A Multicenter Study to Evaluate NEUWAVE Microwave Ablation System Using Ablation Confirmation in Patients With a Soft Tissue Liver Lesion
Phase: NA
Conditions: Cancer of the Liver, Liver Cancer, Neoplasms, Liver
Sponsor: Ethicon, Inc.

 
 
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A Multicenter Study to Evaluate NEUWAVE Microwave 
Ablation System Using Ablation Confirmation in Patients 
with A Soft-Tissue Liver Lesion 
 
Protocol Number: NEU_2017_03 
 
Document 
Effective Date 
Original (version 1.0) 
06 Jul 2018 
Amendment No. 1 (version 2.0) 
06 May 2019 
Amendment No. 2 (version 3.0) 
09 Apr 2020 
Amendment No. 3 (version 4.0) 
26 July 2021 
 
Sponsor: 
 
 
 
NeuWave Medical, Inc.  
3529 Anderson Street 
Madison, WI 53704 
 
 
 
 
 
 
NeuWave Medical Inc. is a subsidiary of: 
 
 
 
 
 
 
Ethicon, Inc. 
 
 
 
 
 
Route 22 West, P.O. Box 151 
 
 
 
 
 
Somerville, NJ  08876 
 
Name of Finished Product: 
NEUWAVE Microwave Ablation System with Ablation 
Confirmation 
 
 
CONFIDENTIALITY STATEMENT 
The information in this document contains trade secrets and commercial information that are privileged 
or confidential and may not be disclosed unless such disclosure is required by applicable law or 
regulations. In any event, persons to whom the information is disclosed must be informed that the 
information is privileged or confidential and may not be further disclosed by them. These restrictions on 
disclosure will apply equally to all future information supplied to you which is indicated as privileged or 
confidential. 

 
 
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Sponsor Signature  
Protocol Number:   
NEU_2017_03 
Protocol Title:   
A Multicenter Study to Evaluate NEUWAVE Microwave 
Ablation System Using Ablation Confirmation in 
Patients with A Soft-Tissue Liver Lesion 
Protocol Amendment 2 Date: 
26 July 2021 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Signature: 
 
 
 
 
 
 
 
 
 
 
Patricia Schleckser 
Senior Director, Clinical Research 
Ethicon, Inc. 
 
Date 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

 
 
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INVESTIGATOR SIGNATURE 
I have read this protocol and agree to conduct this clinical investigation in accordance with the 
design and specific provisions outlined herein. I understand the protocol, and I understand I 
am solely responsible to ensure the investigation is conducted in accordance with Good 
Clinical Practices (GCP), applicable country regulations, the Declaration of Helsinki, the 
signed clinical study contract with the Sponsor, and with the protocol outlined, herein. I will 
make reasonable effort to complete the study within the time period designated by the 
Sponsor.   
I will provide copies of the protocol and all pertinent information to all individuals responsible 
to me who will assist in the conduct of this study. I will discuss this material with them to ensure 
they are fully informed regarding the device and the conduct of the study.  
I will fulfill the requirements of my Institutional Review Board (IRB)/Ethics Committee (EC), or 
other oversight committee, to ensure complete and continual oversight of this clinical 
investigation. I will use an Informed Consent Document approved by the Sponsor and my 
reviewing IRB/EC.  
I agree to report all information or data in accordance with the protocol and, in particular, I 
agree to report any serious adverse events, device related adverse events, or procedure 
related adverse events as defined in this protocol to the Sponsor, and comply with all adverse 
event reporting requirements of my reviewing IRB/EC. I agree to permit the Sponsor, its 
authorized representatives, my reviewing IRB/EC, and any regulatory authority/body access 
to all records relating to the clinical investigation. 
The below signature confirms I have read and understood this protocol and its associated 
amendments or attachments and will accept respective revisions or amendments provided by 
the Sponsor. 
I agree to comply with all other requirements regarding the obligation of clinical Investigators 
and all other pertinent requirements of the Sponsor and government agencies. 
 
 
 
 
 
_________________________________ 
 
 
 
 
_____________________________________ 
Principal Investigator Signature 
Date 
[Principal Investigator printed name] 
 
Name of the site 
 
Address of the site 
 
City, State  
 
Country 
 
 
PLEASE RETAIN A COPY FOR YOUR STUDY RECORDS 

 
 
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TABLE OF CONTENTS 
 
Page 
1.0 
SYNOPSIS .................................................................................................................. 6 
2.0 
GLOSSARY ............................................................................................................... 12 
3.0 
ETHICS...................................................................................................................... 14 
4.0 
INTRODUCTION ....................................................................................................... 15 
5.0 
STUDY OBJECTIVE .................................................................................................. 17 
5.1 
Primary Endpoints .................................................................................................. 17 
5.2 
Secondary Endpoints ............................................................................................. 17 
5.3 
Additional Measurements / Data Collected ............................................................. 18 
6.0 
INVESTIGATIONAL PLAN ......................................................................................... 19 
6.1 
Overall Study Design and Plan - Description .......................................................... 19 
6.2 
Enrollment .............................................................................................................. 19 
6.3 
Inclusion Criteria .................................................................................................... 19 
6.4 
Exclusion Criteria ................................................................................................... 20 
6.5 
Prior and Concomitant Therapy .............................................................................. 20 
6.6 
Screening Failures ................................................................................................. 20 
6.7 
Removal of Patients from the Study ....................................................................... 20 
7.0 
STUDY PROCEDURES ............................................................................................. 22 
7.1 
Procedure Description(s) ........................................................................................ 22 
7.2 
System Overview(s) ............................................................................................... 24 
7.3 
Study Article Codes and Storage Conditions .......................................................... 24 
8.0 
Visits .......................................................................................................................... 25 
8.1 
Visit 1 – Screening ................................................................................................. 25 
8.2 
Visit 2 – Ablation Procedure ................................................................................... 26 
8.3 
Visit 3: 6 Weeks Follow-up ..................................................................................... 29 
8.4 
Unscheduled Visits ................................................................................................. 30 
9.0 
DATA MANAGEMENT AND INTEGRITY ................................................................... 30 
9.1 
Data Completion and Record Keeping ................................................................... 30 
9.2 
Medical Dictionary Coding ...................................................................................... 32 
9.3 
Data Quality Assurance .......................................................................................... 32 
9.4 
Protocol Deviations ................................................................................................ 33 
10.0 STATISTICAL METHODS AND DETERMINATION OF SAMPLE SIZE ..................... 33 

 
 
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10.1 Statistical and Analytical Plans ............................................................................... 33 
10.2 Study Design .......................................................................................................... 33 
10.3 Treatment Assignment ........................................................................................... 33 
10.4 Interval Windows .................................................................................................... 33 
10.5 Primary Endpoint and Associated Hypotheses ....................................................... 34 
10.6 Levels of Significance ............................................................................................. 34 
10.7 Analysis Sets.......................................................................................................... 34 
10.8 Sample Size Justification ....................................................................................... 34 
10.9 Analyses to be Conducted...................................................................................... 34 
11.0 RISKS AND BENEFITS OF THE STUDY .................................................................. 36 
11.1 Comparison with Other Microwave Ablation Systems ............................................. 36 
11.2 Comparison with Radiofrequency Ablation Systems............................................... 37 
11.3 Comparison of MWA With Liver Resection ............................................................. 37 
12.0 ADVERSE EVENTS................................................................................................... 38 
12.1 Definitions .............................................................................................................. 38 
12.2 Reporting Adverse Events ...................................................................................... 40 
13.0 PRODUCT COMPLAINTS ......................................................................................... 41 
13.1 Product Complaint Definition .................................................................................. 41 
13.2 Reporting Product Complaints ................................................................................ 41 
14.0 PUBLICATION PLAN ................................................................................................. 42 
15.0 APPENDICES ............................................................................................................ 43 
16.0 REFERENCE LIST .................................................................................................... 46 
 
 

 
 
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Procedure 
Description 
Patients who meet the eligibility criteria will undergo MWA of at least 
one soft-tissue liver lesion, in accordance with the study site’s 
standard-of-care (SOC) for MWA.  CT will be used throughout the 
ablation procedure for probe placement and margin assessment. 
Sites must use the AC software to assess optimal probe placement 
and to confirm complete ablation with adequate margins.  
All ablations will be performed percutaneously.  The patient will be 
under general anesthesia or deep conscious sedation, and antibiotics 
administered, if applicable, per SOC.  A patient cannot have more 
than three lesions ablated during the procedure. 
Primary Objective  
The primary objective of this study is to examine whether the 
feedback from the AC software impacts the performing physician’s 
(i.e., the individual performing the ablation procedure) decision 
making in terms of probe(s) position or number of ablations based on 
insufficient ablation margins. 
Primary Endpoints 
• 
Percentage of repositions informed by AC due to sub-optimal 
probe placement. 
• 
Percentage of re-ablations informed by AC due to insufficient 
ablation margins. 
Secondary Endpoints 
• 
Technical success 
• 
Technique efficacy 
• 
Hospital resource utilization  
• 
Device and procedure safety through the monitoring of 
adverse events  
• 
Device User Experience questionnaire 
• 
Patient Quality of Life (QOL) questionnaires 
• 
Patient Numeric Pain Rating Scale (NPRS) questionnaire 

 
 
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Inclusion Criteria 
1. A patient with at least one soft-tissue liver lesion ≤ 5cm 
undergoing MWA using the NEUWAVE Microwave Ablation 
System.  Note:  A patient cannot have more than three lesions 
ablated during the procedure.   
2. Intent to use Ablation Confirmation software (any AC software 
version permitted) during the ablation procedure. 
3. Written informed consent to voluntarily participate in the study, 
follow CT scan schedule, and authorize the transfer of his/her 
data to the Sponsor.  
4. Patients ≥ 22 years old. 
5. Performance status 0-2 (Eastern Cooperative Oncology Group 
classification [ECOG]). 
6. Class A or B Functional hepatic reserve based on the Child-
Pugh score. 
7. Lesion must be visualized by non-contrast enhanced CT scan -
or- the patient must tolerate contrast and meet institutional 
guidelines for contrast use based on glomerular filtration rate 
(GFR). 
Exclusion Criteria 
1. Active bacterial infection or fungal infection on the day of the 
ablation. 
2. Patients with implantable pacemakers or other electronic 
implants. 
3. Platelet count < 50,000/mm3. 
4. Patients with uncorrectable coagulopathy at the time of ablation. 
5. Currently breastfeeding or pregnant (latter confirmed by serum 
or urine pregnancy test, per site’s SOC). 
6. Physical or psychological condition which would impair study 
participation. 
7. ASA (American Society of Anesthesiologists) score of ≥ 4. 
8. Use of hydrodissection. 
9. Systemic chemotherapy or radiation therapy for the liver, within 
30 days prior to the study ablation procedure. 
10. INR > 1.8. 
11. Patient has participated in an investigational clinical study within 
30 days of the screening visit for this study. 
12. Patient judged unsuitable for study participation by the 
performing physician for any other reason. 
Safety Assessments 
Patients will be evaluated for device-related or procedure-related 
AEs and all SAEs from the time of first probe puncture (Visit 2) 
through study completion (Visit 3).  
Statistical Analysis  
Categorical 
variables 
will 
be 
summarized 
descriptively 
by 
frequencies and associated percentages. Continuous variables will 
be summarized descriptively by number of patients, mean, standard 

 
 
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deviation, median, minimum, and maximum. Confidence intervals will 
also be provided for procedure-related variables.  
The number and percentage of patients requiring probe repositions 
based on AC prior to the initial ablation will be summarized and a 
95% confidence interval for the percentage will be provided. The 
number and percentage of patients in whom AC indicates repeat 
ablation is indicated based on insufficient margins following the initial 
ablation procedure will be summarized in a similar manner.  
The number and percentage of patients experiencing device-related 
or procedure-related AEs and any SAEs will be summarized at the 
preferred term level. 
Interim Analysis 
There are no plans for interim analyses whose intent will be to stop 
the study early or to adapt the study design or planned number of 
patients.  
Schedule of Activities See Table 1 on the next page. 

 
 
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Abbreviations:  NA = not applicable; Unsched. = Unscheduled Visit. See Glossary on page following notes, below, for all other acronyms and abbreviations. 
Notes: 
1. 
Medical, surgical, and radiation history, including date of diagnosis of soft-tissue lesion under study, hepatitis type and status, smoking status, and biliary manipulation. 
2. 
Liver tissue assessment, if available: categorization of the following; steatosis (mild, moderate, severe); cirrhosis (mild, moderate, severe); microsatellite instability and vascular 
invasion..  
3. 
INR is required but other tests performed, if applicable, per site SOC:  Coagulation tests, including APTT or PTT, PT, and PTA. 
4. 
If applicable, per site SOC:  Liver function tests, including ALB, ALK, ALT, AST, T/D bilirubin, GGT, and TP. 
5. 
If applicable, per site SOC:  Renal function tests, including BUN, creatinine, and electrolytes (sodium, potassium, chloride, and bicarbonate). 
6. 
Complete blood count (CBC) with differential (RBCs, WBCs, platelets, hemoglobin, hematocrit, neutrophils, etc.). 
7. 
Serum or urine pregnancy test for women of childbearing potential only, per SOC. 
8. 
Record all relevant prior medications taken within 30 days prior to Visit 2 and all relevant concomitant medications (i.e., blood-thinning/coagulation, NSAIDs, steroids, 
medications used to treat AEs, and medications used to treat hepatitis, if concurrently treating).  
9. 
Quality of Life questionnaires: EORTC QLQ-C30 and the liver-specific QLQ-HCC18. Questionnaires may be administered up to 72 hours prior to the ablation procedure (Day 0) 
and may be administered over the phone, when needed. 
10. Ultrasound or MRI may be used with or without CT for all screening and post-ablation imaging as per site SOC.    All scans should be sent to Sponsor. 
11. CT must be used for the ‘pre, during, and post ablation’ imaging.  If CT was used with contrast, the physician must record the amount of contrast used.  All scans should be sent 
to Sponsor. 
12. Intended ablation treatment plan details include the probe(s) planned to be used, liver segment(s), max power planned, and total ablation time planned. 
13. After the patient is sedated under general anesthesia or deep conscious sedation, and administered antibiotics, if applicable, per site SOC, the performing physician will follow 
the steps outlined in Section 8.2.  
14. Ablation procedure details include, but not limited to, the following: date and time of procedure; version of AC software; anatomical location of ablations; liver stiffness near 
ablation site (if available); number of ablation cycles, including time, maximum temperature and maximum power used for each ablation cycle per probe; guidance method used; 
number of CT scans performed for probe placement and margin assessment; tissue contraction percentage; number of probe placement attempts per ablation; number and type 
of probe(s) used; the amount of contrast used (if applicable); type of anesthesia; and duration of procedure (first probe placement to last probe removal). Total radiation 
exposure will also be captured from the CT scanner and recorded in the clinical database. Some of the above ablation procedure details will be provided to the site via a report 
generated from NeuWave Medical’s Call Home Database. The study site will review the report and enter the procedure details into the clinical database, as applicable.  
15. Device user experience, to be completed by the performing physician via the AC User Evaluation Questionnaire: the first half following each ablation procedure, and the second 
half following approximately every 5 ablations, per treating physician. 
16. Hospital resource utilization: length of post-ablation hospital stay and time to perform procedure, which includes 3 measures of time: (1) Overall procedure duration, defined as 
the time elapsed between loading CT dataset into the AC system and completion of MWA with probe removal; (2) AC imaging duration, defined as the time elapsed between 
loading CT dataset into AC to plan for the target ablation and last use of AC to plan for the final ablation, and (3) Ablation duration, defined as the time elapsed between first 
ablation probe puncture and removal of the last probe at the completion of the ablation. 
17. Follow-up post-ablation treatment, if applicable, including: If patient has been hospitalized since the initial ablation procedure. 
18. Record reason for unscheduled visit, as well as applicable AEs/SAEs updates to the relevant concomitant medications and/or liver-related concomitant procedures, if applicable. 
19. When applicable, the Screening Visit may occur on the same day as the Ablation Day (Visit 2). 
20. All post-ablation activities should occur prior to subject discharge from the institution.

 
 
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2.0  GLOSSARY 
Table 2. Acronyms/Abbreviations 
Acronyms/ 
Abbreviations 
Terms 
AC 
Ablation Confirmation 
AE 
Adverse Event 
AFP 
Alpha-Fetoprotein 
ALB 
Albumin Concentration 
ALBI 
Albumin-Bilirubin 
ALK 
Alkaline Phosphatase 
ALT 
Alanine Aminotransferase 
APTT 
Activated Partial Thromboplastin Time 
ASA 
American Society of Anesthesiologists 
AST 
Aspartate Aminotransferase 
BMI 
Body Mass Index 
BUN 
Blood Urea Nitrogen 
CBC 
Complete Blood Count 
CEA 
Carcinoembryonic Antigen 
CFR 
Code of Federal Regulations 
CT 
Computed Tomography 
CTC 
Common Terminology Criteria 
DMC 
Data Monitoring Committee 
EC 
Ethics Committee 
ECOG 
Eastern Cooperative Oncology Group 
eCRF 
Electronic Case Report Form 
EDC 
Electronic Data Capture 
EORTC 
European Organization for Research and Treatment of Cancer 
GCP 
Good Clinical Practices 
GFR 
Glomerular Filtration Rate 
GGT 
Gamma-Glutamyl Transpeptidase 
HCC 
Hepatocellular Carcinoma 
HCPs 
Healthcare Professionals 
HGB/HCT 
Hemoglobin/Hematocrit 
HIPAA 
Health Insurance Portability and Accountability Act of 1996 
HPB 
Hepatobiliary 

 
 
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Acronyms/ 
Abbreviations 
Terms 
ICF  
Informed Consent Form 
ID 
Identification 
IFU 
Instructions for Use 
INR 
International Normalized Ratio 
IR 
Interventional Radiologist 
IRB 
Institutional Review Board 
MDR 
Medical Device Problem Report 
MDVR 
Medical Device Vigilance Report 
MedDRA 
Medical Dictionary for Regulatory Activities 
MRI 
Magnetic Resonance Imaging 
MWA 
Microwave Ablation 
NPRS 
Numeric Pain Rating Scale 
NSAIDs 
Non-Steroidal Anti-Inflammatory Drugs 
PACS 
Picture Archiving and Communication Systems 
PDM 
Power Distribution Module 
PI 
Principal Investigator 
PT 
Prothrombin Time 
PTA 
Plasma Thromboplastin Antecedent 
PTT 
Partial Prothrombin Time 
QLQ 
Quality-of-Life Questionnaire 
QOL 
Quality-of-Life 
RBC 
Red Blood Cells 
RFA 
Radiofrequency Ablation 
ROW 
Rest of World 
SAE 
Serious Adverse Event 
SOC 
Standard-of-Care 
T/D/I 
Total/Direct/Indirect (bilirubin) 
TP 
Total Protein 
US 
Ultrasound 
VOC 
Voice-of-the-Customer 
WBC 
White Blood Cells 
 
 

 
 
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3.0  ETHICS 
Institutional Review Board/Ethics Committee 
Participating Investigators will ensure that this protocol, Informed Consent Form (ICF), and if 
applicable, any protocol amendments or other written information provided to the subjects that 
assist in the decision to participate are reviewed by an Institutional Review Board (IRB) or 
Ethics Committee (EC) that complies with governmental requirements. The approving IRB/EC 
will be responsible for the initial and continuing review and approval of this clinical 
investigation. Participating Investigators will be required to promptly report to the IRB/EC as 
required by the IRB/EC’s policies.  
Applicable Regulations  
This study will be conducted in compliance with Good Clinical Practice and in accordance with 
the Declaration of Helsinki, as well as any other applicable local and country regulatory 
requirements. 
Subject Information and Consent  
Regulations concerning the protection of subjects require that informed consent be obtained 
before a subject may participate in any clinical investigation. 
An IRB/EC approved informed consent must be sought from each subject and must be 
appropriately documented in the subject’s medical record prior to initiating the study. It is the 
Investigator’s responsibility to obtain written informed consent from the subject, however, the 
Investigator may delegate this responsibility, if appropriately documented.  
The informed consent process involves the following: giving a subject adequate information 
concerning the study, providing adequate time for the subject to consider all available options, 
responding to the subject’s questions, ensuring that the subject has comprehended this 
information and finally, obtaining the subject’s written consent to participate in this study. All 
subjects in this study should be completely informed about the purpose, risks, benefits, and 
other pertinent details of this study. The informed consent process is careful to avoid the 
perception of any coercion or undue influence on, or inducement of, the subject to participate, 
and does not waive or appear to waive the subject's legal rights. The ICF is presented in 
native, non-technical language that is understandable to the subject. 
Prior to a subject’s participation in this study, an ICF will be signed and dated by the subject 
and person who conducted the consent discussion. The subject will be provided a copy of the 
signed ICF. The ICF and any other written materials provided to the subject to assist in the 
decision to participate must be revised whenever new information becomes available that may 
be relevant to their willingness to participate or continue participation in this study. Revision to 
the ICF and other written materials will receive IRB/EC approval before implementation. Each 
subject will be required to sign any amended ICF (as required by the IRB/EC) and will receive 
a copy of the signed ICF.  
 
 
 

 
 
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Administrative Requirements 
This study is sponsored by NeuWave Medical and will be conducted in approximately 10 study 
sites in the United States and Europe under a single protocol approved by each participating 
site’s IRB/EC prior to implementation. The Principal Investigator (PI) at each study site must 
be qualified by education and experience to perform the study procedure and to assume 
responsibility for the conduct of this study. 
The Data Management and Biostatistics groups of NeuWave Medical will be responsible for 
the analysis of data from this protocol. An electronic data capture (EDC) system will be utilized 
by study site personnel to transfer study data from source records (the first point of clinical 
data capture) onto common electronic case report forms (eCRFs). This system is a web-
based, secure electronic software application (Medidata® Rave, 350 Hudson Street, 9th Floor, 
New York, New York, 10014). This system was designed and is developed and maintained by 
Medidata in a manner that is compliant with national and international Good Clinical Practice 
(GCP) data protection/data privacy and electronic record/electronic signature (e.g., 21 CFR 
Part 11) regulatory requirements.  
Protocol Modifications 
All protocol amendments must be issued by the Sponsor, signed and dated by the Investigator, 
and should not be implemented without prior IRB/EC approval, except where necessary to 
eliminate immediate hazards to the subjects or when the change(s) involves only logistical or 
administrative aspects of the study (e.g., change in monitor, change of telephone number). 
The Investigator will report the protocol amendments to the IRB/EC as per their local 
requirements. 
 
4.0 INTRODUCTION 
Treatment of liver lesions is challenging, with high complication and recurrence rates. Surgery 
is the gold standard, but many patients are not surgical candidates because of comorbidities, 
or the location and nature of the lesions. Thermal ablation has been growing as a treatment 
option because of its minimally invasive nature, low cost, positive outcomes, and low 
complication rates. While outcomes are generally good, the rates of successful removal of 
lesions do not yet approach those of surgical resection and can also be highly variable 
depending on the experience of the interventional radiologist (IR) and the ablation technology 
used. Voice-of-the-Customer (VOC) research sponsored by NeuWave Medical indicated that 
physicians believe that more than half of recurrence in hepatobiliary (HPB) ablation is due to 
incorrect placement of the probes, inability to determine treatment margins, and other limits of 
the technology.  
NeuWave Medical developed Ablation Confirmation (AC) software to help overcome some of 
these inherent limitations. Specifically, AC helps the physician: 

 
 
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• 
Lock the Target: Define / lock the target volume for improved probe placement 
accuracy and margin analysis. 
• 
Evaluate Probe Placement: See the exact proximity of the probe to the target by 
viewing combined target and probe placement scans. 
• 
Confirm Technical Success: Verify technical success of the procedure by viewing 
combined target and ablation margin scans. 
• 
Demonstrate Your Success: Procedure images stored to PACS (picture archiving and 
communication systems) and can be shared to showcase procedure success. 
Ablation Confirmation is a computed tomography (CT) image processing software package 
available as an optional feature for use with NEUWAVE Microwave Ablation System. The 
NEUWAVE Microwave Ablation System is a general-purpose thermal ablation tool used by 
physicians to ablate soft-tissue lesions in a wide variety of tissue and disease states. The 
NEUWAVE Microwave Ablation System has been cleared by the United States Food and Drug 
Administration (FDA) and has been in clinical use since 2011 in the United States. The most 
common applications by clinicians have been the ablation of liver, kidney, and lung lesions. 
Additional, but less common uses have been the ablation of soft-tissue lesions in bone and 
nerve ablation. 
AC is controlled by the user via an independent user interface on a second monitor, which is 
separate from the Ablation System user interface for the ablation procedure. AC imports 
images from CT scanners and facility PACS for display and processing during ablation 
procedures. AC assists physicians in identifying ablation targets, assessing proper ablation 
probe placement, and confirming the adequacy of the ablation margin, as defined by the 
performing physician. AC is not intended for diagnosis. AC is an accessory to the NEUWAVE 
Microwave Ablation System and is not available for sale independently. In this study, the 
NEUWAVE Microwave Ablation System is used only with NEUWAVE Ablation Probes. 
Two types of ablation are primarily used in the liver: radiofrequency ablation (RFA) and MWA. 
Microwave has many advantages over RFA. For example, it does not use conduction to heat 
tissue, rather directly heats the diseased tissue leading to more uniform heating while also 
creating a larger ablation margin around a lesion. MWA also does not use grounding pads, 
which can cause burns on the areas of attachment. Lastly, MWA has faster heating at higher 
temperatures, thereby offering improved performance in tumor necrosis.1  
The NEUWAVE Microwave Ablation System is contraindicated for: 
• 
Use in cardiac procedures. 
• 
Pregnant patients – potential risks to patient and/or fetus have not been established. 
• 
Patients with implantable pacemakers or other electronic implants. Implanted 
electronic devices may be adversely affected by microwave power.  
• 
Use on the central nervous system. 
• 
Endometrial applications. 
All known hazards associated with the use of the NEUWAVE Microwave Ablation System 
have been identified and appropriately mitigated. Design considerations were taken to reduce 
the risks associated with existing MWA systems, including improved system usability and 
cable management.  
The NEUWAVE Microwave Ablation System uses a CO2 cooling system where all other 
microwave systems use sterile water. The risks associated with this cooling system do not 

 
 
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differ from the risks inherent in cryogenic ablation systems, which are widely accepted in 
clinical use. Thus, the NEUWAVE Microwave Ablation System does not introduce new 
hazards or intended uses. 
The information provided by the User Manual and Instructions for Use (IFU) describe the use, 
risks, and benefits of the devices. The risk/benefit profile of the NEUWAVE Microwave 
Ablation System is acceptable for the intended use of the ablation/coagulation of soft-tissue 
relative to other medical alternatives. 
The FDA cleared AC for use in 2015. To date, no adverse complications have been reported 
that were deemed related to AC.  
This is a prospective, single-arm, multicenter study that will generate clinical data using the 
NEUWAVE Microwave Ablation System with Ablation Confirmation in patients undergoing 
microwave ablation (MWA) of a soft-tissue liver lesion. Although all Investigators in this study 
have experience using AC, this is the first clinical study assessing how AC impacts the way 
interventional radiologists perform the ablation.  
 
5.0 STUDY OBJECTIVE 
The primary objective of this study is to examine whether the feedback from the AC software 
impacts the performing physician’s (i.e., the individual performing the ablation procedure) 
decision making in terms of probe(s) position or number of ablations based on insufficient 
ablation margins. 
5.1 Primary Endpoints 
The primary endpoints supporting the study objective are, as follows: 
• 
Percentage of repositions informed by AC due to sub-optimal probe placement. 
• 
Percentage of re-ablations informed by AC due to insufficient ablation margins. 
5.2 Secondary Endpoints 
The secondary endpoints are, as follows:  
• 
Technical success - defined as ablation of the target lesion(s) according to the protocol 
and covered completely with an adequate margin, as defined by the performing 
physician (that is, the ablation zone completely overlaps or encompasses the target 
lesion plus an adequate ablative margin). Technical success will be assessed by the 
performing physician using AC as a tool immediately following the procedure.  
• 
Technique efficacy - defined as ablation of the target lesion(s) according to the protocol 
and covered completely, with an adequate margin, as defined by the performing 
physician (that is, the ablation zone completely overlaps or encompasses the target 
lesion plus an ablative margin), as assessed by imaging at Visit 3. 
• 
Hospital resource utilization based on: 
o Length of post-ablation hospital stay. 
o Time to perform procedure, which includes 3 measures of time: 
• Overall procedure duration, defined as the time elapsed between 
loading CT dataset into the AC system and completion of MWA with last 
probe removal.  

 
 
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• AC imaging duration, defined as the time elapsed between loading CT 
dataset into AC to plan for the target ablation and last use of AC to plan 
for the final ablation. 
• Ablation duration, defined as the time elapsed between ablation first 
probe puncture and removal of the last probe at the completion of the 
ablation. 
• 
Device and procedure safety through the monitoring of adverse events.  Patients will 
be evaluated for all device-related and procedure-related AEs and all SAEs from the 
time of the first probe puncture (Visit 2) through study completion (Visit 3).  
• 
Device User Experience questionnaire (Appendix 2) will be completed by the 
performing physician.  The first half will be completed following each ablation 
procedure and the second half will be completed approximately every 5 ablations (per 
treating physician). 
• 
Patient Quality of Life (QOL) questionnaires as measured by EORTC QLQ-C30 and 
the liver-specific QLQ-HCC18, at Visit 2 (Pre-Ablation) and at Visit 3 (6 weeks post-
ablation). 
• 
Patient Numeric Pain Rating Scale (NPRS) questionnaire at Visit 2 (Pre- and Post-
Ablation) and at Visit 3 (6 weeks post-ablation). 
5.3  Additional Measurements / Data Collected 
• 
Patient demographics. 
• 
Relevant medical, surgical, and radiation history, including date of diagnosis of soft-
tissue lesion under study, hepatitis type and status, smoking status, and biliary 
manipulation. 
• 
Body mass index (BMI), ECOG performance, Child-Pugh score, and ASA score. 
• 
Length of hospital stay (time of admission to post-ablation observation through 
discharge). 
• 
Lesion details (size of the lesion, lesion type, location, and shape).  
• 
Ablation procedure details include the following:  
1. Date and time of procedure. 
2. Version of AC software used. 
3. Anatomical location of ablation(s). 
4. Liver stiffness near ablation site, if available. 
5. Number of ablation cycles, including time, and maximum temperature and 
maximum power used for each ablation cycle per probe.  
6. Guidance method used (ultrasound, CT, or MRI). 
7. Number of CT images performed for probe placement and margin 
assessment. 
8. Tissue contraction percentage selected. 
9. Number of probe placement attempts per ablation. 
10. Number and type of probe(s) used. 

 
 
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11. Amount of contrast used, if applicable. 
12. Type of anesthesia. 
13. Duration of procedure (first probe placement to last probe removal). 
14. Total radiation exposure from the CT scanner. 
Note: Some of the above ablation procedure details will be provided to the site via a report 
generated from NeuWave Medical’s Call Home Database. The study site will review the 
report and enter the procedure details into the clinical database, as applicable. 
 
6.0 INVESTIGATIONAL PLAN 
6.1  Overall Study Design and Plan - Description 
This is a prospective, single-arm, multicenter study that will generate clinical data using 
the NEUWAVE Microwave Ablation System with Ablation Confirmation Software in 
patients undergoing MWA of at least one soft-tissue liver lesion.  Note:  A patient cannot 
have more than three lesions ablated during the procedure. 
6.2  Enrollment 
A minimum of 100 patients will be enrolled in approximately 10 sites, initially in the United 
States and later ROW.  A patient will be considered enrolled upon signing the ICF. 
Enrollment will continue until at least 100 eligible patients have been treated with 
Neuwave MWA and have used the AC software.  
6.3  Inclusion Criteria 
Patients satisfying the following criteria will be eligible to participate in this study: 
1. 
A patient with at least one soft-tissue liver lesion ≤ 5cm undergoing MWA 
using the NEUWAVE Microwave Ablation System.  Note:  A patient cannot 
have more than three lesions ablated during the procedure.   
2. 
Intent to use Ablation Confirmation software (any AC software version 
permitted) during the ablation procedure. 
3. 
Written informed consent to voluntarily participate in the study, follow CT 
scan schedule, and authorize the transfer of his/her data to the Sponsor.  
4. 
Patients ≥ 22 years old. 
5. 
Performance status 0-2 (Eastern Cooperative Oncology Group classification 
[ECOG]). 
6. 
Class A or B functional hepatic reserve based on the Child-Pugh score. 
7. 
Lesion must be visualized by non-contrast enhanced CT scan -or- the patient 
must tolerate contrast and meet institutional guidelines for contrast use 
based on glomerular filtration rate (GFR).

 
 
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6.4  Exclusion Criteria 
Patients who meet any of the following criteria will not be eligible to participate in this 
study: 
1. 
Active bacterial infection or fungal infection on the day of the ablation. 
2. 
Patients with implantable pacemakers or other electronic implants. 
3. 
Platelet count < 50,000/mm3. 
4. 
Patients with uncorrectable coagulopathy at the time of ablation. 
5. 
Currently breastfeeding or pregnant (latter confirmed by serum pregnancy 
test). 
6. 
Physical or psychological condition which would impair study participation. 
7. 
ASA (American Society of Anesthesiologists) score of ≥ 4. 
8. 
Use of hydrodissection. 
9. 
Systemic chemotherapy or radiation therapy for the liver, within 30 days prior 
to the study ablation procedure. 
10. INR > 1.8. 
11. Patient has participated in an investigational clinical study within 30 days of 
the screening visit for this study. 
12. Patient judged unsuitable for study participation by the performing physician 
for any other reason. 
6.5  Prior and Concomitant Therapy 
Excluding systemic chemotherapy or radiation therapy for the liver (up to 30 days prior to 
procedure), patients may continue with their current medical care throughout the duration 
of the study, including medications. All relevant prior and concomitant medications (i.e., 
blood-thinning/coagulation, NSAIDs, steroids, medications used to treat AEs, and 
medications used to treat hepatitis, if concurrently treating) taken within 30 days of Visit 
2 through study completion will be recorded on the Concomitant Medication eCRF page. 
6.6  Screening Failures 
All patients signing consent who do not meet the inclusion and exclusion criteria or who 
do not have the ablation procedure initiated will be recorded as screen failures and the 
reason will be captured on the Inclusion/Exclusion Criteria eCRF, if applicable. In addition, 
the Demographics and Subject Completion/Discontinuation eCRF pages will also be 
completed for all screen failures. 
6.7  Removal of Patients from the Study 
In accordance with the current revision of the Declaration of Helsinki and the Code of 
Federal Regulations, a patient has the right to withdraw from the study at any time for any 
reason without prejudice to his/her future medical care by the physician or the institution. 
Should a patient (or patient’s legally authorized guardian/representative) decide to 
withdraw from the study; all efforts will be made to collect any applicable AEs 
experienced, if applicable, and as defined by this protocol.  

 
 
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Withdrawal of Consent 
If a patient chooses to withdraw early from the study, the patient should contact the study 
site, which will then complete the Subject Completion /Discontinuation eCRF page. When 
a patient’s participation is terminated prior to completing the study, the reason for 
withdrawal is to be documented on the Subject Completion/Discontinuation eCRF and in 
the source documentation.  
Ablation 
The Investigator may withdraw a patient during the ablation procedure for any safety 
reason, including, but not limited to, the following reasons: 
• 
Inability of Investigator to locate and target the lesion. 
• 
Inability of patient to tolerate the anesthesia or deep conscious sedation. 
Note:  If a patient experiences a device-related or procedure-related AE or any SAE 
during probe puncture and is not ablated, this patient should be followed until AE/SAE 
resolution.  If no AE/SAE occurred during probe puncture and the patient could not be 
ablated, the patient should be discontinued. 
 
Death 
When available, the cause of death should be reported via the AE eCRF, per the safety 
reporting timelines in Section 12.0. The Subject Completion/Discontinuation eCRF also 
must be completed. 
Lost to follow-up 
All patients should be encouraged to return for protocol required clinic visits for evaluation 
during the study follow-up period. If a patient is unable to return for a clinic visit or unable 
to be contacted by telephone, attempts to contact the patient should be documented in 
the source documents. Only after failing to contact the patient at the final follow-up visit, 
the patient will be considered lost to follow-up and the primary reason for early termination 
will be completed in the Subject Completion/Discontinuation eCRF. 
Site Termination or Study Termination: 
The Sponsor may terminate a site or the study at any time. When this occurs all patients 
at the site will be withdrawn and documented as early termination. Reasons for site or 
study termination may include, but are not limited, to the following:  
• 
Administrative 
concerns 
(e.g., 
inadequate 
patient 
enrollment, 
Investigator/institution non-compliance, change of business strategy, etc.). 
• 
Safety issues, including reaching any of the complication thresholds, including 
those due to non-compliance, which substantially affect the risk-to-benefit ratio of 
the study patients at a site or for the study as a whole. 
• 
Regulatory body mandates. 
The Investigator also has the right to terminate subject or site participation at any time 
(e.g., for safety reasons or inability to enroll patients). Should termination of a site be 
necessary, the Sponsor will provide procedures for termination. 
 
 

 
 
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7.0  STUDY PROCEDURES 
7.1  Procedure Description(s) 
A multi-disciplinary team at the site will determine, with the help of imaging, whether a 
patient is suitable for ablation of soft-tissue liver lesion. Potential candidates for MWA will 
undergo tests for complete blood count (CBC) with differential.  Test for coagulation, liver 
function, renal function, and alpha-fetoprotein (AFP), will be collected if applicable, per 
SOC. 
Microwave Ablation Procedure 
MWA is a minimally invasive procedure that uses electromagnetic waves to generate 
tissue necrosis. The ablation will be performed with a single high-powered, gas-cooled 
microwave system. This NEUWAVE Microwave Ablation System with Ablation 
Confirmation Software is a CT image processing software package (see Section 7.2 
System Overview for a complete description.) Electromagnetic waves will be delivered to 
the tissue, producing frictional heating to generate tissue necrosis at > 60C.   
In this study, only patients who meet the eligibility criteria will undergo MWA of at least 
one soft-tissue liver lesion utilizing AC, in accordance with the study site’s SOC for MWA.  
A patient cannot have more than three lesions ablated during the procedure.  
To plan the ablation, the performing physician will collect the soft-tissue lesion details: 
e.g., size, lesion type, location, shape.  The patient will be under general anesthesia or 
deep conscious sedation during the procedure, per the site’s SOC.  Using CT and, if 
needed, ultrasound (US) or MRI imaging guidance, the treating physician will insert a 
small probe percutaneously into the lesion.  
CT will be used throughout the ablation procedure for probe placement and margin 
assessment. Sites must use AC to assess optimal probe placement and confirm complete 
ablation with adequate margin.  AC also provides the ability to capture images from the 
NEUWAVE monitor via the “snapshot” feature.  The physician should use snapshots to 
document each key step of the procedure as outlined, below, if the Call Home Imaging 
feature is turned on, though this is not a requirement. 
The physician will perform the ablation per the device’s Instructions for Use (IFU) and the 
performing physician’s clinical judgment.  Duration of procedure and power application 
will be determined by the performing physician based on manufacturer guidelines, with 
adjustment for lesion size, proximity to vulnerable structures, and real-time 
intraprocedural CT scan monitoring. It is suggested that the physician considers using 
more than one probe for lesions ≥ 2cm. 
Steps to Follow During Ablation 
The performing physician will follow the steps listed below:  
• 
Use CT, ultrasound, or MRI to collect the lesion details: e.g., lesion type, 
location, shape, size. If unable to accurately visualize the lesion(s) with non-
contrast enhanced CT, ultrasound, or MRI, the patient must tolerate contrast 
and meet institutional guidelines for contrast used based on glomerular filtration 
rate (GFR).   A CT image is required to define the target with AC. The final 
visualization of the target lesion should be documented using the AC snapshot 
feature to capture the contents of the imaging panels. 
• 
Develop a treatment plan to perform the MWA of the patient’s liver lesion(s) and 

 
 
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capture the details of the treatment plan (probe(s) planned to be used, liver 
segment(s), max power planned, and total ablation time planned) in the study 
database.   
• 
Place probe(s) in target lesion(s). 
• 
Take CT to assess probe placement; repeat as needed. Ultrasound may be 
used in addition to CT. 
• 
Assess if the probe(s) has been optimally placed based on CT interpretation 
alone. 
• 
Use AC to validate probe(s) placement.  Document the visualization of the probe 
location(s) using the AC snapshot feature to capture the contents of the imaging 
panels. 
• 
Reposition, add, or remove probe(s), as needed, based on AC software 
feedback. Repeat as needed. 
• 
Capture changes made to the placement and sequence of the probe(s) as a 
result of AC feedback, if any, in the clinical database.  Document the 
visualization of the final probe location(s) using the AC snapshot feature to 
capture the contents of the imaging panels. 
• 
Once the performing physician is satisfied with the accuracy of the probe(s) 
placement on the target lesion, ablation of the lesion may begin until deemed to 
be complete with adequate margins, as defined by the performing physician. 
• 
Take CT following the ablation procedure and assess if ablation has been 
successfully completed with adequate margins.  
• 
Use AC to confirm complete ablation with adequate margins.  Document the 
visualization of the ablation result using the AC snapshot feature to capture the 
contents of the imaging panels. 
• 
Take action as per AC software for margin assessment (e.g., ablate for more 
time, add probe(s), remove probe[s]) if a complete ablation was not achieved.  
• 
Capture actions, if any, taken to achieve complete ablation based on AC 
software, and enter these actions taken into the clinical database.  Document 
the visualization of the final ablation result using the AC snapshot feature to 
capture the contents of the imaging panels. 
• 
Use AC software and CT imaging to measure the smallest margin diameter 
within the ablation zone as well as the smallest diameter of the entire ablation 
zone. 
All recommendations made by the AC software should be captured in the clinical 
database.  If the performing physician does not follow the AC software recommendation, 
a reason why they did not follow the AC recommendation should be noted.  Not following 
the AC recommendation itself is not a protocol deviation.   
Submitting Scans to the Sponsor 
AC requires a minimum of 3 CT scans taken on the day of ablation, at least one scan 
taken at each of the following 3 timepoints: (1) at baseline/pre-ablation; (2) after final 
probe placement and immediately before ablation; and, (3) after completion of ablation.  

 
 
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The user should also document the AC visualization of procedure steps and decision 
making as outlined, above.   
All required CT scans taken on the day of ablation should be submitted to the Sponsor. 
The scans will allow the Sponsor to potentially improve the software algorithm. 
Total Radiation Exposure  
At all follow-up visits, the physician will use CT or MRI scans to collect the lesion details: 
e.g., size, lesion type, location, shape. The total radiation exposure for each patient will 
be dependent on the number of CT images taken per patient, as well as many other 
factors such as the manufacturer of the scanning equipment. The total radiation exposure 
from the CT scanner on the day of ablation will be captured in the clinical database. 
Ablation Success 
Ablation success will be classified as: 
• 
Technical success, defined as ablation of the target lesion(s) according to the 
protocol and covered completely with an adequate margin, as defined by the 
performing physician (that is, the ablation zone completely overlaps or 
encompasses the target lesion plus an adequate ablative margin). Technical 
success will be assessed by the performing physician using AC as a tool, 
immediately following the procedure. 
• 
Technical failure, defined as ablation of the target lesion(s) with an inadequate 
margin, as defined by the performing physician (that is, the ablation zone does not 
completely overlap or encompasses the target lesion plus an adequate ablative 
margin). This is assessed by the performing physician using AC as a tool, 
immediately following the procedure.  
7.2  System Overview(s) 
Ablation Confirmation Software is a CT image processing software package available as 
an optional feature for use with NEUWAVE Ablation System. NEUWAVE Microwave 
Ablation System is a general-purpose thermal ablation tool used by physicians to ablate 
soft-tissue lesions. In this study, the NEUWAVE Microwave Ablation System is used with 
NEUWAVE Ablation Probes. 
AC software is controlled by the user via an independent user interface on a second 
monitor, which is separate from the user interface for the ablation procedure. AC imports 
images from CT scanners and facility PACS for display and processing during ablation 
procedures. AC assists physicians in identifying ablation targets, assessing proper 
ablation probe placement, and confirming the adequacy of the ablation margin, as defined 
by the performing physician.  AC also provides the ability to capture images from the 
NEUWAVE monitor via the “snapshot” feature.  The physician should use snapshots to 
document each key step of the procedure. 
Refer to the NEUWAVE Microwave Ablation System accompanying documents for a list 
of Warnings and Cautions. 
7.3  Study Article Codes and Storage Conditions 
Study product:  NEUWAVE Microwave Ablation System with Ablation Confirmation 
Software: 

 
 
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participate in the study.  
• CT, MRI, or Ultrasound may be used for screening. If the scan, based on SOC, 
was done within 60 days prior to the day of ablation, it does not need to be 
repeated at the screening visit. Send the scans to the Study Sponsor. 
• Laboratory tests: If these tests, based on site SOC, were completed within 60 
days of Visit 2, they do not need to be repeated at the screening visit.  
a. Coagulation tests, including activated partial thromboplastin time 
(APTT) or partial thromboplastin time (PTT), prothrombin time (PT), and 
plasma thromboplastin antecedent (PTA) may be collected, as 
applicable, per site SOC, but international normalized ratio (INR) is 
required. 
b. If applicable, per site SOC, liver function tests, including albumin (ALB), 
alkaline phosphatase (ALK), alanine aminotransferase (ALT), aspartate 
aminotransferase (AST), bilirubin (direct and total), gamma-glutamyl 
transpeptidase (GGT), and total protein (TP).  
c. If applicable, per site SOC, renal function tests include BUN, creatinine, 
and electrolytes (sodium, potassium, chloride, and bicarbonate). 
d. Complete blood count, with differential (RBCs, WBCs, platelets, 
hemoglobin, hematocrit, neutrophils, etc.). 
e. Alpha-fetoprotein, which serves as a tumor marker (tumor markers are 
molecules in the blood that are higher when a person has certain 
cancers), as per SOC. 
f. Carcinoembryonic antigen (CEA), as per SOC. 
g. Serum or urine pregnancy test, per site SOC, for women of childbearing 
potential only. 
8.2  Visit 2 – Ablation Procedure  
The following procedures will be done before the ablation procedure: 
• Evaluate ECOG performance status. 
• 
QOL questionnaires: EORTC QLQ-C30 and the liver-specific QLQ-HCC18. 
• 
Pain score, using the Numeric Pain Rating Scale. 
• Record any new relevant concomitant medications or changes to existing 
relevant concomitant medications (i.e., blood-thinning/coagulation, NSAIDs, 
steroids, and medications used to treat hepatitis, if concurrently treating). 
• Record any new liver-related concomitant procedures. 
• Confirm that the patient still meets inclusion and exclusion criteria (tests not 
needed to be repeated). 
• Serum urine pregnancy test, per site SOC, for women of childbearing potential 
only. 
• Complete blood count, with differential (RBCs, WBCs, platelets, hemoglobin, 
hematocrit, neutrophils, etc.).Use CT to collect lesion details: e.g., size of lesion, 
lesion type, location, shape. If unable to accurately visualize the lesion with non-

 
 
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contrast enhanced CT, contrast enhanced CT must be used.   Note:  the 
Screening Visit CT and Visit 2 CT may occur on the same date if the patient was 
screened and treated on the same day. 
• Use AC to define the target lesion(s).  The final visualization of the target lesion 
should be documented using the AC snapshot feature to capture the contents 
of the imaging panels. 
• Develop a treatment plan to perform the MWA of the patient’s liver lesion(s) and 
capture the details of the treatment plan (probe(s) planned to be used, liver 
segment(s), max power planned, and total ablation time planned) in the study 
database.  Note:  A patient cannot have more than three lesions ablated during 
the procedure. 
• After the patient is sedated under general anesthesia or deep conscious 
sedation, and administered antibiotics, if applicable, per SOC, the performing 
physician will place the probe in position without the use of Ablation 
Confirmation. Probe placement may be performed using either ultrasound or CT 
scan. 
 
The following procedures will be done during the ablation procedure: 
• Take at least 1 CT scan to determine the location and size of the target lesion(s). 
The scan will be taken after the probe(s) have been positioned and anchored 
via Tissu-LocTM (if used). The performing physician will review the probe 
placement on AC and, if deemed necessary, re-adjust the probe(s) and begin 
ablation. If CT is used with contrast, the physician must record how much 
contrast was used.  Document the visualization of the probe location(s) using 
the AC snapshot feature to capture the contents of the imaging panels. 
• All recommendations made by the AC software should be captured in the clinical 
database.  If the performing physician does not follow the AC software 
recommendation, a reason why they did not follow the AC recommendation 
should be noted.   
• Record any potential device-related or procedure-related AEs or any SAEs. 
• Record any new relevant concomitant medications or changes to existing 
relevant concomitant medications (i.e., medications used to treat adverse 
events). 
• Record any new liver-related concomitant procedures. 
 
The following procedures will be done after the ablation procedure: 
• Use AC to confirm that the ablation has produced adequate margins, as defined 
by the performing physician (i.e., assess technical success). Document the 
visualization of the final ablation result using the AC snapshot feature to capture 
the contents of the imaging panels. use AC and CT imaging to measure the 
smallest margin diameter within the ablation zone as well as the smallest 
diameter of the entire ablation zone.  Device user experience: Performing 
physician evaluates the NEUWAVE Microwave Ablation System with Ablation 
Confirmation by completing the AC User Evaluation Questionnaire: first half of 

 
 
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the questionnaire following each ablation procedure and the second half 
following approximately every 5 ablations, per treating physician.  
• Laboratory tests, as follows:  
o Coagulation tests, including APTT or PTT PT, and PTA are to be 
performed, as applicable, per site SOC, but INR is required.  
o As applicable, per site SOC, liver function tests, including ALB, ALK, ALT, 
AST, T/D/ bilirubin, GGT, and TP. 
o As applicable, per site SOC, renal function tests, including BUN, 
creatinine, 
and 
electrolytes 
(sodium, 
potassium, 
chloride, 
and 
bicarbonate). 
• 
Record any new liver-related concomitant procedures. 
• 
Pain score, using the Numeric Pain Rating Scale. 
• 
Record ablation procedure details, including: 
o Date and time of the ablation procedure. 
o Document the version of AC software used. 
o Document the tissue contraction percentage selected. 
o Amount of contrast used, if applicable. 
o Type of anesthesia. 
o Anatomical location of ablations. 
o Liver stiffness near ablation site, if available. 
o Number of ablation cycles, including time, maximum temperature and 
maximum power used for each ablation cycle per probe. 
o Number of CT scans performed for probe placement and margin 
assessment. 
o Number of probe placement attempts per ablation. 
o Number and type of probe(s) used. 
o Duration of procedure (first probe placement to last probe removal). 
o Time to perform procedure, which includes 3 measures of time: 
1. Overall procedure duration, defined as the time elapsed between 
loading the CT dataset into the into AC and completion of MWA with 
probe removal.  
2. AC imaging duration, defined as the time elapsed between loading 
CT dataset into the AC software system to plan for the target 
ablation and last use of AC to plan for the final ablation. 
3. Ablation duration, defined as the time elapsed between ablation 
probe puncture and removal of the probe at the completion of the 
ablation. 
Note: Some of the above ablation procedure details will be provided to the site via 
a report generated from NeuWave Medical’s Call Home Database, if available. The 

 
 
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study site will review the report and enter the procedure details into the clinical 
database, as applicable. 
• 
Send all required CT, ultrasound, and MRI scans (taken before, during, and after 
ablation) to Study Sponsor. 
• 
Length of hospital stay (from the time the patient is taken into observation post the 
ablation procedure until hospital discharge). 
• 
Capture from the CT scanner, the total radiation exposure.  
• 
Record any potential device-related or procedure-related AEs or any SAEs. 
• 
Record any new relevant concomitant medications or changes to existing relevant 
concomitant medications (i.e., chemotherapy, blood-thinning/coagulation, NSAIDs, 
steroids, medications used to treat AEs, and medications used to treat hepatitis, if 
concurrently treating). 
The study site should follow their SOC for discharging patients after the ablation 
procedure.  
8.3  Visit 3: 6 Weeks Follow-up 
Six weeks (± 3 weeks) after the ablation procedure, the patient will visit the study site and 
the following assessments will occur: 
• 
Evaluate ECOG performance status. 
• 
Perform laboratory tests, as follows:  
o Coagulation tests, including APTT or PTT, PT, and PTA are to be 
performed, as applicable, per site SOC, but INR is required.  
o As applicable, per site SOC, liver function tests, including ALB, ALK, ALT, 
AST, T/D bilirubin, GGT, and TP. 
o As applicable, per site SOC, renal function tests, including BUN, creatinine, 
and electrolytes (sodium, potassium, chloride, and bicarbonate). 
o Alpha-fetoprotein, as per site SOC. 
o Carcinoembryonic antigen, as per site SOC.  
• 
Record any new relevant concomitant medications or changes to existing relevant 
concomitant medications (i.e., chemotherapy, blood-thinning/coagulation, NSAIDs, 
steroids, medications used to treat AEs, and medications used to treat hepatitis, if 
concurrently treating). 
• 
QOL questionnaires: EORTC QLQ-C30 and the liver-specific QLQ-HCC18. 
• 
Pain score, using the Numeric Pain Rating Scale. 
• 
Determine soft-tissue lesion(s) details (e.g., size, lesion type, location, shape) via 
CT or MRI.  
o If CT is used with contrast, record the amount of contrast used.  
o Review soft-tissue lesion(s) details to determine if there is recurrence or 
progression of the ablated lesion(s).  Note:  No additional ablation 
procedures should be performed at this visit as part of this study.  If the 
patient has a progression, they should be treated outside of this study 

 
 
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protocol. 
• 
Record any new, liver-related concomitant procedures. 
• 
Evaluate Technique Efficacy, defined as ablation of the target lesion(s) according 
to the protocol and covered completely, with an adequate margin, as defined by 
the performing physician (that is, the ablation zone completely overlaps or 
encompasses the target lesion plus an ablative margin), as assessed by imaging, 
at Visit 3. 
• 
Record any potential device-related or procedure-related AEs or any SAEs. 
• 
Record date of study completion (Visit 3, or upon patient’s early withdrawal). 
8.4  Unscheduled Visits 
The following data will be collected during each unscheduled visit: 
• 
Reason for the unscheduled visit. 
• 
Record any potential device-related or procedure-related AEs or any SAEs. 
• 
Any update to relevant concomitant medications and liver-related concomitant 
procedures. 
 
9.0 DATA MANAGEMENT AND INTEGRITY 
9.1 Data Completion and Record Keeping 
Source Documents 
Source documents are documents on which information regarding patients is first 
recorded, including printed, optical, or electronic documents. Investigator patient files or 
hospital records generally are the basis of source document information. This includes 
but is not limited to, the following: original patient files; certified copies of patient records, 
hospital/clinic records; original recordings/tracing; digital images from automated 
instruments (e.g., cameras); radiographs; photographic negatives; and, records kept at 
the investigation site, at the laboratories, and at other departments involved in the clinical 
investigation. 
In addition to standard clinical study source documents, the Sponsor’s NEUWAVE 
Ablation System has a functionality that electronically collects procedure data and 
information during the ablation procedure and is transmitted by the NEUWAVE Ablation 
System to NeuWave Medical, after the conclusion of the ablation procedure; this 
information is collectively called the “Call Home Database.” 
 
 
 
 
 
 
 
 
 
 
 
 
 
Relevant ablation procedure details will be provided to the site via a report generated 
from the Call Home Database, if available. The study site will review the report and enter 
the procedure details into the clinical database, as applicable. The Investigator must 
retain reports generated from the Call Home Database, if available, as part of the patient’s 
permanent medical record. The report should be maintained at the site for review, as 
necessary.  

 
 
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Source documents must be retained by the Investigator as part of the patient’s permanent 
medical record. The information in the source documents is used to complete the eCRFs. 
All information captured on the eCRFs should be completely and accurately supported in 
source documentation. Any additional information relevant to the study should be 
included in the source documents. Particularly, any deviations from the protocol or 
procedures should be recorded in the source documents. The Investigator will retain 
originals of all source documents, patient consent forms, and study data. 
Electronic Data Capture 
An EDC system will be used by site personnel to transfer data from source records 
(medical records and/or source document worksheets) onto common eCRFs. This 
system is a web-based, secure electronic software application (Medidata Rave, 
350 Hudson Street, 9th Floor, New York, NY 10014 United States; telephone: 212-918-
1800; Fax: 212-918-1818; toll-free: 877-511-4200). This system was designed and is 
developed and maintained by Medidata, Inc. in a manner that is compliant with national 
and international GCP data protection/data privacy and electronic record/electronic 
signature (e.g., 21 CFR Part 11) regulatory requirements. The EDC system will be used 
to facilitate the collection of all data at the site. Designated site personnel will be 
responsible for entering patient data into the EDC system. 
 
 
 
 
  
Medidata also has an image upload option called Medidata Imaging.  Sites are uploading 
all required images directly to Medidata Imaging.  
A 24/7/365 Help Desk Support line (telephone: 973-659-6780; fax: 973-954-5621; toll 
free: 866-633-4328; Email: helpdesk@mdsol.com) staffed by the outsourced vendor will 
also be available to respond to site and monitor questions. 
Data Collection 
Each EDC eCRF will be completed by the Investigator or designee. Every effort should 
be made to respond to all monitoring and/or data management questions on each eCRF 
as completion of the data is required by the protocol. A unique ID number will identify 
each patient. The patient’s unique ID number will be visible on each eCRF. At no time, 
should the patient name appear on the eCRFs.  
All data should be recorded accurately and completely. The Investigator is responsible 
for reviewing and approving each completed eCRF. The Investigator will document 
assurance of overall review and approval by electronically signing each patient’s 
electronic casebook. 
Data Correction 
Required data corrections to eCRFs will be prompted via automated electronic edit 
checks and/or queries manually created by Sponsor reviewers. The change, the person 
making the change, and the time the change was made to the eCRFs will be automatically 
captured in the audit trail within Medidata Rave. 
Data Privacy 
The collection, use, and disclosure of all personal data, including patient health and 
medical information, are to be maintained in compliance with applicable personal data 

 
 
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protection and security laws and regulations that govern protected health information and 
the informed consent given by each patient. When collecting and processing such 
personal data, appropriate measures are to be taken to maintain the confidentiality of 
patient health and medical information and to prevent access by unauthorized persons. 
Record Retention, Inspection, and Custody 
The Investigator will allow representatives of the Sponsor, the FDA, or other government 
regulatory agencies to inspect all study records, eCRFs, and corresponding portions of 
the patient’s office and/or hospital medical records at regular intervals during the study. 
These inspections are to verify adherence to the protocol, integrity of the data being 
captured on the eCRFs, and compliance with applicable regulations. 
Study reports will not identify patients by name. These reports may be submitted to the 
FDA and/or regulatory authorities.  
If custody of the clinical study records is transferred, notice of such a transfer should be 
given to the Sponsor no later than 10 working days after the transfer occurs. 
9.2  Medical Dictionary Coding 
Medical dictionary coding of medical history and verbatim AEs captured on eCRFs will be 
performed using a coding thesaurus algorithm. The Medical Dictionary for Regulatory 
Activities (MedDRA) and WHODrug dictionaries will be used after data entry and query 
resolution, via auto-encoding and interactive coding processes. 
9.3  Data Quality Assurance 
Steps to be taken to assure the accuracy and reliability of data include the selection of 
qualified Investigators and appropriate sites, review of protocol procedures with the 
Investigator and associated personnel prior to the study, and periodic monitoring visits by 
the Sponsor. The Sponsor will review eCRFs for accuracy and completeness during 
on-site monitoring visits; any discrepancies will be resolved with the Investigator or 
designees, as appropriate. 
Investigator Training 
Prior to screening patients for this study, the PI, sub-Investigators, study coordinators, 
and other designated staff (as applicable) will be provided information on study execution, 
data collection, and procedures specific to this clinical protocol. 
Monitoring 
This study will be monitored by the Sponsor to ensure the following: 
• 
The rights and well-being of the patients are protected. 
• 
The reported data is accurate, complete, and verifiable from source documents 
where utilized. 
• 
The conduct of the study is in compliance with the currently approved 
protocol/amendment, applicable GCPs, and with applicable local/regional 
regulatory requirements. 
The extent and nature of monitoring will be predetermined and agreed to by the Sponsor 
and Investigators. Monitors will comply with established written standard operating 
procedures as well as procedures (i.e., monitoring plan) specified by the Sponsor for 
monitoring this study as characterized in the monitoring plan. 

 
 
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9.4  Protocol Deviations 
A protocol deviation is any noncompliance with the protocol, Good Clinical Practice, or 
protocol-specific requirements. A deviation (any activity conducted outside the 
parameters established by the protocol) can be identified from a number of sources. 
Potential sources include but are not limited to: a member of the Investigator’s staff, a 
Sponsor representative during monitoring visits, or a member of the data management or 
statistical groups when entering or analyzing data. Regardless of the source, it is crucial 
to document the subject level deviation in the protocol deviation eCRF. The Investigator 
will report protocol deviations to the IRB/EC as required by the IRB/EC procedures. 
Assessments or visits that are not completed because they are not SOC at a site should 
not be considered protocol deviations if the protocol specifies that the assessment or visit 
is only to be collected if SOC. 
Steps to be taken to assure the accuracy and reliability of data include the selection of 
qualified Investigators and appropriate sites, review of protocol procedures with the 
Investigator and associated personnel prior to the study, and periodic monitoring visits by 
the Sponsor. The Sponsor will review eCRFs for accuracy and completeness during 
monitoring visits; any discrepancies will be resolved with the Investigator or designees, 
as appropriate. All deviations to the protocol requirements should be documented in the 
source as well as the protocol deviation eCRF. 
 
10.0 STATISTICAL METHODS AND DETERMINATION OF SAMPLE SIZE 
10.1 Statistical and Analytical Plans 
The Sponsor Data Management and Biostatistics groups will be responsible for the 
analysis of data from this protocol. A comprehensive and detailed Statistical Analysis Plan 
will be finalized prior to database lock to supplement the statistical design and analysis 
described in this section. 
Categorical variables will be summarized descriptively by frequencies and associated 
percentages. Continuous variables will be summarized descriptively by number of 
patients, mean, standard deviation, median, minimum, and maximum. Confidence 
intervals will also be provided for procedure-related variables.  
10.2 Study Design 
This is a prospective, single-arm, multicenter clinical study that will generate clinical data 
using NEUWAVE Microwave Ablation System with Ablation Confirmation Software in 
patients undergoing MWA of at least one soft-tissue liver lesion as part of the study site’s 
SOC treatment. 
10.3 Treatment Assignment 
This is a single-arm study where all enrolled patients will be ablated using the NEUWAVE 
Microwave Ablation System and the AC software tool.  
10.4 Interval Windows 
Interval windows are provided in Table1: Schedule of Activities, which appears at the end 
of the Synopsis. No additional interval windows are planned for analysis purposes. 
 

 
 
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10.5 Primary Endpoint and Associated Hypotheses 
The primary objective of this study will be assessed through recording whether feedback 
from the AC software indicates that the probe should be re-positioned prior to ablation as 
well as whether feedback from the AC software after the ablation procedure indicates that 
the margins are insufficient and hence a repeat ablation would be necessary. No 
hypotheses are specified for either of these endpoints as the study is descriptive in nature 
and will be used for estimation purposes. 
10.6 Levels of Significance 
No levels of significance are specified since no hypotheses are planned to be tested. 
10.7 Analysis Sets 
The primary analysis of safety and effectiveness endpoints will be performed on the Full 
Analysis Set, defined as all eligible patients who are enrolled in the study and have the 
AC tool utilized as part of the ablation procedure. 
A Per Protocol analysis set will be defined as all patients who had undergone the ablation 
procedure and have no major protocol deviations. Effectiveness analyses will be repeated 
for the Per Protocol Set. 
10.8 Sample Size Justification 
Given that this is an initial experience with the AC system in a general use population, a 
sample size of a minimum of 100 patients is deemed sufficient for estimating the 
repositioning rate for appropriate sizing of a subsequent study.  With an expected 
repositioning rate of 15%, a sample size of 100 patients will control the half-width of a 
95% confidence interval to less than 7%. 
10.9 Analyses to be Conducted 
Categorical variables will be summarized descriptively by frequencies and associated 
percentages. Continuous variables will be summarized descriptively by number of 
patients, mean, standard deviation, median, minimum, and maximum. Confidence 
intervals will also be provided for procedure-related variables.  
Disposition of Study Patients 
Patient disposition will be summarized using counts and percentages. The number and 
percentage of patients completed and discontinued along with the specific reasons for 
discontinuation will be tabulated by treatment group and in total. 
Demographic and Baseline Characteristics 
Summary statistics will be provided for patient demographics and pre-operative ablation 
characteristics.  
Primary and Secondary Endpoint(s) Analyses 
The number and percentage of patients requiring probe replacement/changes using the 
AC software prior to the initial ablation will be summarized and a 95% confidence interval 
for the percentage will be provided. The number and percentage of patients in whom the 
AC software indicates repeat ablation is indicated based on insufficient margins following 
the initial ablation procedure will be summarized in a similar manner.  
The number and percentage of patients achieving technical success will be summarized 
and a 95% confidence interval will be provided. A similar summary will be provided for 

 
 
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technique efficacy.   
The number and percentage of patients experiencing device-related and procedure-
related AEs and all SAEs from the time of the first probe puncture (Visit 2) through study 
completion, or, if applicable, the day of early withdrawal, will be summarized by MedDRA 
preferred term and system organ class. Ninety-five percent confidence intervals may be 
provided for pre-specified adverse events of interest.  The expected side effects related 
to MWA are as follows: 
• 
Ascites (accumulation of fluid causing abdominal swelling) 
• 
Biloma / bile leak (buildup of the bile within the abdomen / bile leak) 
• 
Bile duct injury 
• 
Bleeding requiring transfusion, embolization, or prolonged hospital stay  
• 
Intrahepatic hematoma 
• 
Pneumothorax or hemothorax 
• 
Organ injury other than the liver (such as gastrointestinal injury/perforation or 
diaphragmatic injury/hernia) 
• 
Fever 
• 
General feeling of tiredness 
• 
Infection 
• 
Liver dysfunction 
• 
Liver abscess 
• 
Nausea 
• 
Pain  
• 
Pneumonia 
• 
Pleural effusion 
• 
Post-ablation syndrome (body’s response to the destroyed lesion appearing as 
flu-like symptoms, including fever, decreased appetite, and general discomfort 
occurring most typically 3 to 5 days after the ablation procedure) 
• 
Skin burn 
• 
Thrombosis (local coagulation nor clotting of the blood int eh circulatory system, 
with or without tube drainage) 
• 
Tumor implantation 
 
QOL questionnaires will be summarized with methodology consistent to the 
recommendations of the specific survey. Additional endpoints will be summarized with 
descriptive statistics.  
Plans for Interim Analysis 
There are no plans for interim analyses whose intent will be to stop the study early or to 
adapt the study design or planned number of patients.  
Ongoing Review 
The Sponsor will also review complications periodically, as per the Safety Management 
Plan.  
Analysis of Safety 
The analysis of safety is summarized above under Primary and Secondary Endpoint 
Analyses.  

 
 
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Handling of Dropouts or Missing Data 
All analyses will be performed only on patients undergoing ablation with the AC software 
tool and only observed data will be analyzed. There will be no imputation of missing data 
for any parameters or for early terminated patients. 
Multicenter Studies 
No adjustment for center is planned in the statistical analysis. However, center specific 
analyses may be conducted pending within-center sample size to understand the effect 
of the performing physician’s techniques and the study site’s SOC may have on the 
overall results.  
Analysis of Subgroups 
 No subgroup analyses are currently planned but may be considered pending the 
distribution of baseline demographic and clinical characteristics. Subgroup analyses, if 
performed, will be specified in the Statistical Analysis Plan. 
 
11.0 RISKS AND BENEFITS OF THE STUDY 
This study may or may not provide any benefits to the patient. However, the Ablation 
Confirmation software is designed to assist physicians in identifying ablation targets, assessing 
proper ablation probe placement, and confirming ablation margins.  
 
While there have been no AEs reported that have been associated with the use of the AC 
software, the AEs that have been reported and associated with the NEUWAVE Microwave 
Ablation System may be categorized as follows: 
1. Mechanical probe breaks due to excessive force applied during probe placement, 
often through and around boney structures and/or cartilage.  
2. Skin burns due to user placing probe improperly close to the patient’s skin or 
delivering power for excess time and power given the probe placement. 
3. Known risks associated with thermal ablation not associated with device failure or 
misuse. 
 
In addition, it is expected but rare to see minimal collection of fluid or blood in the liver, and 
heat damage to the adjacent areas from the CT scan and other imaging done after the 
procedure. These events can occur without any other sign and symptom.  
No patient complications have been reported related to the AC software to date. 
11.1 Comparison with Other Microwave Ablation Systems 
Clinical Efficacy 
The NEUWAVE Microwave Ablation System has the same intended use as other MWA 
systems. The power levels of the NEUWAVE Microwave Ablation System provide clinicians 
with greater flexibility than many of the other systems currently available, including the ability 
to drive 3 probes, in-phase, at one time as well as having a higher top end power (140 W for a 
single probe) than most other systems.  
However, the total power available does not exceed other microwave systems on the market 
and thus does not introduce new risks. Multiple ablation probe types are available. 
 

 
 
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New Hazards or Intended Uses 
All hazards associated with the use of the NEUWAVE Microwave Ablation System have been 
identified and appropriately mitigated. Design considerations were taken to reduce the risks 
associated with existing MWA systems, including improved system usability and cable 
management. The NEUWAVE Microwave Ablation System uses a CO2 cooling system where 
all other microwave systems use sterile water, but the risks associated with this cooling system 
do not differ from the risks inherent in cryogenic ablation systems, which are also widely 
accepted in clinical use. Thus, the NEUWAVE Microwave Ablation System does not introduce 
new hazards or intended uses. 
Clinical Benefit 
The NEUWAVE Microwave Ablation System has the same fundamental science and 
technology as other MWA systems commercially available. MWA has been generally accepted 
by the clinical community to be safe and effective. Hence, one may conclude that the 
NEUWAVE Microwave Ablation System is likewise considered safe and effective. 
To date, more than 25,000 patients in the United States have had ablations performed using 
the NEUWAVE Microwave Ablation System. 
11.2 Comparison with Radiofrequency Ablation Systems 
To date, there is no reported difference in the reported AEs between RFA and MWA.  In a 
meta-analysis by Huo et al,2 MWA and RFA had similar 1-year to 5-year overall survival, 
disease-free survival, local recurrence rate, and AEs.  In terms of AEs, MWA and RFA have 
similarly low rates of complications, as identified in the same meta-analysis by Huo et al. 
11.2.1 Potential Benefit to Patients 
The main benefits to patients from participation in this study are that they will be treated with 
MWA technology. Poulou et al1 compared MWA with RFA and found that MWA attains a more 
predictable ablation zone, permits simultaneous ablation of multiple lesions, and achieves 
larger coagulation volumes in a shorter procedural time. Nevertheless, Poulou et al stated that 
there is no compelling evidence for differences in clinical outcomes, including local recurrence 
rates and survival. The knowledge gained from this clinical study might also help future MWA 
patients being treated with MWA. 
11.3 Comparison of MWA With Liver Resection 
Studies comparing MWA and liver resection are lacking. Chong et al 3  conducted a 
retrospective analysis of patients who received curative liver resection or MWA for 
hepatocellular carcinoma (HCC) evaluated the survival of patients with HCC treated with liver 
resection or MWA and the role of Albumin-Bilirubin (ALBI) score in patient selection for 
treatments. Of the 442 patients who underwent MWA or liver resection for HCC during the 
study period, 63 patients received MWA and 379 patients received liver resection. Analysis of 
the results showed that liver resection offered better overall and disease-free survivals in 
patients with ALBI grade 1. MWA provided a significantly better overall survival (p = 0.025) 
and a trend towards better disease-free survival (p = 0.39) in patients with ALBI grade 2 or 3. 
The authors concluded that liver resection offered superior disease-free survival compared 
with MWA in patients with HCC. However, the ALBI grade could identify patients with worse 
liver function who might gain survival advantage from MWA. 
Microwave ablation is often used in isolation or succession, and occasionally in combination 
with resection. Philips et al4 prospectively reviewed a Hepato-Pancreatico-Biliary database 
that selected patients with multi-focal bilobar disease who underwent MWA with resection or 

 
 
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only microwave. The multimodality approach has significantly improved outcomes for hepatic 
malignancies. Potential benefits and pitfalls from combined resection and ablation therapy in 
patients with complex and extensive bilobar hepatic disease have not been well defined. The 
study examined the records of 108 patients who were treated with ablation alone or 84 patients 
who were treated with combined resection and ablation, who were then compared with similar 
disease-burden patients who underwent resection only. The authors concluded that the use 
of MWA in addition to surgical resection did not significantly increase the morbidities or short-
term outcomes. They also found that the combination with systemic and other local forms of 
therapy, combined resection and ablation is a safe and effective procedure. 
 
12.0 ADVERSE EVENTS 
12.1 Definitions 
Adverse Event 
For this study, an adverse event is defined as any undesirable clinical occurrence in a 
patient that is determined to be device-related or procedure-related by the Investigator.  
All AEs that meet this definition are to be recorded in the eCRF and reported to the 
Sponsor.  All SAEs, regardless of relationship to the study device or procedure, are to be 
collected. 
The Sponsor will review all applicable site-reported AEs and SAEs according to the 
current Safety Monitoring Plan. 
Expected Morbidity/Anticipated Adverse Events 
An expected morbidity/procedural complication is defined as an AE that is known to be 
common or usual in nature, severity, or incidence during ablation of the liver. 
Serious Adverse Event 
It is the Investigator’s responsibility to determine the “seriousness” of an AE using the 
protocol defined terms below. An SAE is an AE that results in one or more of the following 
for this study: 
• 
Life-threatening: The patient was at imminent risk of dying at the time of the 
adverse event. 
• 
Permanent Impairment: An AE that resulted in permanent impairment of a body 
function or permanent damage to a body structure. 
• 
Necessitated Intervention: An AE that resulted in a condition that necessitated 
medical or surgical intervention to preclude permanent impairment of a body 
function or damage to a body structure. 
• 
Required in-patient or prolonged hospitalization. 
• 
A persistent or significant disability or incapacity. 
• 
Resulted in death: An AE that resulted in the patient’s death. 
Notes: 
1. Progression of the disease under study should not be reported as an SAE. 
2. “Death” should not be reported as an AE. The cause of death should be reported as 
an SAE. The only exception is “Sudden Death” when the cause is unknown. 
3. Planned hospitalization for a pre-existing condition is not considered an SAE.  
 

 
 
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Severity of Adverse Events 
It is the Investigator’s responsibility to assess the severity of an AE.  A change in severity 
of a pre-existing medical condition or of a current AE may constitute a new reportable AE. 
In addition, the following guideline may be used to determine the severity of each AE: 
• 
MILD: Awareness of signs or symptoms but does not interfere with the 
patient’s usual activity or is a transient event that resolves without treatment 
and with no sequelae.   
• 
MODERATE: A sign or symptom which interferes with the patient’s usual 
activity. 
• 
SEVERE: Incapacity with inability to do work or usual activities. 
Relationship of Adverse Events 
It is the Investigator’s responsibility to assess the relationship between all AEs and the 
study procedure and device.  Adverse events deemed to have a possible, probable, or 
causal relationship to the procedure or device should be captured in source as part of the 
study and entered into the AE eCRF.  AEs deemed to be Not Related to the procedure 
or device will be noted in source only. The following guidelines should be used in 
determining the relationship of an adverse event to a device, study procedure, or other 
causality: 
Not Related 
Relationship to the procedure or device can be excluded when: 
• The event is not a known side effect of the product category the 
device belongs to or of similar device and procedures; 
• The event has no temporal relationship with the use of the 
device or the procedures; 
• The event does not follow a known response pattern to the 
device (if the response pattern is previously known) and is 
biologically implausible; 
• The discontinuation of the device application or the reduction of 
the level activation/exposure (when clinically feasible) and 
reintroduction of its use (or increase of the level of 
activation/exposure), does not impact on the event; 
• The event involves a body-site or an organ not expected to be 
affected by the device or the procedure; 
• The 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; or 
• To establish the non-relatedness, not all the criteria listed above 
might be met at the same time, depending on the type of 
device/procedure and the event. 
Possible* 
The relationship with the use of the device is weak but cannot be 
ruled out completely. Alternative causes are also possible (e.g., an 
underlying or concurrent illness/condition and/or an effect of another 
device, drug, or treatment). Cases where relatedness cannot be 

 
 
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assessed, or no information has been obtained should also be 
classified as possible. 
Probable* 
The relationship with the use of the device seems relevant and/or the 
event cannot reasonably be explained by another cause, but 
additional information may be obtained. 
Causal 
Relationship* 
The event is associated with the 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 device and procedure  
• The event has a temporal relationship with the device 
uses/application or procedures  
• The event involves a body-site or organ that  
o The device or procedures are applied to  
o The device or procedures have an effect on  
• The 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 
event (when clinically feasible)  
• Other possible causes (e.g., an underlying or concurrent 
illness/clinical condition and/or an effect of another device, 
drug, or treatment) have been adequately ruled out  
• Harm to the subject is due to error in use  
• To establish the relatedness, not all the criteria listed above 
might be met at the same time, depending on the type of 
device/procedure and the event. 
*Indicates definitions of relationship that qualify to be recorded as part of the study for AEs only.  All SAEs, 
regardless of relationship, will be collected. 
 
12.2 Reporting Adverse Events  
All procedure-related and device-related AEs from the time of the first probe puncture 
(Visit 2) through study completion (Visit 3), or from the time of early withdrawal of the 
study, must be reported in the AE eCRF.   
The Investigator is required to report all applicable non-serious AEs to the Sponsor within 
2 weeks of become aware of the adverse events.  All SAEs, regardless of relationship to 
the study device or procedure, are to be reported as soon as possible, but no later than 
72 hours after becoming aware of the event, regardless of relationship to the device or 
study procedure.   
The study site will report applicable AEs and all SAEs to the Sponsor by entering the 
event into the EDC system via the Adverse Event eCRF, which will trigger an automated 
email to the Sponsor. Additional information, including the Investigator’s assessment, 
may be added to the eCRF later.  Any necessary medical management of the event will 
be recorded in the patient’s medical record/source document. If the Sponsor requires 

 
 
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supporting documentation or other information, the Sponsor will contact the study site.  
Data related to AEs and SAEs will be collected until event resolution, until the event is 
considered stable, or until all attempts to determine the resolution of the event are 
exhausted.  All AEs and SAEs that are unresolved at study completion (or early 
termination) will be recorded as ongoing at study end. 
In addition, the following information should be recorded: 
• 
Onset date. 
• 
Resolution date or date of death. 
• 
Severity of the event.  
• 
Action taken. 
• 
Event status (ongoing at study end or resolved). 
• 
Relationship of AE to the ablation device used in the study. 
• 
Relationship of AE to the study procedure. 
• 
Indication of seriousness. 
• 
Was AE anticipated or not. 
The report of an AE or SAE by a site does not constitute an admission that study 
personnel or the user facility (hospital/clinic) caused or contributed to the event. The site 
is responsible for submitting AEs to the reviewing IRB/EC, per their IRB/EC procedures. 
 
13.0 PRODUCT COMPLAINTS 
13.1 Product Complaint Definition 
A product complaint is defined as any written, electronic, or oral communication that 
alleges deficiencies related to the identity, labeling, quality, durability, reliability, safety, 
effectiveness, or performance of a device after it is released for distribution (21CFR 
820.3 (b)). A product complaint may or may not be associated with an AE/SAE.  
Product complaints may include, but are not limited to:  
1. Product contamination; 
2. Defective components; 
3. Device malfunction (the failure of a device to perform as intended for this study); 
4. Poor packaging or product mix-up; 
5. Labeling concerns; 
6. User errors. 
13.2 Reporting Product Complaints 
All product complaints related to devices in the procedure shall be documented 
throughout the clinical investigation.  
The study site must report product complaints related to a device manufactured by 
NeuWave Medical, Inc., in a timely manner after becoming aware of the event.  

 
 
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When any representative of the Sponsor becomes aware of a product complaint, the 
Sponsor representative must notify the Sponsor’s Product Complaint Team With the least 
practical delay of becoming aware of information (if immediate reporting is not possible). 
The Product Complaint Form must be emailed to the Sponsor Customer Complaint team 
at the following email address:  Productcomplaint1@its.jnj.com. One copy of the 
processed form should be kept on-site, and the device should be retained. Sponsor 
representatives will organize collection of the device for evaluation, as needed. 
The product complaint may also be reported by calling 1-877-ETHICON, Option 5. 
 
14.0 PUBLICATION PLAN 
Publication and authorship policies should be determined and aligned with the clinical study 
agreement executed between operating company and each clinical site. Publication of the 
results of this study will be governed by J&J publication policies, including current and 
applicable Medical Device Publication Policy.  Any presentation, abstract, or manuscript will 
be made available for review by the Sponsor prior to submission. Licensing agreements or 
copyrights applying to tools, work products or intellectual property used during the study 
should be observed and clearly displayed on study documentation and publications, wherever 
appropriate. 
All manuscripts of data obtained from this clinical study will be reviewed and approved by the 
Sponsor, and each author, prior to any submission. Current and applicable Medical Device 
Publication Policy will be followed. The Sponsor will require a written agreement for any 
external author(s) prior to initiating any publication. All authors must disclose financial or 
personal affiliations that could be considered a conflict of interest. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

 
 
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15.0 APPENDICES 
 
APPENDIX 1: NUMERIC PAIN RATING SCALE 
 
For the Numeric Pain Rating Scale (NPRS), the patient is asked to indicate the numeric value 
on the segmented scale that best describes his or her pain intensity. 
  

 
 
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APPENDIX 2: ABLATION CONFIRMATION USER EVALUATION QUESTIONNAIRE  
 
A Multicenter Study to Evaluate NEUWAVE Microwave Ablation System Using Ablation 
Confirmation in Patients with A Soft-tissue Liver Lesion 
Protocol Number: NEU_2017_03 
 
The Ablation Confirmation User will complete the table below after each ablation: 
 
Please grade, on a scale of 0 to 5 (strongly disagree to strongly agree), how helpful AC was 
with the following: 
Procedure 
Step 
Definition 
AC Helped Me 
(0-5 scale) 
Comments 
Lesion 
Visualization 
Marking and tracking the target 
(How well the target lesion can be 
seen in the tissue.) 
 
 
Approach 
Planning 
Planning needle position  
(Optimal path selection and 
ablation coverage optimization.) 
 
 
Probe 
Placement 
Understanding probe position 
prior to ablation 
(The entry and movement 
traversing until in final position.) 
 
 
Ablation 
Planning 
Determining power and time to 
deliver to cover target and 
desired margin  
(Probe, time, power, tissue 
contraction [tissue type]) 
 
 
Ablation 
Confirmation 
Evaluating technical success of 
ablation coverage of target plus 
margin  
(Determination of zone of effective 
ablation compared to target lesion 
and desired margin)  
 
 
 
 
 

 
 
Protocol NEU_2017_03 
CONFIDENTIAL 
 
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Amendment No. 3.0 / FINAL 26July2021 
 
The below is completed after approximately every 5 patients are treated by the performing 
physician (i.e., 5 patients are ablated with the NeuWave Microwave Ablation System with 
Ablation Confirmation Software). 
Please grade, on a scale of 0 to 5 (Strongly disagree to strongly agree), how helpful AC was 
with the following: 
• 
AC did not have a significant impact on procedure time or case resources. ____ 
• 
I use AC in every case because it increases my confidence in achieving a successful 
ablation. ____ 
• 
Ablation with NeuWave Microwave is more predictable, consistent, and controllable 
than other thermal ablation technologies. ____ 
• 
Ablation with multiple NeuWave probes is faster and more consistent than repeated 
place and ablate cycles with other thermal ablation technologies. ____ 
• 
Ablation with NeuWave Microwave increases my confidence in achieving a successful 
ablation compared with other thermal ablation technologies. ____ 
 
Additional comments not already captured above: 
_________________________________________________________________________
_________________________________________________________________________
_________________________________________________________________________ 
 
 
 

 
 
Protocol NEU_2017_03 
CONFIDENTIAL 
 
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Amendment No. 3.0 / FINAL 26July2021 
 
16.0 REFERENCE LIST 
 
 
1 Poulou 
LS, 
Botsa 
E, 
Thanou 
I, 
Ziakas 
PD, 
Thanos 
L. 
Percutaneous 
microwave 
ablation vs radiofrequency ablation in the treatment of hepatocellular carcinoma. World Journal of 
Hepatology. 2015;7(8):1054-1063. doi:10.4254/wjh.v7.i8.1054. 
2 Huo YR, Eslick GD. Microwave Ablation Compared to Radiofrequency Ablation for Hepatic Lesions: 
A Meta-Analysis. J Vasc Interv Radiol. 2015 Aug;26(8):1139-1146.e2. doi: 10.1016/j.jvir.2015.04.004. 
Epub 2015 May 28. 
3 Chong CCN, Lee KF, Chu CM, Chan AWH, et al. Microwave ablation provides better survival than 
liver resection for hepatocellular carcinoma in patients with borderline liver function: application of ALBI 
score to patient selection. HPB (Journal of International Hepato-Pancreato-Biliary Association). 2018 
Jan 15. pii: S1365-182X(17)31182-6. doi: 10.1016/j.hpb.2017.12.001. [Epub ahead of print] 
4 Philips P, Scoggins CR, Rostas JK, McMasters KM, Martin RC.  Safety and advantages of combined 
resection and microwave ablation in patients with bilobar hepatic malignancies. Int J Hyperthermia. 
2017 Feb; 33:43.