Protocol

This trial protocol has been provided by the authors to give readers additional information about their work.

Protocol for: Shroyer AL, Hattler B, Wagner TH, et al. Five-year outcomes after on-pump and off-pump coro-
nary-artery bypass. N Engl J Med 2017;377:623-32. DOI: 10.1056/NEJMoa1614341
New England Journal of Medicine Supplement ROOBY-FS Protocol and Appendices

This supplement contains the following items:

1. Original ROOBY-FS protocol ( including the original statistical analysis plan);

2. Original Appendices A through I;

3. Final Appendix E with summary of Appendix E changes; and

4. Final Appendix F with summary of Appendix F changes.

Please note, there were no other changes to the ROOBY-FSs original protocol or to the other

Appendices.
 FORMREVISIONRECORDFOR

CSP#517FSROOBYFOLLOWUPTRIAL

FormChangesfromVersion1,datedJanuary15,2013toVersion1.2,datedMarch31,2015
Form Page DescriptionofChange
51 E1to Deletedthefollowing:
E6 1. DateofAdmission...........................................................................____/____/____
MoDayYear
4. HypertensionorHighBloodPressure?(1=yes,2=no)...........................................____
7. Chroniclungdisease?(1=yes,2=no)...................................................................____
A.Ifyes,.......................................................................................................____
1=mild
2=moderate
3=severe
9. Pulmonaryhypertension?(1=yes,2=no,9=notdocumented).............................____
A.Ifyes,.......................................................................................................____
1=moderate(PAsystolicpressure;3155mmHg)
2=severe(PAsystolicpressure;>55mmHg)
*NOTE:BasedontheCSSECDecember13,2013meeting:Ifnotpulmonaryhypertensionisnot
documented,aclinicalimputationofnoisplanned.Theanalysiswillberunbothwithand
withoutclinicalimputationtoassureconclusionsarerobust.

13. Activeendocarditis?(1=yes,2=no)....................................................................____
17. Unstableangina(withnoMI<7days)?(1=yes,2=no).......................................____
19. Estimateofpatientsejectionfraction)...................................................________%

20. Criticalpreoperativestate?(1=yes,2=no)............................................................____
A.Ifyes,.......................................................................................................____
1=preopshock
2=preopventriculartachycardia
3=preopventricularfibrillation
4=preopsuddencardiacdeathaverted
5=preopcardiacmassage
6=preoponventilator
7=preopinotropesused
8=preopintraaorticballoonpump(IABP)
9=preopacuterenalfailure(anuriaoroliguria<10ml/hour)
10=preopdialysis

21. Historyofcerebrovasculardisease(CVD)?(1=yes,2=no)....................................____

22. Historyofcerebrovascularaccident(CVA)?(1=yes,2=no)...................................____

23. Historyofperipheralvasculardisease(PVD)?(1=yes,2=no)...............................____
34. Serumpotassium..............................................................................____.____mg/dL
37. Totalbilirubin..........................................................................________.____mg/dL

38. Serumalbumin.....................................................................................____.____g/dL
 
40.Brainnatriuriticpeptide(BNP).....................................................____________pg/mL

44. Timeoperationbegan.................................________:________(use24hourclock)

45. Timeoperationended.................................________:________(use24hourclock)

46. TimepatientoutofOR................................________:________(use24hourclock)
50. *Unitsofcryoprecipitategivenduringfirst48hours)................................________

51. DatepatientdischargedfromICU(firsttimeonly).........................____/____/____
MoDayYear

52. TimepatientdischargedfromICU(firsttimeonly)________:________(use24hourclock

53. *PCIproceduresinceleavingOR(within30daysofsurgery)?(1=yes,2=no)......____
55. Clopidogrel(Plavix)administeredpostoperatively?(1=yes,2=no).....................____
 IfYes,
a.Datestarted.....................................................................____/____/____
MoDayYear
 b.Dosage.....................................................................................______mg

56. Aspirinadministeredpostoperatively?(1=yes,2=no)........................................____
IfYes,
a.Datestarted.....................................................................____/____/____
MoDayYear
 
b.Dosage..........................................................................................______mg


57. DuringtheCSP#517studysurgicalinhospitalstayorduringthefirst30day
periodpostoperatively,didthepatienthaveasubsequentcoronaryartery
bypassgraft(CABG)procedure?(1=yes,2=no,3=unknown).............................____

 a.IfYes,whatdate?(firstincidentpostoperative)...............____/____/____
MoDayYear
 b.IfYes,howwasthissubsequentCABGprocedureperformed................____
(1=onpump,2=offpump,3=unknown)


51  Addedthefollowing:

3.Baselineheartrate(beatsperminute)

4.Baselinebloodpressure(mmHg)

8.Renalfunction:ondialysispreoperatively(peritonealorhemodialysis)NoYes
14.Percutaneouscoronaryintervention(PCI)performed<6hourspriortosurgeryNoYes

51 E1 Modifiedthefollowing:

5.Smokingstatus(expandedtimeframes)
  Lastsmoked2weeksto1monthofsurgery
Lastsmoked>1monthto1yearbeforesurgery
Lastsmoked>1yearbeforesurgery
 Historyoftobaccousebutcurrentuse/cessationunknown
 Datanotfound

11.Percutaneouscoronaryinterventionpriortosurgery(removedthefollowingcategories)

2=performed>6hoursbut<12hourspriortosurgery
3=performed>12but<72hourspriortosurgery
4=performed>72hoursbut<7dayspriortosurgery
5=performedgreaterthan7dayspriortosurgery



52 E7to Deletedthefollowing:
E9 
1. ReasonforTermination...................................................................................._____
1=Patientaliveatstudyend
2=Patientlosttofollowup(locationunknown)
3=Patientdied(pleaseanswerQuestions5and6aandb)
4=Other,Specify


MYOCARDIALINFARCTION(MI):

3. Basedonthe2012UniversalMIdefinition,didthepatientexperienceamyocardialinfarctionafter
1yearfollowupfromsurgery?(1=yes,2=no,U=unknown)........................_____

 a.Ifyes,howmanymyocardialinfarctionsdidthepatienthaveduringfollowup?)
 _____

 1.DateoffirstMI(enterUifunknown)..........................____________
2.DateofsecondMI(enterUifunknown).........................____________
3.DateofthirdMI(enterUifunknown)............................____________
4.DateoffourthMI(enterUifunknown)..........................____________
5.DateoffifthMI(enterUifunknown).............................____________
 
NOTE:PleasecompleteSupplementalMIConfirmationFormandgathersupplementarymaterials
forEndpointsCommitteeReview.

REPEATREVASCULARIZATION:

4. Didthepatientexperiencerepeatrevascularizationafter1yearfollowupfromsurgery?
 (1=yes,2=no,U=unknown)........................................................................._____

5. Typeofrevascularization:

a.Percutaneouscoronaryintervention(PCI)(entertotalnumberofprocedures)
....................................................................................................................._____

 1.DateoffirstPCIprocedure(enterUifunknown)........____________
2.DateofsecondPCIprocedure(enterUifunknown)......____________
3.DateofthirdPCIprocedure(enterUifunknown)..........____________
4.DateoffourthPCIprocedure(enterUifunknown)........____________
5.DateoffifthPCIprocedure(enterUifunknown)...........____________

b.Repeatcoronaryarterybypassgrafting(CABG)(totalnumberofprocedures)_____

 1.DateoffirstrepeatCABG(enterUifunknown).........____________
2.DateofsecondrepeatCABG(enterUifunknown).........____________

DEATH: 

6. DateofDeath..............................................................................____________


7. CauseofDeath

a. Notesastothepotentialcause(s)ofdeath(basedonreviewofavailablemedical
chartdata)

b. Primarycauseofdeath.....................................................................____
1=cardiacrelated
2=notcardiacrelated
U=unknown

 c.Detailedinformationaboutprimarycauseofdeath..............................____
1=Accident.......................................................5=Cerebrovascular
2=Suicide..................................................................6=Pulmonary
3=Infection.....................................................................7=Cancer
4=Cardiovascular..............................................................8=Other
U=Unknown
8. Height..............................................................................................________inches
11. Bloodpressuretakenclosesttoterminationdate)..._________/_________mmHg

12. Preoperativefunctionalstatus(selectone).........................................................____
1=Independent
2=Partiallydependent
3=Totallydependent

16. Clopidogrel(Plavix)administeredpostoperatively?(1=yes,2=no)...............____
 IfYes,
a.Datestarted.....................................................................____/____/____
b.Dosage.......................................................................................______mg

17. Aspirinadministeredpostoperatively?(1=yes,2=no).....................................____
 IfYes,
a.Datestarted........................................................................____/____/____
b.Dosage..........................................................................................______mg

18. Serumpotassium............................................................................____.____mg/dL
21.Totalbilirubin..........................................................................________.____mg/dL

22. Totalserumcholesterol.........................................................____________mg/dL

23. Highdensitylipoproteins(HDL).............................................____________mg/dL
25.Triglycerides.............................................................................____________mg/dL
 26. Hemoglobin.................................................................................. ________.____%
27.Brainnatriuriticpeptide(BNP) ____________pg/mL

52 E7 Addedthefollowing:

2. Dateofpatientsstudysurgery
52 E7 Modifiedthefollowing:

1. DateofLastKnownVAornonVAContacttoread
1. Dateclosesttofiveyearsthatdataisavailable
52  AddedForm52Btocollectsameinformationas51exceptforquestion1whichreads

1. DateofpatientslastknownVAcontact
53 E11 ThisformhasbeendeletedandreplacedwithelementsthatwerepreviouslycapturedonForm52to
includethefollowing:

Terminationstatus
MyocardialInfarction
RepeatRevascularization
Death/causeofdeath



Form51SupplementaryRisk,OperativeandPostOperativeData

SITENO. PATIENT# REFERENCECODE DATEFORMCOMPLETED

Month DayYear

FORM51SUPPLEMENTARYRISK,OPERATIVEANDPOSTOPERATIVEDATA

PREOPERATIVERISKCALCULATIONCLINICALINFORMATION:

1. Height(inches).........................................................................................................................

2. Weight(pounds)................................................................................................................

3. Baselineheartrate(beatsperminute)...............................................................................

4. Baselinebloodpressure(mmHg)................................................................ /
Systolic Diastolic

5. Smokingstatus(selectone)

Neversmoked
Lastsmoked<2weeksofsurgery
Lastsmoked2weeksto1monthofsurgery
Lastsmoked>1monthto1yearbeforesurgery
Lastsmoked>1yearbeforesurgery
Historyoftobaccousebutcurrentuse/cessationunknown
Datanotfound

6. Pulmonaryfunction:
a. FEV1(%ofpredicted).................................................................................................
b. Longtermuseofbronchodilatorsorsteroidsforlungdisease...................No Yes

7. Presenceofpulmonaryrales.................................................................................No Yes

8. Ondialysispreoperatively(peritonealorhemodialysis)...................................No Yes

CSP#517FS,SupplementaryDataForm,Version1.2March31,2015 Form51,Page1of5
Form51SupplementaryRisk,OperativeandPostOperativeData

SITENO. PATIENT# REFERENCECODE

    


9.Historyofcerebrovasculardisease(CVD)..............................................................NoYes
Ifyes,
a.Percentcarotidstenosisfrommostrecentstudy..........................................%
b.Priorcarotidprocedure...........................................................................NoYes
c.HistoryofTIA............................................................................................NoYes


10.Preoperativeatrialfibrillation/flutter.................................................................NoYes

11.Congestiveheartfailure(CHF)within2weeksofsurgery...................................NoYes

12.Cardiomegalyfoundonchestxray....................................................................NoYes

13.Priormyocardialinfarction(MI)...........................................................................NoYes
IfYes,specifyintervalpriortosurgery(choose1fromeachcolumnorUnknown):

a. STS b. CICSP c. EuroSCORE
<6hours <7days Anytime<90days
>6hoursbut<24hours >7days >90days
>17days UnknownMITiming UnknownMITiming
>821days  
>21days  
UnknownMITiming  

14.Percutaneouscoronaryintervention(PCI)performed<6hourspriorto
surgery................................................................................................................NoYes

FUNCTIONALSTATUS:

15.a.Independent
b.Partiallydependent
c.Totallydependent
d.Neurologicdysfunction:Ifpartiallyortotallydependent,didpatienthavediseaseseverly
 affectingambulationordaytodayfunctioning? NoYes

CSP#517FS,SupplementaryDataForm,Version1.2March31,2015Form51,Page2of5
Form51SupplementaryRisk,OperativeandPostOperativeData

SITENO.  PATIENT# REFERENCECODE

    



16.NewYorkHeartAssociation(NYHA)functionalClass(Selectone)

a.ClassI
b.ClassII
c.ClassIII
d.ClassIV

17.CanadianCardiologySociety(CCS)functionalClass=IV(Selectone)

a.ClassI
b.ClassII
c.ClassIII
d.ClassIV

PREOPERATIVEMEDICATIONSUSEDWITHINTHELASTMONTH:

18.Aspirin..................................................................................................................NoYes

19.ACE/ARB...............................................................................................................NoYes

20.Betablocker.........................................................................................................NoYes

21.Lipidloweringmedication...................................................................................NoYes
IfyesselecttypeofLLA.Selectbothtypesifappropriate....................StatinNonstatin

22.Digoxin.................................................................................................................NoYes

PREOPERATIVELABORATORYTESTRESULTS:

Providethelaboratoryvaluedrawnclosesttothetimeofsurgery.HemoglobinA1Cmayhavebeen
drawnasmuchas6monthspriortosurgery.Othertestsshouldhavebeendrawnwithin2weeksprior
tosurgery.

23.SerumCreatinine.............................................................................................mg/dL

CSP#517FS,SupplementaryDataForm,Version1.2March31,2015Form51,Page3of5
Form51SupplementaryRisk,OperativeandPostOperativeData

SITENO.  PATIENT# REFERENCECODE

    



24.HemoglobinA1C(ifdiabetic) ...................................................................................%

25.Hemoglobin ...........................................................................................................g/dL

CARDIACENZYMES:(drawnwithin48hourspriortosurgery)

26.TotalCPK..............................................................................................................U/L

27.CPKMB%oftotalOR.ng/mlOR.U/L

28.TroponinI................................................................................................ng/ml
OR
TroponinT(ifInotavailable)..............................................................ng/ml

SUPPLEMENTARYINTRAOPERATIVEDETAILS:

29.TotalCPBtime.............................................................................................................min

30.TotalIschemicTime(crossclamptime)......................................................................min

31.Harvestingtechniqueforsaphenousvein................openconduitminimallyinvasive

MEDICATIONSATDISCHARGE:

32.Didpatientsdischargemedicationsincludeanyofthefollowing.....................NoYes
Ifyes,checkallthatapply

Betablocker   Aspirin
   ACEinhibitor/ARB  Lipidloweringmedication
   Statin
Nonstatin

LABORATORYASSESSMENTSATDISCHARGEANDWITHIN1YEAR:

33.CreatinineatdischargeafterROOBYsurgery.....................................................mg/dL

34.Peakcreatinineduringindexhospitalstay.........................................................mg/dL

CSP#517FS,SupplementaryDataForm,Version1.2March31,2015Form51,Page4of5
Form51SupplementaryRisk,OperativeandPostOperativeData

SITENO.  PATIENT# REFERENCECODE

    



35.Creatinineat30daysafterROOBYsurgery........................................................mg/dL

36.Creatinineat1yearafterROOBYsurgery...........................................................mg/dL

37.Patientondialysisat1yearaftersurgery...........................................................NoYes



Reviewedby_______________________________________Date________________________


CSP#517FS,SupplementaryDataForm,Version1.2March31,2015Form51,Page5of5
Form52ASupplementaryTerminationDataCollecteduptoFiveYears

SITENO. PATIENT# REFERENCECODE DATEFORMCOMPLETED

Month DayYear

FORM52ASUPPLEMENTARYTERMINATIONDATA

Timeframefordatacollecteduptofiveyearsafterpatientsstudysurgery:

MonthDay Year
1. Dateclosesttofiveyearsthatdataisavailable

2. Dateofpatientsstudysurgery

PHYSICALSTATUS:

3. Weight(pounds)EnterAifunknown............................................................................

4. Smokedwithin1yearpriorto5yearorterminationdate............No Yes Unknown

5. CanadianCardiologySociety(CCS)functionalclass(angina)
ClassI
ClassII
ClassIII
ClassIV
Unknown

6. NewYorkHeartAssociation(NYHA)functionalclass
ClassI
ClassII
ClassIII
ClassIV
Unknown

7. Patientondialysis(peritonealorhemodialysis)..........................No Yes Unknown

CSP#517FS,SupplementaryTerminationData,Version1.2March31,2015 Form52A,Page1of2
Form52ASupplementaryTerminationDataCollecteduptoFiveYears

SITENO. PATIENT# REFERENCECODE

8. PrimaryrhythmonmostrecentECGorspecifiedinnotes
Sinus
AtrialfibrillationorAtrialflutter
Other
Unknown
MEDICATIONS:

9. Medications(mostrecentlyprescribed):

a. Betablocker.............................................................................No Yes Unknown

b. ACEInhibitor/ARB....................................................................No Yes Unknown

c. Aspirin......................................................................................No Yes Unknown

d. Lipidloweringmedication:
  Statin......................................................................................No Yes Unknown
  Nonstatin..............................................................................No Yes Unknown

LABORATORYSTUDIES:(ifpatientisdeceased,mustbewithin30daysofdeath)

10. SerumCreatinine.............................................................................................. . mg/dL

a. DateserumCreatininedrawn......................................
(enterAifunknown) Month Day Year

11. Lowdensitylipoproteins(LDL)............................................................................ mg/dL

a. DateLDLdrawn............................................................
(enterAifunknown) Month Day Year

12. HemoglobinA1C(ifdiabetic) .................................................................................. . %

a. DateHgA1Cdrawn.......................................................
(enterAifunknown) Month Day Year

Reviewedby_______________________________________Date________________________

CSP#517FS,SupplementaryTerminationData,Version1.2March31,2015 Form52A,Page2of2
Form52BSupplementaryTerminationDataforLatestKnownVAContact

SITENO. PATIENT# REFERENCECODE DATEFORMCOMPLETED

Month DayYear

FORM52BSUPPLEMENTARYTERMINATIONDATA

TimeframefordatacollectedforthelatestknowncontactwiththeVA:

MonthDay Year
1. DateofpatientslastknownVAcontact

2. Dateofpatientsstudysurgery

PHYSICALSTATUS:

3. Weight(pounds)EnterAifunknown............................................................................

4. Smokedwithin1yearpriorto5yearorterminationdate............No Yes Unknown

5. CanadianCardiologySociety(CCS)functionalclass(angina)
ClassI
ClassII
ClassIII
ClassIV
Unknown

6. NewYorkHeartAssociation(NYHA)functionalclass
ClassI
ClassII
ClassIII
ClassIV
Unknown

7. Patientondialysis(peritonealorhemodialysis)..........................No Yes Unknown

CSP#517FS,SupplementaryTerminationData,Version1.2March31,2015 Form52B,Page1of2
Form52BSupplementaryTerminationDataforLatestKnownVAContact

SITENO. PATIENT# REFERENCECODE

8. PrimaryrhythmonmostrecentECGorspecifiedinnotes
Sinus
AtrialfibrillationorAtrialflutter
Other
Unknown
MEDICATIONS:

9. Medications(mostrecentlyprescribed):

a. Betablocker.............................................................................No Yes Unknown

b. ACEInhibitor/ARB....................................................................No Yes Unknown

c. Aspirin......................................................................................No Yes Unknown

d. Lipidloweringmedication:
  Statin......................................................................................No Yes Unknown
  Nonstatin..............................................................................No Yes Unknown

LABORATORYSTUDIES:(ifpatientisdeceased,mustbewithin30daysofdeath)

10. SerumCreatinine............................................................................................ . mg/dL

a. DateserumCreatininedrawn......................................
(enterAifunknown) Month Day Year

11. Lowdensitylipoproteins(LDL)............................................................................ mg/dL

a. DateLDLdrawn............................................................
(enterAifunknown) Month Day Year

12. HemoglobinA1C(ifdiabetic) .................................................................................. . %

a. DateHgA1Cdrawn.......................................................
(enterAifunknown) Month Day Year

Reviewedby_______________________________________Date________________________

CSP#517FS,SupplementaryTerminationData,Version1.2March31,2015 Form52B,Page2of2
Form53StudyTermination/EndpointsForm

SITENO. PATIENT# REFERENCECODE DATEFORMCOMPLETED

Month DayYear

FORM53STUDYTERMINATION/ENDPOINTSFORM

1. DateofpatientsstudyCABGsurgery....................................
Month Day Year

2. Terminationstatus
Patientaliveatstudyend
Patientlosttofollowup(locationunknown)
Patientdied(pleaseanswerquestions6a,b,andc)
Other,Specify____________________________________________________

MYOCARDIALINFARCTION(MI)

3. Basedonthe2012UniversalMIdefinition,didthepatientexperienceanMIafter
oneyearfollowupfromsurgery?.......................................No Yes Unknown

a. Ifyes,DateoffirstMI...................................................
Month Day Year
b. Classificationofmyocardialinfarction:(selectone)
Type1Spontaneousmyocardialinfarction

Type2Myocardialinfarctionsecondarytoanischemicimbalance

Type3Myocardialinfarctionresultingindeathwhenbiomarkervaluesareunavailable

Type4aMyocardialinfarctionrelatedtopercutaneouscoronaryintervention(PCI)

Type4bMyocardialinfarctionrelatedtostentthrombosis

Type5Myocardialinfarctionrelatedtocoronaryarterybypassgrafting(CABG)

Unknown/unabletodetermine

CSP#517FS,StudyTermination/EndpointsForm,Version1.1August15,2013 Form53,Page1of3
Form53StudyTermination/EndpointsForm

SITENO. PATIENT# REFERENCECODE

REPEATREVASCULARIZATION

4. Didthepatientexperiencerepeatrevascularizationafterone
yearfollowupfromsurgery?...........................................................No Yes Unknown
Ifyes,continue.Ifnoorunknown,gotoquestion5.

a. Percutaneouscoronaryintervention(PCI)...............................No Yes Unknown

1. DateoffirstPCIprocedure......................................
Month Day Year

2. Interventionperformedonthefollowingvessel(s):
LAD Circumflex RCA

1stdiagonal 1stmarginal PL(anybranch)

2nddiagonal 2ndmarginal Acutemarginal

3rddiagonal 3rdmarginal Other

Ramusintermedius PDA(rightorleft) Unknown

b. Repeatcoronaryarterybypassgrafting(CABG)......................No Yes Unknown

1. DateoffirstrepeatCABG.........................................
Month Day Year

2. CABGperformedonthefollowingvessel(s)
LAD Circumflex RCA

1stdiagonal 1stmarginal PL(anybranch)

2nddiagonal 2ndmarginal Acutemarginal

3rddiagonal 3rdmarginal Other

Ramusintermedius PDA(rightorleft) Unknown

CSP#517FS,StudyTermination/EndpointsForm,Version1.1August15,2013 Form53,Page2of3
Form53StudyTermination/EndpointsForm

SITENO. PATIENT# REFERENCECODE

DEATH

5. DateofDeath..........................................................................
Month Day Year
6. CauseofDeath:

a. Notesastothepotentialcause(s)ofdeath(basedonreviewofavailablemedicalchart
data)

_______________________________________________________________

_______________________________________________________________

b. Primarycauseofdeath

Cardiacrelated

Notcardiacrelated(answerquestion6c)
Unknown

c. Detailedinformationaboutprimarycauseofdeath:

Accident Cerebrovascular
Suicide Pulmonary
Infection Cancer
Other,specify:___________________________

Reviewedby_______________________________________Date________________________

ForuseofEndpointCommitteecoordinatoronly.

Finalreviewcompleted.Coordinatorsignature:_______________________________________
Date
Reviewcompletedby:

Concurrenceof2physicianreviewers,or

EndpointsCommitteereview.

CSP#517FS,StudyTermination/EndpointsForm,Version1.1August15,2013 Form53,Page3of3
 APPENDIXFREVISIONRECORDFOR

CSP#517FSROOBYFOLLOWUPTRIAL

ChangestoAppendixFofprotocolVersion1,datedJanuary15,2015
Page Section DescriptionofChange
F1 I Deletedthefollowingtext:PendinganydiscrepanciesbetweentheVAandnonVA
databasematches/mergesascomparedtothemedicalchartreviewsperformed,this
committeewillsystematicallyevaluatethedeaths,nonfatalacutemyocardial
infarction(AMI),andrepeatrevascularizationendpointsusingdefinitionsand
guidelinesestablishedduringtheoriginalCSP#517trial.Thiscommitteewill
systematicallyevaluateallstudydeathsforcardiacversusnoncardiaccauseusing
definitionsandguidelinesestablishedduringtheoriginalCSP#517trial.
Confirmationofmyocardialinfarctionwillalsobeevaluatedbythecommitteeusing
thepublishedAHA/ACC/ECSUniversalMIdefinition.

Insertedthefollowingtext:Thiscommitteewillsystematicallyevaluatealldeaths,
nonfatalacutemyocardialinfarction(AMI),andrepeatrevascularizationendpoints
occurringinthefollowupperiod(post1yearROOBYfollowupvisitthrough5years
postCABGsurgeryandpossiblylonger).
F1 II ChangedresearchnursecoordinatortoEndpointsCommitteenursecoordinator

Deletedthefollowingtext:Dr.ShroyerwillworkwithDr.JosephCollinstocoordinate
anyneededinterraterreliabilityevaluationsoftheEndpointsCommitteemember
assessments.
F1 III Changedfrom
III. Process:TheCommitteewillmeetatleastsemiannually,aswellashold
conferencecallsmoreoftenbasedonthenumbersofreportedcases,ifwarranted.
AlldeathsreportedintheROOBYtrial,aswellasdeathsidentifiedduring
CSPCC/HERCdataextracts(e.g.,VitalStatussearches)maybereviewedif/when
discrepanciesbetweendatasourceshavebeenidentified.Thestudynursewill
preparematerialsfortheEndpointsCommitteereviewwhichinclude(butmaynotbe
limitedto):1)notes,labsandtestsfromthepatientsmedicalrecord,and2)death
certificatesorautopsyreportswhenavailable.

Inaddition,theCommitteewillevaluateandconfirmallreportedmyocardial
infarctions(MI)usingthepublishedAHA/ACC/ECSUniversalcriteria.Thismaybe
accomplishedusingnotes,labsanddiagnostictestsfromthepatientmedicalrecord.
Toassurecompliancewithdatasecurityprocedures,allofthenecessary
documentation(compiledbythestudynurse)willremovepatientidentifierspriorto
sharingthesedocumentswiththeCommitteemembers.Anymaterialsdistributedfor
anEndpointsCommitteemeetingwillbegatheredupbythestudynurseand
shredded.

To:

III. Process:TheCommitteewillmeetmonthlybyconferencecall,withfaceto
facemeetingssemiannuallyasnecessary.Conferencecallsmaybeheldmoreoften
 whentherearealargenumberofcasestoevaluate.
A. Alldeaths,myocardialinfarctions,andrepeatrevascularizations(PCIsand
redoCABGs)occurringafterthe1yearROOBYtrialfollowupperiodwillbeidentified
viaCSPCC/HERCdataextracts(e.g.,VitalStatussearches)andstudynursepatient
followupdatagathering.
B. ThestudynursewillpreparesupportingmaterialsfortheEndpoints
Committeereview,whichmayinclude(butnotbelimitedto):1)notes,labsandtests
fromthepatientsmedicalrecord,and2)autopsyreportswhenavailable.All
gathereddocumentationwillbeblindedastotreatmentarm.Thismaterialwillbe
postedonthestudyssecureVASharePointsite.
C. Toassurecompliancewithdatasecurityprocedures,allofthenecessary
documentationwillremovepatientidentifierspriortosharingthesedocumentswith
theCommitteemembers.WhenCommitteeproceedingsareconductedvia
conferencecalls,deidentifiedpatientmaterialswillbepostedonasecureVA
SharePointsitewithaccessgivenonlytostudypersonnel,includingtheEndpoints
Committeemembers.Whenevertheprocessisconductedinliveconferenceformat
usingprintedmaterials,allpatientmaterialswillbegatheredupattheendofthe
meetingandshredded.
D. DefinitionsandguidelinesestablishedduringtheoriginalCSP#517trialwill
beused.Thiscommitteewillsystematicallyevaluateallstudydeathsforcardiac
versusnoncardiaccause.Confirmationofmyocardialinfarctionwillalsobe
evaluatedbythecommitteeusingthepublishedAHA/ACC/ECSUniversalMI
definition.
E. Endpointsidentifiedforeachpatientwillbeadjudicated(usingavailable
documentationfromthepatientmedicalrecord)bythefollowingprocess:
i. TwoEndpointCommitteeclinicianswillrevieweachpatient.Ifthereis
agreementfromboth,theadjudicationprocesswillbeconsideredsatisfiedanddata
willgoforwardforentry.
ii. Whenthetwocliniciansdonotagreeontheendpoints,thecasewillgo
forwardforreviewanddiscussionbytheentireEndpointsCommittee.Additional
informationgatheringmayberequiredforthisprocess.
iii. TheEndpointsCommitteestudynursewillverifythatagreementbyoneof
thesemethodswasreachedbeforeformsaresentforwardfordataentry.

F3 D.1 Deleted:1. 2007UniversalDefinitionforMyocardialInfarctionTakenfrom:

ThygesenK,AlpertJS,WhiteHDandtheJointESC/ACCF/AHA/WHFTaskForceforthe
RedefinitionofMyocardialInfarction,Universaldefinitionofmyocardialinfarction.
Circulation.2007Nov27;116(22):263453.Asahistoricalreference,thecomponent
partsofthe2007publishedUniversalMIdefinitionwillbegatheredandusedfor
comparison.
 Appendix F

CSP #517- FS
Endpoints Committee - Procedures
I. Purpose: To establish policy and procedure for a CSP #517-FS extension
study Endpoints Committee. This committee will systematically evaluate all
deaths, non-fatal acute myocardial infarction (AMI), and repeat
revascularization endpoints occurring in the follow-up period (post 1-year
ROOBY follow-up visit through 5 years post CABG surgery and possibly
longer).

II. Committee composition: The Committee will be chaired by Dr. Fred Grover
and co-chaired by Dr. Brack Hattler, co-Principal Investigators for this CSP
#517-FS study. It will be composed of clinicians (ideally clinicians who
participated in the original CSP #517 trial) including 2 to 3 cardiac surgeons
and 1 cardiologist. The Committee will be coordinated by the Endpoints
Committee nurse coordinator.

Dr. A. Laurie Shroyer, co-Principal Investigator, will be invited to participate in

all Endpoints Committee meetings as a non-voting member.

III. Process: The Committee will meet monthly by conference call, with face-to-
face meetings semi-annually as necessary. Conference calls may be held
more often when there are a large number of cases to evaluate.
A. All deaths, myocardial infarctions, and repeat revascularizations (PCIs
and redo CABGs) occurring after the 1-year ROOBY trial follow-up
period will be identified via CSPCC/HERC data extracts (e.g., Vital
Status searches) and study nurse patient follow-up data gathering.
B. The study nurse will prepare supporting materials for the Endpoints
Committee review, which may include (but not be limited to): 1) notes,
labs and tests from the patients medical record, and 2) autopsy reports
when available. All gathered documentation will be blinded as to
treatment arm. This material will be posted on the studys secure VA
SharePoint site.
C. To assure compliance with data security procedures, all of the necessary
documentation will remove patient identifiers prior to sharing these
documents with the Committee members. When Committee proceedings
are conducted via conference calls, de-identified patient materials will be
posted on a secure VA SharePoint site with access given only to study
personnel, including the Endpoints Committee members. Whenever the
process is conducted in live conference format using printed materials, all
patient materials will be gathered up at the end of the meeting and
shredded.
D. Definitions and guidelines established during the original CSP #517 trial
will be used. This committee will systematically evaluate all study deaths
for cardiac versus non-cardiac cause. Confirmation of myocardial
infarction will also be evaluated by the committee using the published
AHA/ACC/ECS Universal MI definition.
CSP #517-FS
ROOBY TRIAL FOLLOW-UP EXTENSION
Final CSSEC Protocol: Approved on December 13, 2012/ Modified July 26, 2013

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 E. Endpoints identified for each patient will be adjudicated (using available
documentation from the patient medical record) by the following process:
i. Two Endpoint Committee clinicians will review each patient. If
there is agreement from both, the adjudication process will be
considered satisfied and data will go forward for entry.
ii. When the two clinicians do not agree on the endpoints, the case
will go forward for review and discussion by the entire Endpoints
Committee. Additional information-gathering may be required for
this process.
iii. The Endpoints Committee study nurse will verify that agreement
by one of these methods was reached before forms are sent
forward for data entry.

CSP #517-FS
ROOBY TRIAL FOLLOW-UP EXTENSION
Final CSSEC Protocol: Approved on December 13, 2012/ Modified July 26, 2013

F-2
 Appendix F

CSP #517- FS

Endpoints Committee - Definitions

I. Definitions:

A. Death Verification: When discrepancies between data sources may

arise, the records with divergent information will be evaluated to verify
death. Using the patient medical record (and other information such as
autopsy findings and/or death certificate, if available) the study will make
an official determination as to if death occurred, as well as the date of
death to be recorded.

B. Primary cause of death

i. Cardiac-related:
1. Meets CICSP criteria for operative death
Death within the 30 days after surgery in or out of the
hospital regardless of cause; or within the index
hospitalization regardless of cause; or patient died
greater than 30 days as a direct result of a peri-
operative occurrence (e.g., mediastinitis)
2. Any non-operative death that can be attributed to MI, heart
failure, dysrhythmias, cardiac arrest/sudden cardiac death,
or a subsequent cardiac procedure or surgery.
3. Any sudden death that is not clearly explained otherwise
will be considered sudden cardiac death.

ii. Not cardiac related. Any other known cause of death that is
clearly not a cardiac-related death as defined above.

iii. Unknown. Cause is not known (except sudden unexplained death

which will be considered cardiac arrest), no information about the
death is available, or where a single cause cannot clearly be
attributed.

C. Repeat Revascularization Verification: When discrepancies between

data sources may arise, the records with divergent information will be
evaluated to verify the occurrence of a repeat revascularization
procedure. Using the patient medical record (and other information such
as catheterization laboratory reports and/or cardiac surgical operative
reports, if available) the study will make an official determination as to if
repeat revascularization event(s) occurred, as well as the date(s) for
these event(s) to be recorded.

CSP #517-FS
ROOBY TRIAL FOLLOW-UP EXTENSION
Final CSSEC Protocol: Approved on December 13, 2012/ Modified July 26, 2013

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 D. Definition for Myocardial infarction (MI) confirmation

1. 2012 Universal Definition for Myocardial Infarction:

While myocardial infarction will be reported for study
purposes as Yes or No, the Endpoints Committee will
employ the 2012 Universal Definition for MI (as the primary
definition used) to classify any occurrence by type based
on pathological, clinical and prognostic differences.
(Source: Thygesen K, Alpert JA, Jaffe AS, et. al. Third
universal definition of myocardial infarction. European
Heart Journal (2012) 33, 2551-2567.)

CSP #517-FS
ROOBY TRIAL FOLLOW-UP EXTENSION
Final CSSEC Protocol: Approved on December 13, 2012/ Modified July 26, 2013

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 E. Published Definition for Myocardial infarction (MI) confirmation:

CSP #517-FS
ROOBY TRIAL FOLLOW-UP EXTENSION
Final CSSEC Protocol: Approved on December 13, 2012/ Modified July 26, 2013

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