Rotational Atherectomy Combined With Cutting Balloon to Optimize Stent Expansion in Calcified Lesions
Phase: NA
Conditions: Coronary Artery Disease, Atherosclerosis
Sponsor: Samin Sharma, M.D., F.A.C.C., M.S.C.A.I.

Rotational Atherectomy Combined With Cutting Balloon to Optimize Stent 
Expansion in Calcified Lesions (ROTA-CUT)
PI: Samin Sharma, M.D., F.A.C.C., M.S.C.A.I
NCT04865588
Document Date: 03-23-2023

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Rotational atherectomy combined with cutting balloon to optimize 
stent expansion in calcified lesions 
ROTACUT
STUDY PROTOCOL
Protocol Number: CICR-001-ROT
Version: 11
Date: 02-Mar-2023
Sponsor:
The Icahn School of Medicine at Mount Sinai
Principal Investigators:
Samin K Sharma, MD
Director, Mount Sinai Cardiovascular Clinical Institute
Senior Vice-President, Operations & Quality, Mount Sinai Heart
Director, Interventional Cardiology, Mount Sinai Health System
President, Mount Sinai Heart Network
Anandi Lal Sharma Professor of Medicine (Cardiology)
The Zena and Michael A. Wiener Cardiovascular Institute
The Icahn School of Medicine at Mount Sinai
One Gustave L. Levy Place, Box 1030
New York, NY 10029-6574
Jeffrey W Moses, MD
Professor of Medicine
Director, Interventional Cardiovascular Therapeutics
Columbia University Medical Center, New York, NY
Director, Advanced Cardiac Interventions
St Francis Hospital and Heart Center, Roslyn, NY
Effective Date: 3/23/2023
End Date:2/14/2024

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1
PROTOCOL REVISION HISTORY
Protocol 
Revision Number
Protocol 
Revision Date
Change details
3.0
15 JAN 2021
Initial release
4.0
15 Feb 2021
Response to FDA
5.0
18 Feb 2021
Response to FDA – addition of risk mitigation strategy for trial 
6.0
19 FEB 2021
Response to FDA - Addition of Investigator Agreement requirements
7.0
22 Feb 2021
Addition of secondary endpoints and inclusion/exclusion criteria 
clarification
8.0
22 Jun 2021
Correction of typographical errors
Page 18 - 7.3.3
Intravascular Ultrasound Assessment
Addition of clarification regarding safety measures associated with the 
final IVUS run and blinding of the interventional cardiologist
Page 19 –8.2 Correction of Troponin T to Troponin I as per CRFs 
Page 25 – 11.8 Stopping rules: Addition of stopping rules
Page 31 - 12.5 – Medical Monitor: Addition of a Medical Monitor 
Page 31 –Clinical events committee adjudication is now section 12.6, 
previously 12.5
Page 37 - Addition of References
9.0
17 Aug 2021
Response to FDA:
Page 25 – 11.8 Stopping rules: Clarification on Stopping Rules
Page 31 – 12.6 Clinical events committee adjudication: Clarification
Page 32 - 13.3  Clinical events committee: Clarification
9.1
17 Aug 2021
Response to CMS office:
Page 14 – 6.4.2 SECONDARY ENDPOINTS: Clinical endpoints assessment 
at 30 AND 270 day follow-up; Addition of CCS Class assessment
Page 15 – 7.2 7.2 Schedule of assessments: Addition of CCS class
Page 19 - 8.3 30-day & 270 day Follow-ups: addition of angina status and 
CCS class
Page 25 - 11.5
Anticipated Benefits: Clarification
Other Changes
Correction of typographical errors
Page 15 – 6.5 Screening, Enrollment, and Randomization: Clarification of 
Randomization
Page 25 - 11.7 Justification of Trial– Addition of References
9.2
17-Nov-2021
Response to FDA:
Page 25 – 11.8 Stopping rules: Clarification on Stopping Rules
10
10-Nov-2022
Update to Investigator Information
Page 11 - 6.2 Number of Subjects and Clinical Sites: Update to site 
enrollment allotment
Page 33 - 13.5.2 MONITORING: update to source data verification for 30 
and 270 day Follow-up
Correction of typographical errors
11
02-Mar-2023
Page 11 - 6.2 Number of Subjects and Clinical Sites: Update to site 
enrollment allotment
Effective Date: 3/23/2023
End Date:2/14/2024

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2
PROTOCOL SIGNATURE PAGE
Study Title: Rotational atherectomy combined with cutting balloon to optimize stent 
expansion in calcified lesions (ROTACUT) 
Version: 
11
Sponsor: The Icahn School of Medicine at Mount Sinai
SPONSOR
Signed: ____________________     Date: ________________________
Name: _____________________     Title: ________________________________
PRINCIPAL INVESTIGATORS
Signed: ____________________    Date: ________________________
Name: _____________________ 
 Title: ___________________________________
Signed: ____________________    Date: ________________________
Name: _____________________ 
 Title: ___________________________________
Effective Date: 3/23/2023
End Date:2/14/2024

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TRIAL KEY CONTACT INFORMATION
3.1
Sponsor and Principal Investigator contact details
SPONSOR CONTACTS
PRINCIPAL INVESTIGATORS
Roxana Mehran, MD 
Director, Center for Interventional 
Cardiovascular Research and Clinical 
Trials
The Icahn School of Medicine at Mount 
Sinai
The Zena and Michael A. Wiener 
Cardiovascular Institute
One Gustave L. Levy Place, Box 1030
New York, NY 10029-6574
Email: Roxana.mehran@mountsinai.org
Samin K. Sharma, MD
Director, Mount Sinai Cardiovascular 
Clinical Institute
Senior Vice-President, Operations & 
Quality, Mount Sinai Heart
Director, Interventional Cardiology, Mount 
Sinai Health System
President, Mount Sinai Heart Network
Anandi Lal Sharma Professor of Medicine 
(Cardiology)
The Zena and Michael A. Wiener 
Cardiovascular Institute
The Icahn School of Medicine at Mount 
Sinai
One Gustave L. Levy Place, Box 1030
New York, NY 10029-6574
Email: samin.sharma@mountsinai.org
Jeffrey W Moses, MD
Professor of Medicine
Director, Interventional Cardiovascular 
Therapeutics
Columbia University Medical Center, New 
York, NY
Director, Advanced Cardiac Interventions
St Francis Hospital and Heart Center, 
Roslyn, NY
Email: jeffrey.moses@columbia.edu
Effective Date: 3/23/2023
End Date:2/14/2024

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ARO DIRECTOR
BIOSTATISTICIAN
Roxana Mehran, MD
Director, Center for Interventional 
Cardiovascular Research and Clinial Trials
The Icahn School of Medicine at Mount 
Sinai
One Gustave L Levy Place, Box 1030 New 
York, NY 10029-6574
Email: Roxana.mehran@mountsinai.org
Samantha Sartori, PhD
Director Biostatistics, Center for 
Interventional Cardiovascular Research 
and Clinical Trials
The Icahn School of Medicine at Mount 
Sinai
One Gustave L. Levy Place, Box 1030
New York, NY 10029-6574
Email: Samantha.Sartori@mountsinai.org
ANGIO & IVUS CORE LAB
Yuliya Vengrenyuk, PhD
Director, Angiographic and Intravscular 
Ultrasound Core Laboratory
The Zena and Michael A. Wiener 
Cardiovascular Institute
One Gustave L Levy Place, Box 1030 New 
York, NY 10029-6574
Email: yuliya.vengrenyuk@mountsinai.org 
Effective Date: 3/23/2023
End Date:2/14/2024

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Table of Contents
1
PROTOCOL REVISION HISTORY........................................................................................................2
2
PROTOCOL SIGNATURE PAGE ...........................................................................................................3
3
TRIAL KEY CONTACT INFORMATION.............................................................................................4
3.1
SPONSOR AND PRINCIPAL INVESTIGATOR CONTACT DETAILS ...............................................................4
ABBREVIATIONS AND DEFINITIONS OF TERMS ...................................................................................9
4
BACKGROUND INFORMATION AND RATIONALE......................................................................10
4.1
INTRODUCTION....................................................................................................................................10
4.2
STUDY DEVICES ..................................................................................................................................10
4.3
COMPLIANCE STATEMENT...................................................................................................................10
5
STUDY OBJECTIVES .............................................................................................................................11
6
INVESTIGATIONAL PLAN...................................................................................................................11
6.1
STUDY DESIGN....................................................................................................................................11
6.2
NUMBER OF SUBJECTS AND CLINICAL SITES.......................................................................................11
6.3
STUDY POPULATION............................................................................................................................11
6.3.1
Inclusion Criteria...........................................................................................................................12
6.3.2
Exclusion Criteria ..........................................................................................................................12
6.3.3
Angiographic Specific Exclusion Criteria......................................................................................12
6.4
ENDPOINTS..........................................................................................................................................13
6.4.1
PRIMARY ENDPOINT...................................................................................................................13
6.4.2
SECONDARY ENDPOINTS...........................................................................................................13
6.4.3
Exploratory Clinical endpoints at 30-day follow-up......................................................................14
6.5
SCREENING, ENROLLMENT, AND RANDOMIZATION.............................................................................14
6.6
SUBJECT TERMINATION OR WITHDRAWAL..........................................................................................15
7
STUDY PROCEDURES...........................................................................................................................15
7.1
SUBJECT SCREENING AND INFORMED CONSENT .................................................................................15
7.2
SCHEDULE OF ASSESSMENTS ...............................................................................................................15
7.3
PROCEDURE OVERVIEW.......................................................................................................................17
7.3.1
Study flow chart..............................................................................................................................17
7.3.2
Coronary Angiography ..................................................................................................................18
7.3.3
Intravascular Ultrasound Assessment............................................................................................18
7.3.4
Rotational Atherectomy (RA) Strategy...........................................................................................18
7.3.5
Cutting Balloon Atherotomy (CBA) Strategy.................................................................................19
7.3.6
Procedure Strategy.........................................................................................................................19
8
FOLLOW-UP ASSESSMENTS...............................................................................................................19
8.1
POST-PROCEDURE MANAGEMENT.......................................................................................................19
8.2
DISCHARGE ASSESSMENT....................................................................................................................19
8.3
30-DAY & 270 DAY FOLLOW-UPS........................................................................................................19
8.4
MISSED FOLLOW-UP............................................................................................................................20
8.5
REVASCULARIZATION, CABG, DEATH ...............................................................................................20
9
ENDPOINT ANALYSIS AND STATISTICAL METHODS................................................................21
Effective Date: 3/23/2023
End Date:2/14/2024

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9.1
ANALYSIS POPULATION.......................................................................................................................21
9.2
SAMPLE SIZE RATIONALE....................................................................................................................21
9.3
STUDY ENDPOINT TESTING .................................................................................................................21
9.3.1
Primary Endpoint Hypothesis........................................................................................................21
9.3.2
Secondary Endpoint Testing...........................................................................................................22
9.4
DESCRIPTIVE STATISTICS ....................................................................................................................22
10
METHODS USED TO MINIMISE BIAS...............................................................................................22
10.1
INCLUSION BIAS ..................................................................................................................................22
10.2
ENDPOINT EVALUATION......................................................................................................................22
10.3
REPORTED DATA VERACITY ...............................................................................................................22
10.4
AVOIDING ANALYSIS BIAS..................................................................................................................23
11
RISK ASSESSMENT................................................................................................................................23
11.1
POTENTIAL RISK OF THE ANGIOPLASTY AND ROTAPRO PROCEDURE ..................................................23
11.2
POTENTIAL RISK OF THE WOLVERINE INCLUDE, BUT ARE NOT LIMITED TO: .......................................23
11.3
RISKS ASSOCIATED WITH THE IVUS PROCEDURE................................................................................24
11.4
MEASURES TO MITIGATE RISK TO TRIAL SUBJECTS............................................................................24
11.5
ANTICIPATED BENEFITS ......................................................................................................................25
11.6
ALTERNATIVE THERAPIES...................................................................................................................25
11.7
JUSTIFICATION OF TRIAL.....................................................................................................................25
11.8
STOPPING RULES.................................................................................................................................25
12
SAFETY REPORTING............................................................................................................................26
12.1
DEFINITIONS OF ADVERSE EVENTS AND DEVICE DEFICIENCIES .........................................................26
12.2
CAUSALITY RELATIONSHIP .................................................................................................................28
12.3
INVESTIGATOR REPORTING RESPONSIBILITY ......................................................................................30
12.4
SAFETY REPORTING ............................................................................................................................30
12.5
MEDICAL MONITOR.............................................................................................................................31
12.6
CLINICAL EVENTS COMMITTEE ADJUDICATION ...................................................................................31
13
TRIAL AND DATA MANAGEMENT ...................................................................................................31
13.1
ANGIOGRAPHIC CORE LAB..................................................................................................................31
13.2
INTRAVASCULAR ULTRASOUND CORE LAB ........................................................................................31
13.3
CLINICAL EVENTS COMMITTEE...........................................................................................................32
13.4
PROTOCOL DEVIATIONS ......................................................................................................................32
13.5
STUDY CONDUCT, TRAINING, MONITORING RESPONSIBILITIES & CONFIDENTIALITY........................33
13.6
SUBJECT AUTHORIZATION AND CONFIDENTIALITY.............................................................................33
13.7
DOCUMENTATION REQUIREMENTS......................................................................................................34
13.8
DATA COLLECTION .............................................................................................................................35
13.9
DATA AND DOCUMENT RETENTION ....................................................................................................35
13.10
TRIAL COMPLETION........................................................................................................................35
13.11
FUTURE PLANS................................................................................................................................35
14
STATEMENTS OF COMPLIANCE, CONFIDENTIALITY AND RESPONSIBILITIES..............35
14.1
GOOD CLINICAL PRACTICE STATEMENT .............................................................................................35
14.2
APPLICABLE REGULATIONS AND GUIDELINES ....................................................................................36
14.3
INVESTIGATOR RESPONSIBILITIES .......................................................................................................36
14.4
SPONSOR RESPONSIBILITIES................................................................................................................36
Effective Date: 3/23/2023
End Date:2/14/2024

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15
REFERENCE LIST ..................................................................................................................................37
Effective Date: 3/23/2023
End Date:2/14/2024

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ABBREVIATIONS AND DEFINITIONS OF TERMS
ACS 
Acute Coronary Syndrome 
CABG 
Coronary Artery Bypass Graft 
CAD
Coronary Artery Disease
Cath Lab
Cardiac Catheterization Laboratory
CVA 
Cerebrovascular accident 
DES 
Drug-eluting stent 
EEM
External Elastic Membrane
DM
Diabetes Mellitus
HIPAA
Health Insurance Portability and Accountability Act
ISMMS
Icahn School of Medicine at Mount Sinai
MACE
Major Adverse Cardiovascular Event
MI 
Myocardial Infarction 
NSTEMI
Non-ST Elevation MI
PCI 
Percutaneous Coronary Intervention 
PHI
Protected Health Information
PI
Principal Investigator
RA
Rotational Atherectomy
ST
Stent thrombosis 
STEMI
ST Elevation MI
TIMI
Thrombolysis in Myocardial Infarction
TLR 
Target lesion revascularization 
TVR 
Target vessel revascularization 
UA
Unstable Angina
Effective Date: 3/23/2023
End Date:2/14/2024

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4
BACKGROUND INFORMATION AND RATIONALE
4.1
Introduction
Patients undergoing percutaneous coronary intervention (PCI) for calcified lesions 
experience a high rate of major adverse cardiovascular events, including in the 
contemporary drug-eluting stent era.(1-3) Rotational atherectomy (RA) is an established tool 
in interventional cardiology for treatment of calcified coronary lesions.(4) The primary 
rationale for use of RA is to modify physical attributes of calcified plaque to facilitate balloon 
angioplasty and stent deployment. Although RA is recommended for plaque preparation in 
severely calcified lesions, a large number of patients demonstrate high residual stent 
diameter stenosis after RA and stent implantation resulting in similar restenosis rates and 
major adverse cardiac event (MACE) between patients treated with and without RA.(5, 6) 
Several clinical trials showed no benefits with aggressive strategy for procedural success or 
target vessel revascularization.(7) The study hypothesis is that calcified lesion preparation 
with rotational atherectomy followed by cutting balloon angioplasty (ROTA + CUT) will result 
in increased lumen gain, more optimal stent expansion and decreased MACE compared to 
rotational atherectomy followed by plain old balloon angioplasty (ROTA + POBA) in patients 
with calcified lesions. 
4.2
Study Devices
Model
Manufacturer
Region
Status
ROTAPRO ™ 
Boston Scientific 
Global
Commercially Available
Wolverine ™ Coronary Cutting 
Balloon
Monorail & Over-the-wire
Boston Scientific 
Global
Commercially Available
4.3
Compliance Statement
This study will be conducted in full accordance with all applicable Federal and State laws 
and regulations including 45 CFR 46, and the HIPAA Privacy Rule. Any episode of 
noncompliance will be documented.
The Principal Investigators will perform the study in accordance with the protocol, and will 
report any unexpected problems in accordance with applicable IRB Policies and Procedures 
and all Federal requirements. 
Effective Date: 3/23/2023
End Date:2/14/2024

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5
STUDY OBJECTIVES
The aim of the study is to compare the effect of two lesion modification strategies, 
ROTA+CBA and ROTA+POBA for the treatment of obstructive calcified lesion on minimum 
lumen area (MLA), stent expansion and apposition obtained with IVUS, procedural- and 
short-term clinical outcomes. The primary endpoint will be post-procedural Minimum Stent 
Area (MSA, mm2) assessed by IVUS.  
The secondary aim of the study is to assess the IVUS and quantitative coronary angiography 
(QCA) parameters both acute post device and final (post stent and post dilatation) between 
the ROTA+CBA and ROTA+POBA arms. Further secondary endpoints will include percent 
stent expansion and stent strut malapposition, procedure related complications, and 1 & 9 -
month MACE among the list.
6
INVESTIGATIONAL PLAN
6.1
Study Design
This is a prospective, multi-center randomized pilot study of 60 patients with stable CAD 
undergoing PCI for a de novo calcified lesion with drug eluting stent implantation. Patients 
with target vessel reference diameter of ≥2.5 mm and ≤ 4.0mm, lesion length ≥ 5 mm and 
moderate to severe calcification confirmed by angiography will undergo pre-procedural 
IVUS assessment, if feasible. Subjects with moderate or severe calcification for at least 5 
consecutive mm in a de novo lesion, confirmed by angiography, will be enrolled.   Enrolled 
subjects will be randomized in a 1:1 fashion to either ROTA + CUT or ROTA + POBA group. 
Rotational Atherectomy will be performed using Burr: Artery ratio of 0.4 to 0.6 in both arms. 
Intra-procedural IVUS pullbacks will be performed after lesion preparation, prior to stent 
implantation and after stenting. Upon PCI completion, operators will be blinded to final, post 
angioplasty IVUS results. An unblinded physician will review the results of this final IVUS 
run for safety signals not present on fluoroscopy. All patients will receive a drug-eluting stent 
after plaque preparation. 
6.2
Number of Subjects and Clinical Sites
The pilot study of 60 patients will take place at Mount Sinai Hospital (Dr. Sharma) and St. 
Francis Heart Hospital (Dr. Moses) with up to 48 patients enrolled at each site. All study 
subjects will sign an informed consent.
6.3
Study Population
Patients >18-years-old undergoing PCI for a de novo calcified lesion with planned drug-
eluting stent implantation
Effective Date: 3/23/2023
End Date:2/14/2024

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6.3.1
Inclusion Criteria
A subject who meets all the following criteria potentially may be included in the trial:
1) Patient (or legal guardian) is 18 years if age and understands the trial requirements and
the treatment procedures and provides written informed consent
2) Patient undergoing PCI for a de novo calcified lesion with planned rotational atherectomy
and planned drug-eluting stent implantation of a lesion with target vessel reference
diameter ≥2.5 mm and ≤ 4.0mm, lesion length ≥ 5 mm and moderate to severe
calcification by angiography
3) Patient is eligible for PCI
4) Patient is willing and able to comply with all protocol-required follow-up evaluations
6.3.2
Exclusion Criteria 
A subject who meets any of the following criteria will not be included in the trial:
1) Patient in cardiogenic shock
2) Planned surgery (cardiac and non-cardiac) within 6 months after the index procedure
unless the dual-antiplatelet therapy (DAPT) can be maintained throughout the peri-
surgical period
3) Patient undergoing primary PCI for ST-segment elevation myocardial infarction
4) Subject is pregnant, nursing, or is a woman of child-bearing potential who is not surgically
sterile, < 2 years postmenopausal, or does not consistently use effective methods of
contraception
5) Patient has any other serious medical illness (e.g., cancer, end-stage congestive heart
failure) that may reduce life expectancy to less than 12 months
6) Currently participating in another investigational drug or device study
7)
Patient referred to coronary artery bypass grafting after heart team discussion
6.3.3
Angiographic Specific Exclusion Criteria
8) Lesion(s) with angulation > 45 degrees by visual estimate
9) Lesion(s) stenosis through which a guidewire will not pass.
Effective Date: 3/23/2023
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10)Last remaining vessel with compromised left ventricular function (defined as LVEF
<30%)
11) Saphenous vein grafts
12) Angiographic evidence of thrombus
13) Angiographic evidence of significant dissection at the treatment site
14)Lesion(s) with previously placed stent within 10 mm (visual estimate)
6.4
Endpoints
The following are the planned study endpoints
6.4.1
PRIMARY ENDPOINT

Post-procedural Minimum stent area (MSA in mm2), as assessed by final IVUS
(post Stent and post-dilatation).
6.4.2
SECONDARY ENDPOINTS

IVUS endpoints will be assessed at the following time points
o
Final IVUS (post Stent and post-dilatation)

In-segment Minimum lumen area (mm2), as assessed by IVUS after
stent implantation and (optional) post-dilatation, referenced to the
EEM

Minimum stent expansion (as defined as MSA mm2), as assessed by
IVUS directly after stent implantation and post-dilatation

Mean stent expansion (%) –defined as mean stent area divided by the
mean reference lumen area, where reference lumen area will be the
average of the proximal and distal 10mm to the stent and/or the
reference EEM at the site of MSA

Any dissection

Any malapposition
o
Pre-stent implantation post RA and CBA or POBA

Any dissection

Assessment of calcium fracture

Angiographic endpoints measured in both in-stent, injured and in-segment (defined
as injured or stent (whichever is larger) plus 5mm either end as feasible)
Effective Date: 3/23/2023
End Date:2/14/2024

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o
Acute lumen gain (mm)
o
Final residual diameter stenosis (%)
o
Pre, pre-stent, and final minimum lumen diameter (mm)
o
Pre-stent and final dissection type B or greater
o
Final perforation (Ellis type ≥2)
o
Final side branch closure (≥ 1.5mm)

Device-related endpoints as defined by any problems related to the devices, including
but 
not 
limited 
to: 
balloon 
rupture, 
blade 
detachments, 
difficulty 
in
withdrawing/advancing the device, or other device related problems as identified by
the investigator.

Clinical endpoints at 30-day and 270 day follow-up:
o
All-cause death (and further classified as cardiac and non-cardiac)
o
Myocardial infarction (as defined by the SCAI definition and Universal
definitions, including peri-procedural myocardial infarction)8,9
o
Target lesion revascularization
o
Target vessel revascularization
o
Stent thrombosis (definite/probable)
o
Major bleeding (BARC 3 or 5)
o
Vascular complications
o
Target Lesion Revascularization
o
Functional status (according to CCS class)
6.5
Screening, Enrollment, and Randomization
All patients who are clinically suitable for treatment with a DES and who meet the study 
inclusion criteria while not meeting any study exclusion criteria will be approached for 
inclusion in the study. Subjects who agree to participate will sign an Institutional Review 
Board (IRB) approved study informed consent and will proceed to the cardiac catheterization 
lab for further assessment of the angiographic inclusion and exclusion criteria. 
If the subject meets all inclusion criteria and does not meet any of the exclusion criteria, 
randomization will be performed before planned use of rotational atherectomy, but after the 
guidewire has successfully passed the lesion and the subject will be considered enrolled in 
the study. Randomization will be an integrated functionality of the EDC. 
If the subject fails to meet inclusion/exclusion criteria, s/he will be considered a screening 
failure and will be excluded from data collection. Treatment of screening failures will then 
proceed as would occur within the standard of care outside of the study.
Effective Date: 3/23/2023
End Date:2/14/2024

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6.6
 Subject Termination or Withdrawal
Once enrolled, subjects may discontinue participation at any time by withdrawing informed 
consent or meeting the requirement for termination. Participation in the trial is entirely 
voluntary.  Data from subjects who withdraw from the study will be included in all planned 
study analyses up until the point of withdrawal or exit.  Any subject who is randomized and 
enters the study procedure but for whom the procedure is abandoned prior to attempted 
rotational atherectomy will be exited from the study.
7
STUDY PROCEDURES
7.1
Subject Screening and Informed Consent
All subjects who are clinically suitable for PCI treatment with rotational atherectomy and a 
DES and meet study eligibility requirements will be asked to participate in further screening 
and will be asked to sign a study-specific IRB approved study consent form prior to 
angiography. 
7.2
Schedule of assessments
Assessment
Inclusion and 
Baseline
Procedure
Discharge
30 Days 
(+/-7 d)
(Telephone 
contact)
270 Days
(± 21 d)
(Telephone 
contact)
Demographic 
characteristics
    X
Medical History, cardiac 
history, and risk factors
    X
Angina status
    X
X
X
X
Physical examination1
    X
NYHA class
    X
CCS class
    X
X
X
X
Laboratory 
Assessments2
    X
X4
12-lead
electrocardiogram
    X
X
Previous medications
    X
Clinical 
inclusion/exclusion 
criteria
    X
Informed Consent
    X
Pregnancy test (if 
applicable)
    X
Angiography
X
Effective Date: 3/23/2023
End Date:2/14/2024

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Pre-procedural IVUS (if 
feasible) 
X
Inclusion/exclusion 
criteria
X
Randomization
X
Atherectomy +/- CBA
X
Post-lesion preparation 
IVUS
X
Stenting procedure
X
Postprocedural blinded 
IVUS 
X
Antiplatelet/antithrombo
tic medication
X
X
X
X
Adverse Event 
Assessment
X
X
X
X
Medication changes3
X
X
X
X
1Physical examination: height and weight (at inclusion only), heart rate and blood pressure. CBA – Cutting balloon 
atherectomy
2Hematology and blood chemistry, creatinine, and low-density lipoprotein cholesterol
3Changes to cardiovascular medications collected only.
4In acute patients CK and/or CK-MB or troponin prior to the procedure and in the case of signs/symptoms of myocardial 
infarction/myocardial ischemia. Laboratory assessments including CK and/or CK-MB or Troponin should be done prior to 
procedure and at discharge in patients presenting with signs/symptoms of acute coronary syndrome/myocardial 
infarction/myocardial ischemia. *Patients with STEMI are excluded from the trial (see exclusion criteria 4).
Effective Date: 3/23/2023
End Date:2/14/2024

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Patients with indication for PCI of a calcified 
lesion for which rotational atherectomy is 
deemed indicated
Lesion preparation with Rotational 
Atherectomy (+/- post-stent 
dilatation with high-pressure (20 
atm), non-compliant balloon)
Randomization (1:1)
Informed consent
Post-procedural IVUS (blinded)
Clinical follow-up at 30 days & 270 days (and window)
Lesion preparation with Rotational 
Atherectomy and Cutting Balloon 
Atherotomy (+/- post-stent dilatation with 
high-pressure (max 12 atm) non-
compliant balloon) 
7.3
Procedure overview
7.3.1
Study flow chart 
Effective Date: 3/23/2023
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7.3.2
Coronary Angiography
Coronary angiography for off-line QCA analysis will be performed 1) at baseline, 2) after 
each step of the lesion preparation, and 3) at the end of the procedure. After intracoronary 
injection of 100-200mcg of nitroglycerine, coronary angiography will be performed in two 
orthogonal projections aimed to minimize lesion foreshortening and differing at least 30o of 
rotation. The catheter tip, filled with dye, should be visible for QCA calibration and the lesion 
should ideally be located in the center of the field of view.
7.3.3
Intravascular Ultrasound Assessment
Intravascular ultrasound assessment for off-line analysis will be performed with the following 
strategy The 60Mhz OptiCrosstm IVUS catheter (Boston Scientific, Marlborough, MA, USA) 
using automated pull-back at 1mm/s. The catheter will be advanced at least 5 mm distal to 
the target lesion.
1) at baseline, prior to any intervention, if possible. This IVUS run is optional
2) after lesion preparation defined as RA + POBA or RA + CBA, and
3) at the end of the procedure. This will be following completion of the interventional
procedures per the interventional cardiology investigator.
During the procedure, any additional IVUS runs and assessments deemed clinically
indicated by the treating physician to guide the procedure will not be precluded from
being performed; these will occur prior to the Final post-angioplasty IVUS run.
Only after the operator deems the procedure to be finished, will the final post
angioplasty IVUS run be performed for endpoint assessment. In order to reduce bias,
operators will be blinded to the final IVUS run pullback images and no additional stent
placement or post dilation is allowed after the Final IVUS run. Blinding will be
performed by either turning the IVUS console results away from the primary
investigator in the room, or having the primary investigator turn away, if the former is
not feasible.
To ensure safety, an unblinded physician will be available at the end of the procedure
to review the results of the Final IVUS run for safety signals not present on
fluoroscopy. If the unblinded physician has any safety-related concerns, the operator
will take immediate actions to ensure the safety of the patient.
7.3.4
Rotational Atherectomy (RA) Strategy
Rotational atherectomy will be performed according to the instructions for use and current 
best practices using a maximum burr-to-artery ratio of 0.4-0.6, a burr speed of 140,000 – 
160,000 RPM, and a maximum run duration of 20s. Burr upsizing during the procedure is 
allowed but the maximum burr-to-artery ratio is not to exceed the recommended 0.6. 
Effective Date: 3/23/2023
End Date:2/14/2024

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7.3.5
Cutting Balloon Atherotomy (CBA) Strategy
In patients randomized to RA+CBA, cutting balloon atherotomy using a Wolverinetm cutting 
balloon (Boston Scientific, Marlborough, MA, USA) will be performed after rotational 
atherectomy. The Wolverine cutting balloon will be sized 1:1 relative to the reference vessel 
diameter and the inflation pressure is recommended at 6 ATM and is expected not to exceed 
the device rated burst pressure of 12 ATM. 
7.3.6
Procedure Strategy
The following procedure strategies should be followed in regard to overall treatment strategy 
of the study subject:
o
Additional lesions may be treated during the same procedure or may be staged
according to the discretion of the operator
o
Study subjects are to be maintained on dual antiplatelet therapy or oral
anticoagulation with single or dual antiplatelet therapy according to applicable
guidelines
8
FOLLOW-UP ASSESSMENTS
8.1
Post-procedure Management
Standard of care hospital protocols for the management of patients after treatment with DES 
shall be followed.
8.2
Discharge Assessment
All subjects shall be discharged from the hospital at the discretion of the attending clinical 
team. Per the standard of care, and at some time prior to dismissal, all subjects shall 
undergo an assessment of angina status, a 12-lead ECG, and the following lab 
assessments: hematology and blood chemistry, CK-MB or troponin I, and creatinine. 
Subjects who had acute angina prior to the procedure, or experienced any events between 
the procedure and discharge, will have CK and/or CK-MB or troponin I repeated upon 
discharge. Changes to cardiovascular medications will be collected at discharge as well as 
an assessment of adverse events.
8.3
30-day & 270 day Follow-ups
At 30 days (+/- 7 days) and 270 days (+/- 21 days) the patient shall be contacted by 
telephone at which time information on cardiovascular medication as well as an assessment 
of adverse events, angina status and CCS class will be obtained.
Effective Date: 3/23/2023
End Date:2/14/2024

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8.4
Missed Follow-up
The Investigator(s) will make every attempt to follow the subjects. All subjects will be 
encouraged by the Investigator(s) to report any address or telephone number changes to 
the trial site. Subjects will be informed of the importance of completing the scheduled follow-
up telephone calls even if they are not experiencing any medical issues. If a subject cannot 
be reached for a follow-up visit, or misses a scheduled visit, the visit will be recorded as a 
missed visit as of the date of last attempted contact. The procedure for attempts at contact 
should be three phone calls made and recorded in the study medical record plus mailing of 
a registered letter and contact with the General Practitioner, if allowed per patient consent.  
Study subjects exit the trial when no additional follow-up visits, procedures, or data collection 
are required. A subject is exited from the trial in the following instances:
•
Is lost-to-follow-up (LTFU)
•
Voluntarily withdraws from the trial
•
Death (Cause of death, if available, is to be reported)
•
Completes last trial follow-up visit
•
Investigator withdraws the subject from the trial
Once a subject has exited the trial, no further follow-up contact will be performed. However, 
if premature study exit has occurred, vital status may be obtained from public records if 
allowed by country law.
8.5
Revascularization, CABG, Death
In the event of revascularization of the target lesion, or coronary artery bypass graft (CABG), 
every effort should be made to obtain a copy of the procedure notes as well as any 
accompanying imaging performed.  In the event of the subject’s death, every effort should 
be made to obtain a copy of a death summary/death certificate and any treatment notes. 
Information on the cause of intervention or death will be reported by the investigator(s) and 
reported in the study electronic data capture system.  
Effective Date: 3/23/2023
End Date:2/14/2024

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9
ENDPOINT ANALYSIS AND STATISTICAL METHODS
9.1
Analysis Population
The analysis population is the 60 subjects who were enrolled and randomized to treatment 
with either rotational atherectomy or rotational atherectomy + cutting balloon atherotomy, 
regardless of procedure outcome. The analysis population excludes subjects who signed 
the informed consent but who failed to meet angiographic screening criteria (angiographic 
screen failures).
9.2
Sample Size Rationale
The current study is investigating a novel approach for lesion preparation before stent 
implantation. As there is limited data available to estimate the expected MSA after rotational 
atherectomy + cutting balloon atherectomy strategy, no formal sample size calculation was 
performed. A sample size of 60 patients (total n=60) was chosen for this study.  However, a 
sample size of 60 patients will be powered to detect effect sizes as listed below, given an 
estimated MSA of 5.50mm2 ± 2.36mm2, an equal variance, and a two-sided alpha of 0.05.
Table: Power Calculation
Sample Size
Effect Size
(mean difference in MSA)
Power
60
1.6
0.733
60
1.7
0.783
60
1.8
0.828
60
1.9
0.866
9.3
Study Endpoint Testing
9.3.1
Primary Endpoint Hypothesis
Endpoint 1: Minimal stent area (MSA) at the end of the procedure as assessed by IVUS.
The null and alternate hypotheses for the primary endpoint are
H0:  Mean MSARA = Mean MSARA+CBA
HA:  Mean MSARA  Mean MSARA+CBA
A 2-sided independent samples Student’s t-test will be used with a 2-sided alpha of 0.05 to 
test for differences in MSA between the control (MSARA) and experimental (MSARA+CBA) 
groups.
Effective Date: 3/23/2023
End Date:2/14/2024

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9.3.2
Secondary Endpoint Testing
Time-to-event analyses using Kaplan Meier methods will be performed for dichotomous 
clinical secondary endpoint outcomes, event rates in both groups will be compared using 
the log-rank test. 
A 2-sided independent samples Student’s t-test will be used with a 2-sided alpha of 0.05 to 
test for differences in continuous secondary endpoints between the control and experimental 
groups.
9.4
Descriptive Statistics
Descriptive statistics (arithmetic mean, median as indicated, minimum and maximum and 
standard deviation) will be calculated for continuous variables. Absolute frequencies and 
percentages will be obtained for qualitative variables. Summary statistics will be presented 
according to treatment allocation. 95% Confidence intervals will also be provided. 
All statistical tests will be performed with a two-sided alpha of 0.05 and 95% confidence 
intervals will be presented where applicable, unless otherwise specified.
10 METHODS USED TO MINIMISE BIAS 
The following methods are employed to minimize bias in the study:
10.1 Inclusion Bias
All patients eligible for PCI treatment with rotational atherectomy and subsequent DES 
implantation and who meet the clinical study criteria will be offered participation in the study, 
pending angiographic assessment of angiographic inclusion/exclusion criteria.
10.2 Endpoint Evaluation
An independent Core Lab will evaluate all study angiograms and all study IVUS runs, and 
an independent Clinical Events Committee will adjudicate all Endpoint-eligible Serious 
Adverse Events through the duration of the study.
10.3 Reported Data Veracity
Routine monitoring will be conducted for all reported data according to the study monitoring 
plan.
Effective Date: 3/23/2023
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10.4 Avoiding Analysis Bias
Statistical analysis will be conducted according to a pre-specified Statistical Analysis Plan 
(SAP). 
11 RISK ASSESSMENT
11.1 Potential Risk of the angioplasty and RotaPro procedure
Given subjects enrolled into this protocol will be slated for angioplasty with the use of 
RotaPro irrespective of trial inclusion the risks associated with such procedures are 
presented and reviewed with the patient as a part of the standard of care procedural consent 
process.  
11.2 Potential Risk of the Wolverine include, but are not limited to:

Abrupt closure

Acute myocardial infarction

Angina of unstable angina

Arrhythmias, including ventricular
fibrillation

Arteriovenous fistula

Cardiac tamponade/ pericardial
effusion

Cardiogenic shock

Cerebrovascular accident/ stroke

Coronary aneurysm

Coronary artery bypass grafting
surgery

Coronary artery spasm

Coronary vessel dissection,
perforation, rupture, or injury,
possibly requiring surgical repair or
intervention

Death

Drug reactions, including allergic
reaction to contract medium

Embolism

Hemodynamic compromise

Hemorrhage or hematoma

Hypo/hypertension

Infection

Minor vessel trauma

Myocardial ischemia

Percutaneous re-intervention

Pseudoaneurysm (at vascular
access site)

Pyrogenic reaction

Renal failure

Respiratory insufficiency

Restenosis of the dilated vessel

Side branch occlusion

Slow flow/ no reflow

Thrombosis

Total occlusion of the coronary
artery of bypass

Transient ischemic attack

Vasovagal reaction

Ventricular irritability/ dysfunction

Vessel trauma requiring surgical
repair or intervention

Volume overload
Effective Date: 3/23/2023
End Date:2/14/2024

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11.3 Risks associated with the IVUS procedure
The IVUS device is designed to function as a conventional, rotating core catheter which has 
an excellent safety record.  Experience with IVUS throughout the world has shown that the 
catheter safety profile is low with potential adverse events associated with the IVUS in the 
target lesions at a very low rate (<1%).
Other risks associated with using this device are those associated with percutaneous 
coronary diagnostic (including angiography and IVUS) and treatment procedures. These 
risks may include, but are not limited to, the following:
•
Abrupt vessel closure
•
Access site pain, hematoma or
hemorrhage
•
Allergic reaction (to contrast,
antiplatelet therapy, stent material,
or drug and polymer coating)
•
Aneurysm, pseudoaneurysm, or
arteriovenous fistula (AVF)
•
Arrhythmias, including ventricular
fibrillation
•
Balloon rupture
•
Bleeding
•
Cardiac tamponade
•
Coronary artery occlusion,
perforation, rupture, or dissection
•
Coronary artery spasm
•
Death
•
Embolism (air, tissue, device, or
thrombus)
•
Emergency surgery: peripheral
vascular or coronary bypass
•
Failure to deliver the stent
•
Hemorrhage requiring transfusion
•
Hypotension / hypertension
•
Incomplete stent apposition
•
Infection or fever
•
Myocardial infarction (MI)
•
Pericarditis
•
Peripheral ischemia / peripheral
nerve injury
•
Radiation exposure
•
Renal Failure
•
Restenosis of the stented artery
•
Shock / pulmonary edema
•
Stable or Unstable angina
•
Stent deformation, collapse, or
fracture
•
Stent migration or embolization
•
Stent misplacement
•
Stroke / transient ischemic attack
11.4 Measures to Mitigate Risk to Trial Subjects 
The following measures will be implemented to minimized risk to the trial subjects:

Treating physicians will have considerable experience with both the Rotational
atherectomy device, ROTA PRO, and the wolverine device.

Treating physicians will have considerable experience with IVUS imaging techniques

Study sites will have significant experience with severely calcified lesion
percutaneous coronary intervention
Effective Date: 3/23/2023
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
Serial IVUS measurements will be performed throughout the procedure as specified
above

Final blinded IVUS runs will be read by an experienced interventional cardiologist
before the subject is removed from the catheterization laboratory

Subjects will be rigorously followed over the course of the trial
11.5 Anticipated Benefits
The potential benefit of severely calcified lesion preparation with the combination of 
rotational atherectomy with the RotaPro followed by a cutting balloon with the Wolverine, is 
to maximize the final minimal stent area as assessed by IVUS, that would translate in a 
clinical benefit at follow-up. Indeed, there is ample data supporting that larger stented areas 
at the end of an angioplasty are associated with lower rates of major adverse event or target 
vessel failure at long term follow-up. (10, 11, 12)
11.6 Alternative Therapies
Presently, therapeutic alternatives for patients meeting the ROTACUT inclusion criteria who 
are scheduled for PCI rotational atherectomy include the following:

PCI with rotational atherectomy alone or followed by POBA
11.7 Justification of Trial
The treatment of severely calcified lesions continues to have high rates of major adverse 
cardiovascular events. (1-3) Based upon the literature review presented in the Report of 
Prior Investigation, the utility of cutting balloon device(s) following successful rotational 
atherectomy has demonstrated larger post stent implantation MSA as compared to 
rotational atherectomy and plain balloon.(13-16) This trial is designed to prospectively, and 
in a randomized fashion, evaluate this treatment strategy.  Although there are risks to the 
subjects for participation in the trial, they are anticipated to be similar to the risks of 
undergoing PCI for severely calcified lesion outside of the trial.  The trial endpoints are 
clinically relevant for the patient population targeted, those with severely calcified lesions. 
There are no foreseen differences with regard to sex at birth, age at the time of enrollment 
with respect to this trial endpoints. Therefore, the trial is justified.
11.8 Stopping Rules
A stopping rule based on the occurrence of clinically relevant coronary dissection was 
defined on the basis of literature review. In previous pilot studies evaluating a strategy of 
rotational atherectomy with or without cutting balloon, the meta-analytic incidence of 
coronary dissection was 18% (2-sided 95% upper confidence limit = 28%).(13, 14) 
Therefore, a stopping rule is set at the occurrence of 11 (18% of 60 patients) flow-limiting 
coronary dissections leading to a periprocedural myocardial infarction.(17) That is, if during 
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the enrollment phase, 11 episodes of flow-limiting coronary dissection associated with 
periprocedural myocardial infarction occur, patient recruitment will be terminated. 
If the trial is terminated prematurely or suspended, the sponsor shall promptly inform the 
clinical investigators and regulatory authorities of the termination or suspension and the 
reason(s) for this. The investigator shall then promptly inform the reviewing IRB. The 
sponsor will, as soon as possible, provide a written statement to the investigators to enable 
prompt notification of the IRBs. If the trial is terminated early, follow-up visits will continue 
for all enrolled subjects for the intended length of the study.
12 SAFETY REPORTING
Subjects will be carefully monitored during the study for possible Adverse Events (AEs) from 
the time of enrollment/randomization to the completion of their participation in the study
12.1 Definitions of Adverse Events and Device Deficiencies
 All adverse events shall be will be fully investigated by the Investigator. 
Table: Adverse Event Definitions
Term
Definition
Adverse event (AE)
Any untoward medical occurrence, unintended disease or injury, or 
untoward clinical signs (including abnormal laboratory findings) in subjects, 
users or other persons, whether or not related to the investigational medical 
device
NOTE 1: This definition includes events related to the study medical 
device or the comparator.
NOTE 2: This definition includes events related to the procedures 
involved.
NOTE 3: For users or other persons, this definition is restricted to 
events related to investigational medical devices.
Serious adverse event 
(SAE)
An adverse event that:

led to a death,

led to serious deterioration in the health of the subject, that either
resulted in

a life-threatening illness or injury, or

a permanent impairment of a body structure or a body function, or

in-patient or prolonged hospitalization, or
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
medical or surgical intervention to prevent life-threatening illness or
injury or permanent impairment to a body structure or a body
function,

led to fetal distress, fetal death or a congenital abnormality or birth
defect
NOTE: Planned hospitalization for a pre-existing condition, or a 
procedure required by the CIP, without serious deterioration in 
health, is not considered a serious adverse event.
Device deficiency 
Inadequacy of an investigational medical device related to its identity, 
quality, durability, reliability, safety or performance. This may include 
malfunctions, use error, or inadequacy in the information supplied by the 
manufacturer.
Device malfunction
Failure of an investigational medical device to perform in accordance with 
its intended purpose when used in accordance with the instructions for use 
or CIP.
Adverse device effect 
(ADE)
Adverse event related to the use of an investigational medical device
NOTE 1: This definition includes adverse events resulting from 
insufficient or inadequate instructions for use, deployment, 
implantation, installation, or operation, or any malfunction of the 
investigational medical device.
NOTE 2: This definition includes any event resulting from use error 
or from intentional misuse of the investigational medical device
Serious adverse device 
effect (SADE)
Adverse device effect that has resulted in any of the consequences 
characteristic of a serious adverse event
Unanticipated Adverse 
Device Effect (UADE)
Any serious adverse effect on health or safety or any life-threatening 
problem or death caused by, or associated with, a device, if that effect, 
problem, or death was not previously identified in nature, severity, or 
degree of incidence in the investigational plan or application (including a 
supplementary plan or application), or any other unanticipated serious 
problem associated with a device that relates to the rights, safety, or 
welfare of subjects” (21 CFR 812.3(s)
UADEs must be reported by the clinical investigator to the sponsor and the 
reviewing IRB, as described below:

For device studies, investigators are required to submit a report
of a UADE to the sponsor and the reviewing IRB as soon as
possible, but in no event later than 10 working days after the
investigator first learns of the event (§ 812.150(a)(1)).

Sponsors must immediately conduct an evaluation of a UADE and
must report the results of the evaluation to FDA, all reviewing
IRBs, and participating investigators within 10 working days after
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the sponsor first receives notice of the effect (§812.46(b), 
§812.150(b)(1)).
Use Error
Act or omission of an act that results in a different medical device response 
than intended by the manufacturer or expected by the user
NOTE 1: Use error includes slips, lapses, and mistakes.
NOTE 2: An unexpected physiological response of the subject does 
not in itself constitute a use error.
12.2 Causality Relationship
Relatedness of the AE to the index procedure or the study device itself will be initially 
judged by the investigator. For events eligible for CEC adjudication, the CEC will ultimately 
adjudicate procedure and device-relationship.
Each AE will be classified according to the following levels of causality:
1) Not related: relationship to the device or procedures can be excluded when:

the event is not a known side effect of the product category the device belongs
to or of similar devices and procedures;

the event has no temporal relationship with the use of the investigational
device or the procedures;

the serious event does not follow a known response pattern to the medical
device (if the response pattern is previously known) and is biologically
implausible;

the discontinuation of medical device application or the reduction of the level
of activation/exposure - when clinically feasible – and reintroduction of its use
(or increase of the level of activation/exposure), do not impact on the serious
event;

the event involves a body-site or an organ not expected to be affected by the
device or procedure;

the serious event can be attributed to another cause (e.g. an underlying or
concurrent illness/ clinical condition, an effect of another device, drug,
treatment or other risk factors);

harms to the subject are not clearly due to use error;
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
In order to establish the non-relatedness, not all the criteria listed above might
be met at the same time, depending on the type of device/procedures and the
serious event.
2) Unlikely: the relationship with the use of the device seems not relevant and/or the
event can be reasonably explained by another cause, but additional information may
be obtained.
3) Possible: the relationship with the use of the investigational device is weak but
cannot be ruled out completely. Alternative causes are also possible (e.g. an
underlying or concurrent illness/ clinical condition or/and an effect of another device,
drug or treatment). Cases were relatedness cannot be assessed or no information
has been obtained should also be classified as possible.
4) Probable: the relationship with the use of the investigational device seems
relevant and/or the event cannot reasonably have explained by another cause, but
additional information may be obtained.
5) Causal relationship: the event is associated with the investigational device or
with procedures beyond reasonable doubt when:

the event is a known side effect of the product category the device belongs to
or of similar devices and procedures;

the event has a temporal relationship with investigational device
use/application or procedures;

the event involves a body-site or organ that

the investigational device or procedures are applied to;

the investigational device or procedures have an effect on;

the serious event follows a known response pattern to the medical device (if
the response pattern is previously known);

the discontinuation of medical device application (or reduction of the level of
activation/exposure) and reintroduction of its use (or increase of the level of
activation/exposure), impact on the serious event (when clinically feasible);

other possible causes (e.g. an underlying or concurrent illness/ clinical
condition or/and an effect of another device, drug or treatment) have been
adequately ruled out;

harm to the subject is due to error in use;
In order to establish the relatedness, not all the criteria listed above might be met at the 
same time, depending on the type of device/procedures and the serious event
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12.3 Investigator Reporting Responsibility
At each study visit, the Investigator will determine whether any adverse events (AE) have 
occurred. Adverse events will be recorded in a timely manner on the electronic Case Report 
Form (EDC System) by the Investigator (or any dedicated site personnel) and will include 
event start and stop dates, description of event, severity, and relatedness to the index 
procedure and the study device.  
In the event that the EDC system is not in service or is not otherwise accessible, the CRA 
from the Center for Interventional Cardiovascular Research and Clinical Trials should 
contact the Sponsor per the Safety Management Plan.  
It is understood that complete information about the event may not be known at the time the 
initial report is submitted.  The Investigator should make every attempt to obtain as much 
information as possible concerning the event and ensure that all additional relevant 
information that becomes available is also forwarded to the Sponsor immediately after the 
initial notification (i.e., copy of laboratory exams, MRI or CT imaging, hospitalization reports 
indicating the SAE). All identifying information must be removed from these supporting 
documents and instead the site should use the unique subject identifier.
There are certain events (specified below) that if they occur require expedited (within 48 
hours of knowledge) reporting by the Principal Investigators. 
Following events should be reported as Expedited Events:

Any Serious Adverse Event

Any Device Deficiency

New findings/updated in relation to above reported events
All reported events will be followed until resolution, stabilization or 30 days after the last 
subject enrolled has completed the trial, whichever occurs first.
12.4 Safety Reporting
Depending on the local requirements, or following agreement between both parties, the 
Pponsor or the Principal Investigators will be responsible for performing safety reporting to 
the Ethics Committee according to the relevant local regulatory requirements. 
The Sponsor or Sponsor designee will report all reportable events to FDA.  
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12.5 Medical Monitor
A Medical Monitor will be available to sites on a 24/7 basis for the duration of the trial to 
address protocol related medical questions from participating sites and will review all AEs 
to identify events that require formal reporting measures. 
12.6 Clinical events committee adjudication
The ROTACUT Study will have an independent Clinical Events Committee (CEC) whose 
role it will be to adjudicate all Endpoint-eligible SAEs through to the end of 270-day follow-
up for final endpoint evaluation as well as device and procedure relatedness. The CEC 
members will be blinded to the subjects’ treatment assignments to avoid potential bias 
throughout the course of the study. All CEC activities and the detailed adjudication process 
are regulated by the CEC Charter.
13 TRIAL AND DATA MANAGEMENT
13.1 Angiographic Core Lab
The ROTACUT Angiographic Core Lab is responsible for independently evaluating all 
procedure angiograms submitted by trial sites. The purpose of the Core Lab is to ensure 
unbiased, timely and consistent analysis of the diagnostic data, and for evaluating clinical 
events in subjects over the life of the study.
Angiograms will be sent directly from the investigational sites to the Core Lab via an online 
image upload portal.
13.2 Intravascular Ultrasound Core Lab
The ROTACUT IVUS Core Lab is responsible for independently evaluating all procedure 
IVUS runs submitted by trial sites. The purpose of the Core Lab is to ensure unbiased, timely 
and consistent analysis of the diagnostic data, and for evaluating clinical events in subjects 
over the life of the study.
IVUS runs will be sent directly from the investigational sites to the Core Lab via an online 
image upload portal or manual delivery.
Effective Date: 3/23/2023
End Date:2/14/2024

P a g e | 3 2 
C O N FI D E N TI A L A N D P R O P RI E T A R Y:  T hi s d o c u m e nt a n d t h e i nf or m ati o n c o nt ai n e d t h er e-i n m a y n ot b e 
r e pr o d u c e d, u s e d or di s cl o s e d wit h o ut writt e n p er mi s si o n fr o m t h e Pri n ci p al I n v e sti g at or s.
V er si o n: 1 1 _ dt d 0 2 M ar 2 0 2 3
I D E G 2 1 0 0 3 0
1 3. 3 Cli ni c al E v e nt s C o m mitt e e
T h e R O T A C U T Cli ni c al E v e nt s C o m mitt e e ( C E C) i s a n i n d e p e n d e nt a dj u di c ati n g c o m mitt e e 
w hi c h c o n d u ct s o n g oi n g r e vi e w of all p ot e nti al e n d p oi nt s. T h e C E C c o n si st s of p h y si ci a n s 
wit h s p e ci alt y i n c ar di ol o g y a n d/ or i nt er v e nti o n al c ar di ol o g y, w h o ar e i m p arti al, i n d e p e n d e nt 
of t h e i n v e sti g at or( s) a n d w h o h a v e n o fi n a n ci al, s ci e ntifi c, or ot h er c o nfli ct of i nt er e st wit h 
t h e tri al. T h e a cti viti e s of t h e C E C al o n g wit h t h e d efi niti o n s a n d d et ail e d pr o c e s s ar e 
d e s cri b e d i n t h e C E C C h art er. 
1 3. 4 Pr ot o c ol D e vi ati o n s
A pr ot o c ol d e vi ati o n i s d efi n e d a s a n i n st a n c e of f ail ur e t o f oll o w, i nt e nti o n all y or 
u ni nt e nti o n all y, t h e r e q uir e m e nt s of t h e pr ot o c ol.  T h e I n v e sti g at or i s n ot all o w e d t o d e vi at e 
fr o m t h e st u d y pr ot o c ol e x c e pt t o pr ot e ct t h e ri g ht s, s af et y a n d w ell- b ei n g of h u m a n s u bj e ct s 
u n d er e m er g e n c y cir c u m st a n c e s.
D e vi ati o n s s h all b e r e p ort e d t o t h e tri al S p o n s or r e g ar dl e s s of w h et h er m e di c all y j u stifi a bl e 
or t a k e n t o pr ot e ct t h e s u bj e ct i n a n e m er g e n c y. I n v e sti g at or s will a d h er e t o pr o c e d ur e s f or 
r e p orti n g tri al d e vi ati o n s t o F D A a n d I R B i n a c c or d a n c e wit h t h e a p pli c a bl e l a w s a n d 
r e g ul ati o n s.  
F or r e p orti n g p ur p o s e s, d e vi ati o n s ar e cl a s sifi e d a s m aj or or mi n or:
1 3. 4. 1 M aj or d e vi ati o n s
A m aj or pr ot o c ol d e vi ati o n ( P D) or n o n c o m pli a n c e i s o n e t h at m a y h a v e a si g nifi c a nt i m p a ct 
o n s u bj e ct s af et y or w ell- b ei n g, t h e s u bj e ct’ s willi n g n e s s t o p arti ci p at e i n t h e st u d y, or t h at 
m a y c o m pr o mi s e t h e i nt e grit y of t h e st u d y d at a a n d a n al y si s. E x a m pl e s i n cl u d e:

S u bj e ct e nr oll e d a n d r a n d o mi z e d n ot h a vi n g m et eli gi bilit y crit eri a at t h e ti m e of
i m pl a nt/tr e at m e nt.

I nf or m e d C o n s e nt n ot si g n e d or si g n e d aft er t h e i niti ati o n of n o n- st a n d ar d of c ar e,
r e s e ar c h r el at e d a s s e s s m e nt s.

R e p ort a bl e S af et y E v e nt n ot r e p ort e d t o I R B/ S p o n s or wit hi n t h e r e q uir e d
ti m efr a m e
1 3. 4. 2 Mi n or d e vi ati o n s
A mi n or pr ot o c ol d e vi ati o n or n o n c o m pli a n c e i s u nli k el y t o h a v e a si g nifi c a nt i m p a ct o n 
s u bj e ct s af et y, w ell b ei n g, or i s u nli k el y t o c o m pr o mi s e t h e i nt e grit y of t h e st u d y d at a a n d 
a n al y si s.
N O T E: I nf or m ati o n t h at i s n ot e s s e nti al t o t h e tri al e n d p oi nt s i s n ot c o n si d er e d a d e vi ati o n 
if a b s e nt.
Eff e cti v e D at e: 3/ 2 3/ 2 0 2 3
E n d D at e: 2/ 1 4/ 2 0 2 4

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13.5 Study Conduct, Training, Monitoring Responsibilities & Confidentiality
The study is conducted in accordance with Good Clinical Practice (GCP), the principles of 
the Declaration of Helsinki, and this protocol. The study Investigators are responsible for 
obtaining the appropriate regulatory approvals (e.g., IRB) prior to initiation of the study. The 
Investigator provides current copies of the study protocol to all sub-Investigators or other 
staff responsible for study conduct.
13.5.1 Site Initiation and Training
Site staff will be trained and experienced in performing their delegated tasks. Training may 
be in person, webinar, read and review, or other methods as deemed appropriate. 
Training is documented on an “Individual Training Log”. A “Delegation of Authority Log” is 
completed at each site for all trial staff individual designating which specific clinical trial 
related tasks may be performed. The delegated tasks will determine what the training 
requirements are for each member of the trial support staff.  Technicians performing the 
angiograms do not require any additional training to perform the trial tests, as the requested 
procedures are standard clinical exams used in standard practice.
New research staff members may be trained by previously trained personnel on the study 
protocol and procedures, as long as appropriate documentation of that training is completed.
13.5.2 MONITORING
The Center for Interventional Cardiovascular Research and Clinical Trials, or its designee, 
will conduct site monitoring in accordance with the detail below to ensure that all 
Investigators are in compliance with the protocol.
The following data will be verified by either in-person, on-site review or virtual visits ensuring 
adequate review of source data for verification.
Inform Consent
100%
Inclusion/ Exclusion
100%
Serious Adverse Event(s)
100%
Remaining data fields from enrollment to hospital 
discharge 
3 patients or 10%, whichever is higher, randomly 
selected within each site
30 day and 270 day follow
2 patients or 10%, whichever is higher, randomly 
selected within each site for both 30 day and 270 
day follow up
13.6 Subject Authorization and Confidentiality
Subject authorization and written informed consent must be obtained prior to the subject’s 
enrollment into the study and in accordance with GCP, the Medical Devices Directive and 
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all other applicable standards, regulations (local and national), guidelines and institutional 
policies. Subject confidentiality must be maintained in accordance with GCPs, HIPAA, and 
all other applicable standards, regulations (local and national), guidelines and institutional 
policies.
13.6.1 Investigator Confidentiality
Study Investigators must comply with the applicable provisions of the study Investigator 
Agreement with regard to nondisclosure and confidentiality.
13.7 Documentation Requirements
13.7.1 Source documents
Clinical regulations require that Investigators maintain information in the clinical trial 
subject’s medical records that corroborates data collected on the eCRF. Some examples of 
critical information to be maintained for possible review by regulatory inspectors are:

Medical history and physical condition of the subject before involvement in the clinical
trial sufficient to verify protocol entry criteria

Dated and signed notes in the subject’s medical record on the day of entry into the
clinical trial

Dated and signed notes, and test reports, from each clinical trial visit with reference
to the eCRF for further information, if appropriate (for specific results of procedures
and exams).

Notes regarding concomitant cardiac/diabetic medications taken during the clinical
trial

Subject’s condition upon completion of or withdrawal from the clinical trial
To protect subject confidentiality, the subject’s name must not appear anywhere on the 
source documentation or angiographic imaging sent to trial Sponsor, CEC, or Core Lab.  All 
subject identifiers (i.e. medical record number) are to be obscured. Original copies of all 
data must be kept at the site.
13.7.2 Trial documents
The trial Sponsor will provide pre-printed or electronic forms to each trial site for 
documentation of:

Investigator and site training to the protocol (Individual/Group Training Log)

Financial Conflict of Interest (All Investigators)

Investigator Agreement required by 21 CFR 812.20(b)(5) (All Investigators)

Authorized trial site personnel (Delegation of Authority)

Investigator and site training of EDC utilization (EDC/CRF Training Log)
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
Subject consent and screening (Screening and Enrollment Log)

Monitoring Visit tracking (Site Visit Log)
The site visit is recorded on the appropriate site visit report sent to the Sponsor. During the 
course of the study, all correspondence regarding the trial must be maintained in the 
regulatory binder provided by the trial Sponsor. This regulatory binder must be made 
available for possible audits.
13.8 Data Collection
All required data for this trial are to be collected with standardized electronic Case Report 
Forms (eCRF) for individual subjects.  If for any reason an eCRF is unavailable and/or 
inaccessible, a paper CRF will be provided by the trial Sponsor to be completed, signed by 
the Principal Investigatoror designee and submitted to the trial Sponsor.
13.9 Data and Document Retention
Trial-related correspondence, subject records, consent forms, and source documents are to 
be maintained on file by the trial site. The trial Sponsor requires that it be notified in writing 
if the Principal Investigator wishes to relinquish ownership of the data and information so 
that mutually agreed upon arrangements can be made for transfer of ownership to a qualified 
entity.  Records of each subject’s participation in the trial must be maintained for no less 
than a period of two (2) years after trial closure and submission of the final report to the IRB, 
or longer as dictated by local regulations.
13.10 Trial Completion
A final clinical report shall be compiled once data collection is complete. Such reports include 
all information required and outlined in this protocol. The final report will be provided to IRBs 
and other regulatory agencies as per applicable laws. The final clinical report will be filed in 
the trial master file.
13.11  Future Plans
No changes are planned at this time.
14 STATEMENTS OF COMPLIANCE, CONFIDENTIALITY AND RESPONSIBILITIES
14.1 Good Clinical Practice Statement
This trial will be conducted in compliance with all applicable regulations. The protocol and 
supporting documents for this trial will be reviewed and approved by both FDA and an 
appropriately constituted IRB prior to trial initiation. All reviews and approvals will be in 
accordance with Good Clinical Practice (GCP) and all other applicable standards, 
regulations (local and national), guidelines and institutional policies.
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14.1.1 Protection of subject confidentiality
Subject confidentiality will be maintained in accordance with GCP, HIPAA, and all other 
applicable standards, regulations (local and national), guidelines and institutional policies.
14.2 Applicable Regulations and Guidelines
The applicable regulations must be observed to comply with the trial Sponsor’s policy for 
conduct of clinical studies; they represent good clinical practice. It is the responsibility of the 
investigator(s) and the study Sponsor to comply with the requirements set forth in their 
country specific regulations. 
14.3 Investigator Responsibilities
The trial Investigator(s) will adhere to the trial protocol, Good Clinical Practice, HIPAA, and 
compliance with applicable government and institutional regulations. The trial Investigator(s) 
is responsible for obtaining proper regulatory approvals and reporting to regulatory 
authorities per all applicable regulations. 
The Investigator is responsible for ensuring that this clinical trial is conducted according to 
the Clinical Trial Agreement, Protocol, all conditions of regulatory and IRB approval and 
applicable regulations. Written IRB approval of the protocol and consent forms must be 
provided to the Sponsor prior to the enrolment of any subject in the clinical trial at each site. 
The Investigator is responsible for ensuring that informed consent is obtained from all 
subjects prior to any diagnostic tests or treatments that are outside the standard course of 
treatment that would be followed if this subject was not being considered for enrolment in 
this clinical trial.  Periodic reports should be provided to reviewing boards and protocol 
deviations reported per institution’s IRB policy.
Subjects must be informed that their medical records will be subject to review by the 
Sponsor, its authorized designee or regulatory agencies.  Subjects shall be made aware 
that their de-identified data may be made available to the device manufacturer for regulatory 
submission purposes. Subjects will be informed that they are free to refuse participation in 
this clinical trial without loss of benefits to which they are otherwise entitled, and, that if they 
choose to participate, they may withdraw at any time without prejudice to future care.  The 
informed consent will be provided by each site’s IRB and consent must be obtained by the 
subject.  The original signed informed consent for each subject must be retained by the 
Investigator and is subject to review by the Sponsor.  A copy of the informed consent will be 
provided to the subject.
14.4 Sponsor Responsibilities
The trial Sponsor will adhere to the trial protocol, Good Clinical Practice, HIPAA, and 
compliance with applicable government and institutional regulations. The trial Sponsor is 
responsible for obtaining proper regulatory approvals and reporting to regulatory authorities 
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per all applicable regulations. The Sponsor is responsible for ensuring that this trial will be 
conducted in compliance with all applicable local.  The Sponsor will submit progress and 
final reports to FDA and as applicable to overseeing IRBs. 
The Sponsor will provide Investigators with the information and training required to conduct 
the clinical trial properly and in accordance with the Clinical Investigational Plan (protocol) 
and any amendments, if applicable.  The Sponsor must ensure that IRB approval is obtained 
and remains current, and that the reviewing boards are informed of significant new 
information about the clinical trial.  
The Sponsor is responsible for the conduct and administration of this clinical trial. These 
responsibilities include maintaining regular contact with each trial site ensure compliance 
with this Clinical Investigational Plan and verify that data are reported in a timely manner.
15 REFERENCE LIST
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Safian RD, Feldman T, Muller DW, Mason D, Schreiber T, Haik B, et al. Coronary 
angioplasty and Rotablator atherectomy trial (CARAT): immediate and late results of a 
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10. Fujita T; Takeda T, Hano Y, Takashima N, Yamaji M, Sakaguchi T, Maeda K, Mabuchi 
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11. Kwon O, Lee PH, Lee SW, Brilakis ES, Lee JY, Yoon YH, Lee K, Park H, Kang SJ, 
Kim YH, Lee CW, Park SW. Clinical outcomes of post-stent intravascular ultrasound 
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12. Katagiri, Y, De Maria, GL, Kogame, N, et al. Impact of post-procedural minimal stent 
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Li Q, He Y, Chen L, Chen M. Intensive plaque modification with rotational 
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Tang Z, Bai J, Su S-P, et al. Aggressive plaque modification with rotational 
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Ai H, Wang X, Suo M, Liu JC, Wang CG, Zhen L, et al. Acute- and Long-term 
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Furuichi S, Tobaru T, Asano R, Watanabe Y, Takamisawa I, Seki A, et al. 
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Research Consortium-2 Consensus Document. Circulation. 2018 Jun 12;137(24):2635-
2650.
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End Date:2/14/2024