PainPhase 2NCT03054844
PREMIX vs PREMED Intranasal Lidocaine and Midazolam
A Phase 2 study testing Lidocaine, Lidocaine and midazolam (PREMIX) and Midazolam in people with Pain, run by Columbia University at 1 site in United States.
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. Read more about this study
- Who is it for?
- Ages 6 months to 7 years
- Conditions the study is for
- Pain
- What is being tested?
- Lidocaine, Lidocaine and midazolam (PREMIX) and Midazolam
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 55 participants
- Where
- 1 siteUnited States
- Study dates
- 3 Apr 2017to 10 Oct 2017
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 6 months to 7 years
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- Between the age of ≥ 6 months or ≤ 7 years old
- Undergoing a laceration repair
- Treating physician has determined that patient requires intranasal midazolam to facilitate the laceration repair
Who cannot join
- Weight < 5 kg
- Known allergy to Lidocaine or Midazolam
- Does not speak English or Spanish
- Nasal injury precluding IN medication delivery
- Presence of intranasal obstruction (mucous/blood) not easily cleared with suction or nose blowing
- Baseline motor neurological abnormality (e.g. motor deficit, cerebral palsy)
- Developmental delay, autism, autism spectrum disorder
Trial locations and contacts
1 site in 1 country.
United States1 site
Morgan Stanley Children's Hospital
New York, New York, 10032
About this study
Official title: Comparison of Two Methods Using Intranasal Lidocaine to Alleviate Discomfort Associated With Administration of Intranasal Midazolam in Children.
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.
Read the detailed 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.
- Conditions
- Pain
- Keywords
- Intranasal, Pain, Lidocaine, Midazolam, Emergency department
- Medical subject headings
- Pain, Emergencies
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
LidocaineDrug
Also called PREMED
Lidocaine will be administered before administration of midazolam.
Lidocaine and midazolam (PREMIX)Drug
Also called PREMIX
Lidocaine will be administered as a mixture with midazolam.
MidazolamDrug
Midazolam will be administered either after lidocaine, or as a mixture with lidocaine.
| Study group | Role | What they receive |
|---|---|---|
| PREMED | Experimental | Patients will receive 0.25 mL of IN 4% lidocaine (10 mg) in each naris (total of 0.5 mL/20 mg for both nares) preceding adminstration of IN midazolam. Receives: Drug: Lidocaine; Drug: Midazolam |
| PREMIX | Experimental | Patients will receive midazolam mixed with 0.5 mL of 4% lidocaine (20 mg). Receives: Drug: Lidocaine and midazolam (PREMIX) |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 10 minutes
Secondary outcomes (5)
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).
Measured: 10 minutes
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).
Measured: 10 minutes
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
Measured: 10 minutes
Parental Satisfaction
If my child needed medications to stay calm for a procedure, I would like to use these same medications again.
Measured: 1 minute
Provider Satisfaction
I would like to use this method of administering intranasal midazolam and lidocaine again in the future
Measured: 1 minute
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted16 Feb 2017
- Study start3 Apr 2017
- Primary completion10 Oct 2017
- Study completion10 Oct 2017
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (5)Papers the sponsor has linked to this study.
- Other trials for PainStudies of the same condition, open and under way.
- More trials run by Columbia UniversityThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Investigator, Outcomes assessor
- Enrolment
- 55 participants (actual)
Sponsor and investigators
- Lead sponsor
- Columbia University
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Daniel S Tsze, MD, MPH, Columbia University
- Investigators
- Daniel S Tsze, MD, MPH, Principal investigator, Columbia University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03054844
- Sponsor's protocol ID
- AAAQ6408
- Status last verified
- Aug 2019
- First submitted
- 13 Feb 2017
- Last updated
- 11 Sep 2019
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
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. doi: 10.1097/PEC.0b013e3182624935.
PubMed 22858745Tsze 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.
PubMed 27823876Fenster 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.
PubMed 27387971Godambe 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. doi: 10.1542/peds.112.1.116.
PubMed 12837876Lee-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.
PubMed 20502386
Study at a glance
From the registry record, last updated by the sponsor on 11 Sep 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Comparison of Two Methods Using Intranasal Lidocaine to Alleviate Discomfort Associated With Administration of Intranasal Midazolam in Children.
- ClinicalTrials.gov ID
- NCT03054844
- Acronym / sponsor ID
- AAAQ6408
- Conditions
- Pain
- Keywords
- Intranasal, Pain, Lidocaine, Midazolam, Emergency department
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 55 participants (actual)
- Lead sponsor
- Columbia UniversityUniversity, hospital or other
- Study start
- 3 Apr 2017 (actual)
- Primary completion
- 10 Oct 2017 (actual)
- Study completion
- 10 Oct 2017 (actual)
- First posted
- 16 Feb 2017 (actual)
- Results
- Posted 11 Sep 2019
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed 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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| PREMED | Experimental | Drug: Lidocaine, Drug: MidazolamPatients will receive 0.25 mL of IN 4% lidocaine (10 mg) in each naris (total of 0.5 mL/20 mg for both nares) preceding adminstration of IN midazolam. |
| PREMIX | Experimental | Drug: Lidocaine and midazolam (PREMIX)Patients will receive midazolam mixed with 0.5 mL of 4% lidocaine (20 mg). |
Who may qualify
- Ages
- 6 months to 7 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (3 listed)
- Between the age of ≥ 6 months or ≤ 7 years old
- Undergoing a laceration repair
- Treating physician has determined that patient requires intranasal midazolam to facilitate the laceration repair
Key exclusion criteria (7 listed)
- Weight < 5 kg
- Known allergy to Lidocaine or Midazolam
- Does not speak English or Spanish
- Nasal injury precluding IN medication delivery
- Presence of intranasal obstruction (mucous/blood) not easily cleared with suction or nose blowing
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| LidocaineAlso: PREMEDLidocaine will be administered before administration of midazolam. | Drug | PREMED |
| Lidocaine and midazolam (PREMIX)Also: PREMIXLidocaine will be administered as a mixture with midazolam. | Drug | PREMIX |
| MidazolamMidazolam will be administered either after lidocaine, or as a mixture with lidocaine. | Drug | PREMED |
Primary outcome
Procedural Distress, OSBD-R
Time frame: 10 minutes
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.
5 secondary outcomes
Procedural Pain
Time frame: 10 minutes
Procedural Distress, FLACC
Time frame: 10 minutes
Procedural Distress, Cry Duration
Time frame: 10 minutes
Parental Satisfaction
Time frame: 1 minute
Provider Satisfaction
Time frame: 1 minute
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 11 Sep 2019.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 22858745Tsze 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. doi: 10.1097/PEC.0b013e3182624935.
- Background: PubMed 27823876Tsze 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.
- Background: PubMed 27387971Fenster 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.
- Background: PubMed 12837876Godambe 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. doi: 10.1542/peds.112.1.116.
- Background: PubMed 20502386Lee-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.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Daniel S Tsze, MD, MPH principal investigator
Columbia University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Lidocaine, Lidocaine and midazolam (PREMIX) and Midazolam in people with Pain, run by Columbia University at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 11 Sep 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 11 Sep 2019). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Procedural Distress, OSBD-R (time frame: 10 minutes). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03054844, which also lists 5 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 11 Sep 2019.