[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"health-study-detail:100614231":3},{"organization":4,"outcomesModule":7,"designInfo":39,"detailedDescription":50,"studyPopulation":16,"armGroups":51,"interventions":69,"overallOfficials":16,"centralContacts":106,"locations":114,"responsibleParty":132,"collaborators":16,"id":135,"slug":16,"hasResults":136,"nctId":137,"briefTitle":138,"officialTitle":139,"acronym":140,"eligibilityCriteria":141,"healthyVolunteers":136,"sex":142,"minAge":143,"maxAge":144,"enrollmentInfo":145,"targetDuration":16,"studyType":148,"phases":149,"briefSummary":151,"conditions":152,"keywords":16,"overallStatus":154,"whyStopped":16,"lastUpdateSubmitDate":155,"lastUpdatePostDateStruct":156,"startDateStruct":159,"completionDateStruct":161,"leadSponsor":163,"locationsCount":164},{"fullName":5,"class":6},"University of South Alabama","OTHER",{"primaryOutcomes":8,"secondaryOutcomes":13,"otherOutcomes":16},[9],{"measure":10,"description":11,"timeFrame":12},"Number of Participants with Moderate-to-Severe Pain (FLACC Score ≥4) During PACU Stay","Number of participants experiencing at least one FLACC (Face, Legs, Activity, Cry, Consolability) scale score of 4 or greater during Post-Anesthesia Care Unit stay. FLACC is a validated behavioral pain assessment tool scored 0-10, with scores ≥4 indicating moderate-to-severe pain. FLACC scores assessed every 15 minutes during PACU stay.","From PACU admission to PACU discharge, up to 1 hour",[14,18,21,24,27,30,33,37],{"measure":15,"description":16,"timeFrame":17},"Highest FLACC Pain Score During PACU Stay",null,"From PACU admission to meeting PACU discharge criteria",{"measure":19,"description":20,"timeFrame":17},"Number of Participants Requiring Rescue Analgesia","Number of participants requiring at least one dose of rescue analgesic medication for FLACC score ≥4",{"measure":22,"description":23,"timeFrame":17},"Number of Participants with Respiratory Depression","Number of participants with oxygen saturation below 95% requiring intervention (supplemental oxygen, stimulation, or airway repositioning)",{"measure":25,"description":26,"timeFrame":17},"Number of Participants with Postoperative Nausea and Vomiting","Number of participants experiencing at least one episode of nausea or vomiting",{"measure":28,"description":29,"timeFrame":17},"Number of Participants with Emergence Agitation","Number of participants with Pediatric Anesthesia Emergence Delirium (PAED) scale score ≥10, indicating clinically significant emergence agitation",{"measure":31,"description":32,"timeFrame":17},"PACU Length of Stay","Duration in minutes from PACU admission to meeting discharge criteria",{"measure":34,"description":35,"timeFrame":36},"Parent Satisfaction with Pain Management","Parent-reported satisfaction with pain management assessed on 5-point Likert scale (1=very dissatisfied to 5=very satisfied)","At 24 hours postoperatively",{"measure":38,"description":16,"timeFrame":36},"Need for additional analgesics at home",{"allocation":40,"interventionModel":41,"interventionModelDescription":16,"primaryPurpose":42,"observationalModel":16,"timePerspective":16,"maskingInfo":43},"RANDOMIZED","PARALLEL","TREATMENT",{"masking":44,"maskingDescription":16,"whoMasked":45},"QUADRUPLE",[46,47,48,49],"PARTICIPANT","CARE_PROVIDER","INVESTIGATOR","OUTCOMES_ASSESSOR","Clinical Context Bilateral myringotomy with tympanostomy tube placement is performed in over 600,000 children annually in the United States for treatment of recurrent acute otitis media or chronic otitis media with effusion. Despite being a brief minimally invasive procedure, inadequate postoperative pain control is common and associated with emergence agitation, delayed discharge, increased rescue medication requirements, and parental anxiety.\n\nCurrent Standard of Care Recent large retrospective cohort studies have established the efficacy of multimodal analgesia for pediatric myringotomy and tube placement. Combined intramuscular fentanyl and ketorolac resulted in approximately 23% of children experiencing moderate-to-severe pain in the Post-Anesthesia Care Unit, compared to over 50% with ketorolac alone. These findings support multimodal analgesia as the current standard but also highlight that nearly one in four children still experience inadequate pain control despite optimized systemic therapy.\n\nLimitations of Current Approach The standard opioid-NSAID combination has several limitations: opioid-related side effects including respiratory depression, nausea, vomiting, and sedation; growing concerns about opioid exposure in children; NSAID contraindications in patients with renal impairment, bleeding disorders, or hypersensitivity; systemic distribution with potential for widespread effects; limited duration of action; and residual pain in high-risk subgroups such as younger children and those with normal middle ears.\n\nNerve of Arnold Block as Alternative The Nerve of Arnold, the auricular branch of the vagus nerve, provides sensory innervation to the posterior external auditory canal and tympanic membrane, which is the surgical site for myringotomy and tube placement. Blocking this nerve with local anesthetic offers theoretical advantages including opioid-sparing analgesia with elimination of opioid-related side effects, targeted analgesia directly at the surgical site, extended duration with long-acting local anesthetics, minimal systemic absorption and side effects, and applicability to patients with contraindications to systemic agents.\n\nThe technique involves subcutaneous injection of local anesthetic in the space between the mastoid process and the posterior wall of the external auditory canal. While anatomical studies support consistent nerve location and the block has been described in adult case reports, no randomized controlled trials have evaluated its efficacy and safety compared to standard care in pediatric patients.\n\nStudy Rationale There is a critical gap in high-quality evidence comparing regional anesthesia techniques to systemic analgesia for pediatric myringotomy and tube placement. This study addresses this gap and aligns with national priorities for opioid-sparing pain management strategies.\n\nStudy Design This is a prospective, randomized, double-blind, parallel-group, non-inferiority trial. Three hundred children aged 6 months to 6 years undergoing bilateral myringotomy with tympanostomy tube placement will be randomized in a 1:1 ratio to receive either standard care with intramuscular fentanyl and ketorolac or bilateral Nerve of Arnold block with bupivacaine. Randomization will use a computer-generated sequence with variable block sizes to prevent prediction of treatment assignment.\n\nBlinding Strategy This is a double-blind study with patients, parents, anesthesiologists, surgeons, PACU nurses, and outcome assessors blinded to treatment assignment. Blinding is maintained through use of sham procedures. Patients in the standard care group receive sham Nerve of Arnold blocks with normal saline, while patients in the intervention group receive sham intramuscular injections with normal saline. Study medications are prepared and labeled by the investigational pharmacy with identical appearance.\n\nInterventions Standard Care Group: Patients receive intramuscular fentanyl 2 micrograms per kilogram (maximum 100 micrograms) and intramuscular ketorolac 0.5 milligrams per kilogram (maximum 30 milligrams) administered after induction of anesthesia, plus sham bilateral Nerve of Arnold blocks with normal saline 0.2 milliliters per side.\n\nIntervention Group: Patients receive bilateral Nerve of Arnold blocks with bupivacaine 0.25% solution with 1 in 200000 epinephrine ,0.2 milliliters per side with dexmedetomidine 5 mics per side as adjuvant, plus sham intramuscular injections with normal saline.\n\nAll patients receive standardized general anesthesia with sevoflurane and spontaneous ventilation via face mask or laryngeal mask airway. No additional intraoperative analgesics are administered beyond the study interventions.\n\nRescue Analgesia Protocol Rescue analgesia is available in the Post-Anesthesia Care Unit for patients with FLACC scale scores of 4 or greater, indicating moderate-to-severe pain. First-line rescue medication is oral acetaminophen 20 milligrams per kilogram. Second-line rescue is oral oxycodone 0.1 milligrams per kilogram or intravenous morphine 0.05 milligrams per kilogram for patients unable to take oral medications.\n\nNon-Inferiority Margin The non-inferiority margin is set at 10 percentage points. This margin was selected based on clinical significance and risk-benefit considerations. An increase in the proportion with moderate-to-severe pain from approximately 23% to 33% would remain substantially better than historical controls with ketorolac alone and may be acceptable if offset by opioid-sparing benefits including reduced respiratory depression, nausea, vomiting, and sedation.\n\nSample Size A total of 300 patients will be enrolled, with 150 patients per group. This sample size provides 80% power to detect non-inferiority with a one-sided alpha of 0.025, assuming a baseline rate of 23.5% in the standard care group, an anticipated rate of 25-28% in the intervention group, and accounting for 10% dropout or protocol violations.\n\nStatistical Analysis The primary analysis will use an intention-to-treat approach comparing the proportion of patients with FLACC scores of 4 or greater between groups. Non-inferiority will be declared if the upper bound of the one-sided 97.5% confidence interval for the difference in proportions (intervention minus standard care) is less than 10 percentage points. A per-protocol analysis will be conducted as a sensitivity analysis. Secondary outcomes will be analyzed using appropriate statistical tests including t-tests, chi-square tests, and multivariable regression models. Subgroup analyses will explore effect modification by age group and middle ear condition.\n\nSafety Monitoring All patients will have continuous monitoring of heart rate, blood pressure, respiratory rate, and oxygen saturation during the Post-Anesthesia Care Unit stay. Adverse events will be recorded and graded according to Common Terminology Criteria for Adverse Events. A Data Safety Monitoring Committee will review safety data at regular intervals. Pre-specified stopping rules include rates of serious adverse events exceeding 5% in either group or significant imbalances in adverse events between groups.\n\nStudy Duration Patient enrollment is expected to occur over 18 to 24 months. Each patient will be followed for 24 hours after surgery. Total study duration is anticipated to be 30 months including enrollment, follow-up, data analysis, and manuscript preparation.",[52,60],{"label":53,"type":54,"description":55,"interventionNames":56},"IM Arm standard Care","ACTIVE_COMPARATOR","Patients receive intramuscular fentanyl 2 mcg\u002Fkg (maximum 100 mcg) plus intramuscular ketorolac 0.5 mg\u002Fkg (maximum 30 mg) after induction of anesthesia. Sham bilateral Nerve of Arnold block with normal saline 0.2 mL per side is performed to maintain blinding.",[57,58,59],"Drug: Fentanyl","Drug: Ketorolac","Procedure: Sham Nerve of Arnold Block",{"label":61,"type":62,"description":63,"interventionNames":64},"Nerve block arm","EXPERIMENTAL","Patients receive bilateral Nerve of Arnold block with bupivacaine 0.25% with epinephrine 1:200,000 (0.2 mL per side) plus dexmedetomidine 5 mcg per side (maximum total bupivacaine dose 2.5 mg\u002Fkg) after induction of anesthesia. sham intramuscular injection with normal saline is performed to maintain blinding.",[65,66,67,68],"Procedure: Nerve of Arnold Block","Procedure: Sham Intramuscular Injection","Drug: Dexmedetomidine","Drug: Bupivacaine",[70,75,81,86,90,94,100],{"type":71,"name":72,"description":73,"armGroupLabels":74,"otherNames":16},"DRUG","Fentanyl","Intramuscular fentanyl 2 mcg\u002Fkg (maximum 100 mcg) administered after induction of anesthesia",[53],{"type":71,"name":76,"description":77,"armGroupLabels":78,"otherNames":79},"Ketorolac","Intramuscular ketorolac 0.5 mg\u002Fkg (maximum 30 mg) administered after induction of anesthesia",[53],[80],"Toradol",{"type":82,"name":83,"description":84,"armGroupLabels":85,"otherNames":16},"PROCEDURE","Nerve of Arnold Block","Bilateral Nerve of Arnold block with bupivacaine 0.25%, 0.2 mL per side (total 0.4 mL), administered after induction of anesthesia",[61],{"type":82,"name":87,"description":88,"armGroupLabels":89,"otherNames":16},"Sham Intramuscular Injection","sham intramuscular injections with normal saline to maintain blinding",[61],{"type":82,"name":91,"description":92,"armGroupLabels":93,"otherNames":16},"Sham Nerve of Arnold Block","Bilateral sham Nerve of Arnold block with normal saline 0.2 mL per side to maintain blinding",[53],{"type":71,"name":95,"description":96,"armGroupLabels":97,"otherNames":98},"Dexmedetomidine","Dexmedetomidine 5 mcg per side (10 mcg total) added to bupivacaine solution for Nerve of Arnold block as adjuvant to prolong block duration",[61],[99],"Precedex",{"type":71,"name":101,"description":102,"armGroupLabels":103,"otherNames":104},"Bupivacaine","Bupivacaine 0.25% with epinephrine 1:200,000, 0.2 mL per side (total 0.4 mL, maximum 2.5 mg\u002Fkg) for bilateral Nerve of Arnold block",[61],[105],"Marcaine, Sensorcaine",[107,112],{"name":108,"role":109,"phone":110,"phoneExt":16,"email":111},"Karthik Swamy, MD","CONTACT","251-471-7045","kswamy@health.southalabama.edu",{"name":113,"role":109,"phone":110,"phoneExt":16,"email":111},"Karthik Swamy",[115],{"facility":116,"status":16,"city":117,"state":118,"zip":119,"country":120,"countryCode":121,"cosmosGeoPoint":122,"geoPoint":127,"contacts":128},"Children and Woman's Hospital","Mobile","Alabama","36604","United States","US",{"type":123,"coordinates":124},"Point",[125,126],-88.04305,30.69436,{"lat":126,"lon":125},[129,130],{"name":108,"role":109,"phone":110,"phoneExt":16,"email":111},{"name":131,"role":109,"phone":110,"phoneExt":16,"email":111},"Karthik Swamy, M.D",{"type":133,"investigatorFullName":113,"investigatorTitle":134,"investigatorAffiliation":5,"oldNameTitle":16,"oldOrganization":16},"PRINCIPAL_INVESTIGATOR","Director, Pediatric Anesthesiology, Principal Investigator, Assistant Professor","100614231",false,"NCT07276906","Comparing Intramuscular Fentanyl and Ketorolac With Nerve of Arnold (NOA) Block for Bilateral Myringotomy","A Prospective, Randomized, Double-Blind, Non-Inferiority Trial Comparing Intramuscular Fentanyl and Ketorolac With Nerve of Arnold Block for Postoperative Pain Management in Pediatric Patients Undergoing Bilateral Myringotomy With Tympanostomy Tube Placement","NOA","Inclusion Criteria:\n\nAge 6 months to 6 years\n\nScheduled bilateral myringotomy with tube placement\n\nASA physical status I-II\n\nParent\u002Fguardian consent\n\nExclusion Criteria:\n\n* Allergy to study medications (fentanyl, ketorolac, bupivacaine)\n\nRenal impairment or contraindication to ketorolac\n\nBleeding disorder or anticoagulation\n\nSignificant obstructive sleep apnea (AHI \\>10)\n\nConcurrent surgical procedures beyond BMT\n\nUnilateral procedure only\n\nRecent analgesic use (\\\u003C24 hours)","ALL","6 Months","6 Years",{"count":146,"type":147},300,"ESTIMATED","INTERVENTIONAL",[150],"PHASE4","Background: Bilateral myringotomy with tympanostomy tube (BMT) placement is one of the most common pediatric surgical procedures. Despite its brief duration, many children experience significant postoperative pain. Current standard care typically involves intramuscular (IM) administration of an opioid (fentanyl) combined with a non-steroidal anti-inflammatory drug (ketorolac). While this multimodal approach provides adequate pain control for approximately 75% of children, it is associated with opioid-related side effects including respiratory depression, nausea, vomiting, and sedation. Additionally, nearly one-quarter of children still experience moderate-to-severe pain despite this regimen.\n\nThe Nerve of Arnold block is a regional anesthesia technique that involves injection of local anesthetic near the auricular branch of the vagus nerve, which provides sensory innervation to the external auditory canal and tympanic membrane. This technique offers the potential for targeted, opioid-sparing analgesia with extended duration and minimal systemic side effects. However, high-quality evidence comparing this regional technique to standard systemic analgesia in pediatric patients is lacking.\n\nStudy Objective: This study aims to determine whether the Nerve of Arnold block is non-inferior to the standard combination of IM fentanyl and IM ketorolac in controlling postoperative pain in children undergoing BMT placement.\n\nStudy Design: This is a prospective, randomized, double-blind, non-inferiority trial. Three hundred children aged 6 months to 6 years scheduled for bilateral myringotomy with tympanostomy tube placement will be randomized 1:1 to receive either: (1) Standard care: IM fentanyl (1-2 mcg\u002Fkg) plus IM ketorolac (0.5 mg\u002Fkg) with sham Nerve of Arnold block, or (2) Intervention: Bilateral Nerve of Arnold block with bupivacaine 0.25% plus sham IM injections. Both patients and outcome assessors will be blinded to treatment assignments.\n\nPrimary Outcome: The proportion of patients experiencing moderate-to-severe pain (Face, Legs, Activity, Cry, Consolability \\[FLACC\\] scale score ≥4) in the Post-Anesthesia Care Unit (PACU). Non-inferiority will be declared if the upper bound of the 95% confidence interval for the difference in proportions is less than 10 percentage points.\n\nSecondary Outcomes: Secondary outcomes include mean and maximum FLACC scores, rescue analgesic requirements, respiratory depression, postoperative nausea and vomiting, PACU length of stay, parent satisfaction, and pain at 24 hours postoperatively.\n\nClinical Significance: If the Nerve of Arnold block is shown to be non-inferior to standard care, it could provide a valuable opioid-sparing alternative for postoperative pain management in pediatric ear surgery, potentially reducing opioid-related adverse events while maintaining effective analgesia. This would be particularly beneficial for patients with contraindications to opioids or NSAIDs and aligns with national efforts to reduce opioid exposure in pediatric populations.",[153],"Postoperative Pain","NOT_YET_RECRUITING","2025-12-01",{"date":157,"type":158},"2025-12-11","ACTUAL",{"date":160,"type":147},"2026-01",{"date":162,"type":147},"2026-08",{"name":5,"class":6},1]