PREMIX vs PREMED Intranasal Lidocaine and Midazolam

Pain Clinical Trial

Official title:

Comparison of Two Methods Using Intranasal Lidocaine to Alleviate Discomfort Associated With Administration of Intranasal Midazolam in Children.

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03054844
• Other study ID #: AAAQ6408
• Status: Completed
• Phase: Phase 2
• Start date: April 3, 2017
• Est. completion date: October 10, 2017

Study information

• Verified date: August 2019
• Source: Columbia University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Intranasal (IN) midazolam is an anxiolytic that is commonly used in the pediatric population for procedural anxiolysis in the emergency department (ED) setting to facilitate painful and distressing procedures, such as laceration repairs. Intranasal midazolam is both effective and safe in children. However, due to the acidic nature of midazolam, there is a burning sensation that is associated with the intranasal administration of midazolam. The use of IN lidocaine has been shown to decrease the pain associated with the administration of IN midazolam and other acidic solutions. The IN lidocaine can be given as a premedication (PREMED), where it is sprayed in the nares first to provide topical anesthesia, and then followed by the administration of the IN midazolam. Lidocaine can also be given concurrently with the IN midazolam (PREMIX), where it is mixed with the midazolam and then the combined mixture administered. Both methods have been shown to be effective in decreasing the pain associated with the intranasal administration of acidic solutions, such as midazolam, although the PREMIX method could have the advantage of requiring less number of sprays, and be tolerated better by children. Although both methods have been shown to work, it is not known if the PREMIX method is non-inferior to the PREMED method for decreasing pain and distress associated with administering IN midazolam. Therefore, the investigators aim to determine if the PREMIX method is non-inferior to the PREMED method of using lidocaine to decrease the pain and distress associated with the administration of IN midazolam in children.

Description:

We will enroll 50 children to determine whether the PREMED method is non-inferior to the PREMIX method. We based our sample size on the outcome of pain and distress associated with the administration of IN midazolam, which will be measured using our primary outcome measure of the Observational Scale of Behavioral Distress-Revised (OSBD-R). The OSBD-R is an observational measure of distress that has been well validated in the pediatric population for evaluating painful and distressing procedures, and has been used in children as young as 1 year of age [1,2]. The sample size of 50 patients was determined based on a prestated margin of non-inferiority (delta) of 1.8 (SD 2.25). This value was based on the minimum clinically significant differences used in prior studies of painful procedures in children in the emergency department [3,4,5]. To determine noninferiority using a delta of 1.80 (SD 2.25), with a 1-tailed alpha of 0.025 and power of 80%, we would require 25 patients in each arm, for a total of 50 patients. OSBD-R scores will be determined independently by two blinded trained assessors who will review the videotapes of the study procedures. Interrater reliability of the OSBD-R between the two assessors will evaluated by determining the intraclass correlation coefficient. The period of administration of the midazolam alone in the PREMED group and the period of administration of the midazolam/lidocaine mixture in the PREMIX group are the two phases which will be compared to each other to determine our primary outcome.

Secondary outcome measures of pain and distress associated with IN midazolam administration will include the Children's Hospital of Eastern Ontario Pain Scale (CHEOPS); the Faces-LegsActivity-Crying-Consolability (FLACC) scale; and cry duration. These are all continuous measures that will be analyzed using the independent samples t-test.We will also evaluate parental and provider satisfaction across various domains using a 5-point Likert scale (see attached document for questions to be asked). Responses will be dichotomized into "agree" (i.e. if respondent answers "agree" or "strongly agree") or "disagree" (i.e. if respondent responds "undecided", "disagree", or "strongly disagree") and analyzed using the chi square test.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 55
• Est. completion date: October 10, 2017
• Est. primary completion date: October 10, 2017
• Accepts healthy volunteers: No
• Gender: All
• Age group: 6 Months to 7 Years

Eligibility

Inclusion Criteria:

1. Between the age of = 6 months or = 7 years old

2. Undergoing a laceration repair

3. Treating physician has determined that patient requires intranasal midazolam to facilitate the laceration repair

Exclusion Criteria:

1. Weight < 5 kg

2. Known allergy to Lidocaine or Midazolam

3. Does not speak English or Spanish

4. Nasal injury precluding IN medication delivery

5. Presence of intranasal obstruction (mucous/blood) not easily cleared with suction or nose blowing

6. Baseline motor neurological abnormality (e.g. motor deficit, cerebral palsy)

7. Developmental delay, autism, autism spectrum disorder

Related Conditions & MeSH terms

• Pain

Intervention

Drug:
• Lidocaine
Lidocaine will be administered before administration of midazolam.
• Lidocaine and midazolam (PREMIX)
Lidocaine will be administered as a mixture with midazolam.
• Midazolam
Midazolam will be administered either after lidocaine, or as a mixture with lidocaine.

Locations

Country	Name	City	State
United States	Morgan Stanley Children's Hospital	New York	New York

Sponsors (1)

Lead Sponsor	Collaborator
Columbia University

Country where clinical trial is conducted

United States, 

References & Publications (5)

Fenster DB, Dayan PS, Babineau J, Aponte-Patel L, Tsze DS. Randomized Trial of Intranasal Fentanyl Versus Intravenous Morphine for Abscess Incision and Drainage. Pediatr Emerg Care. 2018 Sep;34(9):607-612. doi: 10.1097/PEC.0000000000000810. — View Citation

Godambe SA, Elliot V, Matheny D, Pershad J. Comparison of propofol/fentanyl versus ketamine/midazolam for brief orthopedic procedural sedation in a pediatric emergency department. Pediatrics. 2003 Jul;112(1 Pt 1):116-23. — View Citation

Lee-Jayaram JJ, Green A, Siembieda J, Gracely EJ, Mull CC, Quintana E, Adirim T. Ketamine/midazolam versus etomidate/fentanyl: procedural sedation for pediatric orthopedic reductions. Pediatr Emerg Care. 2010 Jun;26(6):408-12. doi: 10.1097/PEC.0b013e3181e057cd. — View Citation

Tsze DS, Ieni M, Fenster DB, Babineau J, Kriger J, Levin B, Dayan PS. Optimal Volume of Administration of Intranasal Midazolam in Children: A Randomized Clinical Trial. Ann Emerg Med. 2017 May;69(5):600-609. doi: 10.1016/j.annemergmed.2016.08.450. Epub 2016 Nov 4. — View Citation

Tsze DS, Steele DW, Machan JT, Akhlaghi F, Linakis JG. Intranasal ketamine for procedural sedation in pediatric laceration repair: a preliminary report. Pediatr Emerg Care. 2012 Aug;28(8):767-70. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Procedural Distress, OSBD-R	The Observational Scale of Behavioral Distress-Revised (OSBD-R) is an observational measure of pain and distress shown to have strong validity in children. The scale is an 8-factor, weighted observational scale used to measure distress associated with medical procedures, which has been validated in children and adults aged 1 to 20 years. The total Observational Scale of Behavioral Distress-Revised score is the sum of the scale scores for each phase, with each phase assigned a score from 0 to 23.5 units on a scale (0=no distress, 23.5=maximum distress), based on the frequency and types of behaviors observed during a predetermined number of 15-second intervals during each phase. There were four phases so the range of scores for the total OSBD-R was 0 to 94 units on a scale, with a higher score indicated a greater degree of distress.	10 minutes
Secondary	Procedural Pain	The Children's Hospital of Eastern Ontario Pain Scale (CHEOPS) utilizes six observational factors (cry, facial, verbal, torso, touch, and legs) to evaluate pain in young children and can be used to monitor the effectiveness of interventions for reducing the pain and discomfort of an intervention. This scale rates each behavior numerically, with a score of 4-6 units on a scale representing no pain, and a maximum score of 13 units on a scale representing (most pain perceived).	10 minutes
Secondary	Procedural Distress, FLACC	The Faces, Legs, Activity, Cry, Consolability (FLACC) scale is comprised of five criteria (face, legs, activity, cry, consolability), with a possible score of 0 to 2 units on a scale for each criteria and a possible total score of 0 to 10 units on a scale (0 meaning no pain, 10 meaning most pain).	10 minutes
Secondary	Procedural Distress, Cry Duration	Cry duration was measured in seconds and defined as the time from onset of crying following administration of an IN medication until the cessation of crying sounds and/or tears. If a patient did not cry, the cry duration was zero	10 minutes
Secondary	Parental Satisfaction	If my child needed medications to stay calm for a procedure, I would like to use these same medications again.	1 minute
Secondary	Provider Satisfaction	I would like to use this method of administering intranasal midazolam and lidocaine again in the future	1 minute