An Evaluation of Early Use of the Tortle Midliner and Intraventricular Hemorrhage (IVH) Outcomes in Premature Babies: A Randomized Controlled Trial
Phase: NA
Conditions: Intraventricular Hemorrhage of Prematurity
Sponsor: Orlando Health, Inc.

 
 
CLINICAL RESEARCH PROTOCOL 
 
 
 
An Evaluation of Early Use of the Tortle Midliner and Intraventricular 
Hemorrhage (IVH) Outcomes in Premature Babies: A Randomized 
Controlled Trial 
 
 
Principal Investigator: 
Adrienne C. Alexander, RRT, MHA, DPT 
Pediatric Rehabilitation Services 
Arnold Palmer Medical Center 
92 W. Miller St. 
Orlando, FL  32806 
321. 843.8394 
 
Sub – Investigators:  
Pediatric Rehabilitation Services 
Arnold Palmer Medical Center 
92 W. Miller St. 
Orlando, FL  32806 
321. 843.3269 
 
Philip Vangelakos, PT  
Kristin Horwath, PT, DPT 
Dana Murphy, PT 
Bridget Pine, PT, DPT 
Joanna Wallace, PT, DPT 
Tara Savage, PT, MPT 
 
Developmental Specialist 
Alexander Center for Neonatology 
Winnie Palmer Hospital for Women and Babies 
83. W. Miller St. 
Orlando, FL  32806 
321-841-1478 
 
Linda B. Lowman, M.Ed. 
Yanina M. Alba, MS 
 
 

 
Page 2 of 12 
Regulatory Coordinator: Denise P. Smith, BSN, RNC, RRT-NPS, CPFT, CCRP 
Research and Clinical Trials 
Winnie Palmer Hospital for Women & Babies  
83 W. Miller St., Mail Point 377 
Orlando, FL 32806 
321.841.7816 
 
Study Sites: 
Winnie Palmer for Women & Babies  
Neonatal Intensive Care Unit 
83 W. Miller St. 
Orlando, FL 32806 
321.841.5218 
 
Arnold Palmer Hospital for Children  
Research and Clinical Trials 
92 W. Miller St. 
Orlando, FL 32806 
321.841.7816 
 
Sponsor: 
Tortle Products, LLC 
Study Product: 
Tortle Midliner  
Protocol Number: 
N/A 
 
 Protocol Version: 
       v.03 dated 12/19/2018 
 
 
 

 
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Table of Contents  
 
1. 
Research Synopsis 
 
 
 
 
 
5 
2. 
Background and Significance 
 
 
 
6 
3. 
Objectives 
 
 
 
 
 
 
7 
3.1 
Primary Objective  
 
 
 
7 
3.2 
Secondary Objectives 
 
 
 
7 
4. 
Study design/methodology  
 
 
 
7-9 
5. 
Study Population 
 
 
 
 
 
9 
 
5.1 
Inclusion 
 
 
 
 
 
9 
5.2 
Exclusion Criteria 
 
 
 
 
10 
6. 
Study Duration/ Study Timeline 
 
 
 
10 
7. 
Statistical Analysis Plan 
 
 
 
 
10 
8. 
Informed Consent Process  
 
 
 
10-11 
9.  
Privacy and confidentiality  
 
 
 
11 
10. 
Risk/Benefit  
 
 
 
 
 
11 
 
10.1 
Risks to Participants  
 
 
 
11 
10.2 
Benefits to Participant 
 
 
 
11 
11. 
Safety Monitoring, Interim Analysis, Stopping Rules 
11 
12. 
Conflict of Interest  
 
 
 
 
11 
13. 
Publication and Presentation Plans 
 
 
12 
14. 
References 
 
 
 
 
 
 
12 
15. 
Appendices 
 
 
 
 
 
 
12 
 
15.1     Data Collection Sheets (Baseline, NICU, Day 1,   
 
 
 
 
Day 2, Day 3, Head Ultrasound, Final Clinical  
 
 
 
 
 
Outcome) 
 
 
15.2 
Tortle Bedside Log  
 
 
 
15.3 
Tortle Rehab Assessment Log 
 
 
 
 
 
 
 
 

 
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List of Abbreviations:  
 
Apgar       Appearance, Pulse, Grimace, Activity, and Respiration  
BW 
      birth weight 
DR 
      delivery room 
g               gram 
IVH           intraventricular hemorrhage 
kg              kilogram 
LBW       low birth weight 
NICU        neonatal intensive care unit 
SAE 
      serious adverse event 
VLBW      very low birth weight 
WPH         Winnie Palmer Hospital for Women and Babies 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

 
Page 5 of 12 
 
 
An Evaluation of Early Use of the Tortle Midliner and Intraventricular 
Hemorrhage (IVH) Outcomes in Premature Babies:  
A Randomized Controlled Trial 
 
 
 
1. 
Research Synopsis 
 
1.1 
Study Title 
An Evaluation of Early Use of the Tortle Midliner and Intraventricular Hemorrhage 
(IVH) Outcomes in Premature Babies: A Randomized Controlled Trial 
 
1.2 
Study Population 
The study population will comprise inborn infants ≤30 6/7 weeks gestational age 
undergoing inpatient care in the Neonatal Intensive Care Unit at Winnie Palmer Hospital 
for Women and Babies. 
 
1.3 
Study Design 
This study is a single-site prospective randomized controlled clinical trial. 
 
1.4 
Sample Size 
The investigators for the study at Winnie Palmer Hospital for Women and Babies (WPH) 
anticipate a total enrollment of 150 neonates with 75 in each group (75 in control group 
and 75 in treatment group).  
 
1.5 
Study Duration 
The study duration is estimated to continue until July 30, 2020.  
 
1.6 
Primary Objective 
The primary objective of this study is to determine if infants positioned with the Tortle 
Midliner to optimize midline head positioning will have a better IVH outcome, 
determined by a decrease in rate of occurrence or severity of IVH, when compared to 
infants receiving the standard care (control group) with no Tortle Midliner intervention. 
 
1.7 
Secondary Objectives 
None. 
 

 
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2. 
Background and Significance 
 
Intraventricular hemorrhage (IVH) is defined as bleeding into the ventricles of the 
premature infant brain-the highest risk for the lowest gestational ages. IVH almost always 
occurs between birth and the first 72 hours of life. The four grades of IVH are based on 
the degree of bleeding; the greater the severity of the bleed, the more likely to have a 
poor outcome. Complications can include hydrocephalus, mental retardation, cerebral 
palsy and seizures. Neurologic sequelae can lead to death.  Even for low grade bleeds the 
studies show the negative effects on cognitive scores and an increased incidence of 
learning disabilities. In addition, these same children often suffer from attention deficit 
disorder and other behavioral dysfunctions, which require intervention in order for the 
child to successfully integrate into school and society. 
 
The incidence of IVH in very low birth weight infants (1500g) has declined from 40-50% 
in the early 1980s to 20% in the late 1980s. However, in the last two decades the 
occurrence of IVH has remained stationary. In extremely premature infants weighing 
500-750g, IVH occurs in about 45% of neonates (Philip, Allan, Tito, & Wheeler, 1989). 
 
Since increased risk of IVH can be associated with changes of intracranial pressure, many 
medical protocols supported by the research efforts of Bedwell have established IVH 
bundles which are designed to help reduce fluctuations in intracranial pressure while 
managing the micro-preemie infant during the first few days of life (Bedwell, Bright, & 
Sekar, 2015). 
 
The correlation between IVH and head positioning of the extremely low birth weight 
infants has now made its way into research literature. Malusky suggests that venous 
obstruction can result from increased external pressure on the venous system when the 
micro-preemie infant has their head positioned to the side rather than maintaining a 
neutral position (Malusky & Donze, 2011). With this in mind many neonatal intensive 
care units (NICUs) around the world have instituted practices which include strict neutral 
positioning often combined with raising the head of the bed for all infants <1500 grams 
during their first three-plus days of life. 
 
Therefore, we are aiming to conduct a prospective randomized controlled trial in order to 
answer the research question: Does early use of the Tortle Midliner reduce the incidence 
and/or level of severity of intraventricular hemorrhage if used in infants born at ≤ 30 6/7 
weeks and neutral position is maintained for the first 72 hours of life? We hypothesize 
that the use of early consistent neutral positioning compared to the standard care (nested 
positioning) practiced in the NICU will reduce the risk of intraventricular hemorrhage in 
preterm infants born at ≤ 30 6/7 weeks and have a positive effect on the incidence and/or 
level of severity of intraventricular hemorrhage in this population. 
 
 
 
 

 
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3. 
Objectives 
3.1 
Primary Objective 
The prime objective is to determine if early application of the Tortle Midliner for preterm 
infants, ≤ 3 hours following birth and with subsequent continuous use through 72 hrs. of 
life to ensure maintenance of optimal midline positioning (treatment group), will impact 
the IVH outcome as determined by a reduction in the rate and/or severity of IVH when 
compared to infants receiving the standard regimen of care (control group). 
 
3.2 
Secondary Objectives 
None 
 
4. 
Study design/methodology 
This study will be registered in Clinical Trials (clinicaltrials.gov) with the primary 
endpoint being a difference in IVH incidence and severity. We propose to conduct a 
randomized controlled trial in preterm infants (gestational age ≤30 6/7 weeks) comparing 
the use of the Tortle Midliner and the standard of care practice (Control group).  While 
blinding of study groups is always desirable in randomized studies, this will not be 
possible for this study. 
 
Study Procedure 
After eligibility of the infant is determined and the study informed consent is obtained 
from the parent or legal guardian, subjects will be randomized. 
 
 
Randomization will follow a block randomization table that will determine if the infant 
will go into the group that will be positioned using the Tortle Midliner (Treatment Group) 
or not (Control Group).  
 
All clinical care will be provided with consideration of the gestational age of the subject 
and follow NICU department guidelines and as ordered by physician and/or ARNP 
providers. 
 
The key distinction for this study will be the use of the Tortle Midliner as a positioning 
aid in addition to standard of care for the Treatment Group, as opposed to solely standard 
practice of nesting and the use of rolls and other aids for the Control Group. 
 
Treatment Group 
The application and maintenance of the Tortle Midliner is within the scope of practice 
and skill-set of the NICU nursing and ancillary staff. The device has been in use in the 
WPH NICU since May 2016 when ordered by physician or nurse practitioner.  
 
The use of the Tortle Midliner will be in addition to the NICU department process 
guidelines for positioning relevant to the gestational age of the subject. The Tortle 
Midliner will be applied no later than 3 hours following birth under the supervision of a 

 
Page 8 of 12 
study investigator. The size/fit and application of the device will be according to the 
manufacturer’s guidelines. The neutral midline head position, supine or slightly side-
lying, with a bed elevation between 15° and 30° will be maintained during the first 72 
hours of life. A member of the NICU physical therapy staff will perform and document a 
goniometry measurement (head/neck angle with head midline and perpendicular to 
shoulders, in line with the axial spine and not > than 5° deviation) a minimum of once 
daily during the first 72 hours of life and make any adjustments necessary, which is 
within their scope of practice.  
 
Caregivers will document the NICU integrated flowsheet and the Sunrise electronic 
record with interventions regarding positioning, handling, skin assessment etc. per 
standard practice requirements. 
 
The Tortle Midliner placement will be documented by clinical staff assigned to the 
subject’s care every 2-4 hours on a tracking log. The active study period will end after the 
first 72 hours of life. The positioning device will be removed and the clinical care will 
continue according to NICU guidelines. 
 
In the instance that phototherapy is ordered by the attending physician for babies in the 
treatment group, a compatible Tortle Midliner phototherapy eye shield will be used 
following manufacturer’s size and guidelines. 
 
Control Group  
All clinical care for the control group will be within NICU department process guidelines 
relevant to the gestational age of the subject and as ordered by physician and/or ARNP 
providers. The neutral midline head position with the aid of nesting and/or rolls with a 
bed elevation between 15° and 30° will be maintained throughout position changes 
during the first 72 hours of life, which is standard practice. Caregivers will document the 
NICU integrated flowsheet and the Sunrise electronic record with interventions regarding 
positioning, handling, skin assessment etc. per standard practice requirements. 
 
Data Collection 
At Study Entry 
Basic demographic information and delivery history will be collected. 
 
Maternal Information- Only maternal information contained within the subject’s record 
will be collected; the mother’s record will not be accessed 
Data collection will include: prenatal maternal conditions, maternal medications, mode of 
delivery, and delivery complications. 
 
Clinical Data- collected from birth through the first 72 hours of life: 
Procedures and conditions that may contribute to IVH will be collected, such as: 
sepsis (positive blood culture, vasopressors, steroids, bolus administrations (fluids/meds),  
hypoglycemia (serum glucose <45) or hyperglycemia (serum glucose >200), hypercarbia 
(CO2  >65mmHg), apnea/bradycardic episodes requiring stimulation, patent ductus 

 
Page 9 of 12 
arteriosus, maximum respiratory support, suction events,  line placements (PICC, IV, 
UAC/UVC) and/or needle punctures , UAC/UVC line collections, chest tube insertion, 
and any other noxious event 
 
The subjects in both groups meet criteria for a standard of care head ultrasound at 6-8 
days of life. Results from the head ultrasound report will be captured.  
Clinical Outcomes Data – collected through date of discharge 
The results of the last head ultrasound and/or magnetic resonance imaging (MRI) of the 
brain before discharge will be collected if these additional tests were ordered during the 
hospitalization (as solely determined by the attending neonatologist and not for study 
purposes). 
 
Outcome data will include: days on mechanical ventilation throughout hospital stay, 
discharged home with G-Tube, discharged home on respiratory support (FiO2, 
mode/settings), discharged with shunt, and length of stay (# days). 
 
Adverse Event/Serious Adverse Event 
The device, Tortle Midliner, solely impacts the skin contact areas. Only adverse events 
related to skin breakdown requiring wound care consultation with treatment will be 
reported as an adverse event. The principal investigator will evaluate adverse events 
related to skin integrity. 
 
Any death will be reported as a serious adverse event according to Orlando Health IRB 
policy. 
 
Major Protocol Deviation 
For the purpose of this study, the midline position will be maintained with consistent use 
of the Tortle Midliner for all randomized study subjects in the treatment group (Tortle 
group) from ≤ 3 hours to 72 hours from birth. If the device is not utilized for a period 
greater than 30 consecutive minutes, the situation will be evaluated by the principal 
investigator. A major protocol deviation will be reported if the device was not in place for 
any reason other than the safety or well-being of the subject. 
 
Study Endpoint 
The study period will be the first 72 hours of life with data collection for clinical 
outcomes to continue until discharge from the hospital, transfer to another institution, 
removal or withdrawal from the study, or death. There will be no additional contacts or 
follow-up for subjects beyond those time points. 
 
The primary endpoint for the study is the difference in IVH incidence and severity 
between the two groups from birth through the first 72 hours of life. 
 
 
 

 
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5. 
Study Population 
Each study subject must meet all of the indicated inclusion criteria and none of the 
exclusion criteria noted below: 
 
5.1 Inclusion Criteria 
1. Gestational age less than or equal to 30 6/7 weeks at birth    
2. Less than 3 hours from birth 
3. Informed consent obtained from parent or legal guardian prior to reaching 
time point for randomization 
5.2 
Exclusion Criteria 
1. Presence of genetic/chromosomal abnormality, congenital hydrocephalus, 
congenital neuromuscular disorder, or other diagnosis determined to  impact 
survival or generalizability of results  
2. Unable to participate for any reason based on the decision of the principal 
investigator. 
3. Infants born outside Winnie Palmer Hospital for Women and Babies 
 
6.       Study Duration/ Study Timeline 
Projected start date approx. April 2018 following IRB approval) 
 
• Stage 1 
Enroll subjects following IRB approval  
                        through April 2020 
                                      24 months 
• Stage 2 
Data analysis through July 2020 
 
    3 months 
• Stage 3 
Poster, abstract and/or manuscript through  
 
 
January 2021  
 
 
                6 months 
 
7. 
Statistical Analysis Plan 
Sample Size Determination:  
A sample size of 142 neonates with 71 in each group (71 in control group and 71 in 
intervention group) was determined in order to achieve 80% power to detect a 20% 
difference in IVH between the two groups, using a target rate of IVH of 15% in the 
intervention group. The test statistic used was the two-sided Z test with pooled variance. 
The significance level of the test would be 0.05. 
 
We aim to allow for an additional 5% in sample size to adjust for either voluntary or 
involuntary withdrawal of some of the enrolled subjects. Upon reaching 142 enrollees the 
data will be reviewed. If any baby (ies) within the first 142 enrollees was withdrawn, the 
baby will be replaced according to the original randomized group, up to an additional 8 
babies to ensure the power of the study and maintain a balance between the groups. A 
maximum of 150 babies will be enrolled. 
 
Data Analysis: 
Data analysis will include descriptive statistics with means and proportions. Comparative 
statistics will be used to compare IVH outcomes in the two groups. IVH outcome will be 

 
Page 11 of 12 
determined by a reduction in the rate and/or severity of IVH. Any additional information 
on data points may be described in tables and/or graphs. 
 
8. 
Informed Consent Process 
The patient’s parent or legal guardian will be approached by the principal investigator or 
sub-investigator and the study will be explained in clear, layperson language. All study 
procedures will be disclosed. Risks to the patient will be explained; no individual patient 
benefits will be promised. The patient’s parent or legal guardian will be given the 
opportunity to ask questions and confer with family members and others. If the patient’s 
parent or legal guardian elects to consent to the trial, he/she will sign and date the consent 
form. 
 
The original signed form will remain with the investigator in the study file; a copy will be 
given to the parent or legal guardian and a copy will be filed in the official medical 
record as well. 
 
9. 
Privacy and Confidentiality 
Federal regulations at 45 CFR 46 111 (a) (7) requires that when appropriate, there are 
adequate provisions to protect the privacy of subjects and to maintain the confidentiality 
of data. To maintain confidentiality, only the study investigators and regulatory 
coordinator will have access to the case reports and subject records. All records will be 
kept in a locked, password- protected computer as well. All paper case report forms and 
source documents will be maintained in a secured area within a locked office and 
maintained for a minimum of three years after the completion of the study.  
 
10. 
Risk/Benefit 
This study involves a product, the Tortle Midliner, already on the market and available 
for commercial use for prevention of cranial asymmetry and head preference in infants 0 
to 6 months of age. The product being evaluated is a breathable, cotton, Lycra and foam 
beanie device, with two positioning rolls. The Tortle Midliner has been in use in the 
WPH NICU since May 2016. 
 
10.1 
Risk to participants 
This study involves the use of a product in direct contact with the infant’s skin. There 
remains a very small chance of skin breakdown. Frequent skin assessments (as is the 
standard care practice in the NICU) will help minimize this risk. 
 
10.2 
Benefits to Participants 
The product under evaluation is already approved for use in the neonatal population. 
However, the impact on the rate and severity of IVH has not been studied. As such, it is 
not possible to predict whether or not any direct benefit will result from the use of this 
product to prevent or reduce IVH.  
 
 
 

 
Page 12 of 12 
11.     Safety Monitoring, Interim Analysis, and Stopping Rules 
Safety will be monitored by the review of adverse events and serious adverse events for 
each patient. Any concerns regarding the safety of the device will be evaluated by the 
principal investigator, documented, and reported according to IRB policy. 
 
12. 
Conflict of Interest 
No relevant financial interest or affiliations with any commercial interests for any 
member of the study team 
13. 
Publication and Presentation Plans 
A manuscript will be prepared upon completion of this study and submitted for possible 
publication in a journal with a focus on neonatal or rehabilitation meditation. The data 
may also be presented at future neonatal and/or rehabilitation conferences. 
 
14. 
References 
 
Bedwell, S. M., Bright, B., & Sekar, K. C. (2015). Decrease in Incidence of 
Intraventricular Hemorrhage (IVH) After the Introduction of an IVH Prevention 
Bundle in the NICU. The University of Oklahoma Medical Center.  
Malusky, S., & Donze, A. (2011, November). Neutral Head Positioning in Premature 
Infants for Intraventricular Hemorrhage Prevention: An Evidence-Based Review. 
Neonatal Network, 30(6), 381-396. 
Philip, A., Allan, W., Tito, A., & Wheeler, L. (1989, November). Intraventricular 
Hemorrhage in Preterm Infants: Declining Incidence in the 1980s. Pediatrics, 
84(5), 797-801. 
 
 
15. 
Appendices  
 
 
15.1  Data Collection Sheets (Baseline, NICU, Day 1,  
 
 
 
 
Day 2, Day 3, Head Ultrasound, Final Clinical  
 
 
 
 
Outcome) 
 
 
15.2     Tortle Bedside Log 
 
 
15.3  Tortle Rehab Assessment Log