Clinical trial NCT05010304
Conditions: Penicillin Allergy Penicillin Reaction
Keywords: penicillin allergy
Sponsor: University of Texas Southwestern Medical Center
Start date: 2021-12-09; Completion date: 2023-11-30
Enrollment: 23 participants; Allocation: NA; Intervention model: SINGLE_GROUP

Brief summary:
While reported adverse reactions to penicillins are common, most patients with a penicillin allergy label can safely tolerate penicillins, and elective evaluation for penicillin allergy has been recommended. For low-risk patients, direct oral challenge may be an optimal approach as a delabeling strategy. However, there is a vast disparity between the number of patients with a penicillin allergy label and practicing allergists in the United States, and implementing outpatient primary care-based delabeling strategies in low-risk patients may increase access to delabeling assessments. However, a recent survey of pediatricians identified perceived barriers to implementing penicillin allergy evaluations into their routine care. Significant gaps in knowledge exist regarding the feasibility of this approach involving risk stratification evaluation of reported penicillin adverse reactions and direct amoxicillin challenge procedures in low-risk patients in the pediatric primary care setting. With this, the primary aim of this study is to evaluate the number of patients for which risk-stratification and direct amoxicillin challenge are successfully completed in an outpatient pediatric primary care clinic.

Detailed description:

Arms: arm 1: None
Interventions: intervention 1: Amoxicillin
Intervention descriptions: intervention 1: Two-dose amoxicillin challenge

Protocol documents:
Prot_SAP_000.pdf: 
Title: Penicillin De-Labeling in the Pediatric Primary Care Setting; Protocol  
NCT Number: 05010304 
IRB Approval Date: 11/29/2021 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


IRB STU-2021-0517 
 
PROTOCOL FORM / RESEARCH DESCRIPTION 
 
If an item does not apply to your research project, indicate that the question is "not applicable” – do not leave 
sections blank 
 
Click once on the highlighted entry in each box to provide your response.  Click the item number/letter or word, 
if hyperlinked, for detailed instructions for that question.  If your response requires inserting a table, picture, etc, you 
may need to first delete the box that surrounds the answer and then insert your table or other special document. 
 
 
1.  Purpose and objectives.           List the purpose and objectives: 
 
The goal of this project is to explore the feasibility of implementing a penicillin allergy 
delabeling protocol for low-risk pediatric patients in the primary care setting. Specifically, we 
seek to demonstrate risk-stratification of reported adverse reactions to penicillins and 
completion of direct amoxicillin challenge in low-risk subjects can be performed in the 
outpatient pediatric primary care setting.  
 
 
 
2.  Background. 
• 
Describe past experimental and/or clinical findings leading to the formulation of your study.   
• 
For research involving investigational drugs, describe the previously conducted animal and human 
studies.   
• 
For research that involves FDA approved drugs or devices, describe the FDA approved uses of this 
drug/device in relation to your protocol.   
• 
Attach a copy of the approved labeling as a product package insert or from the Physician’s Desk 
Reference.   
You may reference sponsor’s full protocol or grant application (section number and/or title) or if none, ensure 
background includes references. 
 
Please respond to all components of this item, or clearly indicate which components are not applicable. 
 
a. 
Background 
Reported adverse drug reactions to penicillins are common; however, more than 90% of 
patients with a penicillin allergy label can safely tolerate penicillins (1, 2). Numerous adverse 


outcomes are associated with an unverified penicillin allergy, and elective evaluation for 
penicillin allergy has been recommended (1, 3, 4). 
 
There is a vast disparity between the number of patients with a penicillin allergy label and 
practicing allergists in the United States, with over 30 million penicillin-allergic labeled 
patients and less than 5000 practicing allergists (5, 6). With such a significant prevalence of 
labeled penicillin allergy, no single medical discipline can handle this burden alone; a 
coordinated effort across both primary care and subspecialists will be required to address 
this. As the majority of penicillin allergy labels occur in young childhood, pediatricians are 
uniquely situated to have a significant impact in reducing the long-term consequences of a 
penicillin allergy label through delabeling strategies (1, 5). Direct oral challenge in low-risk 
patients has been recommended as a delabeling strategy for this population (7-9). 
Cumulative studies have now evaluated the safety and efficacy of direct amoxicillin 
challenge in children with a penicillin-allergy label in over 1400 subjects (8-16); the majority 
of studies have taken place in the outpatient allergist setting. Across studies, positive 
challenge rates ranging from 0-13%. The largest study was a single center prospective 
study which defined low-risk allergy patients as an absence of severe cutaneous adverse 
reactions (SCARs); they reported on 818 patients and found a 6% positive challenge rate 
(8). Across the above studies, all reactions were mild and only required treatment with oral 
antihistamines, no epinephrine use was documented in any of these studies.  
  
While there is significant evidence for the safety and efficacy of direct penicillin challenge in 
the evaluation of penicillin allergy, this has not yet been widely implemented in the primary 
care setting. There have been two pilot studies exploring direct amoxicillin challenge in the 
pediatric primary care setting. The first was a retrospective study of 42 children in Australia 
who included children greater than 18 months old. They performed direct amoxicillin 
challenges after 3 months had elapsed from the index reaction. There was a 3% positive 
challenge rate and all reactions resolved with only oral diphenhydramine. The second was a 
prospective study that included 102 children in Ireland and there no positive challenges to 
amoxicillin challenge. This approach has not been studied in the United States. A recent 
survey of US-based pediatricians identified perceived barriers to implementing penicillin 
allergy evaluations into their routine care (17). Significant gaps in knowledge exist regarding 
the feasibility of this approach involving direct amoxicillin challenge procedures in low-risk 
patients in the pediatric primary care setting. 
 
1. 
Castells M, Khan DA, Phillips EJ. Penicillin Allergy. N Engl J Med. 2019;381(24):2338-
51. 
2. 
Shenoy ES, Macy E, Rowe T, Blumenthal KG. Evaluation and Management of 
Penicillin Allergy: A Review. JAMA. 2019;321(2):188-99. 


3. 
Blumenthal KG, Shenoy ES. Is My Child Allergic to Penicillin? JAMA Pediatr. 
2019;173(7):708. 
4. 
Joint Task Force on Practice P, American Academy of Allergy A, Immunology, 
American College of Allergy A, Immunology, Joint Council of Allergy A, et al. Drug allergy: an 
updated practice parameter. Ann Allergy Asthma Immunol. 2010;105(4):259-73. 
5. 
Staicu ML, Vyles D, Shenoy ES, Stone CA, Banks T, Alvarez KS, et al. Penicillin Allergy 
Delabeling: A Multidisciplinary Opportunity. J Allergy Clin Immunol Pract. 2020;8(9):2858-
68 e16. 
6. 
American Academy of Allergy Asthma and Immunology Report on the Allergy and 
Immunology Physician Workforce (1999-2009/10). Rensselaer, NY: The Center for Health 
Workforce Studies; 2012 [Available from: https://www.aaaai.org/Aaaai/media/ 
MediaLibrary/PDF%20Documents/Practice%20and%20Parameters/2012-AI- Physician-
Workforce-Report.pdf. 
7. 
Vyles D, Antoon JW, Norton A, Stone CA, Jr., Trubiano J, Radowicz A, et al. Children 
with reported penicillin allergy: Public health impact and safety of delabeling. Ann Allergy 
Asthma Immunol. 2020;124(6):558-65. 
8. 
Mill C, Primeau MN, Medoff E, Lejtenyi C, O'Keefe A, Netchiporouk E, et al. 
Assessing the Diagnostic Properties of a Graded Oral Provocation Challenge for the 
Diagnosis of Immediate and Nonimmediate Reactions to Amoxicillin in Children. JAMA 
Pediatr. 2016;170(6):e160033. 
9. 
Vyles D, Chiu A, Routes J, Castells M, Phillips EJ, Visotcky A, et al. Oral amoxicillin 
challenges in low-risk children during a pediatric emergency department visit. J Allergy Clin 
Immunol Pract. 2020;8(3):1126-8 e1. 
10. 
Gateman DP, Rumble JE, Protudjer JLP, Kim H. Amoxicillin oral provocation 
challenge in a primary care clinic: a descriptive analysis. CMAJ Open. 2021;9(2):E394-E9. 
11. 
Allen HI, Vazquez-Ortiz M, Murphy AW, Moylett EM. De-labeling penicillin-allergic 
children in outpatients using telemedicine: Potential to replicate in primary care. J Allergy 
Clin Immunol Pract. 2020;8(5):1750-2. 
12. 
Mustafa SS, Conn K, Ramsey A. Comparing Direct Challenge to Penicillin Skin Testing 
for the Outpatient Evaluation of Penicillin Allergy: A Randomized Controlled Trial. J Allergy 
Clin Immunol Pract. 2019;7(7):2163-70. 
13. 
Moral L, Garde J, Toral T, Fuentes MJ, Marco N. Short protocol for the study of 
paediatric patients with suspected betalactam antibiotic hypersensitivity and low risk 
criteria. Allergol Immunopathol (Madr). 2011;39(6):337-41. 
14. 
Chambel M, Martins P, Silva I, Palma-Carlos S, Romeira AM, Leiria Pinto P. Drug 
provocation tests to betalactam antibiotics: experience in a paediatric setting. Allergol 
Immunopathol (Madr). 2010;38(6):300-6. 
15. 
Labrosse R, Paradis L, Lacombe-Barrios J, Samaan K, Graham F, Paradis J, et al. 
Efficacy and Safety of 5-Day Challenge for the Evaluation of Nonsevere Amoxicillin Allergy in 
Children. J Allergy Clin Immunol Pract. 2018;6(5):1673-80. 
16. 
Caubet JC, Kaiser L, Lemaitre B, Fellay B, Gervaix A, Eigenmann PA. The role of 
penicillin in benign skin rashes in childhood: a prospective study based on drug rechallenge. 
J Allergy Clin Immunol. 2011;127(1):218-22. 


17. 
Cherk E, Morris K, Collins CA. Partnering with general pediatricians to delabel 
penicillin allergies in children. Ann Allergy Asthma Immunol. 2020. 
 
 
 
b. 
Current practice 
Currently there is no standard protocol in the Children’s Health pediatric primary care clinic for evaluation of 
penicillin-allergy labels. Most often, children with a penicillin allergy label are referred to the Children’s Health 
pediatric allergy clinic for evaluation of penicillin allergy regardless of their risk status based on the history of 
their index reaction to penicillin.  
 
 
3.  Study Design.  
Describe the study design (e.g., single/double blind, parallel, crossover, etc.)  Consider inserting a scheme to 
visually present the study design. 
 
This study is a prospective, descriptive, single arm study of a convenience sample of children 
from age 2-18 with a history of parent reported penicillin allergy who present to an outpatient 
pediatric clinic for a routine healthcare maintenance visit. 
 
 
4.  Research Plan / Description of the Research Methods:   
4.a.  Provide a comprehensive narrative describing the research methods.   
     1) Provide the order in which tests/procedures will be performed,  
     2) Provide the setting for these events and a description of the methods used to protect privacy during the 
study.   
     3) Provide the plan for data analysis (include as applicable the sample size calculation) 
 
Please respond to all components of this item, or clearly indicate which components are not applicable. 
 
 
Patients will be recruited from the pediatric primary care clinic at the Children’s Health 
Specialty Center Dallas campus who are scheduled for a routine healthcare maintenance 
visit, have a penicillin allergy listed in the electronic medical record, and have consented to 
participate in research activities. Patient caregivers will receive a telephone call, where in a 
study member will introduce the topic of penicillin allergy and delabeling through direct 


amoxicillin challenge and obtain verbal consent to administer a risk-stratifying questionnaire 
evaluating the index reaction and their interest in proceeding with the amoxicillin challenge, 
including reasons for hesitancy and perceived barriers. Subjects with a history of reactions 
consistent with severe cutaneous adverse reactions will be excluded. The study member will 
review the oral amoxicillin challenge procedure and assess caregiver and patient’s interest in 
proceeding with oral amoxicillin challenge.  
 
Subjects who are classified as low-risk and are interested to proceed with direct amoxicillin 
challenge will be sent the consent form through the caregiver’s preference of encrypted email, 
mail, or patient portal MyChart for their review. Caregivers will be provided the option to sign 
the electronic consent form, using an encrypted, secure platform provided through UTSW 
(Docusign/REDCap), and if they choose this option, will be contacted via telephone to review 
the consent form and answer applicable questions. Alternatively, when presenting for their 
healthcare maintenance visit at the pediatric primary care clinic at the Children’s Health 
Specialty Center Dallas campus, the written consent form will be reviewed.. Patients will be 
screened for acute dermatitis or respiratory symptoms. Subjects with acute dermatitis or 
respiratory symptoms at time of evaluation will be excluded. A point of care urine pregnancy 
test will be performed on adolescent female subjects who have begun menstruation; subjects 
who have a positive pregnancy test or who are breastfeeding will be excluded. 
 
A single dose of amoxicillin 50 mg will be administered at the start of the healthcare 
maintenance visit. Subjects will be observed for 10 minutes and if no reaction, will be given a 
second 200 mg dose and observed for a further 50 minutes for immediate reactions, defined 
as onset of urticaria, angioedema, cough, wheezing, rhinitis, repetitive vomiting, diarrhea, 
protracted abdominal pain, or hypotension, and managed accordingly. This direct amoxicillin 
challenge testing is the recommended evaluation for low-risk patients, and the investigatory 
component of this study is if it can be performed in conjunction with a routine healthcare 
maintenance visit in the pediatric primary care setting. During this observation period, 
subjects will have their healthcare maintenance visit with the primary pediatric provider. 
Subjects who have a negative oral challenge will be provided documentation of their 
immediate tolerance of penicillin. Upon completion of challenge, a survey will be administered 
to families to assess the quality of their experience and identify areas for improvement. If 
immunizations are indicated per the CDC vaccination schedule, they will be administered 
after this 60-minute period of observation from the challenge. Subjects will be discharged with 
instructions to contact the pediatrician and study team for any delayed symptoms. We will 
also measure the duration of each subject’s time in the clinic from check in to check out. A 
follow up encounter will occur over the phone at 7-10 days after the date of oral challenge to 
assess for delayed reactions. At 1 year post-challenge, subjects’ penicillin allergy status will 
be assessed in the electronic medical record, and patients who have had penicillin allergy 
label added back to their allergy list will be contacted via telephone to assess reasons for the 


addition of the penicillin allergy label. Descriptive statistics will be used to describe the 
population completing amoxicillin challenge testing.  
 
 
 
4.b.  List of the study intervention(s) being tested or evaluated under this protocol 
 
N/A -  this study does not test or evaluate an intervention.    Skip to item 4.d. 
# 
Study intervention(s) being tested or evaluated under the protocol 
 
 
 
Add or delete rows as needed 
 
Affiliate 
 
Place a check next 
to institution(s) 
where the  
intervention will be 
performed 
Local Standard 
Practice?  
Indicate whether 
the intervention is 
considered 
acceptable 
practice locally for 
applicable 
institutions 
1 
Direct Amoxicillin challenge  
☐ UTSW 
☐ Yes 
☐ PHHS 
☐ Yes 
☒CMC 
☐ Yes 
☐THR 
☐ Yes 
☐TSRH 
☐ Yes 
☐ Other: _____ 
☐ Yes 
2 
Insert study intervention 2 here 
☐ UTSW 
☐ Yes 
☐ PHHS 
☐ Yes 
☐CMC 
☐ Yes 
☐THR 
☐ Yes 
☐TSRH 
☐ Yes 
☐ Other: _____ 
☐ Yes 
 


 
4.c.  Risk:Benefit Analysis of study interventions being tested or evaluated under this protocol 
For each study intervention identified in section 6b above, complete a risk:benefit analysis table. 
 
(Two tables are provided, copy & paste additional tables as needed or delete both tables if this study does not test 
an intervention) 
 
 


4.c. 
Study Intervention #1 
Direct Amoxicillin Challenge 
List each group exposed to this 
intervention on a separate line. 
(e.g., experimental, control, Arm A, Arm B, 
etc) 
Or state All Groups/Subjects 
For each group, list the benefits of this intervention.  (Benefits can be directly from 
the intervention or from a monitoring procedure likely to contribute to the subject’s 
well being).  If there are no benefits, state “none”. 
All groups/subjects 
One benefit will be the accurate diagnosis of current penicillin tolerance status. If 
penicillin tolerant, would have the benefit of using penicillin-based antibiotic 
treatment for future infections and diminishing the harms associated with a 
penicillin-allergy label which include prolonged hospital stays, increased surgical 
site infections, increased rates of Clostridium Difficile infections, and increased 
healthcare utilization costs when compared to patients without a penicillin allergy 
label. Another benefit includes increased access to evaluation, as this evaluation 
would be included within patients’ healthcare maintenance visit and not require a 
separate referral to an allergist with the associated barriers of time and cost with 
seeing another provider.  
 
 
If you are requesting a Waiver of Informed Consent, complete the table below. 
 
If you have a consent form, list the reasonably foreseeable risks in the consent form (and do not complete this section).   
 
List the risks according to the probability (likely, less likely or rare) and magnitude (serious or not serious). 
(include: 1) expected adverse events; 2) rare and serious adverse events; 3) all other psychological, social, legal harms) 
Do not delete frequency.  Frequency must be estimated because it will assist you with determining which adverse events will require 
prompt reporting.   
 
Not serious 
Serious  
Likely 
These risks are expected to occur in 
more than 20 out of 100 subjects. 
• 
 
• 
 
 
Not serious 
Serious 
Less likely  
These risks are expected to occur in 5-
20 subjects or less out of 100 subjects. 
• 
 
• 
 
 
 
Serious 


Rare  
These risks are expected to occur in 
less than 5 subjects out of 100  
 
• 
 
 
4.c. 
Study Intervention #1 
Insert name used in 4.b. 
List each group exposed to this 
intervention on a separate line. 
(e.g., experimental, control, Arm A, Arm B, 
etc) 
Or state All Groups/Subjects 
For each group, list the benefits of this intervention.  (Benefits can be directly from 
the intervention or from a monitoring procedure likely to contribute to the subject’s 
well being).  If there are no benefits, state “none”. 
 
 
 
 
If you are requesting a Waiver of Informed Consent, complete the table below. 
 
If you have a consent form, list the reasonably foreseeable risks in the consent form (and do not complete this section).   
 
List the risks according to the probability (likely, less likely or rare) and magnitude (serious or not serious). 
(include: 1) expected adverse events; 2) rare and serious adverse events; 3) all other psychological, social, legal harms) 
Do not delete frequency.  Frequency must be estimated because it will assist you with determining which adverse events will require 
prompt reporting.   
 
Not serious 
Serious  
Likely 
These risks are expected to occur in 
more than 20 out of 100 subjects. 
• 
 
• 
 
 
Not serious 
Serious 
Less likely  
These risks are expected to occur in 5-
20 subjects or less out of 100 subjects. 
• 
 
• 
 
 
 
Serious 
Rare  
These risks are expected to occur in 
less than 5 subjects out of 100  
 
• 
 
 


 
 


 


 
4.d. List ALL other research procedures or components not listed in table 4.b. 
        The combination of Tables 4b and 4d should account for all of the research 
procedures that will take place during this study. 
 
Consider grouping similar procedures under a single component (e.g., blood work, CT 
= safety assessments) 
 
 
 
# 
Research component 
• 
individual 
procedures 
 
example: 
Eligibility Assessments 
• 
History and 
physical 
• 
Questionnaire 
• 
Laboratory 
tests 
Add or delete rows as 
needed 
Column A 
Local Standard 
Practice Indicate the 
number of times each 
procedure will be 
performed as 
stipulated in the 
research plan that 
would be performed 
if the participant 
were not 
participating in the 
study. 
Column B 
Research Only  
Indicate the number of 
times each procedure will 
be performed solely for 
research purposes 
(meaning that the 
participant would not 
undergo the same number 
of procedures or would not 
undergo the procedure(s) 
at the same frequency if 
they were not participating 
in the study) 
Column D 
Risks 
If you are requesting a Waiver of 
Informed Consent, complete the 
table below. 
 
List the reasonably expected risks for each 
procedure or group of procedures under the 
following categories as appropriate: 
• Serious and likely; 
• Serious and less likely; 
• Serious and rare; 
• Not serious and likely; 
• Not serious and less likely 
1 
Eligibility Assessments 
 
 
 
 
Questionnaire assessing 
Index Reaction and 
hesitancy and barriers to 
pursuing challenge  
 
1 
Not Serious and Less Likely 
2 
Healthcare Maintenance 
Visit 
 
 
 
 
History and Physical 
1 
 
Not Serious and Less Likely 
 
Insert procedure here 
 
 
 
 
Insert procedure here 
 
 
 
3 
Post-challenge 
Assessment 
 
 
 
 
Questionnaire assessing 
post-challenge status 
 
1 
Not Serious and Less Likely 
 
Insert procedure here 
 
 
 
 
Insert procedure here 
 
 
 


4 
Urine Pregnancy Test 
 
 1 
Not Serious and Less Likely 
 
Insert procedure here 
 
 
 
 
Insert procedure here 
 
 
 
 
Insert procedure here 
 
 
 
 
 
 
5.  Safety Precautions.  (Describe safeguards to address the serious risks listed above.) 
a.  Describe the procedures for protecting against or minimizing any potential risks for each of the more than 
minimal risk research procedures listed above. 
NA 
b. Where appropriate, discuss provisions for ensuring necessary medical or professional intervention in the 
event of adverse events, or unanticipated problems involving subjects. 
Risks of Protocol Specified Medications/Procedures 
- 
Adverse reactions to amoxicillin include headache, diarrhea, nausea, vomiting, rash, and allergic 
reactions. Allergic reactions range from mild to severe, and if a patient has an allergic reaction, he/she 
may need oral, IM, or IV medications. The site investigators for this trial are credentialed advanced 
health providers who are trained to recognize and manage systemic reactions. Treatment will be 
available within 60 seconds in the event of a reaction. Emergency medications as listed below will be 
available to treat any allergic reactions.  
- 
Treatment of individual acute allergic reactions during the conduct of the study may include 
antihistamines, epinephrine, -adrenergic agonists, oxygen. The risks of these common medications 
include the following 
o 
Antihistamines: drowsiness, dizziness, constipation, stomach upset, blurred vision, dry 
mouth/nose/throat 
o 
Epinephrine: tachycardia, palpitations, nervousness, sweating, nausea, vomiting, trouble 
breathing, headache, dizziness, anxiety, tremors, pale skin 
o 
-adrenergic agonists: nervousness, shaking, headache, dizziness 
o 
These risks will be minimized by appropriate dosing per guideline management of systemic 
allergic reactions. 
 
c.  Will the safeguards be different between/among groups?   
 
Yes 
 
 
No 
If yes, describe here 
 
  
 
X 

ICF_001.pdf: 
Title: Penicillin De-Labeling in the Pediatric Primary Care Setting; Consent Form 
NCT Number: 05010304 
IRB Approval Date: 10/6/2021 


Title of Study: Penicillin De-Labeling in the Pediatric Primary Care Setting 
 
STU2021-0517, Chow, FormE-Consent-Main, NS, 10-06-21 
 
Page 1 of 9 
 
Consent to be part of a Research Study 
To be conducted at  
Children’s Medical Center of Dallas and any of its affiliated entities 
 
Key Information about this Study  
Most patients labeled as having a penicillin allergy do not have a real allergy and allergy testing is 
recommended. The purpose of this research study is to determine whether recommended penicillin testing 
can be performed in the pediatrician’s office. Participants will undergo a telephone screening visit to determine 
eligibility in the study. Participants who choose to participate in the study will undergo penicillin testing and 
receive amoxicillin when they come to their pediatrician’s visit for their annual well child check exam. This visit 
will take about 2 hours. Follow up phone calls from the study team will occur at 7-10 days after your doctor’s 
visit and again at 1 year.  
 
The greatest risks of this study include the possibility of a reaction to amoxicillin. The most common reaction 
is a rash that resolves with oral antihistamines, which out of 100 people occurs in approximately 5-15. Serious 
reactions such as life-threatening anaphylaxis, which can consist of combinations of symptoms such as rash, 
difficulty breathing, persistent vomiting or diarrhea, and low blood pressure are rare, occurring in less than 1 
patient out of a 1000.  You will undergo penicillin testing under the supervision of your primary care provider 
who is trained to recognize and manage such reactions. The possible benefit of your participating in this study 
is the accurate diagnosis of whether you have a penicillin allergy and limiting the adverse effects of 
unnecessary penicillin avoidance. 
 
If you are interested in learning more about this study, please continue to read below. 
Information about this form 
Enrolling Children or Incompetent Adults 
If you are providing consent for someone else, for example your child, your next-of-kin or someone for whom 
you are the legal guardian or are designated as a surrogate decision maker on a medical power of attorney, 
please note that in the sections that follow, the word “you” refers to the person you are providing consent for.  
 
You may be eligible to take part in a research study.  This form gives you important information about the 
study.   
 
Please take time to review this information carefully.  You should talk to the researchers about the study and 
ask them any questions you have.  You may also wish to talk to others (for example, your friends, family, or a 
doctor) about your participation in this study.  If you decide to take part in the study, you will be asked to sign 
this form.  Before you sign this form, be sure you understand what the study is about, including the risks and 
possible benefits to you. 
 
Please tell the researchers or study staff if you are taking part in another research study. 
 
Your doctor is a research investigator in this study.  S/he is interested in both your medical care and the 
conduct of this research study.  At any time, you may discuss your care with another doctor who is not part of 
this research study.  You do not have to take part in any research study offered by your doctor. 
 
Voluntary Participation - You do not have to participate if you don't want to.  You may also leave the study at 
any time.  If you decide to stop taking part in this research study, it will not affect your relationship with the UT 
Southwestern staff or doctors.  Whether you participate or not will have no effect on your legal rights or the 
quality of your health care. 
 
If you are a medical student, fellow, faculty, or staff at the Medical Center, your status will not be affected in 
any way. 
 
IRB Approved Date: 10/6/2021


Title of Study: Penicillin De-Labeling in the Pediatric Primary Care Setting 
 
STU2021-0517, Chow, FormE-Consent-Main, NS, 10-06-21 
 
Page 2 of 9 
 
General Information – “Who is conducting this research?” 
 
Principal Investigator 
The Principal Investigator (PI) is the researcher directing this study; the PI is responsible for protecting your 
rights, safety and welfare as a participant in the research.  The PI for this study is Timothy Chow, MD, 
Department of Pediatrics at the University of Texas Southwestern Medical Center. 
 
Funding  
The Allergists’ Foundation of the American College of Allergy, Asthma, and Immunology, a non-profit 
organization that promotes scientific research, is funding this study.  This organization is providing money to 
UTSW so that the researchers can conduct the study. 
 
Purpose – “Why is this study being done?” 
While reported adverse reactions to penicillins are common, most patients with a penicillin allergy label can 
safely tolerate penicillins. As such, proactive evaluation for penicillin allergy has been recommended. As the 
majority of people note a penicillin allergy in young childhood, pediatricians are uniquely situated to have a 
significant impact in reducing the long-term consequences of a penicillin allergy label through penicillin testing. 
Penicillin testing performed by primary care providers such as pediatricians has been performed in other 
countries, but has not been done in the United States. 
 
You are asked to participate in this research study of penicillin allergy testing in your pediatrician’s office. There 
are many benefits of correctly diagnosing penicillin allergy, as the majority of patients who had a reaction to 
penicillin will eventually be able to take it again without reaction. Penicillin testing in the pediatrician’s office 
would reduce barriers for testing and increase access to penicillin allergy evaluation.   
 
The researchers hope to learn if penicillin testing can be performed effectively in your pediatrician’s office. 
 
 
A description of this clinical trial will be available on http://www.ClinicalTrials.gov, as required by U.S. Law. This 
Web site will not include information that can identify you. At most, the Web site will include a summary of the 
results. You can search this Web site at any time.  
 
Information about Study Participants – “Who is participating in this research?” 
 
You are being asked to be a participant in this study because you have a penicillin allergy listed in your 
electronic medical health record and you see one of the providers at the Children’s Health Pediatric Group 
Medical District clinic for your healthcare. 
 
How many people are expected to take part in this study?  
This study will enroll approximately 500 study participants. 
 
 
Information about Study Procedures – “What will be done if you decide to be in the research?” 
 
While you are taking part in this study, you will be asked to attend approximately 1 visit with the researchers or 
study staff. You will also have approximately 2 follow up telephone calls. 
 
Screening – After you sign this consent to participate, exams, tests, and/or procedures may be done as 
described below to find out if you can continue in the study; this is called screening. We may be able to use the 
results of exams, tests, and/or procedures you completed before enrolling in this study.  You will be told which 
results we will obtain and which procedures will not have to be repeated.  Many of the procedures are 
IRB Approved Date: 10/6/2021


Title of Study: Penicillin De-Labeling in the Pediatric Primary Care Setting 
 
STU2021-0517, Chow, FormE-Consent-Main, NS, 10-06-21 
 
Page 3 of 9 
 
described below as “standard care” and would be done even if you do not take part in this research study. 
You will be told which ones are for “research only”. 
 
Screening Procedures: Physical examination- the results of the physical examination done as part of your 
standard care will be used. 
 
The research procedures will add approximately 30 minutes to the length of a routine care visit. 
 
The results of the screening exams, tests, and/or procedures will be reviewed to determine whether you will be 
allowed to continue in the study.  If you are not allowed to continue in the study, the researcher will discuss the 
reasons with you. 
 
Study Procedures - as a participant, you will undergo the following procedures: 
 
- 
Study Visit 
o Medical history and physical exam as part of your routine healthcare maintenance visit 
o You will receive a small dose of amoxicillin (1 mL) and you will be observed for 10 minutes 
o If you do not have any symptoms, you will be given a larger dose of amoxicillin (4 mL) and 
observed for 50 minutes. This penicillin testing regimen is standard of care, and we are 
evaluating if it can be done in your pediatrician’s office. This will add approximately 30 minutes 
to the length of a routine healthcare maintenance visit. 
o During the observation period, your healthcare provider will complete your routine healthcare 
maintenance visit  
o When the observation period after your second dose of amoxicillin is completed, you will receive 
any recommended vaccinations that your healthcare provider prescribes. 
o You will then be discharged from the clinic 
- 
Follow up telephone call: you will receive a phone call from a study member 7-10 days after your study 
visit to see if you developed any reactions after you left the clinic. This should take approximately 5-10 
minutes. 
- 
Follow up telephone call: you may receive a phone call from a study member about 10-12 months after 
your visit to follow up on your drug allergies listed in your health record. This should take approximately 
5-10 minutes. 
 
Risks – “What are the risks of participation in the research?” 
 
Risks from the specific research procedures (drug(s), interventions, or procedures) 
There are risks to taking part in this research study.  One risk is that you may have side effects while on the 
study.  
 
Side effects from this study will usually go away soon after you stop taking the amoxicillin. As you will only 
receive one full dose of amoxicillin, the risk of side effects should be minimized. In rare cases, side effects can 
be long lasting or may never go away. 
 
Everyone taking part in the study will be watched carefully for any side effects.  However, the study doctors 
don’t know all the side effects that may happen.  Be sure to tell your study doctor immediately, about any side 
effect that you have while taking part in the study. 
 
The following section will describe the risks related to each your participation in this research study.  You 
should talk to your study doctor about any side effects or other problems that you have while taking part in the 
study.    
 
IRB Approved Date: 10/6/2021


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Side effects can range from mild to serious.  Serious side effects are those that may require hospitalization, are 
life threatening or fatal (could cause death).  The frequency that people experience a certain side effect can 
range from many (likely), few (less likely) or only one or two (rarely).   
Risks and side effects related to the amoxicillin include those which are: 
 
Less Likely, some may be Serious 
In 100 people, approximately 5-15 may have: 
 
Rash which resolves with oral antihistamines 
 
Rare and Serious 
In 1000 people, approximately <1 may have: 
 
Anaphylaxis 
 
Treatment of individual acute allergic reactions during the conduct of the study may include antihistamines, 
epinephrine, b-adrenergic agonists, oxygen. The risks of these common medications include the following 
o Antihistamines: drowsiness, dizziness, constipation, stomach upset, blurred vision, dry 
mouth/nose/throat 
o Epinephrine: tachycardia, palpitations, nervousness, sweating, nausea, vomiting, trouble 
breathing, headache, dizziness, anxiety, tremors, pale skin 
o b-adrenergic agonists: nervousness, shaking, headache, dizziness 
o These risks will be minimized by appropriate dosing per guideline management of systemic 
allergic reactions. 
 
For more information about risks and side effects, ask one of the researchers or study staff. 
 
Risks to an Embryo, Fetus or Breast-fed Infant 
Females: If you are part of this study while pregnant or breast-feeding an infant, it is possible that you may 
expose the unborn child or infant to risks.  For that reason, pregnant and breast-feeding females can not 
participate in the study.  If you can become pregnant, a pregnancy test will be done (using a urine sample), 
and it must be negative before you be a part of this study. 
 
If you do become pregnant during this study, you must tell the researchers immediately. 
 
If your parents or guardian asks, we will tell them the results of your pregnancy test. 
 
 
Are there Risks related to withdrawing from the study?  
If you decide to withdraw from this study early, please discuss your decision with the principal investigator.  
The researcher may ask you to complete study withdrawal procedures at a final telephone visit.  There is no 
risk to you if you do not complete the final withdrawal procedures and you can choose not to participate in 
them. 
 
Are there risks if you also participate in other research studies? 
Being in more than one research study at the same time may increase the risk to you.  It may also affect the 
results of the studies.  You should not take part in more than one study without approval from the researchers.   
 
What if a research-related injury occurs?  
The researchers have taken steps to minimize the known or expected risks.  However, you may still 
experience problems or side effects, even though the researchers are careful to avoid them.  In the event of a 
research-related injury or if you experience an adverse reaction, please immediately contact your study doctor.  
IRB Approved Date: 10/6/2021


Title of Study: Penicillin De-Labeling in the Pediatric Primary Care Setting 
 
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See the section “Contact Information” for phone numbers and additional information.  You may also need to tell 
your regular doctors. 
 
If you are injured or made sick from taking part in this research study, medical care will be provided. This care 
may be billed to you or your insurance. We have no plans to give you money if you are injured. The 
investigator can provide you with more information. 
 
If you sign this form, you do not give up your right to seek additional compensation if you are harmed as a 
result of being in this study. 
 
Benefits – “How could you or others benefit from your taking part in this study?” 
The possible benefit of your participating in this study is the accurate diagnosis of whether you have a penicillin 
allergy. This will be done in the familiar environment of your primary provider, as one benefit of this study is 
that you will not need a referral to see another doctor. If you are determined to not be allergic to penicillin, you 
would have the benefit of using penicillin antibiotic treatment for future infections and reducing the harms 
associated with a penicillin-allergy label which include prolonged hospital stays, increased surgical site 
infections, increased rates of Clostridium Difficile infections, and increased healthcare utilization costs when 
compared to patients without a penicillin allergy label. There is no guarantee or promise that you will receive 
any benefit from this study.   
 
Alternative procedures or course of treatment – “What other options are there to participation in this 
study?” 
There are other options available to you.  Your other choices may include 1) getting treatment or care without 
being in a study, 2) taking part in another study, and 3) getting no treatment 
 
Payments – Will there be any payments for participation? 
 
There will be no payments for participation. 
 
Costs – Will taking part in this study cost anything? 
 
Your health insurance company will be billed for the cost of treatments and procedures that would be done 
whether or not you took part in this study, such as routine healthcare maintenance visit, amoxicillin challenge, 
and management of reactions. It is important to understand that some insurance companies do not cover some 
costs (for example, approved drugs used in a way different from the package instructions). If your insurance 
company does not cover these treatments or procedures, you will be required to pay for them. Ask the 
researchers if you have any questions about what it will cost you to take part in this study (for example bills, 
fees, or other costs related to the research). 
 
Confidentiality – How will your records be kept confidential? 
 
Information we learn about you in this study will be handled in a confidential manner, within the limits of the 
law.  If we publish the results of the study in a scientific journal or book, we will not identify you.  The 
Institutional Review Board and other groups that have the responsibility of monitoring research may want to 
see study records which identify you as a subject in this study.    
 
Research policies require that private information about you be protected and this is especially true for your 
health information.  However, the law sometimes allows or requires others to see your information.  The 
information given below describes how your privacy and the confidentiality of your research records will be 
protected in this study. Medical information collected during this study and the results of any test or procedure 
that may affect your medical care may be included in your medical record. The information included in your 
IRB Approved Date: 10/6/2021


Title of Study: Penicillin De-Labeling in the Pediatric Primary Care Setting 
 
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medical record will be available to health care providers and authorized persons including your insurance 
company. 
 
Research policies require that private information about you be protected and this is especially true for your 
health information.  However, the law sometimes allows or requires others to see your information.  The 
information given below describes how your privacy and the confidentiality of your research records will be 
protected in this study. Medical information collected during this study and the results of any test or procedure 
that may affect your medical care may be included in your medical record. The information included in your 
medical record will be available to health care providers and authorized persons including your insurance 
company. 
 
What is Protected Health Information (PHI)?   
Protected Health Information is information about a person’s health that includes information that would make it 
possible to figure out whose it is.  According to the law, you have the right to decide who can see your 
protected health information.  If you choose to take part in this study, you will be giving your permission to the 
investigators and the research study staff (individuals carrying out the study) to see and use your health 
information for this research study.  In carrying out this research, the health information we will see and use 
about you will include:  your medical history, information that we get from your medical record, information that 
is collected during your participation in the study including medical and treatment history, information you give 
us during your participation in the study such as during interviews or from questionnaires, demographic 
information like your age. 
 
We will get this information by asking you and by looking at your chart at Children’s Health.  
 
How will your PHI be shared?   
Because this is a research study, we will be unable to keep your PHI completely confidential.  We may share 
your health information with people and groups involved in overseeing this research study including: 
 
the Sponsor, American College of Allergy, Asthma, and Immunology, funding the study. The sponsor 
includes any people, entities, groups or companies working for or with the sponsor or owned by the 
sponsor.  The sponsor will receive written reports about your participation in the research. The sponsor 
may look at your health information to assure the quality of the information used in the research. 
 
the members of the local research team. 
 
The Institutional Review Board, Human Research Protection Program Office and the Compliance Office of 
the University of Texas Southwestern Medical Center, and other groups that oversee how research studies 
are carried out.  
 
The Research offices at the University of Texas Southwestern Medical Center, Children’s Medical Center 
of Dallas and any of its affiliated entities 
 
If you decide to participate in this study, you will be giving your permission for the groups named above, to 
collect, use and share your health information.  If you choose not to let these groups collect, use and share 
your health information as explained above, you will not be able to participate in the research study. 
 
Parts of your PHI may be photocopied and sent to a central location or it may be transmitted electronically, 
such as by e-mail or fax. The groups receiving your health information may not be obligated to keep it private.  
They may pass information on to other groups or individuals not named here.  
 
How will your PHI be protected?   
In an effort to protect your privacy, the study staff will use code numbers instead of your name, to identify your 
health information.  Initials and numbers will be used on any photocopies of your study records, and other 
study materials containing health information that are sent outside of the Children’s Health and the University 
IRB Approved Date: 10/6/2021


Title of Study: Penicillin De-Labeling in the Pediatric Primary Care Setting 
 
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of Texas Southwestern for review or testing.  If the results of this study are reported in medical journals or at 
meetings, you will not be identified. 
 
Do you have to allow the use of your health information? 
You do not have to allow (authorize) the researchers and other groups to see and share your health 
information.  If you choose not to let the researchers and other groups use your health information, there will 
be no penalties but you will not be allowed to participate in the study.   
After you enroll in this study, you may ask the researchers to stop using your health information at any time .  
However, you need to say this in writing and send your letter to Timothy Chow, MD at 5323 Harry Hines Blvd, 
Dallas, Texas 75390-8859. If you tell the researchers to stop using your health information, your participation in 
the study will end and the study staff will stop collecting new health information from you and about you for this 
study.  However, the study staff will continue to use the health information collected up to the time they receive 
your letter asking them to stop. 
 
Can you ask to see the PHI that is collected about you for this study?   
The federal rules say that you can see the health information that we collect about you and use in this study.  
Contact the study staff if you have a need to review your PHI collected for this study. 
involved.   
 
How long will your PHI be used?   
By signing this form, you agree to let us use and disclose your health information for purposes of the study until 
the end of the study.  This permission to use your personal health information expires when the research ends 
and all required study monitoring is over. 
 
Contact Information – Who can you contact if you have questions, concerns, comments or 
complaints? 
 
If you have questions now, feel free to ask us. If you develop a reaction after leaving the clinic, please contact 
us using the contact information below. If you have additional questions, concerns, comments or complaints 
later or you wish to report a problem which may be related to this study please contact: 
 
Primary contact: 
Timothy Chow, MD can be reached at 214-456-8490 or at the pager number 972-229-0125. To use the pager, 
you need to have a touch tone (push button) telephone.  Dial the pager number as you would any phone 
number.  When you hear 3 short high pitched beeps, dial in the number where you want the doctor to call you 
back.  Push the # button, hang up and wait for the doctor to return your call. 
 
If primary is not available, contact the pager number 214-822-4829 and ask to speak with Timothy Chow, MD. 
 
The University of Texas Southwestern Medical Center Human Research Protection Program (HRPP) oversees 
research on human subjects.  HRPP and Institutional Review Board (IRB) representatives will answer any 
questions about your rights as a research subject, and take any concerns, comments or complaints you may 
wish to offer.  You can contact the HRPP by calling the office at 214-648-3060. 
 
 
IRB Approved Date: 10/6/2021


Title of Study: Penicillin De-Labeling in the Pediatric Primary Care Setting 
 
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Research Consent & Authorization Signature Section 
If you agree to participate in this research and agree to the use of your protected health information in this 
research, sign this section.  You will be given a copy of this form to keep.  You do not waive any of your legal 
rights by signing this form.  
 
SIGN THIS FORM ONLY IF THE FOLLOWING STATEMENTS ARE TRUE: 
 
You have read (or been read) the information provided above. 
 
Your questions have been answered to your satisfaction about the research and about the collection, 
use and sharing of your protected health information. 
 
You have freely decided to participate in this research or you are voluntarily giving your consent for 
another person to participate in this study because you believe this person would want to take part if 
able to make the decision and you believe it is in this person’s best interest.   
 
You understand that a copy of this signed consent document, information about this study, and the 
results of any test or procedure that may affect your medical care, may be included in your medical 
record. Information in your medical record will be available to health care providers and authorized 
persons including your insurance company. 
 
You authorize the collection, use and sharing of your protected health information (another person’s 
protected health information) as described in this form. 
 
If you turn 18 years old after signing this consent form, we will request you to re-sign the consent as an 
adult if you wish to continue to participate 
 
Surrogate Signature Section  
 
 
 
 
 
 
AM 
PM 
Printed Name of Participant  
 
 
 
Signature of Participant  
Giving Assent 
(If incapable of signing, person 
obtaining consent should initial here) 
 
 
 
Date 
 
Time 
 
 
 
AM 
PM 
Printed Name of Person Giving 
Consent for Participant    
(If applicable) 
 
 
Signature of Person Giving Consent 
Parent/Guardian/Legally 
Authorized Representative 
 
Date 
 
Time 
 
 
 
 
 
 
AM 
PM 
Printed Name of Person 
Obtaining Consent 
 
 
Signature of Person Obtaining 
Consent  
 
 
Date 
 
Time 
 
 
IRB Approved Date: 10/6/2021


Title of Study: Penicillin De-Labeling in the Pediatric Primary Care Setting 
 
STU2021-0517, Chow, FormE-Consent-Main, NS, 10-06-21 
 
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Blind or Illiterate Signature Section  At the time of consent, also complete this section if consent is 
obtained from an individual who is unable to read and/or write but can otherwise communicate and/or 
comprehend English (e.g., blind, physically unable to write, etc.)  
 
Declaration of witness: 
By signing below, I confirm I was present for the entire consent process. The method used for 
communication (e.g., verbal, written, etc.) with the subject was:                                      .   
 
The specific means (e.g., verbal, written, etc.) by which the subject communicated agreement to participate  
was:                                             .          
 
 
 
 
 
 
 
 
AM 
PM 
Printed Name of Witness 
 
 
Signature of Witness 
 
 
Date 
 
Time 
 
  
 
 
 
 
 
 
 
 
IRB Approved Date: 10/6/2021