Clinical trial NCT05383495: Anxiolysis for Laceration Repair in Children
Official title: Anxiolysis for Laceration Repair in Children: A Multicenter Adaptive Randomized Trial
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE3
Conditions: Laceration of Skin
Distress, Emotional
Lead sponsor: London Health Sciences Centre Research Institute OR Lawson Research Institute of St. Joseph's
Sponsor class: OTHER
First posted: 2022-05-20
Enrollment: 300
Sex: ALL
Minimum age (years): 2
Maximum age (years): 12
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Phase III, multicentre, open-label, randomized, three-arm, adaptive trial
Primary purpose: TREATMENT

Brief summary: This is a 3-arm adaptive clinical trial to the optimal light sedative for reducing distress during laceration repair in children. The investigators will compare intranasal (IN) dexmedetomidine, IN midazolam, and nitrous oxide (N20). The primary outcome is the Observational Scale of Behavioral Distress - Revised (OSBD-R).

Detailed description: Accounting for almost half of all procedures performed, lacerations are the most common reason for an ED visit in children. There is consistent evidence that children experience considerable distress during laceration repair, despite routine application of topical anesthetic, lidocaine-epinephrine-tetracaine (LET). Certified child life specialists (CCLSs) can help children cope with distress but are not widely available. Untreated distress in childhood can lead to anxiety, needle phobia, and fear of medical care as adults. The American Academy of Pediatrics and American Academy of Pediatric Dentistry strongly recommend minimizing discomfort and controlling behavior and movement during procedures but there is no specific guidance on laceration repair. Many children require pharmacologic anxiolysis for laceration repair but evidence for the most effective agent is lacking. Although anxiolytics such as midazolam and nitrous oxide (N2O) are frequently used, there are drawbacks including variable efficacy and nasal irritation in the case of midazolam and lack of cooperation in younger children in the case of N2O. IN dexmedetomidine is a potentially effective anxiolytic for laceration repair that could overcome these limitations.

IN dexmedetomidine is a relatively new anxiolytic with sedative and analgesic properties. It is tasteless, non-irritative, and highly concentrated (100 mcg/mL). A maximum dose of 200 mcg/2 mL can be given with 2 pairs of 0.5 mL IN sprays. The investigator's team published a systematic review of IN dexmedetomidine for distressing procedures. It was well tolerated by more than 90% of children and provided adequate anxiolysis in more children (79%) versus conventional anxiolytics (midazolam, chloral hydrate) (60%). Only one trial investigated IN dexmedetomidine in children for laceration repair and 70% were deemed "not anxious" compared to IN midazolam (11%). However, the study focused on initial positioning rather than repair. For proof of concept and to identify the optimal dose and feasibility of IN dexmedetomidine, we completed a pilot of 55 children undergoing laceration repair. All children tolerated IN administration, the consent rate was 82%, and there were no serious adverse events (AE). A dose of 3 mcg/kg balanced efficacy with duration of sedation, in line with others' findings.

Oral midazolam is the most common anxiolytic for laceration repair in children. However, onset and duration of action and efficacy can be unreliable and its bitter taste leads to poor compliance. IN midazolam using a mucosal atomizer device (MAD) is increasingly popular because it overcomes these limitations. Compared to oral midazolam, IN midazolam has a shorter onset of action (28 vs 34 minutes) but causes nasal irritation in up to 40% of patients. In addition, IN midazolam has variable efficacy for laceration repair and more adverse effects compared to nitrous oxide or IN dexmedetomidine. The largest study of IN midazolam was a retrospective study of combination IN midazolam plus fentanyl. A lower dose of midazolam (0.2 mg/kg) resulted in fewer adverse effects (0.7%) than with higher doses (2-5%). Adding IN fentanyl provided superior efficacy where only 2.4% of patients experienced a treatment failure.

The second most common anxiolytic is inhaled N2O, a tasteless gas that is administered in a concentration of 30-70% with oxygen. N2O is safe and effective for minor painful procedures. Peak effect is rapid (2 minutes) and effects dissipate quickly (3 minutes) upon discontinuation. Minor adverse effects occur in less than 10% of patients. However, based on the United Kingdom National Clinical Guideline Centre, it's unclear whether uncooperative children will comply with N2O administration. The investigators' recently completed systematic review of 29 trials of N2O for painful procedures in children found 50% N2O was superior to subcutaneous lidocaine, placebo, and oral midazolam. Only 5 trials focused on laceration repair but they were small and limited by non-validated or no measures of anxiety .

Despite frequent use of anxiolytics such as midazolam and N2O, The investigators' national survey found that 80% of Canadian paediatric ED physicians strongly believed that "children experience significant enough distress to warrant anxiolysis" and it would "improve the patient care experience". To improve care, a rigorous trial of a novel anxiolytic, IN dexmedetomidine, and dissemination of the research findings is needed.

Eligibility criteria: Inclusion Criteria:

i) Age 2-12.99 years \[highest incidence of laceration repair\] ii) Single or grouped lacerations separated by no more than 2 cm for which the treating physician believes repair does not require IV sedation iii) Repair to involve sutures and performed by ED physician or designate (trainee) iv) Child or caregiver desires anxiolysis for laceration repair \[justification: incorporates family preferences based on their prior experiences or beliefs about child's response\] vii) Local anesthesia planned to involve topical anesthetic (LET), infiltrated lidocaine, ring, or thenar block

Exclusion Criteria:

i) Sedative, anxiolytic, or alpha-2-adrenergic receptor agonist \< 24 hours prior to interventions (may compound sedative effect and increase the SAE risk). 24-hours encompasses the duration of sedation of most agents.

ii) Hypersensitivity to any intervention iii) Occlusion of \> 1 nostril due to polyps, septal deviation, or foreign body (may prevent drug absorption) iv) Hemodynamic abnormalities: bradycardia or hypotension \< 2 SD of age-related normal value v) IND contraindications: Pre-existing renal insufficiency, uncorrected mineralocorticoid deficiency, pulmonary hypertension, uncorrected cyanotic heart disease, cardiac conduction disorder, pulmonary hypertension, pulmonary edema, vitamin B12 or folate disorder, phenylketonuria, or psychosis vi) Sedation contraindications: Impaired level of consciousness or respiratory instability vii) N2O contraindications: Conditions associated with potential accumulation of gas within body spaces viii) Suspected or confirmed pregnancy (as reported by patient) ix) Inability to vocalize pain due to motor deficits (unable to apply the OSBD-R) x) Caregiver unable to complete study tasks due to insufficient comprehension of either English or French in the absence of a native language interpreter xi) Weight \>= 65 kg (to avoid under-dosing of INM or IND) x) Not American Society of Anesthesiologists class I (healthy) or II (controlled mild to moderate disease) xii) No concomitant fracture or dislocation requiring orthopedic manipulation

Primary outcomes:
measure: Observational Scale of Behavioral Distress - Revised (OSBD-R)
timeFrame: During preparation, suturing, and recovery (20 minutes)
Secondary outcomes:
measure: Adverse effects
timeFrame: From intervention to 72 hours post-discharge
measure: Need for additional anxiolysis or sedation to facilitate repair
timeFrame: During suturing (10 minutes)
measure: Need for physical restraint
timeFrame: During preparation and suturing (10 minutes)
measure: Late maladaptive behaviors
timeFrame: From discharge to 72 hours post-discharge
Other outcomes:
measure: Compliance with intervention administration
timeFrame: From drug administration through completion of suturing (40 minutes)
measure: Caregiver satisfaction with anxiolysis during laceration repair
timeFrame: At discharge (1 minute)
measure: Child satisfaction with anxiolysis during laceration repair
timeFrame: At discharge (1 minute)
measure: Healthcare provider (physician, nurse, respiratory therapist) satisfaction with anxiolysis during laceration repair
timeFrame: During recovery (1 minute)
measure: Number of healthcare personnel required during repair
timeFrame: During procedure (10 minutes)
measure: Cost of healthcare personnel required at bedside during repair
timeFrame: During procedure (40 minutes)
measure: Cost of interventions
timeFrame: During procedure (40 minutes)
measure: Total ED length of stay
timeFrame: During emergency department visit (2 hours)
measure: Duration of procedure
timeFrame: During procedure (40 minutes)
measure: Post-intervention length of stay
timeFrame: From drug administration to discharge (80 minutes)
measure: Nasal irritation
timeFrame: During IN intervention administration (2 minutes)
measure: Post-procedure length of stay
timeFrame: From suturing to discharge (40 minutes)
measure: Caregiver state anxiety
timeFrame: Immediately prior to Phase II (preparation) (1 minute)
Locations:
city: London
country: Canada
facility: London Health Sciences Centre
state: Ontario
Study officials:
References: