Clinical trial NCT04101890
Conditions: Diaper Dermatitis
Sponsor: Linda Fu
Start date: 2020-03-12; Completion date: 2021-01-02
Enrollment: 5 participants; Allocation: NON_RANDOMIZED; Intervention model: SEQUENTIAL

Brief summary:
Diaper dermatitis is one of the most common dermatologic diseases affecting infants and children. The incidence is highest among those 9-12 months old and it has been reported to affect 7-50% of infants in the US. It is caused by skin exposure to a combination of several factors including: excessive moisture, topical irritants, reduced pH, friction, maceration and bacterial infection. When infants soil their diaper, diaper contents saturate the area raising the pH of the skin above the normal level of 5 or less, and leaving the area highly vulnerable to maceration from friction. Irritants in urine and feces are then able to penetrate the macerated skin, causing inflammation and greater skin friability. An elevation in the skin pH allows pathogenic bacteria to overgrow, and combined with the breakdown in the skin's outer epithelial barrier, can lead to bacterial infection. Theraworx Foam Formulation-Allantoin Liquid by Avadim Technologies, Inc. is a skin protectant with use for temporary protection of minor cuts, scrapes, burns and chapped or cracked skin. As such, Theraworx Foam used in the diaper area may be beneficial for protecting skin against diaper rash wounds, as well as for assisting with wound healing and reducing any associated pain. The purpose of this study is to determine caregivers' perceptions of the benefits of using Theraworx Foam on their infant's diaper area as part of their hygienic routine, including whether they feel the product is pleasant and easy to use, and whether they feel it helps prevent and reduce the severity of diaper dermatitis in their infants 1-14 months old.

Detailed description:

Arms: arm 1: Participants will be given a 4 week supply of Theraworx Spray Foam, an FDA-registered OTC drug (NDC 61594-000), to apply a thin layer to their infant's entire diaper area with every diaper change (2-4 foam pumps or 4-6 sprays depending on the infant's size) for 4 weeks. arm 2: Participants continue their typical diaper care.
Interventions: intervention 1: Diaper care with Theraworx
Intervention descriptions: intervention 1: Theraworx foam formulation to be used as a preventive and treatment agent for diaper rashes

Protocol documents:
Prot_SAP_000.pdf: 
1 
 
 
 
 
 
 
 
 
 
THE HEALTHY BABY BOTTOMS STUDY: 
A TRIAL OF THERAWORX FOAM FORMULATION FOR THE PREVENTION AND 
TREATMENT OF DIAPER DERMATITIS 
 (AVADIM HEALTH, INC.) 
NCT04101890    
1/13/2020 
 
 
Principal Investigator:  
Linda Fu, MD, MS 
Children’s National Health System 
lfu@childrensnational.org 
202-476-3931 
 
 
Co-Investigator:  
Ashley Jones, NP 
 
Research Assistant:  
Rachel Torres, BA 
 
 


2 
 
 
TABLE OF CONTENTS 
 
1. Study Objectives ......................................................................................................................................... 4 
1.1 Primary objective .......................................................................................................................................................... 4 
1.2 Secondary objectives .................................................................................................................................................... 4 
2. Background ................................................................................................................................................. 4 
3. Protocol Design and Overview  .................................................................................................................. 4 
3.1 Study design .................................................................................................................................................................. 4 
3.2 Protocol overview ......................................................................................................................................................... 5 
3.3 Study timeline ............................................................................................................................................................... 5 
4. Participant Eligibility ................................................................................................................................... 5 
4.1 Description of sites enrolling patients .......................................................................................................................... 5 
4.2 Inclusion criteria ............................................................................................................................................................ 5 
4.3 Exclusion criteria ........................................................................................................................................................... 5 
5. Procedures ................................................................................................................................................... 5 
5.1 Recruitment and enrollment ......................................................................................................................................... 5 
5.2 Run-in and trial periods ................................................................................................................................................. 6 
5.3 Surveys .......................................................................................................................................................................... 6 
5.3.1 Baseline, in-person survey ................................................................................................................................ 6 
5.3.2 Weekly, online surveys ..................................................................................................................................... 6 
5.4 Participant reimbursement ........................................................................................................................................... 7 
5.5 Participant schedule of activities .................................................................................................................................. 7 
6. Pharmaceutical information ........................................................................................................................ 7 
6.1 Administration .............................................................................................................................................................. 7 
6.2 Potential/Reported toxicities ........................................................................................................................................ 7 
6.2.5 Product Ingredient List ...................................................................................................................................... 7 
6.3 Agent accountability ..................................................................................................................................................... 8 
6.4 Treatment compliance .................................................................................................................................................. 8 
7. Adverse drug reaction reporting ................................................................................................................ 8 
7.1 Defining and reporting unexpected and serious adverse events ................................................................................. 8 
7.2 Stopping criteria ............................................................................................................................................................ 8 
7.2.1 Individual stopping criteria ............................................................................................................................... 8 
7.2.2 Study stopping criteria ...................................................................................................................................... 9 
8. Patient confidentiality ................................................................................................................................. 9 
9. Statistical analysis plan .............................................................................................................................. 9 
9.1 Outcome assessment .................................................................................................................................................... 9 
9.2 Sample size and power calculation ............................................................................................................................... 9 


3 
 
 
    9.3 Statistical considerations ............................................................................................................................................... 9 
10. References ............................................................................................................................................... 11 
 
 


4 
 
 
1. STUDY OBJECTIVES 
1.1 Primary objective: Determine whether parents perceive Theraworx Foam and Spray to be superior to 
usual care for prevention of diaper dermatitis among infants 1-14 months old. 
• 
Hypothesis #1a: Parents will report fewer total days of diaper dermatitis in their infants when the infants are 
using Theraworx than when they are not. 
• 
Hypothesis #1b: Parents will less likely to report any diaper dermatitis in their infants when the infants are 
using Theraworx than when they are not. 
 
1.2 Secondary objectives:  
Objective #2: Determine whether Theraworx Foam is superior to usual care for reduction of severity of diaper 
dermatitis among infants 1-14 months old. 
• 
Hypothesis #2a: Parents will report less use of adjuvant topical treatments (antifungals, antibacterials, 
steroids) for their infant’s diaper dermatitis when they are using Theraworx than when they are not. 
• 
Hypothesis #2b: Parents will report less severe diaper dermatitis based on visual assessment when their 
infants are using Theraworx than when they are not. 
Objective #3: Determine parents’ satisfaction with Theraworx Foam 
• 
Hypothesis #3a: Parents will find Theraworx easy to apply and remove 
• 
Hypothesis #3b: Parents will find Theraworx pleasant to use (smell, feel, appearance) 
 
2. BACKGROUND 
Diaper dermatitis is one of the most common dermatologic diseases affecting infants and children 
(Tuzun et al., 2015). The incidence is highest among those 9-12 months old and it has been reported to affect 
7-50% of infants in the US (Tuzun et al, 2015, Cohen, 2017, Blume-Petavi & Kanti, 2018). It is caused by skin 
exposure to a combination of several factors including: excessive moisture, topical irritants, reduced pH, 
friction, maceration and bacterial infection (Blume-Petavi & Kanti, 2018). When infants soil their diaper, diaper 
contents saturate the area raising the pH of the skin above the normal level of 5 or less, and leaving the area 
highly vulnerable to maceration from friction. Irritants in urine and feces are then able to penetrate the 
macerated skin, causing inflammation and greater skin friability (Pogacar et al., 2018).  An elevation in the skin 
pH allows pathogenic bacteria to overgrow, and combined with the breakdown in the skin’s outer epithelial 
barrier (statum corenum), can lead to bacterial infection (Pogacar et al., 2018). With the development of more 
advanced and absorbent diapers in recent years, the incidence of diaper dermatitis has subsequently 
decreased (Blume-Petavi & Kanti, 2018). Another primary preventive practice for reducing the risk of diaper 
dermatitis is use of prophylactic barrier creams (Kayaoglu, Kivanc-Altunay & Sarikaya, 2015). Nonetheless, 
while disposable diaper technology has become more advanced, the composition of barrier creams has not. In 
fact, some barrier creams such as those containing zinc oxide may actually contribute to the damage cascade 
leading to diaper dermatitis by increasing the pH of skin (Bartels, et al., 2014). 
 
Theraworx Spray Foam by Avadim Health, Inc. is an FDA-registered OTC drug (NDC 61594-000). The 
marketed product is labelled as a skin protectant with use “for temporary protection of minor cuts, scrapes, 
burns and chapped or cracked skin” with the active ingredient being allantoin. Allantoin is listed on the FDA 
OTC Ingredient List as used for or having reviews pending for use as a wound healing agent, skin protectant 
and external analgesic. As such, Theraworx Foam used in the diaper area may be beneficial for protecting skin 
against diaper dermatitis wounds, as well as for assisting with wound healing and reducing any associated 
pain. The purpose of this study is to determine parents’ perceptions of the benefits of using Theraworx Spray 
Foam on their infant’s diaper area as part of their hygienic routine, including whether they feel the product is 
pleasant and easy to use, and whether they feel it helps prevent and reduce the severity of diaper dermatitis in 
their infants 1-14 months old. This investigation is not intended to be reported to FDA in support of a new 
indication for use, to support any other significant change in the labeling or to support a significant change in 
the advertising. 
 
3. PROTCOL DESIGN AND OVERVIEW:  
3.1 Study design: This study will be conducted as an open-label, unblinded, sequential trial in which we will 
employ a pre- vs. post-intervention design involving a run-in period followed by a trial period for all participants. 
In this way, infants will serve as their own control limiting variability between comparator groups in terms of 


5 
 
 
diaper hygiene practices including frequency of diaper changes and type of diapers, wipes, and other products 
used. 
 
3.2 Protocol overview: 
 
 
 
 
 
 
3.3 Study Timeline: 
 
Study month 
Activity 
1 2 3 4 5 6 7 8 9 10 11 12 
Recruit and enrollment 
x x x x x x x x x  
 
 
Participant run-in period 
x x x x x x x x x  
 
 
Participant experimental period  
x x x x x x x x x 
 
 
Data analysis 
 
 
 
 
 
 
 
 
 
 
x 
x 
 
4. PARTICIPANT ELIGIBILITY 
4.1 Description of sites enrolling participants: Caregivers of infants ages 1-12 months old will be recruited 
from one of the five the Children’s Health Centers (CHCs) at Children’s National Health System. These health 
centers together treat ~30% of all children ages 0-18 years old in DC with Medicaid insurance. The population 
is predominantly minority (African American (85%), Hispanic (8%)) and publically insured (83%). 
 
4.2 Inclusion criteria: Caregivers will be eligible if they can read English at the 8th grade level, and have 
reliable access to the internet and email for 7 weeks. English proficiency and internet access will be verified by 
parental completion of the first online survey within 24 hours of the request. Caregivers must also be a 
custodial guardian of an infant between the ages of 1-12 months old who lives with them, currently wears 
diapers, and has had ≥1 diaper rash in the 2 months preceding recruitment. 
 
4.3 Exclusion criteria: Caregivers will be excluded if their infant is immunocompromised, has a congenital 
disorder, or, on the day of recruitment, has a diaper rash, has a moderate to severe illness requiring 
hospitalization or transfer to the emergency room, or was circumcised <10 days prior. Participants who do not 
complete the first online survey or ≥2 post-intervention online surveys will be excluded from participating in the 
remainder of the study. They will also be excluded if they do not have a stable address at which they can 
receive a package of Theraworx at week 4 and/or are unable to pick it up at Children’s National. 
 
5. PROCEDURES 
5.1 Recruitment and enrollment: Potential participants will be initially identified when bringing their children to 
one of the five Children's Health Centers for care. On days of recruitment (which will be determined via a 
convenience sample based on study personnel scheduling), study personnel will access electronic health 
records to identify potential participants based on the age of their child. Parents of children ages 1-12 months 
old will be approached for study participation in a private treatment room or in the waiting room. Potential 
participants will be told briefly that they may qualify to participate in a 7 week study to help determine the 
effectiveness of a new diaper rash product called Theraworx that is currently being used as a skin protectant 
and for wound care. They will be told that the study will involve using Theraworx with every diaper change for 4 
weeks, and also answering 8 surveys starting with a baseline, in-person survey on the day of enrollment, 
followed by 7 weekly, online surveys. Those who are interested in learning more about the study will be invited 
to a private space (if not already in one) to conduct the screening process, and if applicable, the informed 
consent process (Appendix A). Study eligibility will be assessed using an online screening form with stop logic 
Week 1
Week 2
Week 3
Week 4
Week 5
Week 6
Week 7
Monitor for diaper rash
Usual diaper care
Usual diaper care plus Theraworx Foam Spray
Enrollment, baseline survey 
Online survey 


6 
 
 
(Appendix B). For those who meet eligibility requirements, study staff will obtain written informed consent, 
verbally administer the baseline, in-person survey, obtain several forms of contact information, demonstrate 
how the Theraworx Foam should be used, and train participants in rating rash severity using a modified Diaper 
Dermatitis Scale (Buckley 2016) (Appendix C). 
 
5.2 Run-in and trial periods: There will be a 3 week run-in period starting just after enrollment during which 
time parents will be instructed to continue their usual diapering care including use of any other diaper 
products/creams, and to respond to the weekly survey requests. After completing the run-in period, parents will 
choose to either pick up from the hospital or be sent via Fed-Ex a sufficient supply of Theraworx to last the 4 
week duration of the trial period. Parents will receive written instruction on how to apply the Theraworx with 
every diaper change (Appendix D) and to continue to respond to the weekly survey requests. 
 
5.3 Surveys 
5.3.1 Baseline, in-person survey: Immediately following the informed consent process, study staff will 
verbally administer the baseline, in-person survey to participants (Appendix E). This survey will assess infant 
race/gender, diet (breast/bottle feeding/solid food), daily stool frequency, history of parental and sibling atopic 
dermatitis/childhood eczema, frequency of diaper dermatitis, creams/products used in diaper area (bath soap, 
emollients, diaper wipes); and who is involved in changing diapers (parent, grandparent, sibling, babysitter, 
daycare, etc.). It will also determine participant preference to pick up the Theraworx or have it sent to their 
home, and assess participant accuracy with rating visual severity of diaper rashes according to the modified 
Diaper Dermatitis Scale after being trained by staff. Lastly, participants will be asked to recall total number of 
days their infant had a diaper rash over the last 7 days, and if the number is greater than 0, to rate the rash 
using the modified Diaper Dermatitis Scale. 
 
Upon completion of the baseline, in-person survey, the participant will receive an incentive debit card 
(ClinCard) which will be activated for the patient and charged with $10. The participant will be instructed to 
keep this card for the next 7 weeks to receive future incentive disbursements for completing the online surveys. 
 
5.3.2 Weekly, online surveys: Starting on the first Monday morning that falls at least 8 days from completion 
of the baseline, in-person survey and repeating each of the following Monday mornings for a total of 7 
occurrences, a unique online survey link will be emailed to each participant. Each Sunday beforehand, 
participants will be texted and emailed a reminder to check their emails the next day and to complete the 
survey within 24 hours of receiving the emailed link. Each Monday morning, participants will receive a second 
text message reminder. By each Tuesday at noon, a list will be generated of survey non-respondents who will 
be contacted by phone twice that day by study staff to complete that week’s survey on the phone. Each 
Wednesday morning, ClinCards will be charged with incentive awards for participants who complete the entire 
online survey. Participants who do not complete at least the first online survey will not be eligible to complete 
any further surveys and will be dropped from the study. This will help limit participation to those who can 
demonstrate capacity and willingness to complete the online survey with the intent of minimizing loss-to-follow 
up over the 7-week period of individual enrollment.  
 
Weekly online surveys will assess whether the infant had any diaper dermatitis over the past 7 days, 
and if so, the total number of days with rash, and severity of rash on its worst day (using a modified Diaper 
Dermatitis Scale score (0-8)). It will also assess for any: use of other products and adjuvant therapies in the 
diaper area, diarrheal illnesses, new foods initiated, and changes to their contact information. The surveys 
during the run-in period (weeks 1-3) will confirm whether the participant prefers to pick up the Theraworx or 
have it sent to their home (Appendix F). During the trial period (weeks 4-6), the weekly survey will also assess 
how frequently Theraworx was used, and whether it was applied as a foam and/or spray (Appendix G). The 
final survey at the end of week 7 will be slightly longer since it will also assess satisfaction with Theraworx (in 
terms of its smell, feel, appearance, ease of use, whether they would recommend it to a friend, and how it 
compares to other diaper creams they have used) (Appendix F).  
 
5.4 Participant reimbursement: To promote completion of online surveys and reduce risk of participant loss-
to-follow up, an escalating incentive scale will be used. Completion of the baseline, in-person survey and the 


7 
 
 
first 3 weekly online surveys will be compensated with a $10-per-survey incentive. Completion of the next 3 
surveys will be compensated $15 each. Completion of the longer, final survey will be compensated with a $30 
incentive. Thus, the maximum reimbursement for any one participant over the entire duration of participation 
will be $115. All incentives will be disbursed on ClinCard debit cards. 
 
Survey name 
Baseline 
Week 1 
online 
Week 2 
online 
Week 3 
online 
Week 4 
online 
Week 5 
online 
Week 6 
online 
Final 
survey format 
in person 
online 
online 
online 
online 
online 
online 
online  
reimbursement 
$10 
$10 
$10 
$10 
$15 
$15 
$15 
$30 
 
5.5 Participant schedule of activities: 
Procedures 
T0: Screening/ 
Enrollment/ 
Baseline: 
Day 1 
T1-1 
T1: Day 8* 
T2-1 
T2: Day 15* 
T3-1 
T3: Day 22* 
T4 -1 
T4: Day 29* 
T5-1 
T5: Day 36 
T6-1 
T6: Day 43* 
T7-1 
T7: Final Study 
Contact: Day 50* 
Informed consent 
x 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Baseline survey 
x 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Survey reminder 
text/email/call 
 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
Weekly survey 
(including AE self-
report) 
 
 
x 
 
x 
 
x 
 
x 
 
x 
 
x 
 
x 
Start intervention 
 
 
 
 
 
 
x 
 
 
 
 
 
 
 
 
  * Actual day may be up to 8 days later to allow T1 to occur on the first Monday at least 8 days from T0. 
 
6. PHARMACEUTICAL INFORMATION 
Commercially available Theraworx foam spray will be provided to participating sites by Avadim Technologies 
Inc.  
6.1 Administration: Theraworx will be dispensed for use during the intervention period as several smaller 
volume bottles such that the product can be kept in several settings including the home and daycare if needed. 
The formulation will be dispensed in bottles with and without the foam actuator so parents can choose to apply 
it as a spray or foam per their own preference. During the trial period, parents will be reminded to apply 
Theraworx with every diaper change alone, or as a base layer if they choose to apply it with other products or 
creams.  
 
6.2 Potential/Reported Toxicities 
• 
Acute Eye: Direct eye contact may cause minor irritation. If eye contact occurs, rinse thoroughly 
• 
Acute Skin: No reports of adverse reactions to skin contact. 
• 
Acute Inhalation: None Known 
• 
Acute Ingestion: None Known 
• 
Chronic Effects:  None known  
• 
Medical Conditions Aggravated by Effects: None Known 
 
6.2.5: Product Ingredient List 
• 
Aqua (Water)  
• 
Cocamidopropyl Betaine  
• 
Aloe Barbadensis Leaf Juice  
• 
Colloidal Silver  
• 
Tocopheryl Acetate  
• 
Glycerin  


8 
 
 
• 
Allantoin  
• 
Beta-Glucan  
• 
Citrus Paradisi (Grapefruit) Fruit Extract  
• 
Lauryl Glucoside  
• 
Tetrasodium EDTA  
• 
PEG/PPG-4/12 Dimethicone  
• 
Methylparaben  
• 
Propylparaben  
• 
Parfum (Fragrance) 
 
6.3 Agent accountability: The PI will ensure that Children’s National will maintain a careful record of the 
inventory and disposition of Therworx using a Drug Accountability Record Form. The Children’s National 
Clinical Research Unit Pharmacy will use this form to track lot numbers, expiration dates, and overall inventory 
during the study, at the end of the study and prior to destruction.  
 
6.4 Treatment Compliance: Parents will administer Theraworx spray foam to their children. They will report 
use on the weekly surveys.  
 
7. ADVERSE DRUG REACTION REPORTING 
7.1 Defining and reporting of unexpected and serious adverse events 
Unexpected Adverse Events (UAEs) are defined as events that are not listed in the consent form, and are 
possibly related to the intervention, or are listed but occur more frequently or are more severe than anticipated. 
Serious Adverse Events (SAEs) are defined to include death, life threatening illness, hospitalization or 
prolongation of hospitalization, and persistent/significant disability. Because all intervention will occur at the 
participant’s home unsupervised by study staff, UAEs and SAEs will be reported by the parent on the weekly 
online surveys. Any self-reported SAEs will be documented by study staff using the Children’s National Serious 
Event Reporting System (SERS). Investigators will follow the Children’s National guidelines for reporting SAEs. 
The guidelines are to report the death of a Children’s National subject enrolled in an interventional study if the 
death is unexpected (not due to disease progression) and related or possibly related to the research within 
one (1) business day of learning of the event. A follow-up report must be submitted within two (2) business 
days. All other UAEs and SAEs will be be reported to the IRB within seven (7) business days of learning of the 
event. The investigator will notify the study sponsor at the same time as appropriate. Risks that are described 
in the protocol and consent form (expected AEs), as well as SAEs and UAEs that are unrelated to the 
intervention do not need to be reported to the IRB, unless the expected AE occurs more frequently or is more 
serious than expected. However, we will report all AEs to the DSMB, and subsequently to the IRB in the 
annual continuing review. Any proposed changes in the consent form or research procedures as a result of 
AEs will be prepared by the study team and submitted to the IRB for approval. 
 
7.2 Stopping Criteria 
7.2.1 Individual Stopping Criteria 
• 
All protocol interventions are complete 
• 
Failure to complete the first online survey or ≥2 post-intervention online surveys 
• 
Death 
• 
Lost to follow-up 
• 
Study withdrawal 
• 
Serious Adverse Event 
• 
Discretion of the Study PI, such as the PI decides that continuing in the study would be harmful or no 
longer in the participant’s best interest  
 
7.2.2 Study stopping criteria: 


9 
 
 
• 
The data show a significantly increased risk of serious adverse effects during the experimental phase of 
the study.     
• 
It becomes clear that successful completion of the study is not feasible (e.g. there is an excess of 
patient dropout, missing data, lack of recruitment, etc). 
 
8. PATIENT CONFIDENTIALITY 
To maintain patient privacy, we will be use the database product REDCap as the platform for data entry, 
validation and storage. The REDCap server of Children’s National is located in a locked room in the Clinical 
Research Institute and is password protected. Access to the server is controlled by the group membership 
system residing on the server. In order to gain access to the data on this server, a valid user must be added. 
REDCap security systems require setting up a user account and password for each user to log onto the server 
and then he/she will be given specific permission to access the databases. This permission can only be given 
to data staff by the server administrator with the permission of the PI. While analyses are being conducted, 
data will be stored on password protected computers and backed up on the Children’s National secure server 
which, like the REDCap server, is controlled by a group membership system requiring setting up a user 
account for access. Once analyses have been completed, the data will be removed from the hard drive(s) of 
any computer(s) used for analysis, and will be stored as de-identified electronic files on the CNHS secure 
server. The investigator will grant monitors and auditors from Avadim Technologies Inc. access to participant 
records as needed to audit the data collection process. The patient’s confidentiality will be maintained and will 
not be made publicly available to the extent permitted by the applicable laws and regulations. 
 
9. STATISTICAL ANALYSIS PLAN 
9.1 Outcome assessment: Outcome of interest will be diaper dermatitis as assessed by parental visual 
assessment using a modified Diaper Dermatitis Scale Score (see Appendix C). 
 
9.2 Sample size and power calculation: PASS 15 was used to estimate sample size needed to detect a 
difference of two days of perceived diaper rash between pre- and post-test scenarios using paired t-tests with 
non-parametric adjustment. Allowing for a large standard deviation of up to 5 days and a moderate degree of 
correlation between measures, a sample size of 65 with measures at both time-points would allow for detection 
of statistical difference at 80% power with a two-tailed p-value of 0.05. Assuming a 35% loss to follow up over 
the 7 weeks participation duration, we plan to recruit 100 participants. If recruitment loss exceeds 35% at the 
interim, we will consider raising this number to 150 participants.  
 
9.3 Statistical Considerations 
Hypothesis 1a: Parents will report fewer total days of diaper dermatitis in their infants when the infants 
are using Theraworx than when they are not. To evaluate Hypothesis 1a, total reported dermatitis days over 
the 4 week pre- and post-intervention time-points will be separately summed. For the primary analysis, only 
participants who completed all 8 weekly surveys will be included.  Secondary analyses may consider all 
participants with at least two reports in each of the study periods, with missing values assumed to be the mean 
number of dermatitis days reported by the participant by study period.  Number of dermatitis days during usual 
care (pre-intervention) will be compared to number of dermatitis days following use of the Theraworx Spray 
Foam (post-intervention) using either paired t-test or Wilcoxon signed rank test, as appropriate.   
 
Hypothesis 1b: Parents will be less likely to report any diaper dermatitis in their infants when the 
infants are using Theraworx than when they are not. Occurrence of any dermatitis during the two study 
periods will be coded as “yes” (at least one dermatitis day) or “no” (zero dermatitis days) based on parent 
report of number of dermatitis days.  Differences in occurrence pre- and post-intervention will be explored 
using McNemar’s test. If numbers permit, conditional logistic regression will be considered to evaluate odds of 
dermatitis when using Theraworx Spray Foam compared to usual care.   
 
Hypothesis 2a: Parents will report less use of adjuvant topical treatments (antifungals, antibacterials, 
steroids) for their infant’s diaper dermatitis when they are using Theraworx than when they are not. 
Use of adjuvant topical treatments during each of the study periods will be considered as both a binary variable 
(any or none) as well as frequency of use, defined as number of weeks in which use was reported. Any use 


10 
 
 
pre- vs. post-intervention will be evaluated using McNermar’s test or conditional logistic regression. Number of 
uses will be compared using Wilcoxon signed rank test.  Depending on numbers, marginal homogeneity tests 
may also be considered, treating the number of weeks as categorical variables.  As use during unreported 
weeks will be unknown and difficult to quantify, primary analyses will consider only participants who completed 
all surveys.   
 
Hypothesis 2b: Parents will report less severe diaper dermatitis based on visual assessment when 
their infants are using Theraworx than when they are not. Dermatitis severity will be considered in two 
ways: 1) average severity during each study period and 2) maximum severity during each study period.  Both 
average and maximum severity based on the total score from the visual assessment scale will be compared 
pre- and post-intervention using Wilcoxon signed rank test. As in 1a, for the primary analysis, only participants 
who completed all 8 weekly surveys will be included.  Secondary analyses may consider participants with at 
least two reports in each of the study periods to allow for severity averages during each study period to be 
calculated. 
 
Hypothesis 3a: Parents will find Theraworx easy to apply and remove  
Hypothesis 3b: Parents will find Theraworx pleasant to use (smell, feel, appearance) Descriptive 
statistics (median Likert scale scores and proportions) based on parent report will be used to summarize 
participant satisfaction with Theraworx Spray Foam.   
 
For all analyses, a two-tailed p-value of < 0.05 will be considered significant. Sensitivity analyses based on 
reported Theraworx Spray Foam use, infant age, and infant sex will be considered. Difference in number of 
reported diaper rash days between usual care and Theraworx will be compared between high and low 
Theraworx use groups using Wilcoxon-Mann-Whitney test to assess whether high Theraworx usage improves 
number of diaper rash days better than low usage More complex longitudinal models considering weekly 
outcomes during usual care versus Theraworx Spray Foam using Generalized Estimating Equations may also 
be considered.  
 
 
 


11 
 
 
10. REFERENCES 
Bartels, N.G., Lunnemaann, L., Stroux, A., Kottner, J.,Serrano, J. & Blume-Peytavi, U. (2014) Effect of diaper 
cream and wet wipes on skin barrier properties in infants: A prospective and randomized control trial. Pediatric 
Dermatology, 31(6), 683-691. DOI: 10.1111/pde.12370 
Blume-Peytavi, U. & Kanti, V. (2018) Prevention and treatment of diaper dermatitis. Pediatric Dermatology, 35, 
19-23. Doi:10.1111/pde.13495.  
Buckley, B.S., Mantaring, J.B., Dofitas, R.B., Lapitan, M.C., Montegudo, A. (2016) A new scale for assessing 
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