Clinical trial NCT04337814: The Effect of Combined Oral and Topical Analgesics to Reduce Pain Perception During Electrodiagnostic Testing
Official title: The Effect of Combined Oral and Topical Analgesics to Reduce Pain Perception During Electromyography in Pediatric Population-A Randomized Controlled Trial
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Pain Perception
Keywords: Electromyopharpy
Nerve conduction study
Electrodiagnostic testing
Edx study
EMG
NCS
Lead sponsor: Aga Khan University Hospital, Pakistan
Sponsor class: OTHER
First posted: 2020-04-08
Enrollment: 113
Sex: ALL
Minimum age (years): 6
Maximum age (years): 18
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Double blind placebo controlled randamized controlled trial
Primary purpose: SUPPORTIVE_CARE

Brief summary: Electromyography (EMG) is a useful test for diagnosis and monitoring of lower motor neuron disorders. It is mostly done in conjunction with a Nerve Conduction Study (NCS). Like other invasive medical procedures; electrodiagnostic tests have been known to cause iatrogenic pain for the patient, the intensity of which varies from person to person. Multiple modifiable as well as non-modifiable risk factors associated with EMG pain have been described in literature.Various approaches targeting different mechanisms of pain perception have been tested to make this procedure comfortable for the patients. These approaches range from simple distraction techniques to the use of topical and oral analgesics.Most of these studies have looked at adult population which has, supposedly, better pain tolerance as compared to children. Data on EMG associated pain in pediatric population is scant. This trial will assess the effect of combined oral and topical analgesics to reduce pain perception during NCS and EMG tests in the pediatric population.

Detailed description: Objectives:

To determine the effect of combined oral and topical analgesics (COTA) in reducing pain perception during NCS and EMG tests among the pediatric population.

To compare the effect of COTA and only oral analgesics (OA) in reducing pain perception during NCS and EMG tests among the pediatric population.

Methods:

Study Setting: This study will be conducted at the neurophysiology lab at Aga Khan University Hospital (AKUH)

Study Design: This will be a stratified (6 months - 6 years and 7 - 18 years with balanced randomization), double-blind, placebo-controlled, parallel group study conducted at the neurophysiology lab, AKUH.

Variables:

Independent Variables - Gender, age, weight (Kg), number of muscles sampled, distribution of muscles sampled, end plate noise detection, type of needle used, duration of EMG and NCS test, history of undergoing electrodiagnostic tests in the past, time duration between analgesic intake / application and start of the NCS and EMG test, number of needle insertions needed outside of applied cream area, number of times skin is pierced,result of electrodiagnostic examination, patient in parents lap, electromyographer, study arm.

Dependent Variables - Pain Scores (MBPS and FPS-R)

Interventions/Study Protocol:

The guardians / patients who meet the inclusion criteria, as determined by the neurophysiology fellow or attending, will be instructed to reach the neurophysiology lab on the day of appointment one hour before the expected procedure time. All patients and/or their guardians referred for NCS / EMG will be given a standard explanation regarding the procedure and study details on the day of electrodiagnostic testing by the designated neurophysiology technologist. NCS would be explained as a test that checks the responses of the nerves and the subject will feel small zaps during the procedure. EMG would be explained as a procedure where a thin small microphone will be inserted in multiple muscles of the arm, leg and / or neck and back that will help us in identifying the problem. The word 'needle' and 'electric current' would not be used during this explanation. The guardian and patient, if old enough to understand, will also be explained the study protocol being carried out. Written Informed consent for the procedure itself and the study will be taken at this point by the neurophysiology fellow. Patients (older than 6 years) or their guardians will be instructed on how to administer the FPS-R scale. In addition guardians would be instructed to make sure that patients are not given sugary drinks or breastfeed during 1 hour prior to the procedure. During the study distractions will be kept to a minimum and similar for all patients. Sites of needle insertion will not be rubbed, stroked or tapped at the time of needle insertion. These factors are known confounders in reducing intramuscular injection pain. Those who have given consent will be assigned to one of the three arms of the study according to the randomization schedule; COTA arm (Ibuprofen Syrup and EMLA Cream), OA arm (Ibuprofen Syrup and Plain Cream) or Placebo arm (Plain Syrup and Plain Cream). All patients will be issued their interventions labeled with an allocation sequence according to the randomization schedule from the clinical trials unit (CTU), in a double blind manner, on the day of appointment. The syrup will be given to patients orally (10mg/Kg body weight) at least 1 hour prior to start of procedure. The electromyographer will demarcate all the possible muscle sampling sites required as per study protocol with a non-toxic marker and leave the room. A neurophysiology technologist will apply the cream on all demarcated sites. After application of cream, the site would be covered by an occlusive dressing until NCS / EMG is carried out so as to keep the applied cream in place and prevent accidental ingestion or application on mucosal surfaces by the patient. The patient will be kept under observation for adverse reactions including blanching and local erythema from application of cream till 15 minutes after the NCS / EMG procedure. Observation would be done by Neurophysiology fellow or the Neurophysiology attending. Neurophysiology technologists designated to carry out this exercise would be given combined sessions regarding the application technique to achieve consistency in results.

The EMG will be performed by board certified faculty or neurophysiology fellows under their supervision, each of them having a minimum of 6 months experience in doing electrodiagnostic testing. This involves intramuscular insertion of needle (that has a microphone at its tip) into multiple muscles. The occlusive dressing will be removed and area to be tested wiped with alcohol swabs. Nerve conduction studies will be conducted first followed by the needle procedures. During nerve conduction studies, patients feel an electric current like sensation whenever a nerve is tested. Attempt will be made to keep the needle movements to minimum. The guardian would accompany the child throughout the procedure. If the child wants, he/she would be allowed to sit in the guardians lap during the procedure.

Pain Assessment \& Data Collection:

For children aged 6 months to 6 years pain will be assessed by scoring facial expression, cry and body movements of the children using the Modified Behavioral Pain Scale (MBPS). For children aged 7 years to 18 years the Face Pain Scale-Revised (FPS-R) version will be used. Patients will be scored before NCS, after NCS and after EMG respectively on the data collection form. Two observers blinded to the rest of the study and not involved with carrying out NCS / EMG will be trained to administer these scores. The guardian, who would be unaware of what the child scored, will also be shown the FPS-R and asked to score how much pain patient seemed to feel during NCS and EMG respectively. Regarding FPS-R, the instruction will be to choose the face that most closely resembles the amount of pain being felt. Patient demographics, Clinical characteristics and NCS / EMG procedure characteristics will also be recorded on the form. The data collected will then be entered into an excel sheet at the end of each day.

Sample Size:

Assuming a difference in means of 1.4 with a standard deviation of 1.73 in the control group and 2.17 in the intervention group on the MBPS according to a study assessing effectiveness of EMLA cream for reducing pain during Intramuscular injections in the pediatric population, an alpha level of 0.05 and power of 80 % using a 1-way analysis of variance (ANOVA) test with 3 pairwise comparisons; we will require 35 patients per group. Furthermore, assuming a 10 % dropout rate we will enroll 39 patients per group to account for it.

Randomization:

To achieve comparable groups, randomization will be performed as stratified blocked randomization with random sizes in a 1:1 allocation ratio. Stratification will be done according to the age groups: 6 months - 6 years and 7 - 18 years with varying random block sizes. Allocation to intervention groups according to stratification will be carried out by a computer generated randomization schedule which will list the allocation sequences assigned to each of the three arms. The randomization schedule will only be available with the pharmacist in charge of preparing interventions. Interventions will be prepared in indistinguishable containers containing plain cream and EMLA cream and bottles containing plain syrup and Ibuprofen syrup. The creams will be prepared to be similar in consistency, texture and color. The syrups will also be similar in color and taste. Thirty Nine Intervention packages will be made for each of the intervention arms; COTA arm, OA arm and Placebo arm. Each intervention will be labelled with an allocation sequence according to the randomization schedule by the pharmacist. The independent study officer not involved with the preparation or packaging of interventions and blinded to the rest of the study will issue the intervention for each patient reporting on the day of the appointment. The random allocation sequence would be concealed from the rest of the study investigators / researchers.

Blinding:

Throughout the study the patients, the electromyographers, neurophysiology technologists / observers administering the validated pain scales will be unaware of the intervention assignments.

Safety Management:

The drugs used in intervention arm have FDA approval as analgesics in the study population. Moreover, no prior testing is recommended before administration of these over the counter analgesics. Our study involves a single time use of these drugs only. Possible side effects (1-10%) with Ibuprofen include dizziness, epigastric pain, heart burn, nausea, rash, vomiting and renal failure (\<1%). Possible side effects (\>10%) with EMLA application include application site pallor/blanching, erythema/pain and application site oedema (1-10%), itching. Rare adverse effects (\<1%) include methemoglobinemia and myocardial dysfunction. Patients will be observed for 15 minutes post study for the development of any side effects. If any side effect is observed, patients would be referred to consult respective speciality as deemed appropriate, as per the severity of adverse event. The patient or his/her guardian will bear the expenses. This would be mentioned at the time of taking informed consent.

Data Handling \& Storage:

All patient related data would be kept safe in the custody of designated study officer who would be part of the neurophysiology lab. Informed consent forms would be signed in a separate room.

Statistical Analysis:

Data will be assessed for normality. We will use descriptive statistics for patient demographics, clinical characteristics and NCS / EMG test characteristics, including measures of central tendency and dispersion. Comparisons between three groups on pain perception will be performed using ANOVA. Differences in proportions will be assessed using chi-square test or Fischer exact test where appropriate. Logistic and Linear regression models will be used to assess the effect of patient demographics, clinical characteristics and NCS / EMG test characteristics on patient pain reduction within and across intervention groups. All p-values will be two sided and considered as statistically significant if \< 0.05. All analyses will be conducted by using the Statistical package for social science SPSS (Release 19.0, standard version, copyright © SPSS; 1989-02).

Eligibility criteria: Inclusion Criteria:

- Pediatric patients (6 months to 18 years) referred for NCS / EMG testing to the neurophysiology lab at AKUH

Exclusion Criteria:

* Patients not able to report pain scores on the scales used
* Patients using sedatives and prior analgesics within last 24 hours of study
* Patients with history of upper gastrointestinal tract bleed, renal disease, severe hepatic disease, glucose-6-phosphate deficiency, congenital or idiopathic methemoglobinemia
* Patients with known sensitivity / allergy to Ibuprofen or EMLA cream or their components
* Patients on class I antiarrhythmic drugs
* Patients with breach of skin on topical analgesic/placebo application sites
* Breastfeeding or sugary drink within one hour of start of study

Primary outcomes:
measure: Pain perception of patient during NCS and EMG tests
timeFrame: Pain scores to be recorded immediately after the procedure
Secondary outcomes:
measure: Pain perception of patient according to guardian during NCS and EMG tests
timeFrame: Pain scores to be recorded immediately after the procedure
measure: Effect of Patient demographics, Clinical characteristics and NCS / EMG procedure characteristics on patient pain scores
timeFrame: Pain scores to be recorded immediately after the procedure
Other outcomes:
Locations:
city: Karachi
country: Pakistan
facility: Aga khan University Hospital
state: Sindh
Study officials:
affiliation: Aga Khan University
name: Fazal Rehman, MBBS, FCPS
role: PRINCIPAL_INVESTIGATOR
affiliation: Aga Khan University Hospital, Monash University
name: Haris Hakeem, MBBS, FCPS, FRACP
role: PRINCIPAL_INVESTIGATOR
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