A Prospective, Multi-center, Single Arm Study of BiZact™ on Children and Adolescents Undergoing Tonsillectomy
Phase: NA
Conditions: Tonsillectomy
Sponsor: Medtronic - MITG

BiZact™ Pediatric Clinical Study Protocol  
 
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Clinical Investigation Plan 
Clinical Investigation Plan/Study Title  A prospective, multi-center, single arm study of 
BiZactTM on children undergoing tonsillectomy. 
Clinical Investigation Plan / Study 
Identifier 
MDT17024BZP 
Study Product Name BiZactTM 
Local Sponsors Covidien-Medtronic 
Minimally Invasive Therapies Group 
Surgical Innovations 
5920 Longbow Dr. 
Boulder, CO 80301 
Covidien-Medtronic 
Document Version Version 5.0, 18 March 2019 
Confidentiality Statement 
The information contained in this document is confidential and the proprietary property of 
Medtronic. Any distribution, copying, or disclosure without the prior written authorization of 
Medtronic is strictly prohibited. Persons to whom the information is disclosed must know that it is 
confidential and that it may not be further disclosed by them. 
Covidien LP is an indirect wholly owned subsidiary of Medtronic plc. 
 
 

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1. Investigator Statement 
Study product Name 
BiZact™ 
Sponsors 
Covidien-Medtronic 
Minimally Invasive Therapies Group 
Surgical Innovations 
5920 Longbow Dr. 
Boulder, CO 80301 
Covidien-Medtronic 
Clinical Investigation Plan / Study 
Identifier 
MDT17024BZP 
Version Number/Date  
5.0, 18 March 2019 
I have read the protocol, including all appendices, and I agree that it contains all necessary details for 
me and my staff to conduct this study as described. I will conduct this study as outlined herein and 
will make a reasonable effort to complete the study within the time designated. 
I agree to comply with the applicable regulatory guidelines under which the study is being 
conducted, I agree to ensure that the confidential information contained in this document will not 
be used for any purpose other than the evaluation and conduct of the clinical investigation without 
the prior written consent of Medtronic. Additionally, I will commit to: 
• 
conduct the investigation in accordance with the agreement, the investigational plan, FDA 21 
CFR Part 812 and other applicable FDA regulations, and conditions of approval imposed by 
the reviewing IRB/Ethics Committee, local /regional regulatory requirements; 
• 
supervise all testing of the device involving human subjects; and 
• 
ensure that the requirements for obtaining informed consent are met 
• 
provide sufficient and accurate financial disclosure information and update information if 
any relevant changes occur during the investigation and for one year following the 
completion of the study. 
I will provide all study personnel under my supervision copies of the protocol and access to all 
information provided by Medtronic. I will discuss this material with them to ensure that they are 
fully informed about the products and the study. 
Investigator’s Signature: 
 
 
Investigator’s Name: 
 
 
Institution: 
 
 
Date: 
 
 
 
 

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Table of Contents 
1. 
Investigator Statement .................................................................................................... 2 
Table of Contents ..................................................................................................................... 3 
2. 
Glossary ............................................................................................................................ 6 
3. 
Synopsis ............................................................................................................................ 8 
4. 
Introduction ................................................................................................................... 13 
4.1. 
Background ................................................................................................................... 13 
4.1.1. 
Tonsillectomy Procedure .......................................................................................... 13 
4.1.2. 
BiZactTM Device ....................................................................................................... 13 
4.2. 
Purpose ......................................................................................................................... 13 
5. 
Objectives and Endpoints ............................................................................................... 14 
5.1. 
Objectives ..................................................................................................................... 14 
5.1.1. 
Primary Objective ................................................................................................... 14 
5.2. 
Endpoints ...................................................................................................................... 14 
5.2.1. 
Primary Endpoint .................................................................................................... 14 
5.2.2. 
Secondary Endpoints ............................................................................................... 14 
5.2.3. 
Safety Assessment .................................................................................................. 14 
6. 
Study Design ................................................................................................................... 14 
6.1. 
Duration ........................................................................................................................ 14 
6.2. 
Rationale ....................................................................................................................... 15 
7. 
Product Description ........................................................................................................ 15 
7.1. 
General ......................................................................................................................... 15 
7.2. 
Dosage Form and Route of Administration ........................................................................ 16 
7.3. 
Manufacturer ................................................................................................................. 16 
7.4. 
Packaging ...................................................................................................................... 17 
7.5. 
Intended Population ....................................................................................................... 17 
7.6. 
Equipment ..................................................................................................................... 17 
7.7. 
Product Use ................................................................................................................... 17 
7.8. 
Product Training Requirements........................................................................................ 18 
7.9. 
Product Receipt and Tracking .......................................................................................... 18 
7.10. 
Product Storage ......................................................................................................... 18 
7.11. 
Product Return ........................................................................................................... 18 
7.12. 
Product Accountability ................................................................................................. 18 
8. 
Selection of Subjects ...................................................................................................... 19 
8.1. 
Study Population ............................................................................................................ 19 
8.2. 
Subject Enrollment ......................................................................................................... 19 
8.3. 
Inclusion Criteria ............................................................................................................ 19 
8.4. 
Exclusion Criteria ........................................................................................................... 19 
9. 
Study Procedures ............................................................................................................ 21 
9.1. 
Schedule of Events and Study Schematic.......................................................................... 21 
9.1.1. 
Screening / Baseline Visit ......................................................................................... 22 
9.1.2. 
Surgical Procedure (Day 0) ...................................................................................... 22 
9.1.3. 
Post-Operative Follow-up: Days 1 through 7, Day 10, Day 14 and Day 28 .................... 23 
9.1.4. 
Assessment Instruments .......................................................................................... 24 
9.1.4.1. 
Wong Baker FACES Pain Scale .......................................................................... 24 
9.1.4.2. 
FLACC Behavioral Pain Assessment Scale ........................................................... 24 
9.1.4.3. 
Post-Operative Patient Diary ............................................................................. 24 
9.1.5. 
Return to Clinic: Day 28 (+7) ................................................................................... 24 

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9.2. 
Prior and Concomitant Medications .................................................................................. 25 
9.3. 
Subject Consent ............................................................................................................. 25 
9.4. 
Randomization and Treatment Assignment ....................................................................... 25 
9.5. 
Medication Compliance ................................................................................................... 25 
9.6. 
Assessment of Efficacy ................................................................................................... 26 
9.7. 
Assessment of Safety ..................................................................................................... 26 
9.8. 
Recording Data .............................................................................................................. 26 
9.9. 
Deviation Handling ......................................................................................................... 26 
9.10. 
Subject Status ............................................................................................................ 27 
9.10.1. 
Screened Subjects .................................................................................................. 27 
9.10.2. 
Screen Failures ....................................................................................................... 27 
9.10.3. 
Enrolled Subjects .................................................................................................... 27 
9.10.4. 
Subject Withdrawal or Discontinuation ...................................................................... 27 
9.11. 
Selection of Investigators ............................................................................................ 28 
10. 
Risks and Benefits ....................................................................................................... 29 
10.1. 
Potential Risks ............................................................................................................ 29 
10.1.1. 
Risks of Investigational Medical Device ..................................................................... 29 
10.2. 
Potential Benefits ....................................................................................................... 29 
10.3. 
Risk Benefit Rationale ................................................................................................. 29 
11. 
Adverse Events and Device Deficiencies ..................................................................... 30 
11.1. 
Definitions and Classifications ...................................................................................... 30 
11.1.1. 
Adverse Event (AE) ................................................................................................. 30 
11.1.2. 
Serious Adverse Events (SAE) .................................................................................. 31 
11.1.3. 
Adverse Device Effect (ADE) .................................................................................... 31 
11.1.4. 
Serious Adverse Device Effect (SADE) ....................................................................... 32 
11.1.5. 
Unanticipated Serious Adverse Device Effect (USADE) ................................................ 32 
11.1.6. 
Adverse Event Severity Classification ........................................................................ 32 
11.1.7. 
Adverse Event Relationship Classification .................................................................. 32 
11.1.8. 
Adverse Event Outcome Classification ....................................................................... 34 
11.2. 
Reporting of Adverse Events ........................................................................................ 34 
11.3. 
Adverse Event Recording ............................................................................................. 36 
11.4. 
Study Contact Information .......................................................................................... 36 
11.5. 
Device Deficiencies ..................................................................................................... 36 
12. 
Data Review Committees ............................................................................................ 37 
13. 
Statistical Design and Methods ................................................................................... 37 
13.1. 
Statistical Test Methods .............................................................................................. 37 
13.2. 
Sample Size Determination .......................................................................................... 37 
13.3. 
Analysis Population ..................................................................................................... 38 
13.4. 
Statistical Analysis Endpoints ....................................................................................... 38 
13.4.1. 
Primary Endpoint .................................................................................................... 38 
13.4.2. 
Secondary Endpoint ................................................................................................ 38 
13.5. 
Statistical Analysis of Safety Endpoints ......................................................................... 38 
13.6. 
Handling of Missing Data ............................................................................................. 39 
13.7. 
Interim Analysis ......................................................................................................... 39 
13.8. 
Poolability of Results ................................................................................................... 39 
14. 
Ethics ........................................................................................................................... 39 
14.1. 
Statement(s) of Compliance ........................................................................................ 39 
15. 
Study Administration .................................................................................................. 40 
15.1. 
Monitoring ................................................................................................................. 40 

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15.2. 
Data Management ...................................................................................................... 40 
15.3. 
Direct Access to Source Data/Documents ...................................................................... 41 
15.4. 
Confidentiality ............................................................................................................ 41 
15.5. 
Liability ...................................................................................................................... 41 
15.6. 
Clinical Investigation Plan (CIP)/Protocol Amendments .................................................. 41 
15.7. 
Record Retention ........................................................................................................ 42 
15.8. 
Publication and Use of Information .............................................................................. 42 
15.9. 
Suspension or Early Termination .................................................................................. 43 
15.10. 
Safety Committees ..................................................................................................... 43 
15.10.1. 
Independent Medical Monitor ............................................................................... 43 
15.10.2. 
Steering Committee ............................................................................................. 43 
15.10.3. 
Internal Safety Data Review ................................................................................. 44 
16. 
References .................................................................................................................. 45 
17. 
Version History ............................................................................................................ 46 
 
18. 
Appendices 
18.1. 
APPENDIX A: Instructions for Use (IFU)  
18.2. 
APPENDIX B: Sample of Post-Operative Patient Diary 
18.3. 
APPENDIX C:  Sample of Wong-Baker FACES® Pain Rating Scale 
18.4. 
APPENDIX D: Sample of FLACC Behavioral Pain Assessment Scale 
18.5. 
APPENDIX E: Additional records and reports 
18.6. 
APPENDIX F: List of Investigators and Institutions 
 
 
 
 

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2. Glossary 
Term 
Definition 
ADE 
Adverse device effect:  
Adverse event related to the use of an investigational medical device. 
Note: This definition includes adverse events resulting from insufficient or inadequate instructions for 
use, deployment, implantation, installation, or operation or any malfunction of the investigational 
medical device. 
Note: This definition includes any event resulting from use error or from intentional misuse of the 
investigational medical device. See Clinical Event definition for more information. 
AE 
Adverse event:  
 Any untoward medical occurrence, unintended disease or injury, or 
untoward clinical signs (including abnormal laboratory findings) in subjects, users or other persons, 
whether or not related to the investigational medical device. 
Note: This definition includes events related to the investigational medical device or the comparator.  
Note: This definition includes events related to the procedures involved. 
Note: for users or other persons, this definition is restricted to events related to investigational medical 
devices. 
See Clinical Event definition for more information. 
Assent 
An agreement by an individual not competent to legally give valid informed consent generally because 
of age or mental status   
CIP 
Clinical Investigation Plan Document that state(s) the rationale, objectives, design and proposed 
analysis, methodology, monitoring, conduct and recordkeeping 
of the clinical investigation. 
Note: The term “protocol” is synonymous with “CIP”. However, protocol has many different meanings, 
some not related to clinical investigation, and these can differ from country to country. Therefore, the 
term CIP is used in this International Standard. 
EC 
Ethics Committee: 
Independent body whose responsibility is to review clinical investigations in order to protect the rights, 
safety and well-being of human subjects participating in a clinical investigation. Also known as the 
Institutional Review Board (IRB).  
Note: For the purposes of this International Standard, “ethics committee” is synonymous with “research 
ethics committee,” “independent ethics committee” or “institutional review board”. 
The regulatory requirements pertaining to ethics committees or similar institutions vary by country or 
region. 
eCRF/CRF 
(Electronic) Case Report Form: 
A paper or electronic data collection form, designed to collect information on each subject as required 
by the Study Protocol /Clinical Investigation Plan. 
ENT 
Ear, nose and throat, a subspecialty of medicine dealing with the diagnosis and management of medical 
conditions related to the ears, nose, and throat, also referred to as otolaryngology or 
otorhinolaryngology 
FLACC 
behavioral pain 
assessment 
scale 
Face, Legs, Activity, Cry, Consolability behavioral pain assessment scale:  
A validated pain measurement instrument to assess pain for children age 2 months to seven (7) years of 
age. The scale has five (5) criteria with 0 representing behavior with no pain and 2 representing the 
most pain. 
GCP 
Good Clinical Practice: 
A standard for the design, conduct, performance, monitoring, auditing, recording, analyses, and 
reporting of clinical studies that provides assurance that the data and reported results are credible and 
accurate, and that the rights, integrity, and confidentiality of 
study subjects are protected. 
Hemostasis 
The arrest of bleeding, whether it be by normal vasoconstriction (the vessel walls closing temporarily), 
by an abnormal obstruction (such as a plaque) or by coagulation or surgical means (such as ligation).  
Intra-operative 
Bleeding 
Bleeding that occurs during the course of the surgical operation. 

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Term 
Definition 
IRB 
Institutional Review Board: 
Any board, committee, or other group formally designated by an institution to review, to approve the 
initiation of, and to conduct periodic review of, biomedical research involving human subjects. The 
primary purpose of such review is to assure the protection of the rights and welfare of the human 
subjects. Also known as Ethics Committee (EC). 
LAR 
Legally Authorized Representative: Individual or judicial or other body authorized under applicable law 
to consent, on behalf of a prospective subject, to the subject’s participation in the clinical investigation. 
LAR may be the subject’s parent or parental guardian. For the purposes of this protocol LAR will be 
used, but may be synonymous with parent in cases where a parent is the LAR. 
Likert Scale 
A psychological measurement device that is used to gauge attitudes, values, and opinions, generally 
using a 5-point rating system.  
Peritonsillar 
abscess 
A formation of pus within the peritonsillar space (beside the tonsil) generally formed as the result of 
bacterial infection within the loose connective tissue found in the area.    
SAE 
Serious Adverse Event: 
Adverse event that: 
a) Led to a death, 
b) Led to a serious deterioration in the health of the subject, 
that either resulted in: 
1) Resulted in a life-threatening illness or injury, or 
2) Resulted in a permanent impairment of a body structure 
or a body function, or 
3) In-patient or prolonged hospitalization, or 
4) Medical or surgical intervention to prevent life 
threatening illness or injury or permanent impairment to 
a body structure or a body function, or 
Led to fetal distress, fetal death or a congenital abnormality or birth 
defect. 
Note: Planned hospitalization for a pre-existing condition, or a procedure required by the CIP, without 
serious deterioration in health, is not considered a serious adverse event. 
SADE 
Serious Adverse Device Effect: 
Adverse device effect that has resulted in any of the consequences characteristic of a serious adverse 
event. 
Tonsillectomy 
A surgical procedure to remove the tonsils  
US 
United States 
USADE 
Unanticipated Serious Adverse Device Effect: 
Any serious adverse effect on health or safety or any life-threatening problem or death caused by, or 
associated with, a device, if that effect, problem, or death was not previously identified in nature, 
severity, or degree of incidence in the CIP or application (including a supplementary plan or 
application), or any other unanticipated serious problem associated with a device that relates to the 
rights, safety or welfare of subjects. 
Wong-Baker 
FACES® Scale 
An illustrated pain scale ranging from a happy face at 0 “No Hurt” to a crying face at 10 “Hurts Worst” 
 
 

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3. Synopsis 
Title 
A prospective, multi-center, single arm study of BiZactTM on children 
undergoing tonsillectomy 
Clinical Study Type 
Pre-market Pivotal / IDE Study 
Product Name 
BiZactTM (BZ4212) 
Sponsor  
Medtronic, Minimally Invasive Therapies Group, Surgical Innovations 
Local Sponsors 
Covidien-Medtronic 
Minimally Invasive Therapies Group 
Surgical Innovations 
5920 Longbow Dr. 
Boulder, CO 80301 
Covidien-Medtronic 
Indication under 
investigation  
Tonsillectomy in children (age 2-12 at the time of the procedure, 
inclusive) 
Investigation Purpose 
The purpose of this study is to assess safety and performance with 
the use of the BiZactTM device in tonsillectomy procedures in 
children. 
Product Status 
• 
Food and Drug Administration (FDA) cleared for adult ENT 
procedures including tonsillectomy 
• 
Therapeutic Goods Administration (TGA) License for ENT 
procedures including tonsillectomy in adults, children and 
adolescents.   
Primary Objective(s) 
The primary objective of this study is to assess safety and 
performance with the use of the BiZact™ device in children (ages 2-
12 at the time of the procedure, inclusive) tonsillectomy procedures. 
Study Design 
A prospective, multi-center, single arm, study of BiZact™ on children 
undergoing tonsillectomy. 
Primary Endpoint(s) 
Intra-operative blood loss: The study will be considered a success if 
the mean intra-operative blood loss is less than the mean intra-
operative blood loss associated with conventional tonsillectomy in a 
large meta-analysis (Alexiou et al. 2011). See the Statistics section 
below for more details. 

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Secondary Endpoint(s) 
Study will analyze and describe device performance and patient 
response related to the following: 
o 
Ability to dissect tonsils with investigational medical device 
via Likert Scale (Very Good, Good, Acceptable, Poor, Very 
Poor) 
o 
Usability Challenges 
o 
Ability to achieve hemostasis (arrest of bleeding, as 
assessed by visual inspection of the Investigator) without 
the use of other interventions (e.g. energy device or 
sutures) 
o 
Evaluation of post-operative pain incidence and severity 
measured using the Wong-Baker FACES® Pain Rating Scale 
and FLACC behavioral pain assessment scale 
o 
Analgesic consumption (standard of care) and concomitant 
medications (via patient diary) 
Sample Size 
A minimum of sixty (60) completed procedures, with at least 40% 
study wide in the age range of 2-5 years of age, will be undertaken at 
a minimum of 2 sites in US. When 36 procedures with subjects ≥6 
years of age have been completed (60% of total minimum 
enrollment), enrollment for this age group will close. 
Power considerations are detailed in the Statistics section below.  
Inclusion/Exclusion Criteria 
Inclusion Criteria:  
1. Children subjects 2-12 years of age at time of procedure, 
inclusive  
2. Scheduled to undergo tonsillectomy 
3. The subject and subject’s Legally Authorized Representative 
(LAR) is willing to participate and consents to participate, as 
documented by signed informed consent form and/ or assent 
form (as applicable)  
Exclusion Criteria:  

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1. Subjects undergoing:  
a. Tonsillectomy as a result of cancer 
b. Unilateral tonsillectomy 
2. Subjects with: 
a. Known Bleeding disorders 
b. History of peritonsillar abscess 
c. Craniofacial disorders 
d. Down’s syndrome (Trisomy 21) 
e. Cerebral palsy  
f. 
Major heart disease (including but not limited to; 
right-sided heart failure, left-sided heart failure, 
congestive heart failure, coronary artery disease, 
arrhythmias, chronic heart failure, acute heart 
failure, etc.) 
g. Current tobacco use  
3. Subjects unable to comply with the required study follow-up 
visits 
4. Female subjects pregnant at time of procedure 
5. The subject has comorbidities which, in the opinion of the 
Investigator, will not be appropriate for the study or the 
subject has an estimated life expectancy of less than 6 
months. 
6. The subject is participating or has participated in any drug or 
device research study within 30 days of enrollment. 
Study Procedures and 
Assessments 
Pre-operative & Operative Assessments: 
• 
Demographics 
• 
Histories: Medical, Surgical, Medication 
• 
Urine pregnancy test for females of child bearing potential  
• 
Type of admission 
• 
AE/SAE Assessment 
• 
Pre-operative physical exam (abbreviated) 
• 
Intra-operative bleeding volume (excluding other fluids) 
o Operative field irrigant volume 
o Presence of gastric fluids 
o Volume of stomach juices and blood in suction container 
o Differential weight of any sponges applied to tonsil bed 
to absorb blood 
• 
Surgical performance parameters 
o Operative time - time from the first incision to complete 
hemostasis (arrest of bleeding as assessed by visual 
inspection of the Investigator) of the tonsillar bed 
(excluding time for closing)  

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o Device ease of use 
o Usability challenges 
o Alternate device(s) use (if any) 
o Ability to dissect tonsil with device graded via Likert Scale 
(Very Good, Good, Acceptable, Poor, Very Poor) 
o Tonsil size measurement (mL) 
• 
Concomitant Medications 
• 
Device accountability 
Follow-up Assessments (Forms filled out by subject or parent/LAR on 
post-operative days 1-7, 10, 14 and 28 see full protocol for 
assessment windows): 
• 
Pain level   
• 
Analgesic consumption 
• 
Ability to return to normal diet (via Patient Diary) 
• 
Ability to return to normal activity (via Patient Diary) 
• 
Incidence of post-operative hemorrhage - any primary (≤24 
hours) requiring medical intervention and secondary (>24 
hours) bleeding requiring medical intervention (e.g., cautery, 
admission for observation, or re-operation) 
• 
Incidence of post-operative readmission  
Safety Assessments 
Safety will be assessed as the proportion of subjects with: 
1. Post-operative hemorrhage - any primary (≤24 hours) requiring 
medical intervention and/or secondary (>24 hours) bleeding 
requiring medical intervention (e.g., cautery, admission for 
observation, or re-operation) 
2. Post-operative readmission  
3. Evidence of glossopharyngeal nerve damage (e.g., prolonged 
pain or difficulty swallowing) as diagnosed by the surgeon 
4. Other intra/post-operative complications (complications related 
to device deficiencies) 
5. Other adverse events (e.g., post-operative dehydration, fever, 
etc.) 
6. Localized Infection 
a. Infection confined to a single organ or tissue 
The study will assess the observed rates of device related serious 
adverse events. 

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 Statistics 
The analysis technique will be a 1-sample t-test (or Wilcoxon ranked 
sign if nonparametric test is desired), with a one-sided type I error 
rate (α) of 0.025.  A sample size of 60 is selected to ensure that 
multiple surgeons participate and to create an opportunity for a 
range of subject ages to be enrolled.  Statistical power for a sample 
size of 60 exceeds 99%. 
 
The primary hypotheses of this study are: 
H0: Mean intra-operative blood loss = 31 mL 
HA: Mean intra-operative blood loss < 31 mL 
 
The performance goal of 31 mL derives from a meta-analysis 
comparing modern technology to conventional techniques (i.e. 
electrocautery and cold steel) (Alexiou et al. 2011).  This paper 
included a total of 3139 patients included in thirty-three published 
studies. The values from all of the studies that reported intra-
operative bleeding were combined to calculate a mean blood loss. 
This value encompasses a variety of techniques and technologies and 
a number of different studies to capture a realistic value for 
comparison. 
 
Intraoperative blood loss during tonsillectomy with BiZact™ is 
expected to be low. The expected mean value for the BiZact™ device 
is a conservative estimate derived from data for LigaSure™ and other 
vessel sealing systems in the Alexiou meta-analysis. The expected 
standard deviation is the average of the standard deviation values for 
all studies that reported blood loss in the meta-analysis.   
 
Expected mean for BiZact™: 10 mL 
Expected standard deviation: 15.1 mL 
 
Additionally, descriptive statistics for blood loss will be reported for 
different age groups (ages 2-5 and ages 6-12) as well as for different 
sites, surgeons, and countries.  
 
Secondary endpoints will be evaluated with descriptive statistics. For 
continuous variables, the mean, median, and standard deviation will 
be reported, along with a 95% confidence interval for the mean 
where appropriate.  
 
For categorical data, proportions will be reported, along with 95% 
confidence intervals where appropriate.  
 
 
 
 

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4. Introduction 
 
4.1. Background 
4.1.1. Tonsillectomy Procedure  
Tonsillectomy is one of the most frequently performed otorhinolaryngologic procedures. Aside from 
the conventional technique of cold steel and electrocautery dissection, the introduction of numerous 
energy based tools and techniques allows for the simultaneous dissection and sealing of vessels, 
potentially improving safety and reducing the complications of the procedure (1-3). Generally thought 
of as safe and effective, energy based devices such as laser, Shaw scalpel, electrosurgical devices 
(needle, scissor, or knife), radiofrequency needle ablation device, thermal welding, and Coblator™, use 
heat energy to denature protein, leading to vascular tamponade and hemostasis (arrest of bleeding). 
Unfortunately, a byproduct of using this energy during surgery is the lateral heating of the surgical 
area, which can damage adjacent structures, delay wound healing, increase post-operative pain, and 
increase the subject’s time to return to normal diet and activity (4).  
 
In order to address these concerns, Medtronic has developed BiZact™, a bipolar electrosurgical 
instrument intended for use in open surgical procedures, such as tonsillectomies, where ligation and 
division of vessels, tissue bundles, and lymphatics is desired. BiZact™ is designed as a pistol grip 
radiofrequency (RF) sealer/dissector for use with vessels up to and including 3mm. Compatible with the 
already in use Valleylab™ (LS10, FT10, ForceTriad™) energy platforms, BiZact™ employs bipolar 
electrosurgical RF energy and pressure to ligate vessels interposed between its jaws which can then be 
transected using the built-in knife deployed by the device trigger. Based off of Ligasure™ technology, 
bipolar electrosurgical devices have demonstrated utility for tonsillectomy procedures, providing 
hemostasis while minimizing postoperative pain (5, 6, 8, 9).  
 
4.1.2. BiZactTM Device  
Animal model studies have found BiZact™ to be able to achieve hemostasis and minimize lateral 
thermal spread potentially resulting in reduced post-operative pain. Details of preclinical testing can be 
found within the BiZact™ instructions for use (IFU) and in the Investigator’s Brochure. Additionally, the 
performance of the BiZactTM device is also being evaluated in an adult tonsillectomy pilot study in the 
US and Europe (ClinicalTrials.gov Identifier: NCT02876575).   
 
4.2. Purpose 
The purpose of this study is to assess safety and performance of the BiZact™ device in tonsillectomy 
procedures in children.  Sixty (60) pediatric subjects (ages 2-12 inclusive) will be treated for 
tonsillectomy with BiZact™ enrolled at a minimum of 2 clinical sites across the USA with enrollment and 
completion of the tonsillectomy procedure with the study device not to exceed 36 subjects per site. 
The study will be considered a success if the mean intra-operative blood loss is less than the mean 
intra-operative blood loss associated with conventional tonsillectomy in a large meta-analysis (7). At 
the conclusion of the study, data will be submitted to the FDA for consideration for a pediatric 
indication and for publication.  
 
 

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5. Objectives and Endpoints 
 
5.1. Objectives 
5.1.1. Primary Objective 
The primary objective of this study is to assess safety and performance with the use of the BiZact™ 
device in children (ages 2-12 at the time of the procedure, inclusive) tonsillectomy procedures. 
 
5.2. Endpoints 
5.2.1. Primary Endpoint 
The primary endpoint of this study is the amount of intra-operative blood loss. The study will be 
considered a success if the mean intra-operative blood loss is less than the mean intra-operative blood 
loss associated with conventional tonsillectomy in a large meta-analysis (7). See the Statistical Design 
and Methods (Section 13) for additional details. 
 
5.2.2. Secondary Endpoints 
• 
Ability to dissect tonsils with investigational medical device (Likert Scale: Very Good, Good, 
Acceptable, Poor, Very Poor) and Usability Challenges 
• 
Ability to achieve hemostasis (arrest of bleeding, as assessed by visual inspection of the 
investigator) without the use of other methods (e.g. energy device or sutures) 
• 
Evaluation of post-operative pain incidence and severity measured using the Wong-Baker 
FACES® Pain Rating Scale or FLACC behavioral pain assessment scale 
• 
Analgesic consumption (standard of care) and concomitant medications (via Patient Diary) 
 
5.2.3. Safety Assessment 
The study will assess the observed rates of device-related adverse events. This includes, but is not 
limited to consideration of the following conditions:  
• 
Post-operative hemorrhage 
o Any primary (≦24 hours) requiring medical intervention and/or secondary (>24 hours) 
bleeding requiring medical intervention (e.g., cautery, admission for observation, or re-
operation) 
• 
Post-operative readmission  
• 
Evidence of glossopharyngeal nerve damage as diagnosed by the investigator via subject 
assessment  
• 
Other intra/post-operative complications (complications related to device deficiencies) 
• 
Other adverse events (e.g., post-operative dehydration, fever, etc.) 
• 
Localized Infection 
o Infection confined to a single organ or tissue 
6. Study Design 
 
6.1. Duration 
Including enrollment and follow up time, the current study is estimated to progress for up to 18 
months. During this time, subjects will participate for a maximum of 67 days. Subject screening for 

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eligibility will occur up to 30 days prior to the procedure. Post-procedure, subjects will be assessed for 
pain and their ability to return to normal diet and activity via a patient diary and either the FLACC 
behavioral pain assessment scale (age 2) or the Wong Baker Faces® Scale at days 1 through 7, Day 10 
(+/-1 day), Day 14 (+/-1 day), and Day 28 (+/-1 day), before returning the FLACC/FACES® scales and 
Patient Diary during the return to clinic on day 28 (+7). Please see section 9 for study schematic. 
 
6.2. Rationale 
In order to assess the clinical safety and performance of BiZact™ (BZ4212) on a pediatric population, 
Medtronic is performing a prospective, multi-center, single arm study of BiZact™ on children (2-12 
years of age at the time of the procedure, inclusive) undergoing tonsillectomy. Intra-operative blood 
loss will be assessed as well as post-operative pain and other quality of life aspects for 28 (+7) days 
following the procedure. Pre-clinical testing has found BiZact™ to satisfactorily achieve hemostasis and 
currently a multicenter adult tonsillectomy study is underway in the US and Europe. As a study with no 
comparator, this study does not utilize any randomization or blinding. The BiZact™ device will only be 
used during the course of the tonsillectomy procedure and subjects will be followed for 28 (+7) days to 
monitor bleeding, pain and return to normal diet and activity. If any adverse events are identified they 
will be assessed, reported and documented in the eCRF. 
 
7. Product Description 
7.1. General 
The BiZact™ is a single use bipolar electrosurgical instrument intended for use in general open surgical 
procedures.  It is also indicated for adult ENT procedures, including tonsillectomy, for the ligation and 
division of vessels, tissue bundles, and lymphatics 2-3 mm away from unintended thermally sensitive 
structures.  
 
BiZact™ is a pistol grip RF-based sealer/ dissector similar (design, technology and materials) to current 
Ligasure™ devices. Akin the commercialized device, LF1212 (Ligasure™ small jaw), BiZact™ includes a 
jaw, a deploying knife, a lever to open and close the jaws, and a trigger to deploy the knife and inline 
activation of bipolar energy. The device does not include a rotation knob for rotating the jaws, but the 
device does allow surgeons to perform procedures by switching hands. BiZact™ is compatible with the 
Valleylab™ (LS10 with V1.1 or V1.2 software, ForceTriad with v4.0 software, and FT10 with v2.0 
software) energy platforms, which are able to recognize the device utilizing radiofrequency 
identification (RFID) or barcode capabilities. In total, 120 BiZact™ units will be assigned to this study to 
account for any situations in which more than one device is needed.  
 

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Figure 1: BiZact™ (BZ4212) schematic diagram (left), and device photo (right) 
 
7.2. Dosage Form and Route of Administration 
This instrument creates tissue fusion by application of bipolar electrosurgical RF energy and pressure to 
vessels/tissue interposed between the jaws of the instrument. The tissue fusion can then be transected 
using the built in cutting mechanism. The instrument can be used for vessels and lymphatic tissue up to 
and including 3mm in diameter and tissue bundles. The instrument also incorporates inline RF 
activation, features for grasping and tips for dissection. The instrument is intended primarily for 
surgeons performing tonsillectomies. See Instructions for Use (included in Appendix A) for instructional 
information. 
The BiZact™ device has received the following approvals for the ligation and division of vessels, tissue 
bundles and lymphatics 2-3 mm away from unintended thermally sensitive structures; 
• 
Food and Drug Administration (FDA) indication for adult ENT procedures including 
tonsillectomy (US) 
• 
Therapeutic Goods Administration (TGA) License for ENT procedures including tonsillectomy in 
adults, children and adolescents (AUS)   
This information is contained in the IFU (Appendix A) but the IFU accompanying the device should 
always be consulted. 
 
7.3. Manufacturer 
BiZact™ is manufactured by Covidien (Covidien LP is an indirect wholly owned subsidiary of Medtronic 
plc.).   The Covidien facility located at 5920 Longbow Drive, Boulder, CO is an FDA registered 
establishment (1717344) manufacturing US Class 1 and 2 medical devices in accordance with the 21 
CFR 820 Quality System Regulation.  The site also holds both an ISO 13485 Quality Management 
Certificate (FM 71825) and Full Quality Assurance System Certificate (CE 00500).  Both certificates are 
issued by Boulder’s Notified Body, BSI.  BSI holds annual quality assessments to ensure continued 
compliance to quality processes. 
 

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Components used in the assembly of the device are manufactured by several different suppliers.  All 
suppliers undergo a robust qualification process prior to inclusion on Covidien’s “Approved Supplier 
List.”  Once suppliers are selected, they are audited on a periodic basis per Covidien’s procedures to 
ensure continued adherence to Covidien specifications and standards. Each supplier is assigned a risk 
rating, and this determines the timetable for subsequent audits that are not for cause.    
 
7.4. Packaging 
See Appendix A, Instructions for Use. BiZact™ is provided as a single use disposable product. Each 
instrument is individually packaged and sealed in a Tyvek ® pouch. Six sealed pouches are packaged in 
one shipper case.  
 
In the United States, the BiZact™ devices will be labeled as investigational according to regulations: 
“CAUTION – Investigational Device - Limited by Federal (or United States) Law to Investigational Use.” 
 
For Australia, devices for the study will be shipped accompanied by instructions that the devices are 
indicated for the BiZact™ clinical study use only, to be used by study qualified investigators, and 
consistent with local requirements.  
 
7.5. Intended Population 
The BiZact™ device has received the following approvals or clearances for the ligation and division of 
vessels, tissue bundles and lymphatics 2-3 mm away from unintended thermally sensitive structures; 
• 
Food and Drug Administration (FDA) indication for adult ENT procedures including 
tonsillectomy (US) 
• 
Therapeutic Goods Administration (TGA) License for ENT procedures including 
tonsillectomy in adults, children and adolescents (AUS)  
• 
CE Mark under the Medical Device Directive for use in ENT procedures including 
tonsillectomy in adults, children and adolescents (EU) 
 
7.6. Equipment 
BiZact™ devices are single-use disposable products. If needed, a compatible Valleylab™ generator will 
be supplied and approved by the hospital biomedical department if applicable. Each site will receive or 
be assigned to use a different compatible Valleylab generator for this study. BiZact™ is compatible with 
the Valleylab™ (LS10 with V1.1 or V1.2 software, ForceTriad with v4.0 software, and FT10 with v2.0 
software) energy platforms, which are able to recognize the device utilizing radiofrequency 
identification (RFID) or barcode capabilities after the BiZact™ device is plugged into the Ligasure ™ port 
of the Valleylab generator. There is no need for any necessary calibration or monitoring of the 
equipment to enable use with the BiZact™ device.  
7.7. Product Use 
The BiZact™ device is a bipolar electrosurgical instrument intended for use in open surgical procedures 
where ligation and division of vessels, tissue bundles, and lymphatics is desired. 
 

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The tissue fusion function of the device can be used on vessels (arteries and veins) and lymphatics up 
to and including 3 mm diameter. The BiZact™ device is indicated for use in open general surgical 
procedures. 
 
The BiZact™ device has not been shown to be effective for tubal sterilization or tubal coagulation for 
sterilization procedures, and should not be used for these procedures.  
 
This information is contained in the IFU (Appendix A) but the IFU accompanying the device should 
always be consulted. 
 
7.8. Product Training Requirements 
Each Investigator participating in the clinical study and the associated clinical study staff will receive 
training on the clinical protocol, as well as the BiZact™ device. Investigators and study staff will be 
trained on device characteristics, shelf life and storage requirements, device use, and warnings, 
precautions, contraindications.  
 
7.9. Product Receipt and Tracking 
BiZact™ will be shipped to each site with the shipment form (which includes shipping/ dispersal date, 
the quantity, model, lot, and, serial number and expiration date). Each site will review contents and 
document on the form the confirmation the shipment information is accurate as well as the date 
received. The use of the device for a procedure or disposition of the devices (e.g. if returned due to 
damage upon arrival) will be recorded in the eCRF device tracking section in conjunction with the above 
information. 
 
BiZact™ will be provided to each site upon Sponsor collection and approval of all required regulatory 
documentation.  Additionally, a Valleylab™ generator will be supplied if necessary (see above).  
 
7.10. Product Storage 
Access should be limited to designated study staff only. Study devices should be kept in an area or 
otherwise contained where only qualified study personnel can access the device (i.e. locked or 
secured). This area/container should be kept at ambient temperatures without exposure to water with 
adequate provisions for maintaining ambient temperatures if a loss of power is experienced.  Device 
accountability will be tracked in the electronic case report forms (eCRFs).  If the devices are exposed to 
water or a drastic change in temperature, sites should contact the study team for possible replacement 
devices. 
 
7.11. Product Return 
It is the responsibility of the site to return the Valleylab™ generator to Medtronic within 30 days of the 
End of Study if one was loaned, along with any unused or expired BiZact™ devices. Sites should follow 
instructions and complete all appropriate forms provided by the study team for product return.  
 
7.12. Product Accountability  
Access should be limited to designated study staff only. Device accountability will be tracked in the 
electronic case report forms (eCRFs). It is the site’s responsibility to document the receipt (which 

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includes shipping/ dispersal date, the quantity, model, lot, and, serial number and expiration date), 
disposition of the product (per subject use, including amount used, amount remaining, etc.), transfer (if 
applicable) and return of all unopened investigational medical devices. 
 
8. Selection of Subjects 
8.1. Study Population 
A minimum of sixty (60) completed procedures with subjects ages 2-12 (at the time of the procedure 
inclusive), with at least 40% study wide in the age range of 2-5 years of age, will be undertaken at a 
minimum of 2 sites in US.  When 36 procedures with subjects ≥6 years of age have been completed 
(60% of minimum total enrollment), enrollment for this age group will close. A minimum of five 
surgeons across the 2 sites will participate. 
 
The sample size of 60 was selected to ensure that multiple surgeons participate and to create an 
opportunity for a range of subject ages to be enrolled. Power considerations are detailed below 
(Section 13). 
 
8.2.  Subject Enrollment  
A minimum of 60 subjects will be enrolled in the study at a minimum 2 sites with competitive 
enrollment not to exceed 36 enrolled subjects per site. Subjects’ participation in the study will last 28 
(+7) days post procedure. Subjects will be considered for the study if they meet all of the preoperative 
inclusion criteria and none of the exclusion criteria (Section 8.3, 8.4), and sign the informed consent 
form.   
 
A subject is considered enrolled in the study when the subject’s legally authorized representative signs 
the informed consent form. However, data will not be collected for the study until the subject has 
determined to be eligible for the study and the surgical procedure has begun. No adverse event 
information will be recorded before the procedure has begun. As soon as the tonsillectomy procedure 
has begun and the study device has contacted the patient, the patient must be followed regardless of 
whether or not the procedure has been fully completed with the device . See section 9.10.3 for the full 
definition of enrolled subjects. The procedure will be performed per the institution’s standard practice.   
8.3. Inclusion Criteria 
1. Children subjects 2-12 years of age at the time of the procedure, inclusive  
2. Scheduled to undergo tonsillectomy 
3. The Subject and Subject’s Legally Authorized Representative (LAR) is willing to participate and 
consents to participate, as documented by signed informed consent form and/ or assent form 
(as applicable)   
8.4. Exclusion Criteria 
1. Subjects undergoing:  
a. Tonsillectomy as a result of cancer 
b. Unilateral tonsillectomy 
2. Subjects with: 
a. Known bleeding disorders 
b. Current peritonsillar abscess 
c. Craniofacial disorders 

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d. Down’s syndrome (Trisomy 21) 
e. Cerebral palsy  
f. 
Major heart disease (including but not limited to; right-sided heart failure, left-sided 
heart failure, congestive heart failure, coronary artery disease, arrhythmias, chronic 
heart failure, acute heart failure, etc.) 
g. Current tobacco use  
3. Subjects unable to comply with the required study follow-up visits 
4. Female subjects pregnant at time of procedure. 
5. The subject has comorbidities which, in the opinion of the Investigator, will not be appropriate 
for the study or the subject has an estimated life expectancy of less than 6 months.  
6. The subject is participating or has participated in any drug or device research study within 30 
days of enrollment.  

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9. Study Procedures 
9.1. Schedule of Events and Study Schematic 
 The schematic of the study is presented in the table below. 
 
Screening / 
Baseline 
Day -30 to 0  
Surgery 
(Day 0) 1 
Post-Op6 
Day 1 – Day 
7, 10 & 14  
(Home)  
Post-Op6 
Day 28  
Return to Clinic 
Day 28 
(+7 days) 
Can be combined 
Can be combined 
Informed Consent 1 
X1 
 
 
 
 
Eligibility Criteria 
X1 
 
 
 
 
Urine pregnancy test 
 
X 4 
 
 
 
Demographic data 2 
X 
 
 
 
 
Medical history 
X 
 
 
 
 
Surgical history 
X 
 
 
 
 
Medication history 
X 
 
 
 
 
Analgesic consumption & Concomitant 
medications (via patient diary)  
 
X 
X 
X 
 
Type of admission 
 
X 
 
 
 
Physical Examination (abbreviated) 
 
X 
 
 
 
Intra-operative bleeding volume 
 
X 
 
 
 
Tonsil measurement 
 
X 
 
 
 
Operation time 
 
X 
 
 
 
Device ease of use 
 
X 
 
 
 
Usability Challenges 2 
 
X 
 
 
 
Ability to dissect tonsil via Likert scale 
 
X 
 
 
 
Alternate device used (if any) 
 
X 
 
 
 
Post-operative bleeding 
 
X 
X 
X 
X 
AE, SAE, ADE, USADE Assessment and 
device deficiencies 3 
 
X 
X 
X 
X 
Readmission 
 
 
X 
X 
X 
Record Pain via Wong-Baker FACES® Pain 
Rating Scale or FLACC behavioral pain 
assessment scale 5 
 
 
X 
X 
 
Patient diary 
 
 
X 
X 
 
Return pain scales and diary 5  
 
 
 
 
X 
Device accountability 
 
X 
 
 
 
Protocol deviation collection 
X 
X 
X 
X 
X 
1 Study specific procedures may only be performed after subject has agreed to participate and the signed informed consent 
form. Screening and informed consent are considered as a process that may occur over multiple days within 30 days prior to 
procedure. Any new information about the subject’s eligibility and willingness to participate must be considered prior to the 
tonsillectomy with the investigational device.  
2 See protocol and CRF pages for specific data points 
3 Device-related SAEs will be collected from the start of the procedure as soon as the device is in contact with the subject. If 
any events are ongoing at the last visit Day 28 (+7), they must be followed up to seven (7) days or resolution whichever is 
first.  
4 A negative urine pregnancy test performed within 24 hours prior to surgery will be acceptable to satisfy eligibility criteria. 
This will apply to all “females of child bearing potential.” Local definition and standard of care for testing of “female of child 
bearing potential” will be documented and observed for each site. 
5 For participants age 2, parents will evaluate pain using the FLACC behavioral pain assessment scale as validated 
measurement. All older subjects will utilize the Wong-Baker FACES Pain Rating Scale. 
6   For Days 10,14, and 28, post-operative assessments including pain scales and diary may be completed +/- 1 day but should 
be returned Day 28 (+7). 

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9.1.1. Screening / Baseline Visit 
A screening/baseline visit will be performed within 30 days up to the day of the scheduled procedure 
and may be combined with the Procedure Visit. Subjects’ legally authorized representative will need to 
provide consent prior any procedures specific to the study are undertaken. The purpose and all aspects 
of the study will be explained to the subject and LAR(s). \LAR(s) who agree to study participation must 
sign and personally date the sponsor and IRB/EC-approved informed consent form prior to participating 
in any study activities. Additionally, assent forms will be completed and signed as applicable per IRB/EC 
requirements. 
 
Once informed consent/assent has been obtained according to IRB/EC requirements and eligibility is 
confirmed, the subject’s demographics and medical history will be assessed to include: age, gender, 
weight, ethnicity and race. Relevant medical history will be assessed and included in the electronic case 
report form (eCRF). 
 
The following assessments will be performed within 30 days prior to the scheduled surgical procedure 
and the results recorded on the appropriate subject eCRFs: 
• 
Verification of eligibility criteria 
• 
Demographic data (date of birth, ethnicity, gender height weight) 
• 
Medical history, including comorbidities such as obesity, and underlying conditions that 
necessitated surgery 
• 
Surgical history 
• 
Medication history (such as during pre-operative period) 
• 
Pregnancy test, if applicable (must be within 24 hours prior to surgery) 
• 
Concomitant medication(s) 
Note: All medications will be coded using the World Health Organization (WHO) drug coding 
dictionary. 
 
9.1.2. Surgical Procedure (Day 0) 
The Study Investigator should perform the surgical procedure according to the appropriate standard 
procedures and practices at his/her institution using BiZact™.  BiZact™, in conjunction with other non-
energy surgical tools (e.g. Allis clamp), should be used to complete the entire procedure unless it is 
medically necessary to use another device. Additionally, the following procedures and assessments will 
be performed:  
• 
Type of admission (e.g. inpatient/outpatient) 
• 
AE/SAE assessment 
• 
Pre-operative procedure abbreviated physical examination 
o Including assessment of heart/lungs, neurological, ENT, immune system and vital signs 
(blood pressure, respiration rate, heart rate, temperature) 
• 
Female subjects will undergo a urine pregnancy test, according to institutional and state 
guidelines on assessment of child-bearing potential. If the test is positive, they will be 
withdrawn from the study.  
• 
Intra-operative bleeding volume (If completed within conjunction of adenoidectomy, this 
should be measured prior to adenoidectomy procedure) 
o Record volume of any operative field irrigant used during procedure 
o Record presence of gastric fluids 

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o Record volume of fluid in suction container (i.e. stomach juices and blood) prior to 
stomach drainage and again after 
o Differential weight of any sponges applied to the tonsil bed to absorb blood 
• 
Surgical performance parameters 
o Operative time - time from the first incision to complete hemostasis (arrest of bleeding 
as assessed by visual inspection of the Investigator) of the tonsillar bed (excluding 
closing time)  
o Device ease of use (Easy, Moderate, Difficult) 
o Ability to dissect tonsil with device graded via Likert Scale (Very Good, Good, 
Acceptable, Poor, Very Poor) 
o Usability Challenges (observations of the following): 
 
tissue sticking 
 
tissue slippage  
 
accidental activation  
 
visualization of tip 
o Assessment of any complications during the procedure 
 
Related to bleeding 
• 
If there were any transfusions required and if so how much 
o Other non-investigational medical device alternative procedural devices used (if any),  
 
Operation time used 
 
Tonsil location (Left/Right) 
 
Reason for use  
o Tonsil size measurement (volume) 
• 
Device accountability 
• 
Concomitant medications (including anesthesia) 
Note: All medications will be coded using the World Health Organization (WHO) drug coding 
dictionary.  
 
9.1.3. Post-Operative Follow-up: Days 1 through 7, Day 10, Day 14 and Day 28 
Post-operative hospital stay and AE/SAE assessment will take place by delegated study personnel. 
Additionally, during post-operative days 1 through 7, Day 10 (+/-1 day), Day 14 (+/-1 day), and Day 28 
(+/-1 day), the following assessments will be made: 

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• 
Pain will be assessed via the FLACC behavioral pain assessment scale (age 2) and the Wong-Baker 
FACES® Pain Rating Scale (Ages 3-12) 
• 
Analgesic consumption and concomitant medications 
• 
Ability to return to normal diet via patient diary 
• 
Ability to return to normal activity via patient diary 
• 
Incidence of post-operative hemorrhage - any primary (≦24 hours) requiring medical 
intervention and secondary (>24hrs) bleeding requiring medical intervention (e.g., cautery, 
admission for observation, or re-operation) 
• 
Incidence of post-operative readmission 
• 
AE/SAE reporting 
 
9.1.4. Assessment Instruments 
9.1.4.1. 
 Wong Baker FACES Pain Scale 
The Wong Baker FACES pain scale is an instrument validated for ages 3+ to measure pain, by selecting a 
number on an ordinal 0-10 scale (“0” being no pain and “10” being the worst pain ever). Subjects will 
receive at least eleven copies of the Wong-Baker FACES® Pain Rating scale (below). Prior to the subject 
receiving the scale, the subject ID will be written on each page. On post-operative days 1 through 7, 
Day 10 (+/-1 day), Day 14 (+/-1 day), and Day 28 (+/-1 day), subjects and/or LAR(s) will be instructed to 
indicate the subject’s degree of pain at the same time each morning prior to taking any pain medication 
by marking and dating the appropriate face. 
 
9.1.4.2. 
FLACC Behavioral Pain Assessment Scale 
The FLACC behavioral pain assessment scale is an instrument validated for use for children ages 2 
months 7 years of age to measure pain. A parent or guardian will rate the child’s behavior across five 
(5) domains (Face, Legs, Activity, Crying, and Consolability) on a scale of 0-2 (“0” being no pain behavior 
and “2” being the highest pain behavior). Subjects will receive at least eleven copies of the FLACC 
behavioral pain assessment scale. Prior to the subject receiving the scale, the subject ID will be written 
on each page. On post-operative days 1 through 7, Day 10 (+/-1 day), Day 14 (+/-1 day), and Day 28 (+/-
1 day), parent(s)/ will be instructed to indicate the subject’s degree of pain at the same time each 
morning prior to taking any pain medication by rating the child’s behavior according to the scale’s 
instructions.  
 
9.1.4.3. 
Post-Operative Patient Diary 
The patient diary will be provided to the subject/subject’s LAR. This diary will be used to record any 
adverse events, or medicines that have been taken relative to the tonsillectomy procedure.  The diary 
will also be used to record return to normal eating and living activities. 
 
9.1.5. Return to Clinic: Day 28 (+7) 
On post-operative day 28 (+7) (end of study) the subject will return to the clinic to return their Wong-
Baker FACES® pain rating scale(s) or FLACC Behavioral Pain Assessment Sales(s) and the Patient diary. 
Post-operative day 28 (from section 9.1.3) and Return to Clinic can be combined if both are completed 
on day 28.  
 

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9.2. Prior and Concomitant Medications 
Provided that the medications do not conflict with study-related procedures, or are not indicative of an 
underlying condition that would constitute an eligibility criteria violation, they will follow the normal 
medication regimen as prescribed by their doctor when proceeding with study participation.  No 
specific post-operative regimen will be required for this study. Medications, including medications for 
pain, will be recorded as concomitant medications 
9.3. Subject Consent 
Subjects’ legally authorized representatives will need to provide consent to participate in the study 
prior to any procedures specific to the study are undertaken.  Subjects and/or LAR(s) will be provided 
with a description of the device and procedure; risks, benefits, and alternative procedures; length of 
participation required; method and amount of compensation, if applicable; and information regarding 
injury and confidentiality. Written and verbal communication will include non-technical language that is 
understandable to the subject(s)/LAR(s). Requirements for Informed Consent and, where applicable, 
Assent from the child will be per local IRB and regulatory requirements. The informed consent 
discussion(s) will only be conducted by the principal investigators (PIs) and/or his/her designee, 
provided they are trained in the study. Subjects and/or parent(s)/LAR(s) will be informed that their 
participation in this study is voluntary and they may refuse to participate or discontinue from the study 
at any time. PIs or designees will avoid any coercive language and at no time improperly influence or 
offer improper inducement of subjects to participate or continue participating in the study. At no time 
will any discussion or written language waive or appear to waive the subject’s/ LAR’s legal rights.  
Subjects and parent(s)/LAR(s) will be given ample opportunity to consider the study, read the informed 
consent form, and ask the investigator questions so that they are adequately informed about the 
research. Subjects/ LAR(s) will also be informed that after the investigation visits are completed, the 
subjects will receive the standard medical care, just as they would have, had they not participated in 
the study. The informed consent form must be personally signed and dated by subject and/or 
parent(s)/LAR(s) and investigator at time of consent. Additionally, assent forms will be completed and 
signed as applicable per IRB requirements. The informed consent process will be documented in the 
source records and a copy of the consent will be provided to the subject and/or parent(s)/LAR(s).  
 
If new information becomes available that may affect a subject’s and/or and parent(s)/LAR(s)’s decision 
to continue to take part in the study, this information will be discussed with the subject and LAR(s) by 
the investigator and new consent will be obtained in writing. The informed consent form must be 
personally signed and dated by subject and/or LAR(s) and investigator at time of consent. The informed 
consent process will be documented in the source records and a copy of the consent will be provided 
to the subject and/or and LAR(s).  
 
9.4. Randomization and Treatment Assignment 
No randomization will occur during the course of the study. 
 
9.5. Medication Compliance 
Compliance to the recommended standard of care will be monitored via the at home patient diary. 
Variations in standard care and patient departures from the standard of care will be recorded and 
considered in the analysis, but will not be considered a protocol deviation. 

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9.6. Assessment of Efficacy 
Intra-operative blood loss, procedure time, ability to dissect tonsil, ability to achieve hemostasis, 
analgesic consumption and post-operative pain level will be recorded in the eCRF and used to assess 
efficacy of the BiZact™ device. 
 
9.7. Assessment of Safety 
Safety will be assessed by monitoring the occurrence of adverse events (AEs), serious adverse events 
(SAEs), death, adverse device effects (ADE), unanticipated serious adverse device effects (USADE), 
device deficiencies or the presence of localized infection as defined in Section 10. Assessments will take 
place starting during the procedure as soon as the device is in contact with the subject, through post-
operative day 28 (+7) and will be recorded in the eCRF.  
 
9.8. Recording Data 
This study will utilize an electronic database and eCRF. All data requested on the eCRF are required. 
Study visits or measurements not collected and/or recorded will be considered deviations unless 
otherwise specified. Generally, a source document will be generated for any clinical data points that 
are required for the study.  However, there may be data such as the generation of subject ID, and 
certain aspects of the Adverse Event (AE) information (e.g. date reported, investigator evaluation) 
which may be considered as source. The Principal Investigator or authorized designee(s) must ensure 
the accuracy and completeness of the recorded data and then provide his/her electronic signature on 
the eCRFs.  The Investigator’s electronic signature for specific eCRFs will be documented in compliance 
with local regulations and compliance with the protocol.  Changes to data previously submitted to the 
sponsor will require a new electronic signature by the Investigator to acknowledge/approve the 
changes. 
 
9.9. Deviation Handling 
A study deviation is an event where the Investigator or site personnel did not conduct the clinical study 
according to the Clinical Investigational Plan or Clinical Investigation Agreement. The Investigator is not 
allowed to deviate from the above-mentioned documents except under emergency circumstances to 
protect the rights, safety and well-being of human subjects. 
No changes to the protocol will be permitted without the written approval from Medtronic, the IRB/EC 
and applicable Competent Authority. The investigator must notify Medtronic and the reviewing IRB/EC 
of any deviation from the Investigational Plan when specific to the protection of the life or physical 
well-being of a subject in an emergency. The deviation will be recorded in the eCRF and such notice 
must be given as soon as possible, but in no event later than five (5) working days after the emergency 
has occurred. Except in such an emergency, prior written approval by Medtronic is required for changes 
in or deviations from the Plan. If these changes or deviations affect the scientific soundness of the Plan 
or the rights, safety, or welfare of human subjects the IRB/EC will also be notified. All other deviations 
will be reported per the site’s IRB/EC standard operating procedures. Should any deviations from the 
Investigational Plan occur, these will be reviewed by Medtronic for their clinical significance and 
compliance to the protocol. Repetitive or serious investigator compliance issues may result in the need 
to initiate a corrective action plan, and in some cases, freeze enrolment or ultimately terminate the 
Investigator’s participation in the clinical study.  

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If any Medtronic representative discovers that an investigator is not complying with the signed 
Investigator Agreement, the investigational plan, applicable laws, or any conditions of approval 
imposed by the reviewing IRB/EC, they will report to the clinical study manager and take such steps 
necessary to promptly secure compliance.  If compliance cannot be secured, device shipments to the 
investigator may be discontinued and the investigator’s participation in the investigation terminated. 
Medtronic shall also require such an investigator to dispose of or return the device, unless this action 
would jeopardize the rights, safety, or welfare of a subject. 
 
9.10. Subject Status 
9.10.1. Screened Subjects 
Subjects who are being evaluated for eligibility in the study are considered screened or being screened. 
 
9.10.2. Screen Failures 
Subjects whose LAR(s) provide study consent, but then are determined to be ineligible to participate 
prior to the procedure will be considered screening failures and will not require additional study follow-
up visits. The reason for the screening failure will be clearly delineated on the applicable CRFs.  If a 
subject is being screened to participate and the cohort closes during the screening period (see section 
9.10.1), the subject should be withdrawn by the investigator, and he/she will not receive the surgery 
with the device. 
 
9.10.3. Enrolled Subjects 
A subject is considered enrolled in the study when the subject’s LAR signs the consent. Data will not be 
captured until the subject is determined to be eligible and the tonsillectomy has begun (Day 0).  As 
soon as the tonsillectomy surgical procedure has begun and the BiZactTM device has been in contact 
with the subject, the subject must be followed. Subjects who are enrolled, but discontinue the study 
for any reason prior to the start of the tonsillectomy procedure or usage of the study device, will not be 
followed unless they are later able to complete the tonsillectomy, See section 9.10.4. These subjects 
will not count towards the 60-subject enrollment for the study, nor towards the site enrollment 
maximum (36). In all subject cases where the device was in contact with the subject will be included in 
the intent-to-treat (ITT) population.  The per-protocol population will consist of subjects in the ITT 
population that did not have a major protocol deviation. 
 
9.10.4. Subject Withdrawal or Discontinuation 
Subjects for whom consent has been obtained and are deemed eligible, but later consent is withdrawn 
will be withdrawn from the study, and their enrollment will not count toward the study enrollment, nor 
the maximum site enrollment (36).  In the event the subject/subject’s LAR withdraws consent, the date 
of withdrawal will be documented.   
 
Subjects whose tonsillectomy has been rescheduled, but still wish to participate may participate if the 
dates of consent and screening are within 30 days of the new planned tonsillectomy date. If the new 
tonsillectomy date is more than 30 days after date of screening and/or consent, subjects / LAR(s) who 
wish to participate should be re-consented and re-screened. In this circumstance, this would be 
considered a new subject, and the previous consent and screening materials will be considered as a 
“withdrawn” subject. 

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If the surgeon has begun the tonsillectomy procedure with the intention of using the investigational 
medical device, but does not perform the procedure with the investigational medical device for any 
reason, that subject will not be included in the study nor will their enrollment count toward the 
maximum number of subjects per site or the total of sixty (60) subjects for the final analysis (section 
13.3 Analysis Population).  Only procedures where the investigational medical device has come in 
contact with the subject will be included in the study analysis (see sections 9.10.3 and 13.3 ITT 
population).  If the tonsillectomy procedure has begun, but the investigational device is not used (e.g. 
generator failure), the subject will be removed from the study, and the reason will be document, 
including any device deficiencies. 
 
The reason for study exit will be documented on the applicable electronic case report form (eCRF).  If 
the Study Investigator voluntarily removes a subject from further study participation prior to the 
surgery, supporting documentation must be in place for the rationale and date of removal. Follow-up 
of subjects withdrawn or discontinued after the surgical procedure will be determined by surgeon, but 
will respect the rights and wishes of the subject. Every attempt will be made to contact subjects that 
are noncompliant with study procedures.  Subjects will be considered lost to follow-up once the 
following steps have been taken: 
• 
Two phone calls should be made to the subject/LAR(s).  Each attempt should be clearly 
documented in the source documents and the response or lack thereof should be captured.   
• 
If there is no response to the phone calls, then an official, certified letter should be written to 
the subject/ LAR(s).  A copy of the letter and return or delivery receipts should be retained in 
the subject’s source document. 
• 
Additionally, the site should attempt to reach out to the primary care practitioner to determine 
the status of the subject and document this in the eCRF. 
• 
When all due diligence attempts to contact have been made, after a period of two (2) weeks, 
the subject will be considered Lost to Follow-up.  The Sponsor should be notified and the End 
of Study (EOS) form should be completed.   
 
9.11. Selection of Investigators 
Surgeons who are qualified by training (board certified in otolaryngology in accordance with USand 
hospital guidelines), education, and relevant experience appropriate to the use of the product and 
associated procedures will be considered for participation as investigators in this study. 
Investigators/sites must have adequate time and resources to conduct the study throughout the 
duration of the study and have access to an adequate number of eligible subjects. Investigators/sites 
must be able to comply with applicable Institutional Review Board (IRB) and regulatory requirements. 
Investigator must not be debarred, disqualified, or working under sanctions in applicable regions. 
Qualifications are verified through valid CV and current licensing and maintained with study 
documentation.   
 
 
 
 
 

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10. Risks and Benefits 
10.1. Potential Risks 
10.1.1. Risks of Investigational Medical Device 
The potential risks associated with the standard tonsillectomy procedure include but are not limited to: 
reaction to anesthesia, swelling, bleeding, infection (including fever), nausea, vomiting, dehydration, 
velopharyngeal incompetence, and pain.   
 
The potential risks associated with BiZact™ include: unintended cutting, bruising, tearing, thermal 
burns, or other damage to tissue, arcing, pinching, inadequate/no seal, pain, bleeding, nausea, 
vomiting, and headache. There is also a risk of electromagnetic interference if the patient has an 
implantable electronic device. 
 
In the event of unacceptable bleeding, investigators may use alternate means to achieve acceptable 
hemostasis, just as they would in a typical tonsillectomy procedure. Subjects in the study will be given 
instruction as to what to do in the event of post-operative bleeding in order to minimize any adverse 
effects.  
 
The risk analysis is based on the operation of BiZact™ by trained personnel.  The overall residual risk 
after design risk mitigation strategies and/or design control was deemed acceptable for the BiZact™ 
system.  
 
The instructions for use (IFU) provide instructions on proper use of the device along with warnings and 
precautions to mitigate risk of misuse and notify the surgeon of potential risks. Surgeons will undergo 
training on the device prior to participation in the study.   
 
Reproductive and developmental toxicology studies in animals to evaluate the potential for AEs on 
reproductive ability and effects on the embryo/fetus have not been conducted.  As with any device, 
there is always a risk of a rare or previously unknown side effect developing from the treatment or use 
of the device. 
 
10.2. Potential Benefits 
The potential benefits associated with BiZact™ device usage include, but are not limited to: reduction in 
pain, blood loss, time to return to normal diet, and activity post tonsillectomy procedure as compared 
to conventional tonsillectomy; however, there may be no benefits at all. 
 
10.3. Risk Benefit Rationale 
Post-operative pain and delayed time to normal diet and activity are common challenges after 
tonsillectomy procedures. Aside from conventional cold steel and electrocautery dissection, the 
introduction of numerous energy based tools and techniques allow for the simultaneous dissection and 
sealing of vessels significantly improving safety and reducing the complications of the procedure (1-3). 
In most cases however, these energy based devices use heat to establish hemostasis (arrest of 
bleeding), which can lead to lateral heating and damage to adjacent structures delaying wound healing 
and increasing post-operative pain (4). Thus, the use of the investigational medical device for 

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tonsillectomy presents a similar risk profile and minimal if any increase in risk over other commonly 
used devices. 
 
A positive risk/benefit ratio has been demonstrated with BiZact™ as evidenced by preclinical and 
biocompatibility testing, and a multicenter adult tonsillectomy is currently underway. There were no 
apparent adverse systemic or local effects in any of the preclinical studies using animal models. BiZact™ 
is based off Ligasure™ technology which historically has been shown to be safe and effective for 
tonsillectomy procedures providing adequate hemostasis (arrest of bleeding) while minimizing 
postoperative pain. 
 
The product design, as well as the results of internal studies, support BiZact™ as a class 2 FDA cleared 
for use in adult patients. It is CE-mark and Therapeutic Goods Administration (TGA) Licensed product 
for use in adult and pediatric patients. There are currently no known interactions between the BiZact™ 
device and concurrent medical interventions. 
 
11. Adverse Events and Device Deficiencies 
 
Adverse event (AE) definitions used in this study are based on ISO 14155:2011 (Clinical Investigation of 
Medical Devices for Human Subjects -- Good Clinical Practice).   
 
All AEs and Device Deficiencies will be collected and documented a and Day 0 (after commencement of 
surgery with BiZact™ to 28 (+7) days follow-up. Device Deficiencies not related to an adverse event 
(e.g. damaged out of the box) will be collected from when they are first noticed, regardless of usage in 
a case. 
 
11.1. Definitions and Classifications 
11.1.1. Adverse Event (AE) 
In alignment with ISO 14155:2011 (Section 3.2), an Adverse Event is any untoward medical occurrence, 
unintended disease or injury, or untoward clinical signs (including abnormal laboratory findings) in 
subjects, users or other persons, whether or not related to the investigational medical device.  
 
This definition includes events related to the investigational medical device and the procedures 
involved. For users or other persons, this definition is restricted to events related to investigational 
medical devices. 
 
Adverse Events may include but are not limited to  bleeding, tissue injury, and thermal burns.  
 
For study purposes, the following occurrences are considered to be expected observations following 
surgical procedures (primarily associated with anesthesia) and will not be considered reportable AEs, as 
long as the event is not associated with significant sequelae, does not prolong hospitalization, and 
responds to standard medical therapy:  
• 
Postoperative transient nausea determined to be procedure related within the first 24 
postoperative hours.  
• 
Postoperative transient emesis determined to be procedure related within the first 24 
postoperative hours. 

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• 
Postoperative constipation, determined to be procedure and/or medication related for the 
duration of medication administration for management of pain. 
• 
Postoperative pain that the Investigator considers common and within normal limits for the 
procedure and is well-managed with medication. Pain that the Investigator considers outside 
normal, or is not well-managed with medication, as well as pain that severe (score 7 or higher) 
and ongoing at the end of the study will be captured as an adverse event. 
 
Additionally, the following should not be considered an AE: 
• 
A condition requiring a preplanned procedure unless the condition worsened since enrollment 
• 
A preexisting condition found as a result of screening, unless the condition has worsened since 
enrollment. 
All responses to the above events that require treatment beyond the institution’s standard procedures 
will be reported as AEs. 
 
All AEs observed during the course of this study, regardless of severity or relationship to the device will 
be recorded on the appropriate eCRF. Adverse events regardless of relatedness will be treated per 
standard of care at each institution. For example, the management of pain or bleeding will be at the 
discretion of the treating physician, as he or she is monitoring the patient’s condition.  
 
11.1.2. Serious Adverse Events (SAE) 
In alignment with ISO 14155:2011 (Section 3.37), a serious adverse event (SAE) is any AE that has: 
• 
led to death, 
• 
led to serious deterioration in the health of the subject that either resulted in 
o a life-threatening illness or injury, or 
o a permanent impairment of a body structure or a body function, or 
o in-patient or prolonged hospitalization, or 
o medical or surgical intervention to prevent life threatening illness or injury or 
permanent impairment to a body structure or a body function, or 
• 
led to fetal distress, fetal death, or a congenital abnormality or birth defect. 
NOTE: Planned hospitalization for a pre-existing condition or a procedure required by the clinical 
investigational plan, without serious deterioration in health, is not considered an SAE. 
 
11.1.3. Adverse Device Effect (ADE) 
In alignment with ISO 14155:2011 (Section 3.1), an Adverse Device Effect is an adverse event related to 
the use of an investigational medical device.  
 
This definition includes adverse events resulting from insufficient or inadequate instructions for use, 
deployment, implantation, installation, or operation, or any malfunction of the investigational medical 
device. 
 
This definition includes any event resulting from use error or from intentional misuse of the 
investigational medical device. 
 
Adverse Device Effects will be reported by the Investigator(s). If escalation is required (due to the 
potential need for reporting) ADEs will be reviewed by Medtronic Medical Affairs. Both confirmed and 

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possible device related events will be included in the study report. ADE(s) may be anticipated or 
unanticipated (UADE). 
 
Examples of adverse device effects include but are not limited to: unintended cutting, unintended 
electrical path, or arcing.  
 
11.1.4. Serious Adverse Device Effect (SADE) 
In alignment with ISO 14155:2011 (Section 3.36), a Serious Adverse Device Effect is an adverse device 
effect that has resulted in any of the consequences characteristic of a serious adverse event. 
 
11.1.5. Unanticipated Serious Adverse Device Effect (USADE) 
In alignment with ISO 14155:2011 (Section 3.42), an Unanticipated Serious Adverse Device Effect is a 
serious adverse device effect which by its nature, incidence, severity, or outcome has not been 
identified in the current version of the risk analysis report.  
 
NOTE: Anticipated serious adverse device effect (ASADE) is an effect which by its nature, incidence, 
severity or outcome has been identified in the risk analysis report. 
 
11.1.6. Adverse Event Severity Classification 
Severity will be defined according to the following criteria: 
Mild 
Awareness of event, but easily tolerated 
Moderate 
Discomfort enough to cause some interference with activities of 
daily living (ADL) 
Severe 
Incapacitating, with an inability to perform ADL 
Death 
Death related to AE 
An AE can be classified as severe and not deemed an SAE. Similarly, an SAE is not automatically severe 
in nature. 
 
11.1.7. Adverse Event Relationship Classification 
Causality assessments define the relationship between the use of the medical device (including the 
medical-surgical procedure) and the occurrence of each adverse event, according to MEDDEV 
(Guidelines on Medical Devices, Clinical Investigations: Serious Adverse Event Reporting). The presence 
of confounding factors, such as concomitant medication/treatment, the natural history of the 
underlying disease, other concurrent illness or risk factors shall also be considered. 
 
Each AE will be classified according to five different levels of causality. The sponsor and the 
investigators will use the following definitions to assess the relationship of the serious adverse event to 
the investigational medical device or procedures: 
Not related:  relationship to the device or procedures can be excluded when: 
1. the event is not a known side effect of the product category the device belongs to or of similar 
devices and procedures 
2. the event has no temporal relationship with the use of the device or the procedures; 
3. the serious event does not follow a known response pattern to the medical device (if the 
response pattern is previously known) and is biologically implausible; 

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4. the discontinuation of medical device application or the reduction of the level of 
activation/exposure - when clinically feasible – and reintroduction of its use (or increase of the 
level of activation/exposure), do not impact on the serious event; 
5. the event involves a body-site or an organ not expected to be affected by the device or 
procedure; 
6. the serious event can be attributed to another cause (e.g. an underlying or concurrent illness/ 
clinical condition, an effect of another device, drug, treatment or other risk factors); 
7. the event does not depend on a false result given by the device used for diagnosis, when 
applicable; 
8. harms to the subject are not clearly due to use error; 
9. In order to establish the non-relatedness, not all the criteria listed above might be met at the 
same time, depending on the type of device/procedures and the serious event. 
 
Unlikely: the relationship with the use of the device seems not relevant and/or the event can be 
reasonably explained by another cause, but additional information may be obtained. 
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/ clinical condition or/and 
an effect of another device, drug or treatment). Cases were relatedness cannot be assessed or no 
information has been obtained should also be classified as possible. 
Probable:  the relationship with the use of the device seems relevant and/or the event cannot be 
reasonably explained by another cause, but additional information may be obtained. 
Causal relationship: the serious event is associated with the device or with procedures beyond 
reasonable doubt when: 
1. the event is a known side effect of the product category the device belongs to or of similar 
devices and procedures; 
2. the event has a temporal relationship with device use/application or procedures; 
3. the event involves a body-site or organ that 
a. the device or procedures are applied to; 
b. the device or procedures have an effect on; 
4. the serious event follows a known response pattern to the medical device (if the response 
pattern is previously known); 
5. the discontinuation of medical device application (or reduction of the level of 
activation/exposure) and reintroduction of its use (or increase of the level of 
activation/exposure), impact on the serious event (when clinically feasible); 
6. other possible causes (e.g. an underlying or concurrent illness/ clinical condition or/and an 
effect of another device, drug or treatment) have been adequately ruled out; 
7. harm to the subject is due to error in use; 
8. the event depends on a false result given by the device used for diagnosis, when applicable; 
9. In order to establish the relatedness, not all the criteria listed above might be met at the same 
time, depending on the type of device/procedures and the serious event. 
 
The Sponsor and the Investigators will distinguish between the serious adverse events related to the 
device and those related to the procedures (any procedure specific to the clinical investigation). An 
adverse event can be related both to procedures and the device. Complications of procedures are 
considered not related if the said procedures would have been applied to the subjects also in the 
absence of device use/application. 

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In some particular cases, the event may be not adequately assessed because information is insufficient 
or contradictory and/or the data cannot be verified or supplemented. The sponsor and the 
Investigators will make the maximum effort to define and categorize the event and avoid these 
situations. Where the sponsor remains uncertain about classifying the serious event, it should not 
exclude the relatedness and classify the event as “possible”.  
 
Particular attention shall be given to the causality evaluation of unanticipated serious adverse (device) 
events. The occurrence of unanticipated events related to the use of the device (USADE) could suggest 
that the clinical investigation places subjects at increased risk of harm than was to be expected 
beforehand. 
 
11.1.8. Adverse Event Outcome Classification 
Outcome of the event will be defined according to the following: 
• 
Fatal: This event is determined to be the cause of death.  
• 
Not Recovering/Not Resolved: The event has retained pathological conditions resulting from the 
prior disease or injury. 
• 
Recovered/Resolved: The event has fully resolved at the end of the study. 
• 
Recovering/Resolving: The event is ongoing at the end of the study. 
• 
Unknown: The event has been unclassified at the end of the study. 
 
11.2. Reporting of Adverse Events 
The following events are generally considered reportable during the course of this study and should be 
reported to the sponsor: 
• 
any ADE, SADE, SAE, or USADE 
• 
any Device Deficiency that might have led to an SADE if  
o suitable action had not been taken or  
o intervention had not been made or  
o circumstances had been less fortunate  
• 
new findings/updates in relation to already reported events.  
 
Events will be reviewed by the sponsor to determine any reporting obligations to regulatory bodies and 
IRBs/ECs.  
 

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The following table captures the reporting requirements for this study. Local and regional regulatory 
requirements shall be followed in addition to study requirements. 
  
Type of Event 
Timeframe 
Submit to 
Other Reporting Requirements 
AE 
As soon  as possible but 
no more than 10 working 
days after the day that 
you become aware of 
information from any 
source, that reasonably 
suggests that an AE has 
occurred  
Sponsor/ Device 
Manufacturer  
 
 
Any Death 
As soon as practicable but 
no more than 10 work 
days after the day that 
you become aware of 
information from any 
source, that reasonably 
suggests that a device has 
or may have caused or 
contributed to the death 
of a patient of your facility 
Sponsor/ Device 
Manufacturer and 
Local (IRB/ EC) 
and regional 
regulators (FDA) 
 
 
UADE 
As soon  as possible, but 
in no event later than 10 
working days after the 
investigator first learns of 
the effect.  
Sponsor / Device 
Manufacturer and 
any local/ 
regionally 
required 
regulators 
 
 
All Serious 
Events including 
SAEs, USADEs, 
Serious Injuries 
or Significant 
Safety Issues 
Within 24 hours, but no 
later than 10 work days 
(and/or per local 
requirements) after the 
day that investigator 
becomes aware of 
information, from any 
source, that reasonably 
suggests that a device has 
or may have caused or 
contributed to a serious 
injury to a patient of your 
facility. 
Sponsor / Device 
Manufacturer and 
as per local 
reporting 
requirements. 
 
 

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11.3. Adverse Event Recording  
All observed adverse events (ADEs, UADEs and SAEs) will be collected and documented at the time of 
surgery  to 28 (+7) days follow-up. If the adverse event is recorded at the last subject visit and 
considered serious and device-related, the event should be followed for resolution for up to seven (7) 
days, or until the resolution of the event, whichever is earliest, even if this falls outside the 28 (+7) day 
visit window. To ensure consistency of data collection no new events will be recorded after the 28 (+7) 
day visit window, even if the subject is being followed for resolution of another event. If the adverse 
event is ongoing at the end of the study, and exceeds the follow up time frame, the patient will 
continue to receive standard care with their normal physician, and the event will be listed as ongoing. 
 
Assessment of the occurrence of an AE will be based on changes in the subject’s physical examination, 
laboratory results and/or signs and symptoms. Adverse events will be monitored until a subject 
completes the study unless the Investigator determines the event is related to the device, in which case 
they will be monitored until resolution if possible. Medical care will be provided, as defined in the 
informed consent, for any AE related to study participation. Adverse events will be collected on an AE 
eCRF and applicable source documentation. To the extent possible, the event to be recorded and 
reported is the event diagnosis as opposed to event symptoms (e.g., fever, chills, nausea and vomiting in 
the presence of a clinically diagnosed infection is to be reported as infection only). For the purposes of 
this protocol, only those AEs occurring after enrollment and the commencement of the tonsillectomy 
with the study device will be recorded. 
 
11.4. Study Contact Information 
Questions regarding safety or medical procedures should be directed to Medtronic MITG Medical 
Affairs. All other questions should be directed to Medtronic MITG Surgical Innovations, Clinical 
Research. Sponsor internal clinical research team and field monitor contact information will be 
distributed to sites, to be retained in the study files, and updated as necessary. 
 
Clinical Affairs 
Medical Affairs 
Stephanie Huston, BS, CCRC 
Senior Clinical Research Specialist/ 
Study Manager Medtronic 
MITG Surgical Innovations  
5920 Longbow Dr. 
Boulder, CO 80301 USA 
Phone: (303) 763-0813 
stephanie.r.huston@medtronic.com 
Matthew Savary, MD 
Director of Medical Affairs  
Medtronic 
MITG Surgical Innovations 
5920 Longbow Dr.  
Boulder, CO 80301 USA 
Phone: 203-530-1395 
Matthew.Savary@medtronic.com 
 
11.5. Device Deficiencies 
In alignment with ISO14155:2011 (Section 3.15), a Device deficiency is an inadequacy of a medical 
device related to its identity, quality, durability, reliability, safety or performance, such as malfunction, 
misuse or use error and inadequate labeling. 
 

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All BiZact™ device deficiencies will be documented on the Device Malfunction eCRF and the device 
should be returned to Medtronic for analysis, if possible. Instructions for returning the device will be 
provided.  Device deficiencies should also be documented in the subject’s medical record. 
 
Device deficiencies are NOT to be reported as AEs.  However, if there is an AE that results from a device 
deficiency, that specific event would be recorded on the eCRF. 
 
12. Data Review Committees 
 
There will be no use of data review committees in this study.  Instead, a steering committee and a 
safety review committee will monitor the trial’s progress including trends of data over time and 
scientific relevance of the data collected. Please see section 15.10. These groups will provide oversight 
in terms of scientific validity and the safe conduct of the study. 
 
By nature, this study’s focus is about the amount of intraoperative bleeding, which is expected to be 
low due to the nature of the procedure and the currently available date. Additionally, this is a study of 
3 sites and 60 subjects, with no planned interim analysis, and as such, has a lower burden in terms of 
severity of implications, and degree of data review and analysis compared to a larger study with interim 
data review needs or a study focusing on severe complications or mortality. Per FDA guidance (OMB 
Control No 0910-0581 “The Establishment and Operation of Clinical Trial Data Monitoring Committees 
for Clinical Trial Sponsors” DMCs are “generally recommended for any controlled trial of any size that 
will compare rates of mortality or major morbidity, but a DMC is not required or recommended for 
most clinical studies.” The guidance goes on to list conditions wherein a DMC may offer additional 
protections to study participants. Apart from the use in pediatric population, this study does not meet 
any of the criteria listed wherein a DMC would provide added benefit. Even within this population, the 
study is small and of short planned duration, so it is unlikely that a DMC would be able to provide 
added or more rapid benefit than the steering committee or safety review mechanisms. 
   
13. Statistical Design and Methods 
 
13.1. Statistical Test Methods 
Continuous variables will be summarized using counts, means, standard deviations, medians, minimum 
and maximum. Categorical variables will be summarized using frequencies and percentages. Changes to 
the planned statistical analysis as defined in the protocol will be documented in the statistical analysis 
plan and clinical study report. 
 
13.2. Sample Size Determination 
The analysis technique will be a 1-sample t-test (or Wilcoxon ranked sign if nonparametric test is 
desired), with a one-sided type I error rate (α) of 0.025.  A sample size of 60 subjects is selected to 
ensure that multiple surgeons participate and to create an opportunity for a range of subject ages to be 
enrolled.  Statistical power for a sample size of 60 subjects exceeds 99%. 
 

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13.3. Analysis Population 
The intent-to-treat (ITT) population will consist of all enrolled subjects in the study who have undergone 
tonsillectomy and had contact with the BiZact™ device. The endpoint analyses based on the ITT 
population will be considered the principal analyses.    
The per-protocol (PP) population will consist of all patients in the ITT population who do not have a major 
protocol violation. Analyses on the PP population will provide supporting evidence to the primary results.  
 
13.4. Statistical Analysis Endpoints 
13.4.1. Primary Endpoint 
The primary hypotheses of this study are: 
H0: Mean intra-operative blood loss =31 mL 
HA: Mean intra-operative blood loss < 31 mL 
 
The analysis technique will be a 1-sample t-test, with a one-sided type I error rate (α) of 0.025.  If intra-
operative blood loss data appear to be non-normally distributed (as evidenced by p < 0.05 from a 
Shapiro-Wilk test), a Wilcoxon signed rank test will also be conducted. 
 
The performance goal of 31 mL derives from a meta-analysis comparing modern technology-assisted to 
conventional tonsillectomy (i.e. electrocautery and cold steel) (7).  This paper included a total of 3,139 
patients included in thirty-three published studies.  The values from the studies that reported intra-
operative bleeding were combined to calculate a mean blood loss. This value encompasses a variety of 
techniques and technologies and a number of different studies to capture a realistic value for 
comparison. 
 
Intra-operative blood loss during tonsillectomy with BiZact™ is expected to be low. The expected mean 
value for the BiZact™ device is a conservative estimate derived from data for LigaSure™ and other 
vessel sealing systems in the Alexiou meta-analysis (7). The expected standard deviation is the average 
of the standard deviation values for all studies that reported blood loss in the meta-analysis.   
Expected mean intra-operative blood loss for BiZact™: 10 mL 
Expected standard deviation: 15.1 mL 
 
Additionally, descriptive statistics for blood loss will be reported for different age groups (ages 2-5 and 
ages 6-12) as well as for different sites, surgeons, and countries.  
 
13.4.2. Secondary Endpoint 
Secondary endpoints will be summarized using descriptive statistics. In addition, 95% confidence 
intervals will be provided, unless otherwise noted. For continuous variables, the mean, median, and 
standard deviation will be reported.  For categorical data, proportions will be reported. No hypothesis 
tests are planned 
 
13.5. Statistical Analysis of Safety Endpoints 
The safety endpoints will be analyzed using the ITT population. Proportions of the following events will 
be reported for the study: 
• 
Post-operative hemorrhage 

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o Any primary (≦24 hours) requiring medical intervention and/or secondary (>24 hours) 
bleeding requiring medical intervention (e.g., cautery, admission for observation, or re-
operation) 
• 
Post-operative readmission  
• 
Evidence of glossopharyngeal nerve damage as diagnosed by the investigator via subject 
assessment (e.g., prolonged pain or difficulty swallowing) 
• 
Localized Infection 
o Infection confined to a single organ or tissue 
• 
Other serious device-related adverse events  
 
13.6. Handling of Missing Data 
No data imputation will be performed for missing data.  All practical monitoring and follow-up steps 
will be taken to ensure complete and accurate data collection. Since primary endpoints are assessed 
intra-operatively, it is anticipated that there will be minimal missing data for these endpoints.  
 
13.7. Interim Analysis 
Currently no interim analysis is planned for this study. Should the need arise for an interim analysis, the 
protocol will be revised, and statistical plan will be updated accordingly. Periodic data extractions may 
need to occur in order to provide ongoing feedback for regulatory purposes (e.g. for annual reports), to 
prepare information for periodic reviews of safety information (e.g. counts of adverse events) or to 
assist in the ongoing internal review of data to ensure consistency and validity of data. This is 
considered part of ongoing study management activities, and the endpoints of the study will not be 
formally analyzed. 
 
13.8. Poolability of Results 
Poolability of blood loss data will be assessed for each of the participating investigational sites.  
Descriptive statistics will be reported separately by site.  A one-way ANOVA will test whether there is 
evidence of a difference in mean blood loss between sites.  If this test does not suggest a difference (p-
value ≥ 0.15), data will be pooled across sites for inference (i.e., for the primary hypothesis test and 
95% confidence interval for mean blood loss).  If there is evidence of a difference (p < 0.15 from the 
one-way ANOVA), confidence intervals will be presented separately for each site, and p-values from the 
hypothesis test in Section 8.4.1 will also be calculated separately for each site.   For full details on the 
planned analysis and poolability, see Statistical Analysis Plan (SAP). 
 
14. Ethics 
 
14.1. Statement(s) of Compliance 
This clinical investigation will be conducted in accordance with the ethical principles that have their 
origin in the Declaration of Helsinki, and any regional or national regulations such as FDA regulations 
(US), and ISO 14155:2011 (except conditions specifically excluded as adverse events in Section 11.1.1) 
as appropriate. All principles of the Declaration of Helsinki have been implemented in this clinical study 
by means of the subject informed consent process, IRB/EC approval, clinical study training, clinical 
study registration, publication policy.  

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The clinical investigation will not begin until all necessary approvals/favorable opinions are obtained 
from the appropriate IRB/EC or regulatory authority, as appropriate.  Should an IRB/EC or regulatory 
authority impose any additional requirements, they will be followed.  If any action is taken by a EC/IRB 
with respect to the investigation, that information will be forwarded to the sponsor. 
 
Information regarding the study and study data will be made available via publication on clintrials.gov.  
Additionally, the results of this study will be offered for publication at the conclusion of the study, if 
participating investigators believe the data warrants publication in an appropriate journal. 
 
 
15. Study Administration  
 
15.1. Monitoring  
Site visits will be conducted by an authorized Medtronic representative to qualify potential sites, 
conduct site initiation, ensure compliance, assess informed consent process, monitor study data, 
subjects’ medical records, eCRFs, device accountability, device use and storage, IRB/EC submissions, 
regulatory binder in accordance with current protocol, applicable regulations and standards, and the 
respective local and national regulations and guidelines (if applicable). The Study Investigator and the 
investigating site will permit authorized clinical research personnel and clinical monitors from 
Medtronic or contracted by Medtronic to review completed eCRFs, IRB/EC decisions, and Investigator 
and clinical site records at regular intervals throughout the study as well as permit study-related 
monitoring, audits, EC/IRB review, and regulatory inspection(s) by providing direct access to source 
data/documents. Additionally, subject charts and clinical records will be requested and reviewed so 
that protocol adherence and source documentation can be verified. In instances where data protection 
regulations prohibit the direct examination of hospital records by the study Sponsor or designee(s), the 
Investigator will cooperate in a system of source data verification with the Sponsor.  Monitoring may be 
performed with in person visits or remotely, when applicable. 
 
To ensure the rights, safety, and welfare of study subjects are being maintained, the monitor will 
maintain assurance that all study staff are trained on the study protocol and use of the investigational 
medical devices.  If the monitor discovers that an investigator is not complying with the signed 
Investigator Agreement, the investigational plan, applicable laws, or any conditions of approval 
imposed by the reviewing IRB/EC, the monitor will report to the Sponsor and take such steps necessary 
to promptly secure compliance.  If compliance cannot be secured, device shipments to the investigator 
may be discontinued and the investigator’s participation in the investigation terminated. The monitor 
shall also require such an investigator to dispose of or return the device, unless this action would 
jeopardize the rights, safety, or welfare of a subject. 
 
15.2. Data Management 
Visual and/or computer data review will be performed to identify possible data discrepancies.  In 
regions where applicable, the investigator will clearly mark or provide a sign/data within clinical record 
to indicate that the subject is enrolled in this clinical investigation. Where copies of the original source 
document as well as print outs of original electronic source documents are retained, these shall be 
signed and dated by a member of the investigation site team with a statement that it is a true 
reproduction of the original source document. Manual and/or automatic queries will be created in the 

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Oracle remote data capture (RDC) system and will be issued to the site for appropriate response.  The 
site staff will be responsible for resolving all queries in the database. Medications will be coded under 
the World Health Organization (WHO) dictionary while Medical History, Surgical History and/or Adverse 
Events will be coded in Medical Dictionary for Regulatory Activities (MedDRA). 
 
This study will be using a 21 CFR Part 11 compliant electronic data capture system. All system level 
validation documentation is retained within the Information Systems group. 
 
15.3. Direct Access to Source Data/Documents 
Investigator(s)/institution(s) will permit study-related monitoring, audits, IRB/EC review, and regulatory 
inspection(s), and provide direct access to source data/documents as per local policies and regulations. 
 
15.4. Confidentiality 
All records identifying the subject will be kept confidential and, to the extent permitted by the 
applicable laws and/or regulations, will not be made publicly available.  
 
Subject names will be kept confidential. Only the subject number will be recorded in the eCRF, and if 
the subject name appears on any other document, it must be obliterated. Study findings stored on a 
computer will be stored in accordance with local data protection laws. The subjects will be informed in 
writing that representatives of the sponsor, IRBs/ECs, or Regulatory Authorities may inspect their 
medical records to verify the information collected, and that all personal information made available 
for inspection will be handled in strictest confidence and in accordance with local data protection laws. 
Subjects will also be informed that information regarding the study that does not include subject 
identifiers will be posted on clinicaltrials.gov. 
 
If the results of the study are published, the subject’s identity will remain confidential.  
The investigator will maintain a master list to enable subjects’ records to be identified. 
 
15.5. Liability  
Medtronic maintains appropriate clinical study liability insurance coverage as required under applicable 
laws and regulations and will comply with applicable local law and custom concerning specific 
insurance coverage. If required, a clinical study insurance statement/certificate will be provided to the 
IRB/EC.  
 
15.6. Clinical Investigation Plan (CIP)/Protocol Amendments 
A CIP/Protocol amendment will be prepared when there are revisions that are significant changes or 
corrections, or modifications that impact subject safety, ethical conduct, data integrity or study design. 
CIP/Protocol amendments must undergo review and approval by the sponsor, IRB/EC and any 
appropriate regulatory authority, and will be logged in the document version history (Section 17). 
IRB/EC approval, regulatory authority approval, site training and a new Acknowledgement form will be 
signed and returned before any new procedures take place. 
 

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15.7. Record Retention 
The investigator and the sponsor will maintain the records of the study including all pertinent 
correspondence, the study protocol with any/all amendments, all correspondence with and approval 
from the IRB/EC, the clinical trial agreement, the Investigator Agreement, device accountability 
records, individual subject records, and signed informed consent forms. Subject files, other source data 
and essential documentation kept in the Investigator study files, must be kept for a period of no less 
than 2 years after the latter of the following two dates: the date on which this investigation is 
terminated or completed, or the date that the records are no longer required for purposes of 
supporting a premarket application; Medtronic will also retain the study records according to 
Medtronic policy, whichever prevailing policy or regulation may be longer. Records may need to be 
maintained by the Principal Investigator for a longer duration if national regulations require or if agreed 
to in writing with Medtronic. All data and documents should be made available if requested by relevant 
authorities.  
 
15.8. Publication and Use of Information 
The Medtronic Publication and Authorship Policy is aligned with the International Committee of 
Medical Journal Editors (ICMJE) recommendations (www.icmje.org). Medtronic will seek to publish, in 
appropriate peer-reviewed journals and scientific conferences, results of clinical studies where human 
subjects are involved, regardless of outcome. While study results are owned by Medtronic, all data on 
which a publication is based will be made available to all authors as required for their participation in 
the publication process. Furthermore, data may be published or used by study investigators provided 
that such publication or use is in accordance with this protocol, the Medtronic Publication and 
Authorship Policy, and the Clinical Investigation Agreement. Investigators must submit a copy of all 
manuscripts and/or abstracts to Medtronic for review and comment 30 days prior to planned 
submission. Medtronic acknowledges that its right to review and comment shall relate solely to the 
proprietary, licensing, and/or confidential rights Medtronic may have in such proposed publication, 
rather than whether such results and/or opinions are favorable to Medtronic. 
 
The publication of post-hoc analyses, regional results, or single-center experiences based on 
multicenter clinical studies should not precede that of the primary multicenter publication, and should 
cite the primary publication whenever possible, as required by specific journal and scientific meeting 
guidelines.  
 
Medtronic involvement in a publication (e.g., funding of the study; sponsor of the study; collection, 
analysis, and interpretation of data; professional writing assistance) must be disclosed according to 
journal-specific policies, submission requirements, and prevailing editorial standards, in addition to 
those specified by International Committee of Medical Journal Editors. Authors must ensure that an 
acknowledgement/disclosure statement is included in the body of the manuscript for Medtronic to 
review for accuracy. All authors must also disclose financial or personal affiliations that could be 
considered conflicts of interest as per journal/conference requirements. 
 
To enable health care providers, payers, and subjects access to the wealth of Medtronic’s research, 
Medtronic will report its scientific data in accordance with the principles outlined in the Guidance 
Document on Registration and Reporting Results of Company-Sponsored Clinical Trials Under FDAAA 
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15.9. Suspension or Early Termination  
Medtronic or appropriate regulatory authorities reserve the right to suspend or discontinue the study 
at any stage, with written notice to all investigators, all institutions, all reviewing IRBs (US), any 
investigator(s) in communication with the EC (Australia), all subjects and subjects’ personal physicians 
and any applicable regulatory agencies. Similarly, investigators may withdraw from the study at any 
time, subject to providing written notification to Medtronic 30 days prior to the date they intend to 
withdraw from study participation. However, Medtronic and investigators will be bound by their 
obligation to complete the follow-up of subjects already enrolled in the study. The subjects must be 
followed according to the clinical protocol, and any additional information obtained during subject 
follow-up shall be reported to Medtronic on the appropriate eCRF, provided subjects have not 
withdrawn individually. The above paragraph relates to the withdrawal of a site from the study, not the 
withdrawal of individual subjects. For individual subject withdrawal, see section 9.10.4. 
 
15.10. 
Safety Committees 
15.10.1. 
Independent Medical Monitor 
The Sponsor will utilize an Independent Medical Monitor to provide medical review and adjudication of 
pre-specified adverse events in support of protocol defined endpoint data after the site investigator 
has provided his or her initial assessment of the event. The Independent Medical Monitor will be a 
qualified, board-certified otolaryngology surgeon that is not affiliated with an investigative center.  
 
Throughout the course of the study and during the review of adverse events, the Independent Medical 
Monitor will be blinded to the investigational site and Investigator(s) and shall make decisions about 
relatedness, severity, etc. independent of Medtronic personnel. Adverse events will be provided to the 
independent medical monitor, at minimum, on a monthly basis to adjudicate. 
 
In alignment with current Medtronic safety policies, the most conservative assessment of the event 
between the site investigator and the medical monitor will be documented and acted upon as 
appropriate (i.e. if the medical monitor evaluates an event as not related but the site has considered 
the event possibly related, the event will remain categorized as possibly related), and reported as such 
both internally to the internal safety data review committee, to post-market vigilance, and to external 
agencies as needed.  
 
The medical monitor may be contacted by the internal study team or the internal safety data review 
team for additional expertise to aid in decision making and recommendations should the need arise. 
 
15.10.2. 
Steering Committee 
The Steering Committee will consist of Investigators participating in this study, as well as relevant 
members of Medtronic Clinical and Medical Affairs in supportive roles. As noted, investigators for the 
studies are qualified as part of site qualification procedures and are board-certified otolaryngology 
surgeons. The role of the Steering Committee is to make recommendations on the design and conduct 
of the study, the analysis of data, and the communication of results in alignment with the Medtronic 
Publication and Authorship Policy. The Steering Committee will also be presented with aggregate 
adverse event data during typical Steering Committee meetings, as described in the Steering 
Committee Charter; this review will aid in the interpretation of the meaning of the collective data and 

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potentially help guide study conduct and definitions if additional clarity is needed (e.g. definition of a 
type of adverse event for consistency across study sites). Because this committee is comprised of 
investigators from the study, it will not be considered fully impartial, but can make recommendations 
to the internal safety review team and the internal study team. 
 
15.10.3. 
Internal Safety Data Review 
Internal safety data reviews will consist of a representative of the safety team (registered nurse), an 
internally employed Medtronic physician, a statistician, the project manager or designee as 
representative from the study, a member of clinical research leadership for research decision 
escalation and support as well as representative of quality or post-market vigilance reviews.  The 
independent medical monitor may be consulted if there is a need for clarification of event reviews, for 
additional expertise is needed for decision making around the conduct of the study, or for additional 
interpretation of aggregated adverse event information.  
 
The function of this group will be to review safety trends on a periodic basis during the study, as well as 
any trends or events on an ad hoc basis (e.g. should any unexpected events occur), to monitor subject 
safety, and to provide guidance regarding the continued safety of enrolled subjects. These meetings 
are held at least on a quarterly basis during study enrollment, but are also more frequent if necessary 
(e.g. due to more rapid enrollment), and conducted as urgently as possible in the event of an 
unexpected frequency or type of adverse event.  As this team will have the access to aggregate 
information on the severity, relatedness, and expectedness of adverse events for the overall study, and 
between study sites, as well as post-market vigilance data for the product where it is commercially 
available, this team will have the necessary data and the ultimate responsibility to make decisions 
regarding holding enrollment at a site or for the entire study or stopping/terminating a study site or the 
entire study. The procedure by which safety events will be evaluated individually and in aggregate 
form, is detailed in the Clinical Safety Management and Potential Complaint Plan.  
 
 

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16. References 
1. 
Younis RT, Lazar RH. History and current practice of tonsillectomy. Laryngoscope. 2002;112(8 Pt 
2 Suppl 100):3-5. doi: 10.1002/lary.5541121403. PubMed PMID: 12172228. 
2. 
Timms MS, Temple RH. Coblation tonsillectomy: a double blind randomized controlled study. J 
Laryngol Otol. 2002;116(6):450-2. doi: 10.1258/0022215021911031. PubMed PMID: 12385358. 
3. 
Karatzias GT, Lachanas VA, Sandris VG. Thermal welding versus bipolar tonsillectomy: a 
comparative study. Otolaryngol Head Neck Surg. 2006;134(6):975-8. doi: 
10.1016/j.otohns.2006.03.003. PubMed PMID: 16730541. 
4. 
Sinha UK, Gallagher LA. Effects of steel scalpel, ultrasonic scalpel, CO2 laser, and monopolar 
and bipolar electrosurgery on wound healing in guinea pig oral mucosa. Laryngoscope. 
2003;113(2):228-36. doi: 10.1097/00005537-200302000-00007. PubMed PMID: 12567074. 
5. 
Prokopakis EP, Lachanas VA, Benakis AA, Helidonis ES, Velegrakis GA. Tonsillectomy using the 
Ligasure vessel sealing system. A preliminary report. Int J Pediatr Otorhinolaryngol. 2005;69(9):1183-6. 
doi: 10.1016/j.ijporl.2005.03.042. PubMed PMID: 15961165. 
6. 
Lachanas VA, Prokopakis EP, Bourolias CA, Karatzanis AD, Malandrakis SG, Helidonis ES, et al. 
Ligasure versus cold knife tonsillectomy. Laryngoscope. 2005;115(9):1591-4. doi: 
10.1097/01.mLg.0000172044.57285.b6. PubMed PMID: 16148700. 
7. 
Alexiou VG, Salazar-Salvia MS, Jervis PN, Falagas ME. Modern technology-assisted vs 
conventional tonsillectomy: a meta-analysis of randomized controlled trials. Arch Otolaryngol Head 
Neck Surg. 2011;137(6):558-70. doi: 10.1001/archoto.2011.93. PubMed PMID: 21690508. 
8. 
Pang Y, Gong J, Huang J, He S, Zhou H. Coblation tonsillectomy under surgical microscopy: A 
retrospective study. J Int Med Res. 2016;44(4):923-30. doi: 10.1177/0300060516628705. PubMed 
PMID: 27217239. 
9. 
Pang YT. Paediatric tonsillectomy: bipolar electrodissection and dissection/snare compared. J 
Laryngol Otol. 1995;109(8):733-6. PubMed PMID: 7561495. 
 
 

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17. Version History 
Version 
Summary of Changes 
Author(s)/Title 
1.0 
• 
Not Applicable, New Document 
Nicholas Paquette,  
Senior Medical Writer 
 
Tianna Aronson, MPH 
Clinical Project 
Manager 
 
2.0 
• 
FDA Requested Clarifications including: 
o Clarification related to number of sites 
o Definitions of ITT and per protocol population 
o Inclusion of specific “usability challenges” data 
collection 
o Updates for consistency and clarity related to risks 
of procedure and device, as well as the collection 
period for these events 
Tianna Aronson, MPH 
Clinical Project 
Manager 
 
Greg Sindberg,  
Senior Medical Writer 
 
3.0 
• 
Removal of subjects age 13 or older to focus study on 
pediatric population (ages 2-12), along with adjustment of 
related consent/assent language 
• 
FDA requested clarifications including: 
o Adjustments to the assessment of poolability of 
data 
o Clarification that each site will receive or be 
assigned to a different generator 
o Clarification on reportable adverse events 
o Clarification on role of data review/ other 
committees responsible for safety and integrity of 
data 
• 
Minor adjustments to device information and removal of 
Appendix B, to indicate Investigator’s Brochure (IB) will exist 
as a separate document. 
• 
Minor/Administrative changes including: 
o Section numbering and order change due to 
template revision  
o Updated patient diary sample 
o Updated FLACC scale sample 
Tianna Aronson, MPH 
Clinical Project 
Manager 
 
Greg Sindberg,  
Senior Medical Writer 
 
4.0 
• 
Clarification to Section 8.2, minor formatting changes 
Tianna Aronson, MPH 
Clinical Project 
Manager 

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5.0 
• 
Removal of Australia as a Sponsor Site 
• 
Removal of Australia as a clinical site 
• 
Decrease from 3 to 2 clinical sites 
• 
Increase to 36 from 24 subject per site 
• 
Decrease from 6 surgeon investigators to 5 surgeon 
investigators 
• 
Clarification of Adverse Event reporting timeline  
• 
Change in Sponsor Contact from Tianna Aronson to 
Stephanie Huston 
• 
Removal of Australian IFU 
Stephanie Huston, BS, 
CCRC Senior Clinical 
Research 
Specialist/Study 
Manager 
 

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18. Appendices 
18.1. APPENDIX A: Instructions for Use (IFU) 
The copies of the IFU contained in this appendix have been inserted from the controlled file. Please 
note the IFU for the United States and for Australia are included and have different indications. The 
English version of the IFU for Australia is included herein, directly following the United States IFU. 
Always refer to the IFU provided with the device itself, in case of any labeling change, and delay in the 
update in this appendix. 

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United States IFU 
 
 
 
 
 

BiZact™ Pediatric Clinical Study Protocol 
Appendices 
 
MDT17024BZP 
Version 5.0  
Appendix A, Page 3 of 8  
 
Medtronic Confidential 
This document is electronically controlled  
 
056-F275, v3.0 Clinical Investigation Plan Template 
United States IFU 
 
 
 

BiZact™ Pediatric Clinical Study Protocol 
Appendices 
 
MDT17024BZP 
Version 5.0  
Appendix A, Page 4 of 8  
 
Medtronic Confidential 
This document is electronically controlled  
 
056-F275, v3.0 Clinical Investigation Plan Template 
United States IFU 
 
 
 

BiZact™ Pediatric Clinical Study Protocol 
Appendices 
 
MDT17024BZP 
Version 5.0  
Appendix A, Page 5 of 8  
 
Medtronic Confidential 
This document is electronically controlled  
 
056-F275, v3.0 Clinical Investigation Plan Template 
United States IFU 
 
 
 

BiZact™ Pediatric Clinical Study Protocol 
Appendices 
 
MDT17024BZP 
Version 5.0  
Appendix A, Page 6 of 8  
 
Medtronic Confidential 
This document is electronically controlled  
 
056-F275, v3.0 Clinical Investigation Plan Template 
United States IFU 
 
 
 

BiZact™ Pediatric Clinical Study Protocol 
Appendices 
 
MDT17024BZP 
Version 5.0  
Appendix A, Page 7 of 8  
 
Medtronic Confidential 
This document is electronically controlled  
 
056-F275, v3.0 Clinical Investigation Plan Template 
United States IFU 
 
 
 

BiZact™ Pediatric Clinical Study Protocol 
Appendices 
 
MDT17024BZP 
Version 5.0  
Appendix A, Page 8 of 8  
 
Medtronic Confidential 
This document is electronically controlled  
 
056-F275, v3.0 Clinical Investigation Plan Template 
United States IFU 
 
 

BiZact™ Pediatric Clinical Study Protocol 
Appendices 
 
MDT17024BZP 
Version 5.0 
Appendix B, Page 1 of 4  
 
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18.2. APPENDIX B: Sample of Post-Operative Patient Diary 
The Post-Operative Patient Diary will be kept as a separate document. A sample is provided below, and 
subject to change. 
 
 

BiZact™ Pediatric Clinical Study Protocol 
Appendices 
 
MDT17024BZP 
Version 5.0 
Appendix B, Page 2 of 4  
 
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This document is electronically controlled  
 
056-F275, v3.0 Clinical Investigation Plan Template 
 
 
 

BiZact™ Pediatric Clinical Study Protocol 
Appendices 
 
MDT17024BZP 
Version 5.0 
Appendix B, Page 3 of 4  
 
Medtronic Confidential 
This document is electronically controlled  
 
056-F275, v3.0 Clinical Investigation Plan Template 
 
 

BiZact™ Pediatric Clinical Study Protocol 
Appendices 
 
MDT17024BZP 
Version 5.0 
Appendix B, Page 4 of 4  
 
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056-F275, v3.0 Clinical Investigation Plan Template 
 
   

BiZact™ Pediatric Clinical Study Protocol 
Appendices 
 
MDT17024BZP 
Version 5.0 
Appendix C, Page 1 of 1 
 
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18.3. APPENDIX C:  Sample of Wong-Baker FACES® Pain Rating Scale 
 The Wong Baker FACES pain rating scale will be provided to sites as a separate document. A sample is 
provided below, and subject to change. 
 
 
 
Date of Assessment: _________________     Time of Assessment: _______________ 
 

BiZact™ Pediatric Clinical Study Protocol 
Appendices 
 
MDT17024BZP 
Version 5.0 
Appendix D, Page 1 of 2 
 
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18.4. APPENDIX D: Sample of FLACC Behavioral Pain Assessment Scale 
 The FLACC Behavioral Pain Assessment scale will be provided to sites as a separate document. A 
sample is provided below, and subject to change. 
 
 

BiZact™ Pediatric Clinical Study Protocol 
Appendices 
 
MDT17024BZP 
Version 5.0 
Appendix D, Page 2 of 2 
 
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BiZact™ Pediatric Clinical Study Protocol 
Appendices 
 
MDT17024BZP 
Version 5.0 
Appendix F, Page 1 of 1 
 
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18.5. APPENDIX E: Additional records and reports 
There are no additional records or reports other than those required in Subpart G of the IDE 
regulations.  
 

BiZact™ Pediatric Clinical Study Protocol 
Appendices 
 
MDT17024BZP 
Version 4.0 
Appendix G, Page 1 of 1 
 
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18.6. APPENDIX F: List of Investigators and Institutions 
Investigative Sites information including addresses, contact information, Principal Investigators, their 
respective IRBs/ECs, and will be retained in a separate document from the body of the clinical 
investigation plan document. This will be provided to investigative sites and updated as necessary.