportunity to advance to more aggressive
  glucose control at 24 48 hrs if indicated)
• Adjust IV saline rate if indicated after each
  glucose check
• Same procedure whether eating or not

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Shifting from Q1 to Q3 hour glucose checks in
control group

• First glucose check for SHINE study treatment
  protocol as soon as saline bag ready to drip
• Q 1hr check for first 4 glucose checks (one check
  to start and then four more)
• After the 4th Q 1 hr check, start glucose checks
  on Q 3hr schedule, but skip 1st scheduled check
  if lt1 hr from previous check unless it is a SQ
  insulin dosing time

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Sliding Scale Insulin Level Changes

• All patients on Level 1 for first 24 hours (start
  time is time of randomization)
• Advance level only if indicated at 24 48 hrs
• At end of 1st 24 hrs, advance to Level 2 only if
  the latest 2 glucose levels 180 mg/dL otherwise
  stay on Level 1
• At end of 48 hrs, advance to next level (2 or 3)
  only if the latest 2 glucose levels 180 mg/dL
  otherwise stay on current level
• Level 3 includes one-time SQ basal insulin
  (Lantus) given at end of 48 hrs (sliding scale
  insulin doses for Level 3 are the same as Level
  2)
• Do not backwards/go down a level unless
  safety monitor recommends

21
Sliding Scale Insulin Level Changes
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Level 3 Control TreatmentBasal Insulin

• Level 3 is only level on sliding scale that
  includes basal insulin
• To calculate basal insulin dose - add all the
  insulin units given in the previous 24 hrs 40
  of that total is the dose of basal insulin to be
  given once as close as possible to 48 hrs from
  randomization (round up if gt.5, round down if
  lt.5)
• Use only glargine (Lantus) insulin for basal
  insulin
• After one-time dose of SQ basal insulin
  continue schedule for SQ sliding scale insulin
  Level 3 (same as Level 2 sliding scale)

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Control Group - Meals

• 60 gram carbohydrate diet per meal should be
  ordered
• NO estimate of meal consumption required and NO
  meal insulin given in control group (only SQ
  sliding scale insulin at 0600, 1200, 1800 and
  2400 if indicated)
• Pts should eat only after their glucose check and
  the SQ insulin has been given as needed at 600,
  1200, and 1800. (If meal arrives before these
  times, hold until time for glucose check and
  insulin dose if indicated)
• Only protocol-approved snacks during the 72 hour
  SHINE treatment protocol

24
Intervention Group
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Intervention GroupInitiation of Treatment

• Enter orders/notify pharmacy
• Start SHINE laptop and select Intervention Group
• Re-check glucose when IV insulin infusion is
  ready
• Start IV insulin infusion per GlucoStabilizer
  recommendation

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Getting Started
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Intervention Group Computer Screen
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Intervention GroupContinuation of Treatment

• Recheck and enter glucose in GlucoStabilizer
• Adjust IV insulin drip per GlucoStabilizer
  recommendation
• For pts that are PO or receiving bolus tube
  feeds, give meal insulin per protocol
• For pts that are NPO or receiving continuous tube
  feeds, give SQ saline 0.05 cc after check closest
  to 0900 and 2100 to simulate SQ insulin
  injections in control group

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Intervention Group Meals

• Order 60 gram carbohydrate diet for breakfast,
  lunch dinner for pts who are eating or on bolus
  tube feeds
• PO - Allow 20 minutes from start of eating then
  estimate the proportion of meal consumed
• Bolus tube feeds estimate proportion of bolus
  given
• SQ meal insulin (rapid acting analog) given based
  on proportion of meal consumed dose recommended
  per GlucoStabilizer
• Only protocol-approved snacks during 72 hour
  SHINE study treatment period

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Intervention Group SQ Meal Insulin for PO pts

• Meal consumed all or nearly all
• Enter 60 carb meal into GlucoStabilizer
• Give dose of meal insulin recommended
• Meal consumed none or nearly none
• DO NOT make an entry into GlucoStabilizer
• DO NOT give meal insulin
• Meal consumed partial or in between
• Enter 30 carb meal into GlucoStabilizer
• Give dose of meal insulin recommended

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Intervention Group Meal Insulin Computer Screens
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Data Entry

• Standard chart documentation is required per site
  procedure
• Additionally, glucose and study treatment data
  will be entered in control treatment screen of
  study laptop

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Special situations

• Hypoglycemia
• Pauses in study protocol
• Discontinuing study protocol lt 72 hours
• Transition from study protocol

34
Hypoglycemia ProtocolsGeneral Concepts

• The hypoglycemia prevention and management
  protocol begins when glucose falls lt80 mg/dL
• But, actual hypoglycemia is defined as lt70 mg/dL
• Severe hypoglycemia (primary safety outcome) is
  defined as lt40 mg/dL
• Any glucose level that falls lt70 mg/dL requires
  additional info
• Laboratory serum glucose level send but give
  D50 before result available
• Symptomatic or asymptomatic assessment

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Hypoglycemia ProtocolsGlucose lt80 mg/dL

• STOP all SQ and IV study treatments
• Give D50 slow IV push
• Control Group 1/2 ampoule (25 ml)
• Intervention Group per GlucoStabilizer
• Recheck glucose
• Control Group q 15 min and give another ½
  ampoule (25 ml) D50 as long as glucose lt80 mg/dL
• Intervention Group q 15 min per GlucoStabilizer

36
Hypoglycemia ProtocolsAdditional steps for
glucose lt70mg/dL

• Send serum sample for glucose to lab. Do not
  delay D50.
• DO NOT draw serum sample from IV line where D50
  given
• Hypoglycemia symptomatic questionnaire q15 min.
  Once BGgt70mg/dL or symptoms have resolved, one
  final assessment is required.
• Neuro check each time glucose lt70 mg/dL
• NIHSS for worsening as soon as possible if 4
  point increase on the NIHSS from previous and
  persistent, recheck in 24 hrs
• Once glucose 80 mg/dL, resume treatment
  protocols

37
Pauses in SHINE Control Treatment Protocol

• When restarting protocol, if glucose checks or SQ
  insulin were
• NOT missed, maintain schedule. Resume saline
  infusion at the next scheduled glucose
• MISSED, immediately check the POC glucose upon
  return and resume IV saline. If SQ insulin
  dosing time was missed, give SQ insulin if
  indicated immediately. Return to schedule for
  glucose checks and subcutaneous insulin
  injections.
• Do not check glucose levels lt1 hour apart unless
  it is a scheduled dosing time.
• Do not give SQ insulin injections lt3 hours apart.

38
Pauses in SHINE Intervention Treatment Protocol

• When able to restart protocol, recheck glucose
• Use result of glucose check to resume IV insulin
  drip
• If IV drip off for lt3 hrs, use Resume option in
  GlucoStabilizer
• If IV drip off for 3 hrs, use Start New Drip
  option in GlucoStabilizer
• If a meal is eaten late, give SQ meal insulin
  with meal per protocol
• If SQ saline dose was missed (NPO or continuous
  tube feed pts)
• Give 0.05 cc SQ saline
• If next saline dosing time in lt3 hrs, then skip it

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Study treatment by group and nutritional status
      SHINE TREATMENT GROUP SHINE TREATMENT GROUP
            INTERVENTION GROUP CONTROL GROUP
  NUTRITIONAL STATUS Eating PO meals or Bolus Tube Feeds     IV insulin plus Subcutaneous meal insulin injections   How much IV Insulin? Per GlucoStabilizer recommendation   How many units SQ meal insulin? Per GlucoStabilizer recommendation based on proportion of meal consumed given 20 minutes after start of meal  3x/day _at_ 0600, 1200, 1800 IV saline plus Subcutaneous sliding scale insulin injections    How much IV saline? Per Sliding Scale Control Treatment Screen How many units SQ insulin? Per Sliding Scale Control Treatment Screen Finger stick glucose check _at_ 0300,0600,0900,1200,1500,1800,2100,2400 (Insulin dosing only _at_0600, 1200, 1800, 2400)
  NUTRITIONAL STATUS NPO or Continuous Tube Feeds IV insulin plus Subcutaneous saline injections  How much IV Insulin? As per recommendation of GlucoStabilizer How much SQ saline? 0.05 ml of SQ saline _at_ time of glucose check nearest 0900 and 2100 IV saline plus Subcutaneous sliding scale insulin injections    How much IV saline? Per Sliding Scale Control Treatment Screen How many units of SQ insulin? Per Sliding Scale Control Treatment Screen Finger stick glucose check _at_ 0300,0600,0900,1200,1500,1800,2100,2400 (Insulin dosing only _at_0600, 1200, 1800, 2400)
  NUTRITIONAL STATUS NPO or Continuous Tube Feeds IV insulin plus Subcutaneous saline injections  How much IV Insulin? As per recommendation of GlucoStabilizer How much SQ saline? 0.05 ml of SQ saline _at_ time of glucose check nearest 0900 and 2100 IV saline plus Subcutaneous sliding scale insulin injections    How much IV saline? Per Sliding Scale Control Treatment Screen How many units of SQ insulin? Per Sliding Scale Control Treatment Screen Finger stick glucose check _at_ 0300,0600,0900,1200,1500,1800,2100,2400 (Insulin dosing only _at_0600, 1200, 1800, 2400)
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Discontinuation of SHINE Treatment

• Any study pt clinically ready for hospital
  discharge prior to 72 hrs of treatment may be
  discontinued from SHINE protocol (not a protocol
  deviation)
• 6 hrs prior to discharge
• D/C SHINE study infusion (insulin or saline)
• D/C SHINE sliding scale SQ insulin protocol
• GlucoStabilizer Drip Weaning Report (24 hr
  insulin total) available for review for
  intervention group only
• Any subsequent SQ insulin Rx at discretion of
  treating physician should be gt3 hrs after last
  SHINE SQ insulin
• Oral diabetes Rx per treating team

41
Transition to Standard Care

• Per ADA guidelines scheduled subcutaneous insulin
  that delivers basal, nutritional and correction
  components is preferred.
• Consider that oral agents are not recommended in
  hospitalized patients, but may be initiated or
  resumed in anticipation of discharge per ADA
  guidelines.
• Consider individualized discharge planning per
  ADA guidelines

42
Summary Clinical Study Outcomes

• Primary Study Outcome 3 month mRS
• Primary Safety Outcome frequency of severe
  hypoglycemia (lt40 mg/dL) in intervention group
  versus control group
• Additional Outcomes
• 6 week phone call mRS by phone, SAEs
• 3 month - BI, NIHSS, QOL

43
Outcome Visits

• Assessor for outcomes visits must be blinded to
  treatment
• Visits
• 6 week visit by phone
• mRS and SAEs
• 3 month visit in person
• mRS, NIHSS, BI, SSQOL
• SAEs
• Unblinding survey (patient and investigator)

44
Bedding for SHINE patients
45
Bedding for SHINE Patients

• Hospitals have different regulations for
  unit/level of care required for insulin drip
• For the 72 hours of study treatment, all patients
  must be bedded in a location that would support
  and allow delivery of insulin drip therapy.
• Must not differentially bed intervention and
  control patients as this will bias the study due
  to differential level of care

46
Bedding for SHINE Patients

• If your hospital supports insulin drip therapy in
  ICU, step down, stroke unit floor level
  settings
• May bed any pt in any one of these insulin drip
  supporting environments according to clinical
  need
• If your hospital supports insulin drip therapy in
  ICU, step down, stroke unit BUT NOT in floor
  level settings
• May only bed any pt in ICU, SDU, ASU and may not
  bed any pt on the floor during the 72 hr study
  treatment period regardless of treatment group
  (intervention or control)

47
Bedding for SHINE Patients

• If your hospital ONLY supports insulin drip
  therapy in ICU then
• All SHINE patients must be cared for in ICU for
  72 hours unless discharged
• OR
• There must be a special plan in place with your
  institution to manage this

48
Pharmacy
49
Treatment Assignment

• Randomization generated by study team in WebDCU
• Study team provides copy of treatment assignment
  to pharmacy (may be faxed, scanned or delivered
  in person)

50
Study Treatment by Group
Control Group Intervention Group
IV Infusion Normal saline 0.9 Sodium Chloride Human regular insulin Humulin R, Novolin R
Subcutaneous Injections Human regular insulin Humulin R, Novolin R AND Basal insulin (Level 3 only) glargine (Lantus) Rapid acting analog insulin lispro (Humalog), aspart (Novolog) or glulisine (Apidra) OR Normal saline 0.9 Sodium Chloride
51
Control Group Study Treatment
Control Group
IV infusion Normal saline Per sliding scale (continuous)
Subcutaneous injections Human regular insulin Per sliding scale (_at_ 0600, 1200, 1800 2400) AND Basal insulin (Level 3 only) 40 of insulin requirement during previous 24 hrs (_at_ 48 hrs)
52
Intervention Group Study Treatment
Intervention Group
IV infusion Human regular insulin (11) Per GlucoStabilizer (continuous)
Subcutaneous injections Rapid acting analog insulin (meal insulin) Per GlucoStabilizer _at_ 0600, 1200 1800 OR Normal saline 0.05 mL _at_ 0900 2100
53
D50 for Hypoglycemia Prevention and Management

• D50 stored to allow immediate availability
• Glucose lt80mg/dL ?
• Control group - 25 ml (1/2 amp)
• Intervention group - individualized dose per
  GlucoStabilizer

54
Control Screens Orange Background
55
Intervention Screens Blue Background
56
Site Pharmacy Plan

• Establish site-specific pharmacy plan prior to
  initiation
• Retain one empty infusion bag for each study
  patient for monitoring

57
SHINE Allowed Insulins
Insulin Treatment Type Control Treatment Group Intervention Treatment Group
SQ sliding scale Regular human Humulin R, Novolin R Not Allowed
SQ basal Slow acting glargine (Lantus) ONLY Not Allowed
SQ meal Not Allowed Rapid acting analog humalog (Lispro), novolog (Aspart), glulisine (Apidra)
IV Not Allowed Regular human Humulin R, Novolin R
Insulin syringes YES YES
Insulin pens NO NO
58
Lead Nurse Role
59
Role of the Lead Nurse

• Work closely to advise research team on training
• Assist the nursing staff in implementing study
  protocol
• Super-user of protocol and GlucoStabilizer
• Anticipate issues during study treatment and
  provide input as study team develops resources
• Give feedback to research team

60
Clinical nurses play pivotal role

• Initiate treatment drip and SQ injections
• Check glucose per GlucoStabilizer or control
  sliding scale schedule
• Review level of sliding scale in control group
• Meals - estimate consumption administer meal
  insulin dosing (intervention group only)
• Maintain blind for patient and family
• Initiate hypoglycemia prevention management
  (glucose lt80mg/dL)
• Transition of care from shift to shift
• Manage pauses in study treatment
• Transition off study protocol

61
Maintaining the Blind

• IV infusion pumps - SHINE Study Drug
• Subcutaneous injections drawn up outside of
  view of patient/family
• Study drug labeling
• Study laptops placement in room lock screen
  option
• Conversations with study patient/family

62
Regulatory requirements and Site monitoring
63
Overview of Regulatory RequirementsPeople
Documents
Document Required for
CV PI, Co-Is, Primary/Secondary SCs, Lead Pharmacist
HIPAA Certification PI, Co-Is, Primary/Secondary SCs
HSP/CITI Certification PI, Co-Is, Primary/Secondary SCs
Medical License PI, Co-Is, Primary/Secondary SCs (if licensed), Lead Pharmacist
SHINE Protocol Training PI, Co-Is, Primary/Secondary SCs
SHINE Data Training Primary/Secondary SCs
SHINE Investigators Agreement PI, Co-PI
NIHSS Certification PI, Co-Is, Primary/Secondary SCs who will assess
mRS Certification PI, Co-Is, Primary/Secondary SCs who will assess
64
Overview of Regulatory RequirementsSpoke
Documents
Document Purpose
SHINE Nursing Inservice Sign-in Sheet Documentation of site-specific training of clinical nursing staff who will be managing the SHINE protocol
SHINE Pharmacy Plan Documentation of the sites logistical plan for notifying pharmacy of a SHINE subject, preparing/labeling of the first and subsequent bags of insulin/saline, and maintenance of the study protocol over the treatment period.
65
Overview of Regulatory RequirementsSpoke
Documents

• Institutional FWA
• IRB Applications Correspondence
• IRB Application Submittals (include application
  and cover page of supplemental materials) and
  study approvals
• IRB-Approved Informed Consent Forms (Send to
  shine-milestones_at_umich.edu for approval prior to
  IRB submittal)
• IRB Study Modification Notifications
• IRB Close-Out Notification and Acknowledgement
• Delegation of Authority Log
• CLIA Certification

66
Personnel Changes

• Study team members must be listed on the
  Delegation of Authority Log please keep DOA log
  on WebDCU current
• Study team members must be assigned roles in
  WebDCU Project Spoke Team Member table
• Regulatory Parameters Document lists specific
  requirements
• Nursing staff and pharmacy staff (with the
  exception of the lead pharmacist/pharmacy
  contact) do not need to be added to the DOA log
  or the Project Spoke Team Member table.

67
Regulatory Readiness

• Site should notify CCC when regulatory ready
  after IRB approval is received and all regulatory
  docs are uploaded
• CCC confirms required documents schedules
  readiness call w/ key personnel from SHINE site
  study team.
• Site will complete Readiness Checklist and
  provide prior to readiness call.
• Following the call, if no action items required,
  the site will be notified that they are released
  to begin enrollment.
• If action items are required, these must be
  resolved prior to being released to enrollment.

68
Site Monitoring Schedule

• Study Initiation Visit
• Readiness Call
• Routine Interim Monitoring Visits
• At least one visit per year
• Close-Out Visit

69
Site Monitoring Schedule

• Timing of visits
• First visit to each site after subject 1
  enrolled and completed treatment period

70
Reporting Adverse Events
71
Reporting Adverse Events

• Adverse Events (AEs) are . . . any untoward
  medical occurrence in a subject that was not
  previously identified which does not necessarily
  have a causal relationship to the study drug
• Events existing prior to randomization should not
  be reported as AEs, unless there is a change in
  severity
• AEs (both serious and non-serious) are reported
  on the Adverse Event CRF

72
Reporting Adverse Events

• Report the diagnosis, not the symptoms
• Fever, cough, chest pain, crackles pneumonia
• Death, surgery, intubation, etc. are not adverse
  events. They are outcomes of adverse events

73
Reporting Adverse Events

• All AEs will be coded centrally using MedDRA
• 1 AE per CRF
• Avoid abbreviations/colloquialisms
• AEs that cant be coded will be queried
• All AEs must be reported through completion of
  study treatment.
• All SAEs must be reported through End of Study.

74
Serious Adverse Events

• fatal
• life-threatening
• result in hospitalization/prolongation of
  hospitalization
• result in disability/congenital anomaly
  
• OR
• require intervention to prevent permanent
  impairment or damage

75
Data Entry Timelines for AEs

• Non-serious AEs must be entered and
• submitted into WebDCUTM within 5 days of data
  collection
• SAEs must be entered and submitted into WebDCUTM
  within 24 hours of the time that the study team
  receives knowledge of the event

76
Reporting SAEs

• To assist in review by medical safety monitors,
  SAEs require additional information
• Detailed description of the event
• Relevant tests/laboratory data
• Relevant history and pre-existing conditions
• Concomitant meds
• Do not identify any subject, physician, or
  institution by name.

77
Reporting SAEs

• Site data enters and submits AE CRF into WebDCUTM
• Automatic e-mail notification to Project Manager
• PM reviews narrative - If CRF is sufficient, an
  automatic email notification will be sent to the
  Internal Quality and Safety Reviewer (IQSR)

78
Reporting SAEs

• IMM reviews narrative - If AE data is sufficient,
  an automatic email notification will be sent to
  the external Independent Safety Monitor (ISM
  -Thomas Bleck, MD)
• ISM reviews the event and indicates whether the
  event is serious and unexpected
• PM closes review process

79
SAE Reporting

• DSMB requires expedited reporting of all SAEs
• Site PIs are responsible for reporting the SAE to
  their IRB according to local requirements
• Site PIs responsible for submitting follow-up
  information into WebDCUTM as it becomes
  available.

80
Hypoglycemia Reporting

• Site PI must report to ISM if a subject has 3 or
  more episodes of hypoglycemia within a 24 hour
  period.
• Call the SHINE study hotline [phone] ext 2)
• ISM will determine if the level of sliding scale
  insulin should be adjusted or if insulin drip
  protocol should discontinued

81
Study Contacts - Emergencies
Category Contact Name Business Hours Number 24 Hour Contact
Protocol emergency questions PI on call 800-915-7320 ext 1 800-915-7320 ext 1
Eligibility questions PI on call 800-915-7320 ext 1 800-915-7320 ext 1
GlucoStabilizer emergencies PI on call 800-915-7320 ext 1 800-915-7320 ext 1
Randomization Catherine Dillon Karen Briggs 843-792-3980 843-876-1919 MUSC Emergency Randomization
Safety emergencies Thomas Bleck, MD  (Back up Independent MSM Shyam Prabhakaran, MD, MS) 800-915-7320 ext 2 800-915-7320 ext 2
82
Study Contacts Routine Issues
Category Contact Name Business Hours Number
WebDCU support and passwords Catherine Dillon/Karen Briggs 843-792-3980 843-876-1919
Routine safety questions/SAE Catherine Dillon/Karen Briggs 843-792-3980 843-876-1919
CRF questions Karen Briggs 843-792-3980
Protocol, Pharmacy and Laptops Amy Fansler 434-982-6027
Contracts and invoicing Valerie Stevenson (NETT sites)/Amy Fansler (ancillary sites) 734-232-2131   434-982-6027
Regulatory questions Arthi Ramakrishnan 734-936-2454
83
This concludes the SHINE Protocol Training.
Please click on the link below and complete the
training certificate. Email this certificate to
your Study Coordinator.

• SHINE Protocol Training Certificate