Clinical trial NCT04275336
Conditions: Child, Hospitalized
Keywords: Children venipuncture related pain and stress EMLA distraction techniques
Sponsor: Children's Hospital of Fudan University
Start date: 2020-02-01; Completion date: 2020-05-12
Enrollment: 354 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
To evaluate whether an integration of pharmacological and non- pharmacological interventions is more effective than either one of intervention in pain reduction during pediatric peripheral venipuncture.

Detailed description:
Intravenous infusion is a routing practice of drug administration for hospitalized children.However numerous studies have shown that venipuncture is a major source of pain of children during their hospitalization which can lead to moderate to severe pain and cause fear, stress and anxiety in children if there is no effective pain management.

The current pain relieving methods include pharmacological (i.e. topical anesthetic) and non-pharmnacological (i.e. distraction techniques) interventions. pharmacological There are scarce evidences supporting that a combination of pharmacological and non-pharmacological interventions can enhance children's abilities in coping with their pain and stress during the venipuncture. EMLA cream is a main pharmacological intervention in managing needle-related pain which can penetrate the cuticle and epidermal layer of intact skin, enter the dermis where nerve endings are located, and relieve pain. However pharmacological interventions have proven inadequate in mitigating pain and stress.The main non-pharmacological alternatives is distraction techniques. There are extremely limited data studies on merging pharmacological and non-pharmacological interventions to compensate for each other's inadequacies. Hence, this study aimed to evaluate the effect of combining both topical anesthetic and distraction techniques in comparison with either of the interventions applied singly.

This study adopts a randomized, blind, controlled intervention trial. Participants will be randomly assigned to three groups: EMLA group, Distraction group and Combined group (EMLA cream plus distraction techniques). The outcomes will be measured by self-reported pain, parent-reported pain and observer-reported pain. Salivary cortisol level will be measured by the ultra sensitive Cortisol Saliva ELISA Assay Kit. Other physiological metrics like heart rate, SpO2, and other intravenous cannulation factors will be rated and recorded.

Arms: arm 1: The specialist nurse who is to perform IV cannulation determine the puncture site. A thick layer of cream (lidocaine and propiocaine 2.5%/2.5%) will be applied on a 1x1 cm2 area of skin on the cannulation site. The transparent dressing will be left in place for 30 minutes, then remove and clean with a sterile cotton swab. Then nurse performed IV cannulation for them. arm 2: The multiple distractions including toy whistles, cartoon books, a TV showing cartoons, and various electronic products with video games will be provided for the children to choose and play with. They are also taught breathing exercises (i.e. inhaling through the nose for 3 seconds and exhaling for 5 seconds, while they are counting) if they are willing. A play therapist play with the children for 5 min. prior to and throughout the venipuncture procedure. arm 3: both EMLA cream and distraction techniques will be used. EMLA cream will be applied on the pre-puncture site for 30 minutes as the EMLA group, then 5 minutes before the venipuncture, the play therapist encourage them to choose their favorite toys to play with or to learn breathing exercises. During IV cannulation the play therapist will also continue distracting the child with toys.
Interventions: intervention 1: EMLA application intervention 2: Distraction techniques intervention 3: EMLA cream and distraction techniques
Intervention descriptions: intervention 1: A thick layer of cream (lidocaine and propiocaine 2.5%/2.5%) will be applied on a 1x1 cm2 area of skin on the cannulation site. The transparent dressing will be left in place for 30 minutes, then remove and clean with a sterile cotton swab. Then nurse perform IV cannulation for them. intervention 2: Multiple distractions including toy whistles, cartoon books, a TV showing cartoons, and various electronic products with video games will be provided for the children to choose and play with. They will also be taught breathing exercises (i.e. inhaling through the nose for 3 seconds and exhaling for 5 seconds, while they are counting) if they are willing. A play therapist play with the children for 5 min. prior to and throughout the venipuncture procedure. intervention 3: both EMLA cream and distraction techniques will be used. EMLA cream will be applied on the pre-puncture site for 30 minutes as the EMLA group, then 5 minutes before the venipuncture, the play therapist encourage them to choose their favorite toys to play with or to learn breathing exercises. During IV cannulation the play therapist will also continue distracting the child with toys.

Protocol documents:
Prot_SAP_000.pdf: 
Pharmacological and Non-pharmacological Interventions in Management of Peripheral 
Venipuncture related Pain: A Randomized Clinical Trial 
NCT04275336 
DATA: August 4,2020 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


 
STUDY PROTOCOL  
Aim 
This study aims to examine the effectiveness of three different interventions including EMLA 
cream, distraction techniques and the integrating of EMLA cream and distraction techniques in 
managing venipuncture pain and stress of children.   
 
Design 
A three-arm parallel, randomized controlled trial will be applied in this research. Eligible 
participants will be randomly assigned to into three groups: EMLA group, distraction group and 
combined group. 
 
Interventions 
Hard copies of informed consent will give to all parents, while children’s assent and eligibility 
data will be obtained from face-to-face interviews. Eligible children will be randomly assigned to 
into three groups: EMLA group, distraction group and combined group. Nurses will explain the 
pain rating scales, pharmacological and non-pharmacological techniques, and the usage of 
intravenous cannulation. Every child will be accompanied by a parent throughout the whole 
process. At baseline, patients’ age, sex and ethnicity will be recorded before they are grouped.  
 
The nurse who will perform venipuncture for children had 10 years of venipuncture experience 
in the pediatric ward. The intravenous cannula used is 19 gauge x 0.7-in. needle and the whole 
procedure adhere to standard IV cannulation procedures. While cannulation is ongoing, an 


observer monitor the children and complete the revised-FLACC scale (r-FLACC). The observer, 
a senior pediatric nurse from the surgical department who had received pain assessment training, 
watch the procedure through real-time surveillance video. The HR and SpO2 of children will also 
be recorded.  
 
Transparent waterproof adhesive skin dressing will use to fix the cannulation. The children and 
parents will give their own Wong Baker and r-FLACC ratings as soon as the procedure is over. 
The sample of saliva will be take using the cortisol saliva ELISA assay kit for quantitative 
determination of salivary cortisol levels to evaluate children’s stress during venipuncture. Any 
adverse effects resulted from the IV cannulation or EMLA cream will be observed and recorded 
during their entire hospitalization.  
 
For the EMLA group , the specialist nurse who perform IV cannulation will determine the 
puncture site.  A thick layer of EMLA cream (lidocaine and propiocaine 2.5%/2.5%) will be 
applied on a 1x1 cm2 area of skin on the cannulation site. The transparent dressing will be 
covered on the cannulation site for 30 minutes, then remove it and clean the skin with a sterile 
cotton swab. Then nurse will perform IV cannulation for them.  
 
For the distraction group , multiple distractions including toy whistles, cartoon books, TV 
showing cartoons, and various electronic products with video games will be provided for 
children to choose. They will be also taught breathing exercises (i.e. inhaling through the nose 
for 3 seconds and exhaling for 5 seconds, while they are counting) if they are willing. A play 
therapist play with the children for 5 minutes prior to and throughout the venipuncture 
procedure. 


For the combined group , both EMLA cream and distraction techniques will be used.  EMLA 
cream will be applied on the pre-puncture site for 30 minutes as the EMLA group, then the play 
therapist will encourage children to choose their favorite toys and play that with them 5 minutes 
before venipuncture or to do breathing exercises as the distraction group. During IV cannulation 
the play therapist will continue distracting the child with toys.  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


STATISTICAL ANALYSIS PLAN 
Statistical Package for Social Sciences (SPSS Inc., Chicago, IL, USA) for Windows (version 22.0) with 
statistical significance set to p < 0.05.  
To answer the question that is there significant statistical difference in venipuncture pain score among 
lidocaine group, Attention diversion group and Combination group, Mann Whitney and Kruskal-Wallis 
will be used to compare the 2 and 3 groups respectively. The results will be present in a table in the form 
of median and interquartile range if the data is non-abnormal distribution. Otherwise, use mean±standard 
deviation to describe the data.  
To answer the question that is there significant statistical difference in children’s salivary cortisol among 
lidocaine group, Attention diversion group and Combination group. Mann Whitney and Kruskal-Wallis 
will be used to compare the 2 and 3 groups respectively. The results will be present in a table in the form 
of median and interquartile range if the data is non-abnormal distribution. Otherwise, use mean±standard 
deviation to describe the data.  
To answer the question that is there significant statistical difference in children’s HR, SpO2 and 
venipuncture related findings like venipuncture times, venipuncture duration and indwelling needle 
duration of every child, Mann Whitney and Kruskal-Wallis will be used to compare the 2 and 3 groups 
respectively. The results will be present in a table in the form of median and interquartile range if the data 
is non-abnormal distribution. Otherwise, use mean±standard deviation to describe the data.  
To answer the question that what’s the preference for toys of children in Attention diversion group and 
Combination group, frequency distribution percentage will be used. To answer the question that is there 
significant statistical difference of children’s choice in toys between Attention diversion group and 
Combination group, the chi-square test will be used. All the data will be present in a table in the form of 
median and interquartile range if the data is non-abnormal distribution. Otherwise, use mean±standard 
deviation to describe the data.  

ICF_001.pdf: 
Pharmacological and Non-pharmacological Interventions in Management of Peripheral Venipuncture related 
Pain: A Randomized Clinical Trial 
NCT04275336 
DATA: August 4,2020 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


 
Inform consent form for children and their parents  
CHILDREN’S HOSPITAL OF FUDAN UNIVERSITY 
This inform consent form for the children and their parents who will be invited to participate in research, 
entitled “Pharmacological and Non-pharmacological Interventions in Management of Peripheral 
Venipuncture related Pain: A Randomized Clinical Trial” 
[Name of Principal Investigator] Yu Zhuowen 
[Name of Organization] Children’s Hospital of Fudan University  
[Name of Sponsor] None 
[Name of Proposal and version]：Pharmacological and Non-pharmacological Interventions in 
Management of Peripheral Venipuncture related Pain: A Randomized Clinical Trial 
This Informed Consent Form has two parts: 
               1.Information Sheet (to share information about the research with you) 
               2.Certificate of Consent (for signatures if you agree to take part) 
You will be given a copy of the full Informed Consent Form 
PART I: Information Sheet 
Introduction 
• 
I am Yu Zhuowen, the head nurse of department of Pneumology and Gastroenterology.  My team and 
I are doing research on pharmacological and non-pharmacological interventions in management of 
peripheral venipuncture related pain. I am going to give you information and invite you to be part of 
this research. Before you decide, you can talk to anyone you want to with about the research. When I 
introduce information, you can ask me what words you don’t understand and I will explain them to 
you. If you have questions later, you also can ask the staff or me. 
Purpose of the research 
This study aims to examine the effectiveness of three different interventions including EMLA cream, 
distraction techniques and the integrating of EMLA cream and distraction techniques in managing 
venipuncture pain and stress during venipuncture of children.   
 
Type of research intervention  
This research will involve three different interventions which will implement by nurse staff and/or game 
therapist during the intravenous cannulation. You and your child will be randomly assigned to 1) EMLA 
group where your child will be applied EMLA cream on the venipuncture site 30 minutes before the 


intravenous cannulation, 2) distraction group where your children will engage in games for 5 minutes 
during intravenous cannulation, or 3) combined group where your child will be applied EMLA cream for 
30 minutes then engage in the game for 5 minutes  
before the intravenous cannulation.  
 
Participant selection 
 
I will invite children who will schedule to undergo the peripheral venipuncture during their 
hospitalization. The following inclusion criteria are for the children: 1) children aged 3 to 16 years; 2) 
Children who will receive their first peripheral intravenous puncture.    
 
Voluntary participation 
 
Your participation in this research is entirely voluntary. It is your choice whether to participate or not. 
Whether you choose to participate or not, all the services you receive at this clinic will continue and 
nothing will change. If you choose not to participate in this research project, you will offer the treatment 
that is routinely offered in this ward, and we will tell you more about it later. You may change your mind 
later and stop participating even if you agreed earlier. 
 
Information on the Trial Drug [EMLA cream] 
 
The drug we are testing in this research is called eutectic mixture of local anesthetics (EMLA) cream 
containing 25mg lidocaine and 25mg propiocaine per gram. It has been test before with people who have 
the peripheral venipuncture in reducing pain and stress. We are now want to combine it with distraction 
techniques and test whether they have effectiveness in reducing pain and stress in venipuncture in 
pediatric ward.  
 
The EMLA cream is made by Beijing Zi Guang Pharmaceutical Co. Ltd. You should know that it has few 
side effect. This product can produce local reactions at the application site, which are more common in 
pallor, erythema (redness) and edema. These reactions are mostly transient and mild. Burning or itching 
sensation may also occur in the initial stage of use, but it is relatively rare. 
Allergic reactions to amide local anesthetics (the most severe reaction is anaphylactic shock) are rare. 
High-dose prilocaine can cause the level of methemoglobin in the blood to increase. 
 
One of three groups of this study will not be given the EMLA cream, instead, they will be distracted 
before and during the venipuncture using several toys (distractions) they choose.  
 
Procedures and Protocol  
 
Because we have no idea if the combined EMLA and distractions is better than single using of one of 
them. We need to compare the three. To do this, we will put people taking part in this research into three 
group. Eligible participants were randomly assigned on the three groups, via a computer- generated 
sequence. 
 
For the EMLA group , the specialist nurse who is to perform IV cannulation determine the puncture site.  
A thick layer of cream (lidocaine and propiocaine 2.5%/2.5%) will be applied on a 1x1 cm2 area of skin 
on the cannulation site. The transparent dressing is leave in place for 30 minutes, then remove and clean 
with a sterile cotton swab.  Then nurse perform IV cannulation for them.  
 
For the distraction group, multiple distractions including toy whistles, cartoon books, a TV showing 
cartoons, and various electronic products with video games will be provided for the children to choose 


and play with. They will be also taught breathing exercises (i.e. inhaling through the nose for 3 seconds 
and exhaling for 5 seconds, while they are counting) if they are willing. A play therapist play with the 
children for 5 min. prior to and throughout the venipuncture procedure. 
 
For the combined group , both EMLA cream and distraction techniques will be used.  EMLA cream will 
be applied on the pre-puncture site for 30 minutes as the EMLA group, then 5 minutes before the 
venipuncture, the play therapist will encourage them to choose their favorite toys to play with or to learn 
breathing exercises. During IV cannulation the play therapist also continue distracting the child with toys.  
 
The healthcare workers will be looking after you and the other participants very carefully during the 
study.  If there is anything you are concerned about or that is bothering you about the research please talk 
to me or one of the other researchers. 
 
You and you children will ask to rate your child’s pain during venipuncture using the different pain rating 
scales. And we will also take a little saliva of your child to get their salivary cortisol level to rate their 
stress. Additionally, your child’s SpO2, heart rate during the intravenous cannulation will also be 
recorded.  
 
Side effects 
As already mentioned, the EMLA cream have some unwanted effects. .  However, we will follow you 
closely and keep track of any unwanted effects or any problems. We may use some other medicines to 
decrease the symptoms of the side effects or reactions. Or we may stop the use of one or more drugs.  If 
this is necessary we will discuss it together with you and you will always be consulted before we move to 
the next step.  
 
Risk 
By participating in this research  it is possible that you will be at greater risk than you would otherwise 
be. For example, by using the the integrating of EMLA cream and distraction techniques, child’s pain and 
stress become greater. you should be aware of the possibility. If something unexpected happens, we 
remedy it as possible as we can. 
  
Benefits 
If you participate in this research, you will have the following benefits: you will get a gift. Additionally， 
any interim illnesses will be treated at no charge to you. There may not many benefit for you but your 
participation is likely to help us find the answer to the research question.  There may not be any benefit to 
help us find best method in management children’s venipuncture pain and stress.  
 
Confidentially  
The information that we collect from this research project will be kept confidential. Information about 
you that will be collected during the research will be put away and no-one but the researcher will be able 
to see it. Any information about you will have a number on it instead of your name. When finish the 
study, all information about collected data will lock up in the special box and label it, and after keep it for 
two years then burning it in order to protect it confidentially about subjects’ information. 
 
Sharing the results 
The knowledge that I get from this study will be shared with you before it is made widely available to the 
public. Confidential information will not be shared. 
 
Right to Refuse or Withdraw 


The participant does not have to agree to take part in this research if you do not wish to do so you may 
stop you from participating in the research at any time that you wish without you losing any of your 
rights. 
 
Who to Contact 
If you have any questions you may ask me now or later or you wish to ask questions later, you may 
contact me: Yu Zhuowen, Email: yzw100@126.com 
 
PART II: Certificate of Consent 
This section should be written in the first person and have a statement similar to the one in bold below. If 
the participant is illiterate but gives oral consent, a witness must sign. A researcher or the person going 
over the informed consent must sign each consent. The certificate of consent should avoid statements that 
have "I understand…." phrases. The understanding should perhaps be better tested through targeted 
questions during the reading of the information sheet (some examples of questions are given above), or 
through the questions being asked at the end of the reading of the information sheet, if the potential 
participant is reading the information sheet him/herself.   
 
I have read the foregoing information, or it has been read to me. I have had the opportunity to ask 
questions about it and any questions that I have asked have been answered to my satisfaction.  I consent 
voluntarily to participate as a participant in this research. 
 
Print Name of Participant__________________  
 
 
 
 
Signature of Participant ___________________ 
Date ___________________________ 
 
Day/month/year 
  
 
 
 
 
 
If illiterate 
A  literate witness must sign (if possible, this person should be selected by the participant and should have 
no connection to the research team). Participants who are illiterate should include their thumb-print as 
well.   
 
I have witnessed the accurate reading of the consent form to the potential participant, and the individual 
has had the opportunity to ask questions. I confirm that the individual has given consent freely.  
 
Print name of witness_____________________             AND         Thumb print of participant 
Signature of witness ______________________ 
Date ________________________ 
                Day/month/year 
 
 
 
Statement by the researcher/person taking consent 
I  have accurately read out the information sheet to the potential participant, and to the best of my ability 
made sure that the participant understands that the following will be done: 
1. 
2. 
3. 
I confirm that the participant was given an opportunity to ask questions about the study, and all the 
questions asked by the participant have been answered correctly and to the best of my ability. I confirm 
that the individual has not been coerced into giving consent, and the consent has been given freely and 
voluntarily.  
   


 A copy of this ICF has been provided to the participant. 
 
Print Name of Researcher/person taking the consent________________________ 
 
 
 
 
Signature of Researcher /person taking the consent__________________________ 
Date ___________________________  
 
 
                 Day/month/year