Evaluation of Efficacy of Use of TubeClear® to Restore Patency to Occluded Enteral Access Devices in Pediatric Patients (Phase I)
Phase: NA
Conditions: Enteral Nutrition
Sponsor: Children's Hospital of Philadelphia

 
Template version: July 26, 2012 
Title: 
Evaluation of Efficacy of Use of TubeClear® to Restore Patency to 
Occluded Enteral Access Devices in Pediatric Patients 
Short Title 
TubeClear®  Evaluation in Pediatric Patients 
NCT Number 
Document Date: 
NCT02724631  
November 8, 2018 
 
 
 
 

 
 
 
 
 
ii 
 
ii
Title: 
Evaluation of Efficacy of Use of TubeClear® to Restore Patency to 
Occluded Enteral Access Devices in Pediatric Patients 
Short Title 
TubeClear®  Evaluation in Pediatric Patients 
Drug or Device Name(s): TubeClear®  
FDA IND 
Not applicable 
Regulatory Sponsor: 
Actuated Medical, Inc. 
310 Rolling Ridge Drive 
Bellefonte, PA 16823  
eIRB Number 
14-011488 
Protocol Date: 
February 8, 2016 
Amendment 1 Date: June 17, 2016 
Amendment 3 Date: January 12, 2018 
Amendment 2 Date: October 17, 2017 
Amendment 4 Date: November 8, 2018 
Study Sponsor:   
Actuated Medical, Inc. 
310 Rolling Ridge Drive 
Bellefonte, PA 16823 
United States 
 
Site Co-Investigators: 
Vijay Srinivasan, MD 
The Children’s Hospital of Philadelphia 
Suite 8566, Critical Care Medicine 
8th Floor NE  Main 
34th Street and Civic Center Blvd 
Philadelphia, PA, 19104 
Phone 215-590-5505 
email: srinivasan@email.chop.edu 

 
 
 
 
 
iii 
 
iii 
Sharon Y. Irving, PhD, CRNP 
The Children’s Hospital of Philadelphia 
3401 Civic Center Blvd.  
7th Floor Main, 7NE29 
Philadelphia, PA 19104 
Phone 215-430-3474 
Email: irvings@email.chop.edu  
Anne Marie Cahill 
The Children’s Hospital of Philadelphia 
3401 Civic Center Blvd 
3rd Floor Main 
Philadelphia, PA 19104 
Phone 267-425-7122 
Email: cahill@email.chop.edu  

  
 
 
 
 
iv 
 
iv
TABLE OF CONTENTS 
ABBREVIATIONS AND DEFINITIONS OF TERMS................................................................................ VI 
ABSTRACT ......................................................................................................................................................... 1 
1 
BACKGROUND INFORMATION AND RATIONALE ............................................................... 5 
1.1 
INTRODUCTION ..................................................................................................................................... 5 
1.2 
NAME AND DESCRIPTION OF INVESTIGATIONAL PRODUCT OR INTERVENTION ..................................... 7 
1.3 
FINDINGS FROM NON-CLINICAL AND CLINICAL STUDIES ..................................................................... 8 
1.3.1 
Non-Clinical Studies ....................................................................................................................... 8 
AGE (YEAR) .................................................................................................................................................... 11 
JEJUNUM THICKNESS (MM) .............................................................................................................................. 11 
0 – 4 ................................................................................................................................................................ 11 
0.6 – 0.8........................................................................................................................................................... 11 
5 – 9 ................................................................................................................................................................ 11 
10 – 14 ............................................................................................................................................................ 11 
1.3.2 
Clinical Studies ............................................................................................................................. 12 
1.4 
SELECTION OF DRUGS AND DOSAGES................................................................................................. 13 
1.5 
RELEVANT LITERATURE AND DATA ................................................................................................... 13 
1.6 
COMPLIANCE STATEMENT .................................................................................................................. 13 
2 
STUDY OBJECTIVES ................................................................................................................... 14 
2.1 
PRIMARY OBJECTIVE (OR AIM) .......................................................................................................... 14 
2.2 
SECONDARY OBJECTIVES (OR AIM) .................................................................................................... 14 
3 
INVESTIGATIONAL PLAN ......................................................................................................... 16 
3.1 
GENERAL SCHEMA OF STUDY DESIGN ............................................................................................... 16 
3.1.1 
Screening Phase ............................................................................................................................ 16 
3.1.2 
Study Treatment Phase .................................................................................................................. 17 
3.1.3 
Follow-up Phase ........................................................................................................................... 18 
3.2 
ALLOCATION TO TREATMENT GROUPS AND BLINDING ...................................................................... 18 
3.3 
STUDY DURATION, ENROLLMENT AND NUMBER OF SITES ................................................................. 19 
3.3.1 
Duration of Study Participation .................................................................................................... 19 
3.3.2 
Total Number of Study Sites/Total Number of Subjects Projected ................................................ 19 
3.4 
STUDY POPULATION ........................................................................................................................... 19 
3.4.1 
Inclusion Criteria .......................................................................................................................... 19 
3.4.2 
Exclusion Criteria ......................................................................................................................... 20 
4 
STUDY PROCEDURES ................................................................................................................. 21 
4.1 
SCREENING VISIT ............................................................................................................................... 21 
4.2 
STUDY TREATMENT PHASE ................................................................................................................ 21 
4.3 
FOLLOW-UP PHASE ............................................................................................................................. 24 
4.4 
UNSCHEDULED VISITS ........................................................................................................................ 24 
4.5 
CONCOMITANT MEDICATION ............................................................................................................. 24 
4.6 
RESCUE MEDICATION ADMINISTRATION ............................................................................................ 25 
4.7 
SUBJECT COMPLETION/WITHDRAWAL ............................................................................................... 25 
4.7.1 
Early Termination Study Visit ....................................................................................................... 25 
5 
STUDY EVALUATIONS AND MEASUREMENTS ................................................................... 26 
5.1 
SCREENING AND MONITORING EVALUATIONS AND MEASUREMENTS ................................................ 26 
5.1.1 
Medical Record Review ................................................................................................................. 26 
5.1.2 
Physical Examination .................................................................................................................... 27 
5.1.3 
Vital Signs ..................................................................................................................................... 27 
5.1.4 
Laboratory Evaluations................................................................................................................. 27 

  
 
 
 
 
v 
 
v
5.1.5 
Pregnancy Testing ......................................................................................................................... 27 
5.1.6 
Other Evaluations, Measures ........................................................................................................ 27 
5.2 
EFFICACY EVALUATIONS ................................................................................................................... 28 
5.2.1 
Diagnostic Tests, Scales, Measures, etc. ....................................................................................... 28 
5.3 
PHARMACOKINETIC EVALUATION ...................................................................................................... 28 
5.4 
SAFETY EVALUATION ......................................................................................................................... 28 
6 
STATISTICAL CONSIDERATIONS ........................................................................................... 30 
6.1 
PRIMARY OBJECTIVE .......................................................................................................................... 30 
6.2 
SECONDARY OBJECTIVES (OR AIM) .................................................................................................... 30 
6.3 
STATISTICAL METHODS...................................................................................................................... 32 
6.3.1 
Group Allocation Flow Chart for Phase IIB ................................................................................. 32 
6.3.2 
Baseline Data ................................................................................................................................ 32 
6.3.3 
Primary Objective Analysis ........................................................................................................... 32 
6.3.4 
Secondary Objective Analysis ....................................................................................................... 33 
6.3.5 
Pharmacokinetic Analysis ............................................................................................................. 34 
6.3.6 
Safety Analysis .............................................................................................................................. 34 
6.4 
SAMPLE SIZE AND POWER .................................................................................................................. 34 
6.5 
INTERIM ANALYSIS ............................................................................................................................ 35 
7 
STUDY DEVICE ............................................................................................................................. 36 
7.1 
DESCRIPTION ...................................................................................................................................... 36 
7.1.1 
Packaging ...................................................................................................................................... 36 
7.1.2 
Labeling ........................................................................................................................................ 36 
7.1.3 
Dosing ........................................................................................................................................... 36 
7.1.4 
Treatment Compliance and Adherence ......................................................................................... 37 
7.1.5 
Device Accountability ................................................................................................................... 37 
8 
SAFETY MANAGEMENT ............................................................................................................ 38 
8.1 
CLINICAL ADVERSE EVENTS .............................................................................................................. 38 
8.2 
ADVERSE EVENT REPORTING ............................................................................................................. 38 
9 
STUDY ADMINISTRATION ........................................................................................................ 39 
9.1 
TREATMENT ASSIGNMENT METHODS................................................................................................. 39 
9.1.1 
Randomization............................................................................................................................... 39 
9.1.2 
Blinding ......................................................................................................................................... 39 
9.1.3 
Unblinding .................................................................................................................................... 39 
9.2 
DATA COLLECTION AND MANAGEMENT ............................................................................................ 39 
9.3 
CONFIDENTIALITY .............................................................................................................................. 40 
9.4 
REGULATORY AND ETHICAL CONSIDERATIONS.................................................................................. 40 
9.4.1 
Data and Safety Monitoring Plan ................................................................................................. 40 
9.5 
DATA COLLECTION AND MANAGEMENT ............................................................................................ 40 
9.5.1 
Risk Assessment ............................................................................................................................. 42 
9.5.2 
Potential Benefits of Trial Participation ....................................................................................... 42 
9.5.3 
Risk-Benefit Assessment ................................................................................................................ 43 
9.6 
RECRUITMENT STRATEGY .................................................................................................................. 43 
9.7 
INFORMED CONSENT/ASSENT AND HIPAA AUTHORIZATION ............................................................ 43 
9.8 
PAYMENT TO SUBJECTS/FAMILIES ..................................................................................................... 44 
10 
PUBLICATION ............................................................................................................................... 45 
11 
REFERENCES ................................................................................................................................ 46 
 

  
 
 
 
 
vi 
 
vi
ABBREVIATIONS AND DEFINITIONS OF TERMS 
AE 
 
Adverse Event 
Pain Scales 
 
Include but are not limited to: 
Face, Legs, Activity, Cry, Consolability (FLACC) 
 - > 7 years of age; may be used in the older child  
Revised Face, Legs, Activity, Cry, Consolability 
(rFLACC) 
- > 7 years of age; may be used in the older child 
FACES Pain Scale Revised (FPS-R) 
- > 3 years of age; may be used in the older 
neurologically impaired, non-verbal child  
Numeric Pain Scale  
- > 8 years of age; cognitively intact patients, 
able to self-report 
AMI 
 
Actuated Medical, Inc. 
BMI 
 
Body Mass Index 
BSA 
 
Body Surface Area 
CHOP 
 
The Children’s Hospital of Philadelphia 
DOB 
 
Date of Birth 
EAD 
 
Enteral Access Device 
 
 
 
J  
 
Jejunostomy Tube  
ND  
 
Nasoduodenal Tube  
NG 
 
Nasogastric Tube 
NJ 
 
Nasojejunal Tube 
AMT GJ 
 
Applied Medical Technology, Inc. Gastrojejunal 14 Fr 
Tube 
EAD(A) 
 
Adult Feeding and Decompression Access Device ND, NG, NJ, 
G, and J Tubes of size 10 – 18 Fr, 10 – 140 cm 
EAD(P) 
 
Pediatric Enteral Access Device ND, NG, and NJ 6 – 8 Fr, 38 – 
140 cm; and NG tube (Corflo, Corpak MedSystems) used as a J 
tube inserted through a G tube 6 – 8 Fr, 38  – 140 cm; GJ tube 
(AMT) 14 Fr, 38 – 140 cm (15 – 55 in) 
EAD(P) 
Adverse Event 
 
EAD displacement, EAD damage, enteral tract tissue injury 

 
 
 
 
 
 
 
vii 
 
vii 
EHR 
 
Electronic Health Record 
EPIC 
 
Integrated Electronic Health Record system used at The 
Children’s Hospital of Philadelphia  
Fr 
 
French gauge (conventional unit of measure used to describe 
tube diameter size (1 Fr = 0.33 mm)) 
IR 
 
Interventional Radiology 
MRN 
 
Medical Record Number 
MUSC 
 
Medical University of South Carolina 
NIH / NICHD 
 
National Institutes of Health / National Institute of Child Health 
and Human Development 
PCU 
 
Progressive Care Unit 
PICU 
 
Pediatric Intensive Care Unit 
SBIR 
 
Small Business Innovation Research 
Tube 
 
Feeding tube  
USA 
 
United States of America 

 
 
 
1 
 
ABSTRACT  
Context:  
Occluded enteral access devices (EADs) are a significant problem for pediatric patients, with 
occlusion rates ranging from 12.5% to 35%. Occluded EADs can lead to extended times of 
decreased energy intake, resulting in patients quickly exhausting their energy reserves and 
developing dehydration with electrolyte abnormalities. Current methods used to restore 
patency to an occluded EAD at The Children’s Hospital of Philadelphia (CHOP) involve 
application of enzymes and chemicals (e.g., Clog Zapper), which have variable rates of timely 
success. If these methods are unsuccessful and patency cannot be restored, the EAD must be 
replaced and may require radiological intervention with exposure to radiation and contrast 
material. TubeClear® addresses this clinical need to safely and efficaciously restore patency 
to occluded EADs at the patients’ bedside while the EAD remains in the patient. Additionally, 
this reduces the need to transport the patient to the radiology suite with subsequent exposure 
to radiation and contrast material for EAD location conformation after replacement.  
Objectives:  
1) To evaluate feasibility and tolerability of TubeClear® to restore patency in occluded 
EAD(P)s, and 2) to compare efficacy of TubeClear® to the CHOP Standard Treatment to 
restore patency in occluded EAD(P)s. 
Study Design:  Phased Study (n=64). 
Phase I:  Feasibility and tolerability of TubeClear® intervention in consecutive eligible 
Subjects (n=15) with occluded EAD(P)s who have not attained their 18th birthday. 
Following successful completion of Phase I as deemed by the IRB, the Study will proceed to 
Phase IIA and IIB to run concurrently. 
Phase IIA:  Ability of TubeClear® intervention to restore patency in consecutive eligible 
Subjects (n=15) with occluded EAD(P)s who have not attained their 11th birthday. 
Phase IIB: Randomized efficacy comparison between TubeClear® intervention (experimental, 
n=17) and CHOP Standard Treatment (control, n=17) in eligible Subjects with occluded 
EAD(P)s who are between 11 years of age and have not attained their 18th birthday. 
Setting:   
This Study will take place in the CHOP Pediatric Intensive Care Unit (PICU),Progressive 
Care Unit (PCU), and Interventional Radiology Department (IR).   
Inclusion criteria: 
1. Males or females who have not attained their 18th birthday (Phase I), or 
Males or females who have not attained their 11th birthday (Phase IIA), or 
      Males or females between 11 years of age and have not attained their 18th birthday (Phase 
IIB) 
2. Indwelling occluded EAD(P) that is either: 

 
 
 
2 
 
a. ND, NG, NJ tube composed of Polyvinyl Chloride (PVC) and Polyurethane 6 – 8 
Fr, 38 – 140 cm; or 
b. NG tube (Corflo, Corpak MedSystems) used as a jejunal tube inserted through a 
gastrostomy tube, 6 – 8 Fr, 38 – 140 cm 
c. GJ (AMT) tube 14 Fr, 38 – 140 cm (15 – 55 in) 
Exclusion criteria: 
1. Ward of the state 
2. Positive pregnancy test/ Pregnant females 
3. Any active gastrointestinal abnormalities or malformations, including but not limited to 
infections, inflammation, obstruction, and/or recent abdominal surgery or trauma 
4. Constant dependency on the EAD(P) for a glucose source (e.g. hyperinsulinism states) 
5. Unable to tolerate water volume needed for the EAD(P) flush 
6. Allergies to the contrast agent(s) used in post-Intervention radiological imaging 
7. Measured total length of EAD(P) less than 38 cm (15 inches) - from external port to 
EAD(P) distal end 
8. Unknown length of EAD(P) 
9. Attending physician declines enrollment based on clinical judgement 
10. Subject attains 18 years of age during study duration 
 
Study Interventions and Measures:   
TubeClear® is the investigational device being studied and is deemed by the FDA to be non-
significant risk for use in this study (Appendix D).   
Potential eligible Subjects will be identified by screening the electronic health records. An 
occlusion is defined by direct identification of a clog or through a feeding pump alarm that 
sounds when patency of an EAD(P) is disrupted. Eligible subjects who meet 
inclusion/exclusion criteria will be approached for informed consent and, when applicable, 
assent to participate in the study. Eligible subjects may be enrolled more than once and up to 
a maximum of three times in the study for each instance of EAD(P) occlusion. 
In Phase I, all enrolled subjects will receive the TubeClear® intervention. If the TubeClear® 
intervention is unable to restore EAD(P) patency, further steps to restore patency of the 
occluded EAD will be determined by the clinical team per usual practice. 
In Phase IIA, all enrolled subjects will receive the TubeClear® intervention. If the TubeClear® 
intervention is unable to restore EAD(P) patency, further steps to restore patency of the 
occluded EAD will be determined by the clinical team per usual practice. 
In Phase IIB, subjects will be randomized into either TubeClear® intervention or CHOP 
Standard Treatment. If either intervention is unable to restore EAD(P) patency, further steps 
to restore patency of the occluded EAD will be determined by the clinical team per usual 
practice. 
Primary Endpoints: 

 
 
 
3 
 
The Phase I primary endpoints are feasibility and tolerability.  Feasibility will be defined as 
ability of the user to operate TubeClear® from clearing stem insertion into the occluded 
EAD(P) through activation to patency restoration. Tolerability will be defined as ability of the 
Subject to withstand TubeClear® intervention. 
The Phase IIA primary endpoint is ability of TubeClear® intervention to establish patency in 
Subjects with occluded EAD(P)s. 
The Phase IIB primary endpoint is the efficacy of TubeClear® intervention to restore EAD(P) 
patency compared to CHOP Standard Treatment. 
Secondary Endpoints: 
In Phase I, Subjects will be monitored for 1) pain, using established age-appropriate pain 
scales, 2) physiologic changes in vital signs, 3) distress related EAD(P) events, and 4) adverse 
events related to TubeClear® use.  
In Phase IIA, Subjects will be monitored for 1) pain, using established age-appropriate pain 
scales, 2) physiologic changes in vital signs, 3) distress related EAD(P) events, and 4) adverse 
events related to TubeClear® use. 
In Phase IIB, Subjects will be monitored for 1) pain, using established age-appropriate pain 
scales, 2) physiologic changes in vital signs, 3) distress related EAD(P) events, and 4) adverse 
events related to either group.  
Safety Monitoring: 
This study will incorporate a data and safety monitoring plan with medical monitor to review 
study data for adverse events to ensure the safety of study subjects. Following the use of either 
standard treatment or TubeClear® intervention, all Subjects will receive an abdominal 
radiograph with contrast. Radiographs will be reviewed by a radiologist (blinded to the study) 
to assess for tube integrity and location, and enteral tract tissue injury that may be attributable 
to either intervention. 
In all phases, surveillance will include assessment for adverse events related to the respective 
study intervention (i.e. EAD(P) displacement, EAD(P) damage, enteral tract tissue injury) and 
will continue for three (3) days. Patients who are discharged from the hospital prior to 3 days 
will be followed up by phone until completion of 3 days following study interventions. All 
adverse events will be reported to the IRB and medical monitor.  
Statistical Analysis: 
Data from Phase I and Phase IIA will be observational in nature and will not test a hypothesis.  
In Phase IIB, intention-to-treat analysis will be used to compare the efficacy of the TubeClear® 
intervention to the CHOP Standard Treatment in accordance with the CONSORT guidelines. 
Exploratory-per-protocol analysis will also be reported.   
 
 
Figure 1: Study Flow Chart 

 
 
 
4 
 
 
Table 1. Schedule of Study Procedures 
 
Study Phase 
PHASE I     
n=15 
PHASE IIA 
PHASE IIB 
 
n=15 
n=34 
Screening - Review Health Record for Eligibility 
X 
X 
X 
Informed Consent/Assent 
X 
X 
X 
Medical History/Labs/Medication/Health Record Review 
X 
X 
X 
Pregnancy Test, if not documented as completed in EMR 
X 
X 
X 
Radiograph Review – pre TubeClear®  Intervention or Standard Treatment 
X 
X 
X 
Physical Exam/Pain Assessment Pre – Day of TubeClear®  or Standard Treatment 
X 
X 
X 
Study Intervention - TubeClear®  Intervention 
X 
X 
 
Randomization to TubeClear®  Intervention or Standard Treatment 
 
 
X 
Physical Exam/Pain Assessment Post – Day of TubeClear®  or Standard Treatment 
X 
X 
X 
Radiograph Review – Post TubeClear®  Intervention  or Standard Treatment 
X 
X 
X 
Physical Exam/Pain Assessment/ Day 1 Follow up  
X 
X 
X 
Physical Exam/Pain Assessment/ Day 2 Follow up 
X 
X 
X 
Physical Exam/Pain Assessment/ Day 3 Follow up 
X 
X 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Adverse Event Assessment 
X 
X 
X 

 
 
 
5 
 
1 
BACKGROUND INFORMATION AND RATIONALE 
1.1 
Introduction 
Approximately, seven (7) million enteral access devices (EADs) are placed in the United 
States of America (USA), annually.1 Recent literature reports as many as 24% of pediatric 
patients require an EAD(P) during their hospital stay.2 With a reported 6.4 million  
hospitalized pediatric patients in 2009 across the US3, it can be estimated that as many as 1.5 
million children may have an EAD(P) during their hospital stay. An important limitation of 
EADs is that they can become occluded.i Reported EAD occlusion rates range from 12.5% to 
35%.3-8 Using 25% as an approximate occlusion percent, USA medical facilities treat over 1.7 
million occlusions (adults and pediatrics) annually. Assuming twenty (20)ii minutes of nursing 
time at a mean of $55.24/houriii, occluded EADs cost the USA healthcare system over 
$30million, annually.   
Current methods to restore patency to an occluded EAD(P) used at The Children’s Hospital 
of Philadelphia (CHOP) involve application of enzymes and chemicals (e.g., Clog Zapper), 
which have variable rates of timely success. If these methods are unsuccessful and patency 
cannot be restored, the EAD must be replaced and may require radiological intervention with 
exposure to radiation and contrast material.   
TubeClear® addresses this clinical need to safely and efficaciously restore patency to occluded 
EADs at the patients’ bedside while the EAD remains in the patient. Additionally, this reduces 
the need to transport the patient to the radiology suite with subsequent exposure to radiation 
and contrast agent for EAD location conformation after replacement. The TubeClear® System 
is comprised of a reusable Control Box and a single use Clearing Stem (Figure 1A). The 
Control Box Model 101 and Clearing Stem Model TC-0608 [EAD(P) Clearing Stem Design], 
to be used in this Study, are FDA clearediv for use with occluded EADs in adult patients.v 
Specifically, the Clearing Stem Model TC-0608 has been approved by the FDA for use with 
6-8 Fr EADs measuring 38cm-140cm in adults. 
 
i Occlusions are clogs, blockages, or obstructions of feeding formula, medications, supplements, ground food, or aspirated 
contents. Occlusions can be a complete blockage or a partial blockage resulting in a “sluggish” tube in accordance with the 
FDA-cleared indications for the TubeClear System. Occlusions are called clogs in the TubeClear® Operator’s Manual and 
the Directions for Use (packaging insert) to agree with colloquial terminology used by end users. 
ii Conclusions of Clinician Focus Groups, July 2009. 
iii Nursing Time:  Bureau of Labor Statistics (www.bls.gov), mean hourly wage for Registered Nurses is $33.23/hour + 25% 
fringe rate + 33% overhead rate = $55.24. 
iv For medical devices that receive USA market sale permission via the FDA 510(k) regulatory path, the product is said to be 
“cleared” whereas for medical devices that receive USA market sale permission via the FDA Premarket Approval (PMA) 
path the product is said to be “approved”.  TubeClear® followed a FDA 510(k); therefore, TubeClear® was cleared by the 
FDA for USA market sale in EAD(A)s. 
v TubeClear® Control Box Model 101 is also CE Marked for adults and pediatrics and available for sale in the EU. 

 
 
 
6 
 
Clearing Stem models for ND, NG, NJ, G, and J Tubes of size 10 – 18 Fr, 10 – 140 cm and 
ND, NG, NJ, and J Tubes of size 6 – 18 Fr, 15 – 36 cm for adults have been FDA cleared.vi,vii 
TubeClear® has been demonstrated to be safe and effective in bench and animal testing 
(Section 1.3.1), and has been successfully evaluated in more than 17 adult patients (Section 
1.3.2). 
 
In bench testing, TubeClear® restored patency to the occluded 14 Fr 48 inch long NE EAD in 
an average of 2.8 minutes, compared to 42.1 minutes for warm water and 57.5 minutes for 
enzyme treatment (Table 2, and TP-5007-079 and TR-5007-079). The shorter time to restore 
patency with TubeClear® reduces interruptions in nutrition and medication dosing from almost 
an hour to minutes. In the 17 adult documented cases, patency was restored and no pain was 
documented (Appendix E). 
 
vi FDA 510(k) Clearance Numbers: K121571 (6/2012), K123659 (12/2012), K131052 (8/2013), K172556 (6/2016), K163092 
(12/2016) see Appendix A. 
vii TubeClear® for EAD(A)s is CE Marked for adults and pediatrics and available for sale in the EU. 
(A) 
(B) 
Figure 2: (A) TubeClear® Control Box Model 101 with attached Clearing Stem Model NE-1043. (B) 
Illustration of Clearing Stem insertion into EAD.  The Control Box remains external to the Patient.  
The Collar (see circled inset) limits the depth to which the Clearing Stem can be inserted; therefore, 
the Clearing Stem does not reach the EAD distal ports (see square inset). 
Method 
Number of 
Runs 
Number of Runs 
Unclogged 
Average 
Procedure Time 
TubeClear 
30 
30 
2.8 minutes 
Warm Water 
30 
26 
42.1 minutes 
Enzyme Treatment 
30 
29 
57.5 minutes 
 
Table 2:  Bench Testing evaluated at AMI with Levin 14 Fr 48 inch long nasoenteral tubes.x   

 
 
 
7 
 
The setting for the 
proposed Study is a 
large, tertiary, urban, 
pediatric hospital.  It is 
appropriate as pediatric 
patients who develop 
an occluded EAD(P) 
are often current in-
patients being managed 
for 
pre-existing 
medical and/or surgical 
conditions.  viii 
1.2 
Name 
and 
Description 
of 
Investigational 
Product 
or 
Intervention 
TubeClear® 
is 
comprised of a reusable 
Control Box and a 
single use Clearing Stem 
(Figure 2A).  The 
Control Box is to be located 
and operated between 
six (6) inches and twenty-
five (25) inches away 
from the patient (Figure 
2B). The Control Box 
contains a motor that creates 
a linear reciprocating 
motion (i.e., forward and 
backward motion).  The Clearing Stem contains a proximal end magnet.  The magnet is 
connected to a specially designed flexible wire that is encased in a plastic sheath.  The 
proximal end of the Clearing Stem connects to the Control Box via a magnetic connection.    
The Operator manually inserts the distal end of the Clearing Stem (Figures 2B and 3), (set to 
the EAD length, measured in centimeters, cm) into the proximal end of the EAD.  The 
Operator then turns the Control Box motor ‘on’ and manually directs the Clearing Stem’s 
progression along the inside of the EAD.  The distal Clearing Stem tip acts on the occlusion 
mechanically breaking up the occlusion restoring EAD patency. 
The TubeClear® occlusion clearing procedure (Figure 4) is an iterative process of adding 20-
50ml of warm water then inserting the Clearing Stem and allowing the distal wire tip to act 
on the occlusion for approximately 30 seconds, moving the Clearing Stem backward and 
forward approximately 10 cm (4 in) several times to disperse loosened occlusion particles, the 
Clearing Stem is removed and aspiration of the broken occlusion particles is performed by the 
Operator. This process is repeated until the Clearing Stem Collar (also interchangeably known 
 
viii Half of the occlusions were made from 2:1 ratio coagulated protein and ground medical. Half from1:1 ratio of feeding 
formula and fiber. Enzyme Treatment was Clog Zapper (Corpak MedSystems (Buffalo Grove, IL)).  . 
Figure 
4: 
 
TubeClear 
iterative 
occlusion clearing procedure. 
Figure 3:  Clearing Stem 
with design features. 

 
 
 
8 
 
as Depth Limiter hereinafter), preset to the measured EAD cm length, reaches the proximal 
port of the EAD (Figure 2B, circled inset).   
Additional Information and Background on TubeClear® can be found in Appendices A - E. 
1.3 
Findings from Non-Clinical and Clinical Studies  
1.3.1 Non-Clinical Studies 
Performance evaluations were conducted via Bench and Animal Testing (Appendix C).  The 
TubeClear® Control Box model (i.e., Model 101) used in Bench and Animal Testing will be 
used in this Study. Therefore, the Control Box operation does not change for this Study.  The 
EAD(A) and EAD(P) Clearing Stem designs are the same except that the EAD(P) Clearing 
Stem design is optimized for smaller lumens, and the Operator sets the collar (Figure 5). The 
Clearing Stem design changes for the smaller lumens do not change the Bench Testing 
outcomes; therefore, the EAD(A) Clearing Stem Bench Testing applies to the EAD(P) 
Clearing Stem design. Additionally, Benchtop verification and validation testing has been 
completed to confirm substantial equivalence of safety and effectiveness (as per 21 CFR 
807.100) of the EAD(P) Clearing Stem to the FDA cleared EAD(A) Clearing Stem 
(K131052).  The 510(k) submission for the EAD(P) Clearing Stem was cleared by the FDA 
for the adult indication (K131052/K163092/K172556). The test protocols and reports used in 
510(k) submission K131052 are included in Appendix C.  The test protocols and reports used 
in the EAD(P) Clearing Stem submission are included in Appendix C.2.  The Control Box is 
the same between the EAD(A) and the EAD(P).  Therefore, all test protocols and reports 
pertaining to the Control Box can be found in Appendix C. 
For the EAD(P), an Operator Set collar (Figure 5) that 
is placed by the Operator is necessary to match varying 
EAD(P) lengths. Safety of this change with potential 
for Operator error was tested via an in-vitro and in-vivo 
animal models. Efficacy was also examined in the 
animal testing and found to be consistent with previous 
EAD(A) results. 
The Bench Testing focused on five (5) criteria: 1) 
Technical, 2) Efficacy, 3) Safety, 4) Usability and 5) 
Ambient Noise. Animal Testing focused on Safety and 
Efficacy.  Clinical Testing was not required for the 
FDA cleared EAD(A) indication.  Testing was 
compliant with CFR 21, Part 820 – Quality System 
Regulation and ISO 13485:2003 – Medical Devices – Quality Management Systems. (Non-
Clinical Studies data, test protocols and test reports in Appendix C). 
Bench Testing 
1) 
Technical testing for the TubeClear® EAD(A) Clearing Stem included electrical 
safety, product specifications verification, product shelf life, transportation vibration, and 
packaging integrity (TP-4010-005, TP-4010-006, TP-4010-018, TP-4010-019, TP-4010-
 
Figure 
5: 
Placement 
of 
the 
Operator Set Collar 

 
 
 
9 
 
028, TR-4010-005, TR-4010-005-1, TR-4010-006, TR-4010-006-8, TR-4010-018, TR-
4010-018-1, TR-4010-019, and TR-4010-028-1).  Intertek Electrical: 100791030CLE-001 
IEC 60601-1-6, 100791030CLE-003 IEC 60601-1, 100791030CLE-004 IEC. Since the 
EAD(A) and EAD(P) Clearing Stem designs are the same except for optimization for smaller 
lumens and Operator-set collar, the technical test results for the EAD(A) Clearing Stem design 
are applicable to the EAD(P) Clearing Stem design.   
 
Additional technical testing has been completed for the EAD(P) Clearing Stem design which 
included product specifications verification, product shelf life, transportation vibration, and 
packaging integrity (TP-4021-022, TP-4017-013, TP-4017-014, TR-4021-022, TR-4017-
013-1, TR-4017-013-2, and TR-4017-014).  Intertek Electrical safety testing did not change 
between the two models. 
2) 
Efficacy was tested in a variety of EADs of different lengths, diameters, and material 
properties.  TubeClear® EAD(A) Clearing Stem successfully restored patency (TP-5007-079, 
and TR-5007-079).  Since the designs are similar for the EAD(A) and EAD(P) Clearing Stems 
and the same Control Box will be used, the Efficacy Test results for the EAD(A) Clearing 
Stem designs are applicable to the EAD(P) Clearing Stem design. 
 
Efficacy testing has been completed for the EAD(P) Clearing Stem design (TC-0608).  
TubeClear® successfully restored patency (TP-4021-018, TP-4017-001 and TR-4021-018 
TR-4017-007, see Figure 6). 
 
Figure 6: (TOP): The TC-0608 Clearing Stem (TubeClear-orange) was more successful (14/15=93%) 
at clearing clogs compared to warm water flushes (blue, 3/15=20%, p = 0.0002) and Clog Zapper 
enzymes (green, 5/15=33%, p = 0.002); (BOTTOM): Active nursing time and total procedure time for 
clearing various clog types (easy, medium and hard) using TubeClear with TC-0608 (orange), warm 
water flushes (blue) and Clog Zapper enzymes (green) with percentages representing success of 
different methods with different types of clogs (Kruskal Wallis, p<0.05), N=5 clog/treatment/clog 
formulation. 

 
 
 
10 
 
TC-0608 was used in preliminary testing to clear five (5) total occlusions in AMT GJ tubes, 
14 Fr (Figure 7). Three (3) of these clogs were defined as “soft” clogs (i.e., Type 3) made out 
of feeding formula and fiber. The remaining two (2) clogs were defined as “hard” clogs (i.e., 
Type 1 and 2ix) made of crushed medication and coagulated protein. TC-0608 successfully 
restored patency to all five (5) GJ tubes, although it was noted that the Clearing Stem “moved 
smoothly, but slowly after encountering the second bend” of the GJ tube. Overall, it should 
be noted that while clearing 14 Fr AMT GJ tubes, the operator may feel an increase in 
resistance at the second bend of the GJ tube, but the TC-0608 Clearing Stem Model is capable 
of restoring full patency to this type of feeding tube. 
 
3) 
Safety testing verified that TubeClear® EAD(A) Clearing Stem did not cause physical 
damage to the EAD, excess EAD movement or migration, or EAD heating due to friction 
caused by actuation (TP-4010-009, TP-4010-026, TR-4010-009-2, and TR-4010-026). Since 
the designs are similar for the EAD(A) and EAD(P) Clearing Stems and the same Control Box 
will be used, the Safety Test results for the EAD(A) Clearing Stem designs are applicable to 
the EAD(P) Clearing Stem design.  
 
Safety testing has been completed for the EAD(P) Clearing Stem design.  This testing verified 
that TubeClear® did not cause physical damage to the EAD, excess EAD movement or 
migration, or EAD heating due to friction caused by actuation (TP-4021-017, TP-4021-019, 
TR-4021-017, and TR-4021-019). 
4) 
Usability Testing conducted in accordance with FDA Draft Guidance for Industry and 
Food and Drug Administration Staff - Applying Human Factors and Usability Engineering to 
Optimize Medical Device Design.  It was concluded that TubeClear® EAD(A) Clearing Stem 
is reasonablyx safe and effective for the intended users, uses, and use environments (TP-4010-
015, and TR-4010-027).  Since the designs are similar for the EAD(A) and EAD(P) Clearing 
 
ix See AMI Work Instruction WI-7.3.003 
x Conclusion per recommendations of Guidance Documents (Medical Devices and Radiation-Emitting Products) - Draft 
Guidance for Industry and Food and Drug Administration Staff - Applying Human Factors and Usability Engineering to 
Optimize Medical Device Design. Center for Devices and Radiological Health, 2011. (Accessed Dec 20, 2013, at 
http://www.fda.gov/MedicalDevices/DeviceRegulationandGuidance/GuidanceDocuments/ucm259748.htm.) 
 
Figure 7: Cross-section of the gastric portion (left) 
and jejunal portion (right) of an AMT GJ feeding 
tube. 

 
 
 
11 
 
Stems and the same Control Box will be used, the Usability Test results for the EAD(A) 
Clearing Stem designs are applicable to the EAD(P) Clearing Stem design. Additionally, for 
this Study, the Operator’s will all be trained by Actuated Medical Staff (Appendix F). 
 
Usability testing has been completed for the EAD(P) Clearing Stem design.  It was concluded 
that TubeClear® is reasonablyix safe and effective for the intended users, uses, and use 
environments (TP-4017-012 and TR-4017-012). 
5) 
Ambient Environment Noise Level Testing was performed on the TubeClear® Control 
Box during simulated operating conditions. The Control Box motor generates sound during 
operation; therefore, the sound was measured to determine if it would significantly increase 
the noise levels in the clinical environment (TP-5007-050, TR-5007-050 and TR-5007-050-
2). The Control Box ‘on’ noise level is very similar to the ambient noise level of an ICU; 
therefore, it is not anticipated to increase patient distress in the PICU, PCU, or IR. 
In-vitro Animal Testing 
Safety was evaluated in an over-insertion mode (contrary to the Instructions for use) in an in-
vitro animal model.  For normal operation, a depth control collar limits the insertion of the 
Clearing Stem into the EAD; thus prevents the Clearing Stem tip from exiting the EAD.  To 
test safety, ex-vivo porcine stomach and small intestine tissue samples with thicknesses similar 
to humans of age 0 to 39 years of age were examined in the simulated over-insertion mode. A 
porcine model was selected due to similarity of gastric features to that of humans aged 0 to 39 
years4. The range of intestinal thickness (jejunum) for human ages 0 to 39 years is 0.6 – 1.0 
mm (Table 3). Tissue samples from the porcine intestine tissue used for testing were between 
0.284 mm and 1.0 mm as measured via two independent methodologies. 
As such, it was concluded that the tissue samples used for this safety testing were 
representative of both adult and pediatric patients and the results of the testing are applicable 
to both populations (TR-4010-022). 
The EAD(A) Clearing Stem was advanced at a rate of 65-70 mm/min to simulate actual use. 
The maximum force of the Clearing Stem tip on the tissue sample was 3.597 N. The 
advancement of the Clearing Stem stopped when the wire was observed to be bent at 
approximately 45o. In the 60 trials run, the Clearing Stem caused small indentations, but no 
full puncture was observed (TP-4010-008, and TR-4010-008).   
 
Table 3:  Jejunum Thickness in Different Age Groups 
Age (Year) 
Jejunum Thickness (mm) 
0 – 4  
0.6 – 0.8 
5 – 9 
0.7 – 0.9 
10 – 14 
0.7 – 0.9 
15 – 19 
0.8 – 1.0 
20 – 29 
0.8 – 1.0 
30 – 39 
0.8 – 1.0 

 
 
 
12 
 
This testing was repeated for the EAD(P) Clearing Stem design.  Tissue samples from the 
porcine intestine (jejunum) tissue were on average between 0.62 mm and 0.92 mm.  It was 
concluded through statistical analysis that this was representative of both adult and pediatric 
patients and the results of the testing are applicable to both populations.  No punctures of 
porcine intestine (jejunum) tissue samples were achieved in a realistic worst-case misuse test 
scenario (TP-4021-020 and TR-4021-020). 
In-vivo Animal Testing 
The safety and efficacy of the Alpha (first design iteration) EAD(P) TubeClear® Clearing 
Stem design was tested in a live porcine model at the Medical University of South Carolina.  
Use of TubeClear® was performed in a porcine model to simulate pediatric insertion by M. 
Michael Swindle, VMD, a veterinarian, Mark H. Delegge, MD, FACG, CNSP, AGAF, 
FASGE, a gastroenterologist, conducted the standard Intervention and Kristi L. Helke, DVM, 
Ph.D., a board certified pathologist, conducted the pathology evaluations.   
1) 
The efficacy of the EAD(P) Clearing Stem in clearing EAD(P)s with simulated 
occlusions was evaluated in a porcine model. Patency was restored in an average time of 2.37 
minutes (TP-5017-009, TR-5017-009 and TR-5017-010).   
2) 
Safety was evaluated in an over-insertion mode (contrary to the Instructions for use).  
For normal operation, a depth control collar limits the insertion of the Clearing Stem into the 
EAD; thus prevents the Clearing Stem tip from exiting the EAD. To test safety, the collar was 
removed, and the Clearing Stem’s distal tip was intentionally advanced approximately 2.5cm 
beyond the distal end of the EAD(P) so that the distal tip contacted and remained in contact 
with the porcine mucosal intestinal tissue for six (6) minutes while in ‘on mode’ (TP-4010-
008, and TR-4010-008). No evidence suggested TubeClear® (consistent to instructions for 
use) produced intestinal trauma beyond that which can be caused by insertion of an EAD(P). 
In the over-insertion situation (inconsistent to instructions for use), the Clearing Stem caused 
lesions that were highly localized, but no full puncture was observed.   
1.3.2   Clinical Studies 
Human Pharmacokinetics 
TubeClear® is a medical device. Therefore, human pharmacokinetics is not applicable. 
Clinical Data from Field Use in Adults (including post-marketing surveillance data) 
To date, one patient has been enrolled in an IRB approved TubeClear® clinical Study. The 
Study was at Walter Reed National Military Medical Center, but was terminated after the PI 
retired from the armed forces. TubeClear® restored patency, and there was no report of 
discomfort during use (Appendix E).  
Once TubeClear® was FDA cleared for commercial use, several hospitals conducted post-
marketing evaluations. Wexner Medical Center at the Ohio State University evaluated the 
device and completed evaluation questionnaires (Appendix E). Three other facilities have 
used TubeClear® and provided results (Appendix E). All seventeen (17) TubeClear® 

 
 
 
13 
 
applications in adults were successful in restoring patency. No adverse events or 
pain/discomfort in patients were reported.    
TubeClear® undergoes an annual Post-Market Surveillance study. No adverse events or other 
significant issues have been reported by end users thus far. Moreover, FDA maintains an 
adverse event database known as MAUDE (Manufacturer and User Facility Device 
Experience), where end users report adverse events for medical devices for public disclosure. 
No adverse events have been reported to MAUDE for TubeClear® since original market 
clearance in 2012. 
Clinical Studies in Children 
To date, there have been no IRB-approved pediatric clinical studies.   
A single male pediatric off-label use of TubeClear® has been reported for compassionate care 
in a 14 Fr NG EAD. This pediatric use was successful without any adverse event or patient 
discomfort. 
1.4 
Selection of Drugs and Dosages 
TubeClear® is a medical device.  Therefore, selection of drugs and doses is not applicable.   
1.5 
Relevant Literature and Data 
The established age-appropriate pain scales used in this study have been validated and cited 
extensively.5-7    
1.6 
Compliance Statement 
This Study will be conducted in full accordance with all applicable Children’s Hospital of 
Philadelphia (CHOP) Research Policies and Procedures and all applicable Federal and State 
laws and regulations including 45 CFR 46, 21 CFR Parts 50, 54, 56, 312, 314 and 812 and 
Good Clinical Practice. All episodes of noncompliance will be documented. 
The investigators will conduct the Study in accordance with this protocol, obtain informed 
consent and, where applicable, assent, and will report unanticipated problems involving risks 
to Subjects or others in accordance with the CHOP IRB Policies and Procedures and all 
Federal requirements. Collection, recording, and reporting of data will be accurate and will 
ensure the privacy, health, and welfare of research Subjects during and following Study 
completion.  
 
 

 
 
 
14 
 
2 
STUDY OBJECTIVES  
The objectives of this study are to 1) evaluate feasibility and tolerability of TubeClear® to 
restore patency in occluded EAD(P)s, and 2) compare efficacy of TubeClear® to the CHOP 
Standard Treatment to restore patency in occluded EAD(P)s. This study will be carried out in 
phases – Phase I followed by Phase IIA and IIB to run concurrently. The objective of Phase I 
is to evaluate feasibility and tolerability of TubeClear® intervention to restore patency in 
occluded EAD(P)s in patients who have not attained their 18th birthday. The objective of Phase 
IIA is to measure the ability of TubeClear® intervention to restore patency in occluded 
EAD(P)s in a younger age group i.e. patients who have not attained their 11th birthday. The 
objective of Phase IIB is to compare efficacy of TubeClear® intervention with the CHOP 
Standard Treatment to restore patency in occluded EAD(P)s in patients who are between 11 
years of age and have not attained their 18th birthday using a randomized controlled design.   
For the purpose of this Study, EAD(P)s are  ND, NG, and NJ 6 – 8 Fr, 38 – 140 cm; NG tube 
(Corflo, Corpak MedSystems) used as a J tube inserted through a G tube, 6 – 8 Fr, 38  – 140 
cm; and AMT GJ tube, 14 Fr, 38 – 140 cm (15 – 55 in). In all phases, if the study intervention 
is unable to restore EAD(P) patency, further steps to restore patency will be carried out by the 
clinical team per usual practice. 
2.1 
Primary Objective (or Aim) 
The primary objectives of this study are to 1) evaluate feasibility and tolerability of 
TubeClear® to restore patency in occluded EAD(P)s, and 2) compare efficacy of TubeClear® 
to the CHOP Standard Treatment to restore patency in occluded EAD(P)s. 
The primary endpoints in Phase I are feasibility and tolerability of TubeClear® intervention.  
Feasibility will be defined as ability of the user to operate TubeClear® device (as per 
instructions and training in Appendix F) from insertion of the clearing stem into the occluded 
EAD(P) through device activation to patency restoration. Tolerability will be defined as 
ability of the Subject to undergo TubeClear® intervention.   
The primary endpoint in Phase IIA is the ability of TubeClear® intervention to restore 
patency in Subjects with occluded EAD(P)s. This will be termed as EAD(P) patency 
restoration and will be measured by the ability to flush the EAD(P) with 10 ml of air within 
five (5) minutes after completion of the intervention.  
The primary endpoint of Phase IIB is the efficacy of TubeClear® intervention compared to 
CHOP Standard Treatment to restore patency in Subjects with occluded EAD(P)s. EAD(P) 
patency restoration will be measured by the ability to flush the EAD(P) with 10 ml of air 
within five (5) minutes after completion of either intervention.  
 
2.2 
Secondary Objectives (or Aim) 
The secondary objectives of this study are to assess subject pain, changes in physiological 
parameters, distress related EAD(P) events and adverse events related to the interventions. 

 
 
 
15 
 
In Phase I, Subject pain will be assessed before and after use of TubeClear® intervention using 
established age-appropriate pain scales. Acute changes in physiologic parameters will be 
measured, including changes in heart rate, blood pressure and respiratory rate.  Distress related 
EAD(P) events which may be manifested by pulling or yanking of the EAD(P) will be 
monitored in relation to intervention.  Following the TubeClear® intervention, each Subject 
will receive an abdominal radiograph with contrast. Radiographs will be reviewed by a 
radiologist (blinded to the study) for EAD(P) adverse events (i.e., EAD(P) displacement, 
EAD(P) damage, enteral tract tissue injury) attributable to the TubeClear® intervention.   
In Phase IIA, Subject pain will be assessed before and after use of TubeClear® intervention 
using established age-appropriate pain scales. Acute changes in physiologic parameters will 
be measured, including changes in heart rate, blood pressure and respiratory rate.  Distress 
related EAD(P) events which may be manifested by pulling or yanking of the EAD(P) will be 
monitored in relation to intervention.  Following the TubeClear® intervention, each Subject 
will receive an abdominal radiograph with contrast. Radiographs will be reviewed by a 
radiologist (blinded to the study) for EAD(P) adverse events (i.e., EAD(P) displacement, 
EAD(P) damage, enteral tract tissue injury) attributable to the TubeClear® intervention. 
In Phase IIB, Subject pain will be assessed before and after use of either intervention using 
established age-appropriate pain scales. Acute changes in physiologic parameters will be 
measured, including changes in heart rate, blood pressure and respiratory rate.  Distress related 
EAD(P) events which may be manifested by pulling or yanking of the EAD(P) will be 
monitored in relation to either intervention. Following either intervention, each Subject will 
receive an abdominal radiograph with contrast. Radiographs will be reviewed by a radiologist 
(blinded to the study) for EAD(P) adverse events (i.e., EAD(P) displacement, EAD(P) 
damage, enteral tract tissue injury) attributable to either intervention. Incidence of adverse 
events attributable to the intervention (i.e. EAD displacement, EAD damage, enteral tract 
tissue injury) following the intervention will be monitored and reported in both groups. 
In all phases, surveillance will include daily assessment for adverse events related to the 
respective study intervention (i.e. subject pain, feeding intolerance, EAD(P) displacement, 
EAD(P) damage, enteral tract tissue injury) and will continue for three (3) days. Patients who 
are discharged from the hospital prior to 3 days will be followed up daily by phone until 
completion of 3 days following study interventions.  
 
 

 
 
 
16 
 
3 
INVESTIGATIONAL PLAN 
3.1 
General Schema of Study Design 
This Study will be carried out in phases in the CHOP Pediatric Intensive Care Unit (PICU),  
Progressive Care Unit (PCU), and/or Interventional Radiology Department (IR). Phase I will 
study the feasibility and tolerability of TubeClear® intervention to restore EAD(P) patency in 
consecutive eligible Subjects (n=15) with occluded EAD(P)s who have not attained their 18th 
birthday. 
After completion of Phase I, a detailed summary of the 15 enrolled subjects will be submitted 
to the IRB for review of protocol compliance/feasibility, incidence of Adverse Events (if any), 
and subject pain/tolerability. Following successful completion of Phase I as deemed by the 
IRB, the Study will proceed to Phase IIA and IIB to run concurrently.  
Phase IIA will measure the ability of TubeClear® intervention to restore patency in 
consecutive eligible Subjects (n=15) with occluded EAD(P)s who have not attained their 11th 
birthday.  
Phase IIB will consist of a randomized efficacy comparison between TubeClear® intervention 
(experimental, n=17) and CHOP Standard Treatment (control, n=17) in eligible Subjects with 
occluded EAD(P)s who are between 11 years of age and have not attained their 18th birthday. 
The overall Study Design is summarized in the Study Flow Chart (Figure 1).  
3.1.1 Screening Phase 
In Phase I, potential Subjects are pediatric patients who have not attained their 18th birthday, 
and are admitted to the CHOP PICU, PCU, or IR with an existing or a newly inserted EAD(P) 
that becomes occluded.  
In Phase IIA, potential Subjects are pediatric patients who have not attained their 11th birthday, 
and are admitted to the CHOP PICU, PCU, or IR with an existing or a newly inserted EAD(P) 
that becomes occluded. 
In Phase IIB, potential Subjects are pediatric patients who are between 11 years of age and 
have not attained their 18th birthday, and are admitted to the CHOP PICU, PCU, or IR with 
an existing or a newly inserted EAD(P) that becomes occluded. 
Patients will become eligible once an occlusion in the EAD(P) is reported and they meet all 
inclusion/exclusion criteria for the Study. An occlusion is defined by direct identification of a 
clog or through a feeding pump alarm that sounds when patency of an EAD(P) is disrupted. 
Potential eligible Subjects will be identified by screening the electronic health records (EHR). 
In addition, CHOP staff may notify the research personnel when there is a potential Subject. 
Eligible subjects will be approached for informed consent and, when applicable, assent to 
participate in the study. If ineligible, research personnel will document patient information to 
prevent further consideration. Eligible subjects may be enrolled more than once and up to a 
maximum of three times in the study for each instance of EAD(P) occlusion. 

 
 
 
17 
 
3.1.2 Study Treatment Phase 
Following informed consent (assent when applicable) and prior to enrollment into any of the 
study phases (Phases I, IIA and IIB), female patients > 10 years of age or those who have 
experienced the onset of menses must have a documented NEGATIVE  pregnancy test (urine 
or blood). 
In Phase I, all enrolled subjects will receive the TubeClear® intervention. Prior to the 
intervention, the location of the EAD(P) will be determined based on review of radiographs. 
The Investigator may obtain a new radiograph if the EAD(P) location is uncertain. The 
Investigator will determine the length and diameter of the EAD(P) from the EHR and/or the 
length marking (in cm) at the exit point of the EAD(P) from the body surface orifice. The 
Operator-set Collar on the clearing stem of TubeClear® will be placed corresponding to the 
EAD(P) measured length recorded by the Investigator. The TubeClear® Instructions for Use 
(i.e., Operator’s Manual) will be followed by the user to restore patency to the EAD(P). 
EAD(P) patency restoration will be measured by the ability to flush the EAD(P) with 10 ml 
of air within five (5) minutes after completion of the intervention. After successful air 
flushing, aspirate will be extracted through the EAD(P), and the pH of the contents checked 
to confirm location according to CHOP standard of care. Following confirmation of correct 
EAD(P) placement, 5-20 ml of water will be flushed through the EAD to assure continued 
patency. Following the TubeClear® intervention, the Subject will receive an abdominal 
radiograph with contrast. A radiologist (blinded to the study) will assess the radiographs for 
adverse events (i.e., EAD(P) displacement, EAD(P) damage, enteral tract tissue injury) 
attributable to the intervention. If the TubeClear® intervention is unable to restore EAD(P) 
patency, further steps to restore patency of the occluded EAD will be determined by the 
clinical team per usual practice. 
In Phase IIA, all enrolled subjects will receive the TubeClear® intervention. Prior to the 
intervention, the location of the EAD(P) will be determined based on review of radiographs. 
The Investigator may obtain a new radiograph if the EAD(P) location is uncertain. The 
Investigator will determine the length and diameter of the EAD(P) from the EHR and/or the 
length marking (in cm) at the exit point of the EAD(P) from the body surface orifice. The 
Operator-set Collar on the clearing stem of TubeClear® will be placed corresponding to the 
EAD(P) measured length recorded by the Investigator. The TubeClear® Instructions for Use 
(i.e., Operator’s Manual) will be followed by the user to restore patency to the EAD(P). 
EAD(P) patency restoration will be measured by the ability to flush the EAD(P) with 10 ml 
of air within five (5) minutes after completion of the intervention. After successful air 
flushing, aspirate will be extracted through the EAD(P), and the pH of the contents checked 
to confirm location according to CHOP standard of care. Following confirmation of correct 
EAD(P) placement, 5-20 ml of water will be flushed through the EAD to assure continued 
patency. Following the TubeClear® intervention, the Subject will receive an abdominal 
radiograph with contrast. A radiologist (blinded to the study) will assess the radiographs for 
adverse events (i.e., EAD(P) displacement, EAD(P) damage, enteral tract tissue injury) 
attributable to the intervention. If the TubeClear® intervention is unable to restore EAD(P) 
patency, further steps to restore patency of the occluded EAD will be determined by the 
clinical team per usual practice. 

 
 
 
18 
 
In Phase IIB, subjects will be randomized into either TubeClear® intervention or CHOP 
Standard Treatment using a predetermined computer generated randomization sequence 
stored in opaque sealed envelopes. Prior to the intervention, the location of the EAD(P) will 
be determined based on review of radiographs. The Investigator may obtain a new radiograph 
if the EAD(P) location is uncertain. The Investigator will determine the length and diameter 
of the EAD(P) from the EHR and/or the length marking (in cm) at the exit point of the EAD(P) 
from the body surface orifice. If randomized to TubeClear®, the Operator-set Collar on the 
clearing stem of TubeClear® will be placed corresponding to the EAD(P) measured length 
recorded by the Investigator. The TubeClear® Instructions for Use (i.e., Operator’s Manual) 
will be followed by the user to restore patency to the EAD(P). If randomized to CHOP 
Standard Treatment, the CHOP protocol to restore patency to occluded EAD(P) will be 
followed. EAD(P) patency restoration will be measured by the ability to flush the EAD(P) 
with 10 ml of air within five (5) minutes after completion of the intervention. After successful 
air flushing, aspirate will be extracted through the EAD(P), and the pH of the contents checked 
to confirm location according to CHOP standard of care. Following confirmation of correct 
EAD(P) placement, 5-20 ml of water will be flushed through the EAD to assure continued 
patency. Following either intervention, the Subject will receive an abdominal radiograph with 
contrast. A radiologist (blinded to the study) will assess the radiographs for adverse events 
(i.e., EAD(P) displacement, EAD(P) damage, enteral tract tissue injury) attributable to the 
intervention. If either intervention is unable to restore EAD(P) patency, further steps to restore 
patency of the occluded EAD will be determined by the clinical team per usual practice. 
3.1.3 Follow-up Phase 
Surveillance will include assessment for any adverse event(s) related to the intervention (i.e. 
EAD(P) displacement, EAD(P) damage, enteral tract tissue injury) and will continue for up 
to three (3) days following interventions in all study phases regardless of study intervention 
allocation. Clinical Assessment Measurements (i.e., pain, feeding tolerance, and usual 
measures to determine EAD(P) location) will be performed prior to, immediately following, 
and for up to three days after the intervention. Patients who are discharged from the hospital 
prior to three days will be followed up daily by phone for Clinical Assessment Measurements 
i.e., pain, feeding tolerance and EAD(P) location as assessed by caregiver until post 
Intervention day three. 
3.2 
Allocation to Treatment Groups and Blinding 
All Subjects in Phase I and Phase IIA of the Study will receive TubeClear® to restore patency 
of the occluded EAD(P).   
All Subjects in Phase IIB will be randomized into the TubeClear® intervention (experimental) 
or CHOP Standard Treatment (control) group according to a predetermined computer 
generated randomization sequence. The randomization sequence will be kept in individual 
opaque sealed envelopes to be opened after the Subject is consented and enrolled in Phase 
IIB.  To ensure an appropriate balance of participation in both the experimental and control 
groups, balanced, permuted block randomization will be used, as Phase IIB is not blinded. 

 
 
 
19 
 
3.3 
Study Duration, Enrollment and Number of Sites 
3.3.1 Duration of Study Participation 
The duration of study participation per Subject will be up to three (3) days in each phase 
following initiation of intervention. Clinical Assessment Measurements (i.e., pain, feeding 
tolerance, and usual measures to determine EAD(P) location) will be performed prior to, 
immediately following, and for up to three (3) days. Surveillance will include assessment for 
any adverse event(s) related to the intervention (i.e. EAD(P) displacement, EAD(P) damage, 
enteral tract tissue injury) and will continue for up to three (3) days. Patients who are 
discharged from the hospital prior to three days will be followed up daily by phone for Clinical 
Assessment Measurements i.e., pain, feeding tolerance and EAD(P) location as assessed by 
caregiver until post Intervention day three. The Subject’s actual time spent receiving the study 
intervention will vary based on whether the Subject is randomized to the TubeClear® 
intervention or CHOP Standard Treatment. It is estimated that the TubeClear® intervention 
will take thirty (30) minutes per Subject, including time to prepare and set up the device. It is 
estimated that CHOP Standard Treatment will take four (4) hours per Subject, including time 
to prepare for the application of CHOP Standard Treatment. 
3.3.2 Total Number of Study Sites/Total Number of Subjects Projected 
The Study will be conducted at one site, the Children’s Hospital of Philadelphia (CHOP) in 
the Pediatric Intensive Care Unit (PICU), Progressive Care Unit (PCU), and Interventional 
Radiology Department (IR). A total of 64 Subjects will be enrolled in this Study – 15 in Phase 
I and 49 in Phase II. 
3.4 
Study Population 
3.4.1 Inclusion Criteria 
1. Males or females who have not attained their 18th birthday (Phase I) 
      Or 
      Males or females who have not attained their 11th birthday (Phase IIA) 
      Or 
      Males or females between 11 years of age and have not attained their 18th birthday (Phase 
IIB) 
2. Indwelling occluded EAD(P) that is either: 
a. ND, NG, NJ tube composed of Polyvinyl Chloride (PVC) and Polyurethane 6 – 8 
Fr, 38 – 140 cm; or 
b. NG tube (Corflo, Corpak MedSystems) used as a J tube inserted through a G tube, 
6 – 8 Fr, 38 – 140 cm 
c. GJ tube (AMT) 14 Fr, 38 – 140 cm (15 – 55 in) 

 
 
 
20 
 
3.4.2 Exclusion Criteria 
1. Ward of the state 
2. Positive pregnancy test/ Pregnant females 
3. Any active gastrointestinal abnormalities or malformations, including but not limited to 
infections, inflammation, obstruction and/or recent abdominal surgery or trauma 
4. Constant dependency on the EAD(P) for a glucose source (e.g. hyperinsulinism states) 
5. Unable to tolerate water volume needed for the EAD(P) flush 
6. Allergies to the contrast agent(s) used in post-Intervention radiological imaging 
7. Measured total length of EAD(P) less than 38 cm (15 in) - from external port to EAD(P) 
distal end 
8. Unknown length of EAD(P) 
9. Attending physician declines enrollment based on clinical judgement 
10. Subject attains 18 years of age during study duration 
Subjects that do not meet all of the enrollment criteria will not be enrolled. Any violations of 
these criteria will be reported in accordance with IRB Policies and Procedures.  
 
 

 
 
 
21 
 
4 
STUDY PROCEDURES  
Table 1 lists the study procedures in all study phases. 
4.1 
Screening Visit 
• Potential eligible Subjects are patients in the PICU, PCU, or IR that are identified to 
have an occlusion of their EAD(P)s during the current admission.  
• Potential eligible Subjects will be identified by screening the electronic health records 
(EHR). In addition, CHOP staff may notify the research personnel when there is a 
potential Subject.  
• For a potential Subject who meets the inclusion/exclusion criteria, the Investigator will 
discuss the Study with the parent/guardian and obtain informed consent.   
• Where appropriate, the Investigator will discuss the Study with the pediatric patient 
and obtain assent.   
4.2 
Study Treatment Phase 
General overview of Study Treatment Phase - Phase I: 
• Female patients > 10 years of age or those who have experienced the onset of menses 
must have a documented NEGATIVE pregnancy test (urine or blood). 
• Subject’s most recent radiograph will be obtained and reviewed by the Investigator to 
identify EAD(P) characteristics and tube tip location, as well as pre-existing 
abnormalities, including damage to EAD(P) and/or tissue, if any.   
• The Investigator has the option to order a new radiograph prior to the intervention if 
there is uncertainty about the status of the EAD(P) tube tip location and characteristics. 
• The Subject’s Nurse will obtain standard baseline measures of Subject pain.   
• EAD(P) length will be determined by review of Subject EHR and/or markings on the 
EAD(P).  The Investigator will place the Operator-set Collar to the same length 
determined by review of Subject’s chart and/or markings on the EAD(P). 
• Data will be gathered or abstracted from the EHR prior to, during the Subject receiving 
the intervention, and through the follow-up period.  This data includes subject name, 
date of birth, contact information for parent/guardian, age, sex, race, ethnicity, weight, 
stature, BMI, location (PICU/PCU/IR), dates of hospitalization (length of stay), 
medical record number (MRN), contact serial number (CSN), diagnosis, procedures 
performed, medications administered, laboratory and radiology results, ventilator 
parameters (if ventilated), severity of illness, nutrition information, information on 
EAD and clog, and physical assessments with vital signs (patient temperature, heart 
rate, respiratory rate, blood pressure and pain level). 

 
 
 
22 
 
• The patient’s Nurse will obtain standard measures of Subject pain following 
intervention. 
• Intervention is deemed successful if EAD(P) is able to be flushed with 10 ml of air 
within five (5) minutes following the Intervention.  The Intervention is deemed 
unsuccessful if EAD(P) is unable to be flushed with 10 ml of air within five (5) minutes 
following the Intervention.  
• Subject will receive a portable abdominal radiograph with contrast agent following the 
intervention.  The radiologist (blinded to the study) will assess and report the 
abdominal radiographs post-intervention for adverse events (i.e., EAD(P) 
displacement, EAD(P) damage, enteral tract tissue injury) attributable to the 
intervention. Study procedures carried out in IR may utilize low-dose fluoroscopy as 
an alternative to the portable abdominal radiograph. 
• If the intervention is unable to restore EAD(P) patency, further steps to restore patency 
will be determined by the clinical team per usual practice. 
General overview of Study Treatment Phase – Phase IIA  
• Female patients > 10 years of age or those who have experienced the onset of menses 
must have a documented NEGATIVE pregnancy test (urine or blood). 
• Subject’s most recent radiograph will be obtained and reviewed by the Investigator to 
identify EAD(P) characteristics and tube tip location, as well as pre-existing 
abnormalities, including damage to EAD(P) and/or tissue, if any.   
• The Investigator has the option to order a new radiograph prior to the intervention if 
there is uncertainty about the status of the EAD(P) tube tip location and characteristics. 
• The Subject’s Nurse will obtain standard baseline measures of Subject pain.   
• EAD(P) length will be determined by review of Subject EHR and/or markings on the 
EAD(P). The Investigator will place the Operator-set Collar to the same length 
determined by review of Subject’s chart and/or markings on the EAD(P). 
• Data will be gathered or abstracted from the EHR prior to, during the Subject receiving 
the intervention, and through the follow-up period.  This data includes subject name, 
date of birth, contact information for parent guardian, age, sex, race, ethnicity, weight, 
stature, BMI, location (PICU/PCU/IR), dates of hospitalization (length of stay), 
medical record number (MRN), contact serial number (CSN), diagnosis, procedures 
performed, medications administered, laboratory and radiology results, ventilator 
parameters (if ventilated), severity of illness, nutrition information, information on 
EAD and clog, and physical assessments with vital signs (patient temperature, heart 
rate, respiratory rate, blood pressure and pain level). 
• The patient’s Nurse will obtain standard measures of Subject pain following 
intervention. 

 
 
 
23 
 
• Intervention is deemed successful if EAD(P) is able to be flushed with 10 ml of air 
within five (5) minutes following the Intervention.  The Intervention is deemed 
unsuccessful if EAD(P) is unable to be flushed with 10 ml of air within five (5) minutes 
following the Intervention.  
• Subject will receive a portable abdominal radiograph with contrast agent following the 
intervention.  The radiologist (blinded to the study) will assess and report the 
abdominal radiographs post-intervention for adverse events (i.e., EAD(P) 
displacement, EAD(P) damage, enteral tract tissue injury) attributable to the 
intervention. Study procedures carried out in IR may utilize low-dose fluoroscopy as 
an alternative to the portable abdominal radiograph. 
• If the intervention is unable to restore EAD(P) patency, further steps to restore patency 
will be determined by the clinical team per usual practice. 
General overview of Study Treatment Phase – Phase IIB 
• Female patients > 10 years of age or those who have experienced the onset of menses 
must have a documented NEGATIVE pregnancy test (urine or blood). 
• Subject will be randomized to either TubeClear® intervention (experimental) or CHOP 
Standard Treatment (control) group according to randomization sequence. 
• Subject’s most recent radiograph will be obtained and reviewed by the Investigator to 
identify EAD(P) characteristics and tube tip location, as well as pre-existing 
abnormalities, including damage to EAD(P) and/or tissue, if any.   
• The Investigator has the option to order a new radiograph prior to the intervention if 
there is uncertainty about the status of the EAD(P) tube tip location and characteristics. 
• The Subject’s Nurse will obtain standard baseline measures of Subject pain. 
• Subject will receive TubeClear® intervention or CHOP Standard Treatment based on 
the randomization assignment. 
• If randomized to TubeClear®, EAD(P) length will be determined by review of 
Subject’s EHR and/or markings on the EAD(P). The Investigator will place the 
Operator-set Collar to the same length determined by review of Subject’s chart and/or 
markings on the EAD(P). The TubeClear® Instructions for Use (i.e., Operator’s 
Manual) will be followed by the user to restore patency to the EAD(P).  
• If randomized to CHOP Standard Treatment, the CHOP protocol to restore patency to 
occluded EAD(P) will be followed. 
• Data will be gathered or abstracted from the EHR prior to, during the Subject receiving 
either intervention, and through the follow-up period.  This data includes subject name, 
date of birth, contact information for parent/guardian, age, sex, ethnicity, weight, 
stature, BMI, location (PICU/PCU/IR), dates of hospitalization (length of stay), 

 
 
 
24 
 
medical record number (MRN), contact serial number (CSN), diagnosis, procedures 
performed, medications administered, laboratory and radiology results, ventilator 
parameters (if ventilated), severity of illness, nutrition information, information on 
EAD and clog, and physical assessments with vital signs (patient temperature, heart 
rate, respiratory rate, blood pressure and pain level). 
• Nursing assessment using the appropriate scale of the Subject’s pain prior to and 
following the respective intervention will be abstracted from the medical record. 
• Intervention in either group is deemed successful if EAD(P) is able to be flushed with 
10 ml of air within five (5) minutes following the respective intervention.  The 
intervention is deemed unsuccessful if EAD(P) is unable to be flushed with 10 ml of 
air within five (5) minutes following the intervention.  
• Subject will receive a portable abdominal radiograph with contrast agent following 
either intervention.  The radiologist (blinded to the study) will assess and report the 
abdominal radiographs post-intervention for adverse events (i.e., EAD(P) 
displacement, EAD(P) damage, enteral tract tissue injury) attributable to the 
intervention. Study procedures carried out in IR may utilize low-dose fluoroscopy as 
an alternative to the portable abdominal radiograph. 
• In either group, if the intervention is unable to restore EAD(P) patency, further steps 
to restore patency will be determined by the clinical team per usual practice. 
 
4.3 
Follow-up Phase 
Follow-up surveillance will include assessment for any adverse event(s) related to the 
intervention (i.e. EAD(P) displacement, EAD(P) damage, enteral tract tissue injury) and will 
continue for up to three (3) days following interventions in all study phases regardless of study 
intervention allocation. Clinical Assessment Measurements (i.e., pain, feeding tolerance, and 
usual measures to determine EAD(P) location) will be performed prior to, immediately 
following, and for up to three days after the intervention. Patients who are discharged from 
the hospital prior to three days will be followed up daily by phone for Clinical Assessment 
Measurements i.e., pain, feeding tolerance and EAD(P) location as assessed by caregiver until 
post Intervention day three. 
4.4 
Unscheduled Visits 
There are no anticipated unscheduled visits in this Study.  
4.5 
Concomitant Medication 
All prior and concomitant medications used within 1 day prior to the Subject’s Study 
Intervention procedure and through the end of the Study Intervention will be recorded.  The 
total doses of medications administered throughout this time will be included.   

 
 
 
25 
 
4.6 
Rescue Medication Administration 
There are no Rescue Medications administered in this Study.    
4.7 
Subject Completion/Withdrawal 
Subjects may withdraw from the Study at any time without any change in their clinical 
management for any reason that the Subject, parent(s) or guardian(s) provide. They may also 
be discontinued from the Study at the discretion of the Principal Investigator if any significant 
Adverse Events (AEs) occur, or if the attending physician requests discontinuing a Subject if 
there is a perceived interference with a planned procedure. The Principal Investigator or the 
Study Sponsor may also withdraw Subjects who are not compliant with the Study plan, or to 
protect the Subject for reasons of safety or for administrative reasons. It will be documented 
whether or not each Subject completes the clinical Study. If the Principal Investigator becomes 
aware of any serious, related adverse events after the Subject completes or withdraws from 
the Study, they will be recorded in the source documents as well as on the Case Report Forms 
(CRF) with appropriate notification to the IRB. 
4.7.1 Early Termination Study Visit 
Subjects who withdraw from the Study will receive care according to CHOP standard 
procedures without any change to their clinical care.  Adverse events from Study Intervention 
will be assessed for up to three (3) days following Intervention or until patient discharge 
(whichever is earlier).  Patients who are discharged from the hospital prior to three days will 
be followed up daily by phone for Clinical Assessment Measurements (i.e., pain, and feeding 
tolerance) until post Intervention day 3. 
 
 

 
 
 
26 
 
5 
STUDY EVALUATIONS AND MEASUREMENTS 
5.1 
Screening and Monitoring Evaluations and Measurements 
5.1.1 Medical Record Review 
Information from the medical record will be recorded and used for this study.  This 
information will include medical history, information about your condition, lab and radiology 
results, medications, treatments, vital signs, and the response to treatments.  We will be 
reviewing the medical record throughout the study. 
We plan to follow-up all subjects for 3 days post-intervention in all study phases. It is possible 
that some study subjects might be discharged from the hospital prior to this endpoint. In such 
instances, we will need to contact the parent/guardian of the subject (as third party and not 
part of research procedures) and administer the follow-up questionnaire on a daily basis (till 
post-intervention day 3). As we cannot predict which subject is likely to be discharged prior 
to 3 days, we will obtain contact information for parents/guardians of all subjects at the time 
of obtaining informed consent.  
Variables that will be abstracted from the EHR will include the following. 
• Basic demographic information including subject name, medical record number 
(MRN), account number (CSN), Date of birth (DOB), race, ethnicity, sex, age at time 
of Study Intervention, weight, stature, calculated BMI, location (PICU/PCU/IR) and 
dates of hospitalization (length of stay) 
• Contact information of parent/guardian will be collected to follow-up subjects for 
study related events, (in case subject is discharged prior to post-intervention day 3)  
• Type of EAD(P) 
• Date and place of EAD(P) insertion 
• Length of EAD(P) 
• EAD clog information 
• Medications  
• Nutrition 
• Diagnoses 
• Procedures 
• Severity of illness 
• Ventilator parameters (if applicable) 
• Medications administered through EAD(P) preceding clog 

 
 
 
27 
 
• Nutrition administered through EAD(P) preceding clog 
• Past Medical History 
• Past Surgical History 
• Established age-appropriate pain scales 
• Laboratory results and radiology results 
5.1.2 Physical Examination 
Confirmation of EAD(P) occlusion will be made by CHOP staff according to CHOP protocol.   
Documentation of Subject’s clinical status (i.e., abdominal exam for contour, symmetry, etc.) 
will be reviewed and/or assessed by Investigator. 
5.1.3 Vital Signs 
Vital signs will be collected both as part of routine clinical care (baseline and daily follow-
up) and research procedures (before, during and after the study interventions). Baseline vital 
signs and daily follow-up vital signs will be extracted from the EHR (EPIC).    
5.1.4 Laboratory Evaluations 
None. 
5.1.5 Pregnancy Testing 
Prior to being enrolled in the study, a urine/blood pregnancy test will be performed for female 
Subjects ≥ 10 years of age OR females who have experienced the onset of menses.  
5.1.6 Other Evaluations, Measures 
Portable abdominal radiograph with contrast agent after intervention (and portable abdominal 
radiograph, prior to intervention, if needed).  
Clinical Patient Assessment Measurements (i.e., pain, feeding tolerance, and usual measures 
to determine EAD(P) location) will be performed prior to, immediately following, and for up 
to three (3) days after all interventions. Patients who are discharged from the hospital prior to 
three days will be followed up daily by phone for Clinical Assessment Measurements i.e., 
pain, feeding tolerance and EAD(P) location as assessed by caregiver until post intervention 
day three.  
Age Appropriate Pain Scale Assessments (these scales include, but are not limited to):  Face, 
Legs, Activity, Cry, Consolability (FLACC) Scale; Revised Face, Legs, Activity, Cry, 
Consolability (rFLACC) Scale; FACES Pain Scale revised (FPS-R); Numeric Pain Scale; 
Nursing judgment 

 
 
 
28 
 
Behavioral Likert scale and Generic Behavioral Analysis developed in conjunction with The 
Food and Drug Administration (FDA) will be used to assess subject behaviors during the 
study intervention. The Behavioral Likert Scale will be used by the study investigators to 
objectively assess subject behavior, while the Generic behavioral Analysis consists of 
questions that will be administered by the study investigators to the subject and their 
parent/guardian to assess their subjective assessment of the study intervention. 
EAD(P) air and water flush. 
5.2 
Efficacy Evaluations 
Efficacy (i.e. patency restoration) will be measured by the ability to flush the EAD(P) with 10 
ml of air within five (5) minutes following the intervention by the investigator. 
5.2.1 Diagnostic Tests, Scales, Measures, etc. 
With the exception of abdominal radiographs as described, and the pain, stress and behavioral 
scales used, there are no other diagnostic tests, scales, or measures used for this Study.  
5.3 
Pharmacokinetic Evaluation 
There is no pharmacokinetic evaluation for this Study.    
5.4 
Safety Evaluation 
The FDA has deemed TubeClear® to be non-significant risk for use in this study (Appendix 
D). Following successful restoration of EAD(P), a portable abdominal radiograph with 
contrast agent will be obtained. A radiologist (blinded to the study) will assess the radiographs 
for adverse events related to the respective Intervention and report results. 
Subjects will be monitored for the occurrence of adverse events defined as any untoward or 
unfavorable occurrence.  A description of all events will be recorded in the Study database. 
Anticipated adverse events (AE), or “TubeClear® Specified Events” include: EAD 
displacement, EAD perforation and enteral tract tissue injury. 
The relationship of each event to the study protocol will be classified according to severity, 
expectedness and relatedness by the bedside clinicians and recorded. 
Unanticipated Problems (UP) involving risk to Subjects or others will also be tracked.  UP 
includes any incident, experience, or outcome that is unexpected, related or possibly related 
to Intervention, and suggests that research places Subjects or others at greater risk for harm.  
An AE is a reportable Serious Adverse Event (SAE) if it is serious, unexpected and related or 
possibly related to the Intervention. 
Expedited reporting timeline for all SAE and unanticipated problems related to the 
Intervention or from protocol violations:  

 
 
 
29 
 
a. Principal Investigator or designee will notify their local IRB, medical monitor 
and AMI within 24 hours of the event.  
A full narrative report describing the event within 7 calendar days will be submitted to the 
local IRB, medical monitor and AMI.  Such reports will include a detailed description of the 
SAE/UP, an explanation of the basis for determining that the event represents a SAE/UP, and 
a description of any corrective actions that are proposed in response to the SAE/UP. 
 
 

 
 
 
30 
 
6 
STATISTICAL CONSIDERATIONS 
6.1 
Primary Objective 
The primary objectives of this study are to 1) evaluate feasibility and tolerability of 
TubeClear® to restore patency in occluded EAD(P)s, and 2) compare efficacy of TubeClear® 
to the CHOP Standard Treatment to restore patency in occluded EAD(P)s. 
The primary endpoints in Phase I are feasibility and tolerability of TubeClear® intervention.  
Feasibility will be defined as ability of the user to operate TubeClear® device (as per 
instructions and training in Appendix F) from insertion of the clearing stem into the occluded 
EAD(P) through device activation to patency restoration. Tolerability will be defined as 
ability of the Subject to undergo TubeClear® intervention.   
The primary endpoint in Phase IIA is the ability of TubeClear® intervention to restore 
patency in Subjects with occluded EAD(P)s. This will be termed as EAD(P) patency 
restoration and will be measured by the ability to flush the EAD(P) with 10 ml of air within 
five (5) minutes after completion of the intervention.  
The primary endpoint of Phase IIB is the efficacy of TubeClear® intervention compared to 
CHOP Standard Treatment to restore patency in Subjects with occluded EAD(P)s. EAD(P) 
patency restoration will be measured by the ability to flush the EAD(P) with 10 ml of air 
within five (5) minutes after completion of either intervention. 
6.2 
Secondary Objectives (or Aim) 
The secondary objectives of this study are to assess subject pain, changes in physiological 
parameters, distress related EAD(P) events and adverse events related to the interventions. 
In Phase I, Subject pain will be assessed before and after use of TubeClear® intervention using 
established age-appropriate pain scales. Acute changes in physiologic parameters will be 
measured, including changes in heart rate, blood pressure and respiratory rate.  Distress related 
EAD(P) events which may be manifested by pulling or yanking of the EAD(P) will be 
monitored in relation to intervention. Following the TubeClear® intervention, each Subject 
will receive an abdominal radiograph with contrast. Study procedures carried out in IR may 
utilize low-dose fluoroscopy as an alternative to the portable abdominal radiograph. 
Radiographs will be reviewed by a radiologist (blinded to the study) for EAD(P) adverse 
events (i.e., EAD(P) displacement, EAD(P) damage, enteral tract tissue injury) attributable to 
the TubeClear® intervention.   
In Phase IIA, Subject pain will be assessed before and after use of TubeClear® intervention 
using established age-appropriate pain scales. Acute changes in physiologic parameters will 
be measured, including changes in heart rate, blood pressure and respiratory rate.  Distress 
related EAD(P) events which may be manifested by pulling or yanking of the EAD(P) will be 
monitored in relation to intervention.  Following the TubeClear® intervention, each Subject 
will receive an abdominal radiograph with contrast. Study procedures carried out in IR may 
utilize low-dose fluoroscopy as an alternative to the portable abdominal radiograph. 
Radiographs will be reviewed by a radiologist (blinded to the study) for EAD(P) adverse 

 
 
 
31 
 
events (i.e., EAD(P) displacement, EAD(P) damage, enteral tract tissue injury) attributable to 
the TubeClear® intervention. 
In Phase IIB, Subject pain will be assessed before and after use of either intervention using 
established age-appropriate pain scales. Acute changes in physiologic parameters will be 
measured, including changes in heart rate, blood pressure and respiratory rate.  Distress related 
EAD(P) events which may be manifested by pulling or yanking of the EAD(P) will be 
monitored in relation to either intervention. Following either intervention, each Subject will 
receive an abdominal radiograph with contrast. Study procedures carried out in IR may utilize 
low-dose fluoroscopy as an alternative to the portable abdominal radiograph. Radiographs 
will be reviewed by a radiologist (blinded to the study) for EAD(P) adverse events (i.e., 
EAD(P) displacement, EAD(P) damage, enteral tract tissue injury) attributable to either 
intervention. Incidence of adverse events attributable to the intervention (i.e. EAD 
displacement, EAD damage, enteral tract tissue injury) following the intervention will be 
monitored and reported in both groups. 
In all phases, surveillance will include daily assessment for adverse events related to the 
respective study intervention (i.e. subject pain, feeding intolerance, EAD(P) displacement, 
EAD(P) damage, enteral tract tissue injury) and will continue for three (3) days. Patients who 
are discharged from the hospital prior to 3 days will be followed up daily by phone until 
completion of 3 days following study interventions. 
1. Intervention time (measured in minutes) is the time interval between commencement 
of intervention and achievement of EAD(P) patency (if successful).      
2. Physiological parameters will be recorded from the Subject’s EHR. 
3. Distress related EAD(P) events which may be manifested by pulling or yanking of the 
EAD(P) will be monitored and recorded by Research Personnel or the Subject’s nurse. 
 
 
 
 
 
 
 

 
 
 
32 
 
6.3 
Statistical Methods 
6.3.1 Group Allocation Flow Chart for Phase IIB  
6.3.2 Baseline Data  
R Statistical Software8 (Vienna, Austria) and G*Power9,10 version 3.1.9.2 (Düsseldorf, 
Germany) will be used for data analysis. Prior to performing analyses, standard data cleaning 
Interventions will be applied. These Interventions include: screening the data for data-entry 
errors, checking for outliers, assessing the extent and pattern of missing data, and checking 
that appropriate assumptions of normality are met whenever necessary. Exploratory 
assessments will include the influence of covariates (i.e., the clinically relevant variables to 
be recorded) on outcome measures. Graphical displays, as appropriate, will be included as 
part of data analysis.  
Baseline and demographic characteristics and other data will be summarized by standard 
descriptive summaries (e.g., means and standard deviations for continuous variables such as 
age, and percentages for categorical variables such as gender). 
6.3.3 Primary Objective Analysis 
Data from Phase I and Phase IIA will be observational and will not test a hypothesis. Data on 
feasibility and tolerability from Phase I and data on EAD(P) patency restoration will be 
reported as counts and percentages.  
 
Figure 8: Group Allocation Flow Chart (Phase IIB) 

 
 
 
33 
 
In Phase IIB, the primary objective is efficacy comparison between TubeClear® intervention 
and CHOP Standard Treatment.  EAD(P) patency restoration will be measured by the ability 
to flush the EAD(P) with 10 ml of air within five (5) minutes following the Intervention. 
Efficacy is the proportion of EAD(P)s restored to patency in each group. A chi-square analysis 
(or Fisher’s exact test) will be performed to compare the efficacy of TubeClear® intervention 
to the CHOP Standard Treatment. Intention-to-treat analysis will be used to compare the 
efficacy of the TubeClear® intervention to the CHOP Standard Treatment. Patients will be 
analyzed according to their randomized allocation. Full reporting of any deviations from 
random allocation and missing responses will be recorded and assessed in accordance with 
the CONSORT guidelines. Exploratory-per-protocol analysis will also be reported.  
6.3.4 Secondary Objective Analysis 
Data from Phase I and Phase IIA will be observational and will not test a hypothesis. Data on 
1) pain, using established age-appropriate pain scales, 2) physiologic changes in vital signs, 
3) distress related EAD(P) events, and 4) adverse events related to TubeClear® use will be 
described and reported as counts and percentages. 
In Phase IIB, the secondary objectives between TubeClear® intervention and CHOP Standard 
Treatment include comparison of 1) time to intervention, 2) pain using established age-
appropriate pain scales, 3) physiologic changes in vital signs, 4) distress related EAD(P) 
events, and 5) adverse events related to either group.  
1. A log-rank test will be performed to compare intervention time of TubeClear® 
intervention to the CHOP Standard Treatment15.    
2. A Wilcoxon rank sum test will be performed to compare differences in subject pain 
and discomfort between TubeClear® intervention and CHOP Standard Treatment.   
3. A t-test will be performed if the distributions are normal (or non-parametric 
equivalent, if the distributions are not normal) to compare differences in physiologic 
changes (i.e. vital sign changes) between TubeClear® intervention and CHOP 
Standard Treatment. 
4. A Wilcoxon rank sum test will be performed to compare differences in distress related 
EAD(P) events (i.e. subject behavior such as pulling/yanking) between TubeClear® 
intervention and CHOP Standard Treatment.   
5. A chi-square analysis (or Fisher’s exact test) will be performed to compare the 
proportions of adverse events (i.e., EAD(P) displacement from the intervention; 
EAD(P) damage from the intervention; any enteral tract tissue perforation from the 
intervention) in TubeClear® intervention and CHOP Standard Treatment. 
Intention-to-treat analysis will be used to compare the secondary endpoints between the 
TubeClear® intervention and the CHOP Standard Treatment. Patients will be analyzed 
according to their randomized allocation. Full reporting of any deviations from random 
allocation and missing responses will be recorded and assessed in accordance with the 
CONSORT guidelines. Exploratory-per-protocol analysis will also be reported. 

 
 
 
34 
 
6.3.5 Pharmacokinetic Analysis 
No pharmacokinetic analysis is needed in this medical device Study.    
6.3.6 Safety Analysis 
All Subjects entering the Study will be included in the safety analysis.  Clinical Patient 
Assessment Measurements (i.e., pain, feeding tolerance, and usual measures to determine 
EAD(P) location) will be performed prior to, immediately following, and for up to three (3) 
days after all Interventions. Clinically significant changes will be addressed and managed by 
the Subject’s medical team, but recorded, reported, and followed by the Study team. 
Surveillance will include assessment for any adverse event(s) related to the intervention (i.e. 
EAD(P) displacement, EAD(P) damage, enteral tract tissue injury) and will continue for up 
to three (3) days following interventions in either group. Patients who are discharged from the 
hospital prior to three days will be followed up daily by phone for Clinical Assessment 
Measurements i.e., pain, feeding tolerance and EAD(P) location as assessed by caregiver until 
post intervention day three. 
6.4 
Sample Size and Power 
Sample size has been selected such that the power (1- β) of primary endpoints is 1-β ≥ 0.8, 
with α = 0.05.   
• 
The efficacy of TubeClear® is expected to be at least 95% based on previous bench 
testingxi. The efficacy of CHOP Standard Treatment is expected to be about 50% based 
on focus group conclusions.xii  Sample size results, displayed graphically, are as follows: 
 
xi TP-5007-079 and TR-5007-079 
xii Conclusions of Clinician Focus Groups, July 2009 

 
 
 
35 
 
To ensure proper power is achieved a sample size of 17 Subjects in each group is 
needed (Figure 9). 
• The efficiency of TubeClear® (Intervention time of TubeClear® to the CHOP Standard 
Treatment) is expected to be at least one standard deviation (40 minute difference of 
average time, 0.243 minute standard deviationxiii) greater than that of CHOP Standard 
Treatment based on bench testing.xiv  Therefore, a sample size of 17 in each group is 
more than sufficient to show statistical significance of the desired effect.   
6.5 
Interim Analysis 
No interim analysis will be performed.  Phase I results will be complied into a report and 
submitted to the IRB for review. Continuation into Phases IIA and IIB will be determined by 
the IRB based on the reported results of Phase I.  
 
 
 
xiii40 minute difference = 42.8 minute average time for Standard Treatment – 2.8 minute average time for tube clear (data 
from section 1.1, Table 2 of protocol). 0.243 standard deviation is calculated from data in TR-5007-079. 
xiv TR-5007-079 
Figure 9: Sample size as a function of power at three different alpha levels 

 
 
 
36 
 
7 
STUDY DEVICE 
7.1 
Description 
TubeClear® is the investigational device.  TubeClear® is intended to clear the occlusions in 
EAD(P)s. TubeClear® is comprised of a reusable Control Box and a single use Clearing Stem.  
TubeClear® is currently FDA cleared for use ONLY and SOLELY in clearing 
occlusions/clogs from EAD(A)s. Clearing Stem models for ND, NG, NJ, G, and J Tubes of 
size 10 – 18 Fr, 10 – 140 cm and ND, NG, NJ, G, and J Tubes of size 6 – 18 Fr, 15 – 36 cm 
for adults have been FDA cleared (Appendices A-E). The FDA has deemed TubeClear® to 
be non-significant risk for use in this study (Appendix D). 
This Study evaluates the use of TubeClear® in pediatric patients for the restoration of EAD(P) 
patency. The Clearing Stems being evaluated in this Study will be used with Pediatric Enteral 
Access Device ND, NG, and NJ 6 – 8 Fr, 38 – 140 cm; NG tube (Corflo, Corpak MedSystems) 
used as a jejunal tube inserted through a gastrostomy tube, 6 – 8 Fr, 38  – 140 cm; and AMT 
GJ tube, 14 Fr, 38 – 140 cm (15 – 55 in).   
TubeClear® use will be compared to the CHOP Standard Treatment for restoring patency in 
occluded EAD(P) by efficacy and TubeClear® related adverse events will be monitored and 
reported. CHOP Standard Treatment administration during this Study will follow standard 
protocol at CHOP. 
7.1.1 Packaging 
TubeClear® is comprised of a reusable Control Box and a single use Clearing Stem. Both the 
Control Box and Clearing Stem are non-sterile. The Control Box can be stored in a custom 
carrying case or mounted to an IV pole. The exterior surfaces of the Control Box are to be 
wiped between uses with the disinfectant method used as part of CHOP’s standard procedure 
for medical equipment that enters a patient’s room. The Clearing Stems are disposable (for 
one-time use only) and individually packaged in a sealed bag. Each sealed bag contains a 
Clearing Stem and Directions for Use. The Directions for Use are a reference for using 
TubeClear® but do not replace the need to read, understand, and follow the TubeClear® 
Operator’s Manual (i.e., Instructions for Use).  
7.1.2 Labeling 
TubeClear® Control Box is packaged with an Operator’s Manual. Operators are responsible 
for reading, understanding, and following the Operator’s Manual. Each Clearing Stem bag is 
labeled for the specific Clearing Stem Model, including EAD type, Fr size, Clearing Stem 
Model number, Clearing Stem Model color, intended use, cautions, and warnings.  
7.1.3 Dosing 
TubeClear® does not require dosing.  In this Study, the Investigator will determine the EAD(P) 
length by Subjects chart or markings on the EAD(P). The Investigator will place the Operator-
set Collar on the Clearing Stem to the centimeter marking that corresponds with the HER 

 
 
 
37 
 
and/or markings on the EAD(P). CHOP Standard Treatment will be administered according 
to CHOP standard protocol. 
7.1.4 Treatment Compliance and Adherence 
The Study intervention does not require ongoing treatments. Therefore, no compliance or 
adherence to ongoing treatment is needed.   
7.1.5 Device Accountability 
Records of the Study device (TubeClear®), and its disposition will be maintained by the Study 
Coordinator. These records will include device reception, device supply orders, device 
dispensing records, and disposition forms (in addition to model number and any other 
identifying information on the individual Clearing Stem). These records will be examined 
during the course of the Study by the Investigators and the Study Sponsor. The purpose of 
these records is to ensure to regulatory authorities and the Sponsor that the investigational 
device will not be distributed to any person who is not a Study Subject under the terms and 
conditions set forth in this protocol. At Study completion, all device supplies, including 
partially used and empty containers, must be returned to the Study Sponsor with the exception 
of the used Clearing Stems. 
 
 

 
 
 
38 
 
8 
SAFETY MANAGEMENT 
8.1 
Clinical Adverse Events 
Clinical adverse events (AEs) (any unfavorable and unintended sign including an abnormal 
finding, symptom or disease associated with the use of a medical intervention, regardless of 
whether it is considered related to the medical intervention, that occurs during the course of 
the Study) will be monitored throughout the Study. While no clinical adverse events are 
anticipated, potential adverse events include: 
• Clearing Stem exits the distal end of the EAD(P) and punctures the intestinal mucosal 
membrane. 
• Clearing Stem causes damage to the EAD(P) that requires replacement of the EAD(P). 
• A possible clinical adverse event for either intervention would be that the occluded 
medication is bolus flushed into the Subject’s digestive system when patency is 
restored. The medication will have a varying rate of absorption in the digestive system 
that may cause unanticipated side effects to the Subject depending on the medication’s 
safe therapeutic range. However, when using the TubeClear® occlusion clearing 
procedure (Figure 4) (i.e., an iterative process of partially clearing the occlusion then 
aspirating the broken occlusion particles, repeating until the collar reaches the EAD 
external ports (Figure 2B) would minimize potential for this clinical adverse event.  
Since the medication is periodically aspirated from the EAD(P), the final EAD(P) 
patency flush should contain minimal medication.  
• The contrast used in the post-intervention radiograph could result in an allergic 
reaction to contrast agent. The post-intervention radiograph will also incur a dose of 
radiation. However, this dose replaces the dose that would be received for EAD(P) 
replacement if the occlusion was not cleared. 
8.2 
Adverse Event Reporting  
The Investigator is responsible for recording and reporting unanticipated problems related to 
research that occurs during and after the Study Intervention. The plan for AE reporting is 
consistent with CHOP IRB Guidelines.   
Since TubeClear® is a non-significant risk device (Appendix D) in adults, serious adverse 
events (SAEs) are not expected. If any unanticipated problems related to the research 
involving risks to Subjects or others occur during the course of this Study (including SAEs), 
they will be reported to the IRB in accordance with CHOP IRB SOP 408: Unanticipated 
Problems Involving Risks to Subjects. AEs that are not serious but are notable and could 
involve risks to Subjects will be summarized in narrative or other format and submitted to the 
IRB at the time of continuing review.  

 
 
 
39 
 
9 
STUDY ADMINISTRATION 
9.1 
Treatment Assignment Methods 
9.1.1 Randomization 
A randomization sequence will be generated by computer program by the Study Sponsor for 
the randomized efficacy comparison in Phase IIB. The Study Team will be responsible for 
maintenance and execution of randomization sequence. The randomization sequence will be 
kept in individual sealed envelopes to be opened after the Subject is consented and enrolled 
in the Study. To ensure an appropriate balance of participation in both the TubeClear® 
intervention and CHOP Standard Treatment Groups, balanced, permuted block randomization 
will be used, as the Study is not entirely blinded.  
9.1.2 Blinding 
This Study will be blinded to the radiologist reading the abdominal radiographs post-
intervention. The Study will not be blinded to the Investigators, Study Nurse, or other research 
staff due to the nature of the interventions in this Study.   
9.1.3 Unblinding 
This is not applicable to this Study, as the Investigators, Study Nurse, and research staff are 
not blind to the Intervention. 
9.2 
Data Collection and Management 
The Study plan for collection and management of records is consistent with CHOP Policy A-
3-6: Acceptable Use of Technology Resources that defines the requirements for encryption 
and security of computer systems.   
1. Confidentiality will be protected by utilizing a code number as the only identifier for 
each Subject and the master list will be kept under lock and key by the Study 
Coordinator with access limited to the Investigators or Study Sponsor. All Study 
computer files will be password protected.        
2. Data security will be maintained by having a backup copy of the password-protected 
file on the Study Coordinator’s office computer, with the original in one of the 
CHOP’s secure research servers in a separate protected drive. 
3. All Subjects will be given a unique identification number. This identification number 
will be used on all Study forms and materials, except the Enrollment Log where the 
number is assigned. Only the primary Study team will have access to the Enrollment 
Log and will keep the Enrollment Log under secured lock and key.  Study data 
including links (key) to PHI will be retained for at least 2 years after last marketing 
approval per FDA regulations.        

 
 
 
40 
 
9.3 
Confidentiality 
All data and records generated during this Study will be kept confidential in accordance with 
Institutional policies and HIPAA on Subject privacy and the Investigator(s) will not use such 
data and records for any purpose other than conducting the Study. Confidentiality will be 
protected by utilizing a code number as the only identifier for each Subject and the master list 
(i.e., Enrollment Form) will be kept secured with access limited to the immediate Study team 
only. 
No identifiable data will be used for any future research Study without first obtaining IRB 
approval. The Investigator will obtain a data use agreement between the provider of the data 
(the Investigators) and any recipient researchers (both internal and external to CHOP) before 
sharing a limited dataset (PHI limited to birth date, date of admission, date of visit, date of 
service, and ZIP code).     
9.4 
Regulatory and Ethical Considerations 
9.4.1 Data and Safety Monitoring Plan 
This study will incorporate a data and safety monitoring plan with a medical monitor to ensure 
adequate human subject protection. The medical monitor (TBD) will review study data 
monthly for adverse events to ensure the safety of study subjects. The medical monitor will 
be a physician knowledgeable in pediatric critical illness and unrelated to the study. The study 
PI will be notified of all serious adverse events within 24 hours of knowledge of event. 
Notification will be by any member of the study staff who is made aware of a serious adverse 
event. Study data are collected daily by the research personnel, and therefore review for 
SAE/AE’s occurs daily while patients are actively on the study protocol. Identification of an 
SAE will prompt chart review by the site PI to determine possible relatedness to the study 
protocol. Should study subjects have serious adverse events related to study interventions, the 
PI will report these to the IRB, the Medical Monitor, and AMI to determine continuation of 
the study protocol within 24 hours of being notified of an SAE. 
Oversight for the conduct of the Study will be provided by the Investigators. Adverse events 
are not anticipated, but any occurring will be documented and reported according to IRB 
policies and procedures. Study personnel will be solely responsible for data collection and 
verification. Confidentiality will be protected by utilizing a code number as the only identifier 
for each Subject and the master list (i.e., Enrollment Form) will be kept secured with access 
limited to the immediate Study team only.   
• Investigators are responsible for oversight in conducting the Study.  
• Study Sponsor will conduct monthly monitoring of the Study to verify that the protocol 
is being followed, data collected accurately, and reports filed as required. 
9.5 
Data Collection and Management 
1. Confidentiality of the data will be ensured through the following     

 
 
 
41 
 
• A master list will be used and kept separate from other data forms. The master list will 
contain enrolled and screened patients and will link Personal Health Information (PHI) 
to the Subject ID number. This list will be kept in two forms: 1) an electronic file that 
will be kept on a secure clinical research drive maintained by the Department of 
Anesthesiology and Critical Care Medicine and 2) a paper file that will be kept in a 
locked file cabinet in the office of the PI, Co-PI, or Research Coordinator. 
• The Subject ID# will be used to organize the demographic information (containing 
PHI), and data collection forms for enrolled Subjects. This information will be 
electronically stored on the password-protectedREDCap website provided through 
CHOP. (https://tiu.research.chop.edu/redcap/redcap/index.php?action=create). Paper 
copies of the coded data only will be kept in binders or file folders in a locked office 
cabinet. 
2. Security.   
• Demographic information (containing PHI), and data collection forms for enrolled 
Subjects will be stored on the password-protected REDCap website as well as a 
backup on a secure clinical research drive maintained by the Department of 
Anesthesiology and Critical Care Medicine. Paper copies of the coded data only will 
be kept in binders or file folders in a locked office cabinet. 
3. Anonymization, de-identification or destruction.   
• Study data including links (key) to PHI will be retained for at least 2 years after last 
marketing approval per FDA regulations. Completed consent forms and their 
associated assent will be maintained for 6 years following Study closure or 
publication. De-identified data will be maintained for 6 years as well. 
4. REDCap 
• Data used for publishing will be managed and stored using the research-focused 
electronic data capture system REDCap, under an agreement with the software’s 
development consortium, led by Vanderbilt University. REDCap supports two secure, 
web-based applications designed exclusively to support data capture for research 
studies. REDCap is a PHP web application served by Apache Tomcat over a 128 bit 
SSL connection using a signed certificate. The application relies on a Study-specific 
data dictionary defined in an iterative self-documenting process that will be conducted 
by all members of the research team. The data dictionary is the foundation for custom 
case report form design and validated coding of variables. Authentication of research 
staff will be performed via LDAP using CHOP’s enterprise Active Directory service.  
The application generates a complete audit trail of user activity, provides reporting, 
and has an automated export mechanism to common statistical packages (SAS, SPSS, 
Stata, R/S-Plus). 

 
 
 
42 
 
• The REDCap project used in this study will be validated to 21 CFR Part 11 
requirements for controlled system access and electronic signatures, as data gathered 
from this study may be used in an FDA premarket notification (i.e., 510(k)). REDCap, 
as an overall software system, has the required components for compliance to Part 11. 
However, each individual project must be made compliant by adding in applicable 
features. Access will be limited to study personnel only, the electronic signatures will 
be enabled, study personnel will be delegated the appropriate role within the REDCap 
project to ensure that only a PI or co-PI can electronically sign a Subject record. AMI 
will compose a Software Requirements Document (identifying requirements that the 
REDCap project will need for compliance), a Validation Protocol (procedure to verify 
compliance to Part 11), and a Validation Report (execution of the Validation Protocol). 
The Validation Report will serve as documentation of the REDCap project compliance 
to Part 11 and will be maintained in the Regulatory Master File (RMF) by AMI. Lastly, 
AMI will compose an Instructions for Use document for filling out subject records 
within REDCap, which the study personnel will be trained on.The REDCap MySQL 
database is replicated in real time to a completely redundant instance of MySQL. The 
redundant instance is available for restoration of the primary database or for manual 
failover in the case of primary database failure. Time-stamped backup files are made 
from the replicated database daily by CHOP Research Information Systems using 
automated backup routines. Backup files are encrypted and transferred to a secure file 
server accessible only to designated personnel. A rolling seven-day window of backup 
files is maintained in an immediately available online state, with a larger window 
maintained in a compressed file archive available at a reduced speed of access. Daily 
destructive database backup files are stored on the database server and are deleted only 
after successful backup of the entire database to file. In the event of data error, loss or 
corruption, Research Personnel will work with CHOP Research Information Systems 
to determine the most appropriate recovery strategy. 
• Data and backups are stored in the CHOP Research Information Systems Storage Area 
Network (SAN). Access to the SAN directories where data are stored will be limited 
to Research Information Systems personnel, with authentication performed using 
CHOP’s enterprise Active Directory service.  
9.5.1 Risk Assessment 
The FDA has deemed TubeClear® to be non-significant risk for use in this study (Appendix 
D). TubeClear® is currently FDA cleared for use ONLY and SOLELY in clearing 
occlusions/clogs from EAD(A)s (Appendix A).  
9.5.2 Potential Benefits of Trial Participation 
The potential benefit to the Study Subjects is restored EAD(P) patency so that treatment via 
EAD(P) can continue and so EAD(P) removal and replacement procedure(s) are avoided.  
Results from this Study will benefit future individuals with an occluded EAD(P) by 
developing a method to restore patency to the EAD(P). TubeClear® addresses this clinical 

 
 
 
43 
 
need to safely and efficaciously restore patency to occluded EADs at the patients’ bedside 
while the EAD remains in the patient. 
9.5.3 Risk-Benefit Assessment 
The potential Study benefits outweigh the potential risks. When an EAD(P) becomes occluded 
and patency cannot be restored, the EAD(P) must be replaced. Risks associated with EAD(P) 
replacement vary depending on the type of EAD(P) to be replaced. Risks associated with NG, 
ND, NJ replacement include nasopharyngeal irritation and pain, incorrect EAD(P) placement, 
EAD(P) coiling, perforation of lung, esophagus, stomach or small intestines, aspiration and 
abscess.11,12 Risks associated with G and J  EAD(P) replacement include loss of access, 
bleeding, infection, fistulas, aspiration, and perforation of abdominal organs.12 Risks 
associated with GJ EAD(P) replacement include loss of access, bleeding, infection, and 
leakage.13,14 These risks are reduced by reducing or eliminating EAD(P) replacement for 
Subjects selected for Study participation. Risks of the Study related to the post treatment 
radiograph with contrast include allergic reaction to the contrast agent and radiation dose. The 
risk for allergic reaction to contrast agent is low as most Subjects will have received contrast 
agent during initial EAD(P) placement. The risk of exposure to radiation is not substantially 
changed as an abdominal radiograph and/or fluoroscopy would be utilized to replace an 
EAD(P) and EAD(P) replacement will be reduced or eliminated with the Study. Subjects 
selected for Study participation will be monitored closely for adverse events, although no 
adverse events are anticipated. It is possible that younger Subjects may be enrolled before 
and/or in disproportionate numbers than older Subjects as younger Subjects may be more 
likely to experience EAD(P) occlusions. 
9.6 
Recruitment Strategy 
Subjects will be recruited from patients in the CHOP PICU, PCU, and/or IR that are identified 
to have an occlusion of their EAD(P)s during the current admission. Potential eligible Subjects 
will be identified by screening the electronic health records (EHR). In addition, CHOP staff 
may notify the research personnel when there is a potential Subject. The Research Personnel 
will screen potential Subjects using the protocol inclusion and exclusion criteria. Information 
about this study will be disseminated electronically via email and described on the PICU 
website on the intranet. 
9.7 
Informed Consent/Assent and HIPAA Authorization 
The Investigator will be responsible for obtaining informed consent from the parent/guardian 
and patient assent, if appropriate. The Investigator will provide a detailed description of the 
Study and allow adequate time for questions and discussion. The Investigator will ascertain 
Study comprehension by asking the parent/guardian and, if appropriate, the eligible Subject 
to describe the Study. Parent/guardian and, if appropriate, the eligible Subject will be provided 
with as much time as needed to make a determination on Study participation.  Parent/guardian 
and, if appropriate, the eligible Subject will sign the informed consent/assent form.  Interpreter 
services or language line will be utilized to obtain consent for non-English speaking potential 
Subjects using short forms and Study Summary documents. Coercion will be avoided by 
allowing the parent/guardian and, if appropriate, the eligible Subject ample time to elect Study 

 
 
 
44 
 
participation and by inviting the parent/guardian and, if appropriate, the eligible Subject to 
seek counsel from other family members, friends, and medical professionals about the Study.  
HIPPA authorization will be included in the informed consent/patient assent form. Once 
signed, the forms will be maintained in a secured place with access limited to the immediate 
Study team only. 
 
9.8 
Payment to Subjects/Families 
There is no payment to Subjects/families for participation in this Study.   
 
 
 

 
 
 
45 
 
10 PUBLICATION 
Publication of Study results will not contain Subject identifying information. 
 
 

 
 
 
46 
 
11 REFERENCES 
1. 
ARMY Medical Field Feeding Operations. In: ARMY, ed. Washington, DC2003. 
2. 
Lyman B, Kemper C, Northington L, et al. Use of Temporary Enteral Access Devices 
in Hospitalized Neonatal and Pediatric Patients in the United States. Journal of 
Parental and Enteral Nutrition: American Society for Parenteral and Enteral Nutrition; 
2015. 
3. 
Yu H, Wier L, Elixhauser A. Hospital Stays for Children, 2009. Healthcare Cost and 
Utilization Project: Agency for Healthcare Research and Quality; 2011. 
4. 
Haber H, Stern M. Intestinal Ultrasonography in Children and Young Adults: Bowel 
Wall Thickness is Age Dependent. J. Ultrasound Med2000:315-321. 
5. 
Merkel S, Shayevitz J, Voepel-Lewis T, Malviya S. The FLACC: A Behavioral Scale 
for Scoring Postoperative pain in Young Children. Vol 23. Pediatric Nursing: Practice 
Applications of Research; 1997. 
6. 
Malviya S, Voepel-Lewis T, Burke C, Merkel S, Tait AR. The revised FLACC 
observational pain tool: improved reliability and validity for pain assessment in 
children with cognitive impairment. Pediatric Anesthesia. 2006;16(3):258-265. 
7. 
Hicks C, von Baeyer C, Spafford P, van Korlaar I, Goodenough B. The Faces Pain 
Scale – Revised: toward a common metric in pediatric pain measurement. Vol 93. 
Pain: Elsevier; 2001:173-183. 
8. 
R, Core, Team. R: A Language and Environment for Statistical Computing. Vienna, 
Austria: R Foundation for Statistical Computing; 2014. 
9. 
Faul F, Erdfelder E, Lang A-G, Buchner A. G*Power 3: A flexible statistical power 
analysis program for the social, behavioral, and biomedical sciences. Behavior 
Research Methods. 2007;39(2):175-191. 
10. 
Faul F, Erdfelder E, Lang A-G, Buchner A. Statistical power analyses using G*Power 
3.1:Tests for correlation and regression analyses. Behavior Research Methods. 
2009;41(4):1149-1160. 
11. 
Durai R, Venkatraman R, Ng PC. Nasogastric tubes. 2: Risks and guidance on 
avoiding and dealing with complications. Nurs Times. 2009;105(17):14-16. 
12. 
Beyer P. Complications of Enteral Feedings. In: Matarese LE, Gottschlich MM, eds. 
Contemporary nutrition support practice : a clinical guide. 2nd ed. Philadelphia: 
Saunders; 2003:215-226. 
13. 
Rosenberg J, Amaral J, Sklar C, et al. Gastrostomy and gastrojejunostomy tube 
placements: outcomes in children with gastroschisis, omphalocele, and congenital 
diaphragmatic hernia. Radiology. 2008;248(1):247-253. 
14. 
Friedman J, Ahmed S, Connolly B, Chait P, Mahant S. Complications associated with 
image-guided gastrostomy and gastrojejunostomy tubes in children. Pediatrics. 
2004;114(2):458-461. 
15. 
Sedgwick P. Statistical tests for independent groups: time to event data. BMJ 
2012;345:e5257-e5257. 
 

 
 
 
47 
 
Appendices 
 
Appendix A:   FDA 510k clearance documentation for K121571, K123659, K131052, 
K163092, and K172556.. 
Appendix B:  Research Plan and Device Description: National Institutes of Health, Eunice 
Kennedy Shriver National Institute of Child Health and Human Development 
Phase II Small Business Innovation Research Grant: In-Patient Pediatric 
Gastrojejunal 
Tube 
Cleaner 
Eliminating 
Surgical 
Intervention 
(2R44HD065365-02). 
Appendix C:   Test Reports and Test Protocols for the EAD(A) Clearing Stems listed in this 
Protocol in numerical order. 
Appendix C.2: Test Reports and Test Protocols for the EAD(P) Clearing Stem design listed 
in this Protocol in numerical order. 
Appendix D:  FDA & Walter Reed Heath Care System NSR Determination. 
Appendix E: TubeClear® Clinical and Trial Evaluation Forms 
Appendix F: TubeClear® Training Procedure