Dataset Information

Adaptive randomised controlled non-inferiority multicentre trial (the Ketodex Trial) on intranasal dexmedetomidine plus ketamine for procedural sedation in children: study protocol.

ABSTRACT:

Introduction

Up to 40% of orthopaedic injuries in children require a closed reduction, almost always necessitating procedural sedation. Intravenous ketamine is the most commonly used sedative agent. However, intravenous insertion is painful and can be technically difficult in children. We hypothesise that a combination of intranasal dexmedetomidine plus intranasal ketamine (Ketodex) will be non-inferior to intravenous ketamine for effective sedation in children undergoing a closed reduction.

Methods and analysis

This is a six-centre, four-arm, adaptive, randomised, blinded, controlled, non-inferiority trial. We will include children 4-17 years with a simple upper limb fracture or dislocation that requires sedation for a closed reduction. Participants will be randomised to receive either intranasal Ketodex (one of three dexmedetomidine and ketamine combinations) or intravenous ketamine. The primary outcome is adequate sedation as measured using the Paediatric Sedation State Scale. Secondary outcomes include length of stay, time to wakening and adverse effects. The results of both per protocol and intention-to-treat analyses will be reported for the primary outcome. All inferential analyses will be undertaken using a response-adaptive Bayesian design. Logistic regression will be used to model the dose-response relationship for the combinations of intranasal Ketodex. Using the Average Length Criterion for Bayesian sample size estimation, a survey-informed non-inferiority margin of 17.8% and priors from historical data, a sample size of 410 participants will be required. Simulations estimate a type II error rate of 0.08 and a type I error rate of 0.047.

Ethics and dissemination

Ethics approval was obtained from Clinical Trials Ontario for London Health Sciences Centre and McMaster Research Ethics Board. Other sites have yet to receive approval from their institutions. Informed consent will be obtained from guardians of all participants in addition to assent from participants. Study data will be submitted for publication regardless of results.

Trial registration number

NCT0419525.

SUBMITTER: Poonai N

PROVIDER: S-EPMC7733175 | biostudies-literature | 2020 Dec

REPOSITORIES: biostudies-literature

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Publications

Adaptive randomised controlled non-inferiority multicentre trial (the Ketodex Trial) on intranasal dexmedetomidine plus ketamine for procedural sedation in children: study protocol.

Poonai Naveen N Coriolano Kamary K Klassen Terry T Heath Anna A Yaskina Maryna M Beer Darcy D Sawyer Scott S Bhatt Maala M Kam April A Doan Quynh Q Sabhaney Vikram V Offringa Martin M Pechlivanoglou Petros P Hickes Serena S Ali Samina S

BMJ open 20201210 12

<h4>Introduction</h4>Up to 40% of orthopaedic injuries in children require a closed reduction, almost always necessitating procedural sedation. Intravenous ketamine is the most commonly used sedative agent. However, intravenous insertion is painful and can be technically difficult in children. We hypothesise that a combination of intranasal dexmedetomidine plus intranasal ketamine (Ketodex) will be non-inferior to intravenous ketamine for effective sedation in children undergoing a closed reduct ...[more]

PMID: 33303457

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Project description:BackgroundProcedural sedation and analgesia (PSA) is frequently required to perform closed reductions for fractures and dislocations in children. Intravenous (IV) ketamine is the most commonly used sedative agent for closed reductions. However, as children find IV insertion a distressing and painful procedure, there is need to identify a feasible alternative route of administration. There is evidence that a combination of dexmedetomidine and ketamine (ketodex), administered intranasally (IN), could provide adequate sedation for closed reductions while avoiding the need for IV insertion. However, there is uncertainty about the optimal combination dose for the two agents and whether it can provide adequate sedation for closed reductions. The Intranasal Dexmedetomidine Plus Ketamine for Procedural Sedation (Ketodex) study is a Bayesian phase II/III, non-inferiority trial in children undergoing PSA for closed reductions that aims to address both these research questions. This article presents in detail the statistical analysis plan for the Ketodex trial and was submitted before the outcomes of the trial were available for analysis.Methods/designThe Ketodex trial is a multicenter, four-armed, randomized, double-dummy controlled, Bayesian response adaptive dose finding, non-inferiority, phase II/III trial designed to determine (i) whether IN ketodex is non-inferior to IV ketamine for adequate sedation in children undergoing a closed reduction of a fracture or dislocation in a pediatric emergency department and (ii) the combination dose for IN ketodex that provides optimal sedation. Adequate sedation will be primarily measured using the Pediatric Sedation State Scale. As secondary outcomes, the Ketodex trial will compare the length of stay in the emergency department, time to wakening, and adverse events between study arms.DiscussionThe Ketodex trial will provide evidence on the optimal dose for, and effectiveness of, IN ketodex as an alternative to IV ketamine providing sedation for patients undergoing a closed reduction. The data from the Ketodex trial will be analyzed from a Bayesian perspective according to this statistical analysis plan. This will reduce the risk of producing data-driven results introducing bias in our reported outcomes.Trial registrationClinicalTrials.gov NCT04195256 . Registered on December 11, 2019.

Project description:Breast lumpectomy is usually performed under general or local anesthesia. To the best of our knowledge, whether conscious sedation with intranasal dexmedetomidine and local anesthesia is an effective anesthetic technique has not been studied. Thus, the present study aimed to investigate the effectiveness of conscious sedation with intranasal dexmedetomidine combined with local anesthesia in breast lumpectomy, and to identify its optimal dose. A prospective randomized, double-blinded, placebo-controlled, single-center study was designed, and patients undergoing breast lumpectomies were recruited based on the inclusion and exclusion criteria. All patients were randomly allocated to four groups: i) Local anesthesia with 0.9% intranasal saline (placebo); local anesthesia with ii) 1 µg.kg-1; iii) 1.5 µg.kg-1; or iv) 2 µg.kg-1 intranasal dexmedetomidine. The sedation status, pain relief, vital signs, adverse events, and satisfaction of patient and surgeon were recorded. Patients in the three dexmedetomidine groups were significantly more sedated and experienced less pain compared with the placebo group 45 min after intranasal dexmedetomidine administration and during 30 min in the post-anesthesia care unit. Patients in the 1.5 µg.kg-1 group were more sedated compared with the 1 µg.kg-1 group (without reaching statistical significance), whereas the 1.5 µg.kg-1 group exhibited a similar level of sedation 45 min after intranasal dexmedetomidine administration compared with the 2 µg.kg-1 group. In addition, patients in the 1 and 1.5 µg.kg-1 group experienced no adverse hemodynamic effects. Patient and surgeon satisfaction were greater in the 1.5 µg.kg-1 group compared with the 1 and 2 µg.kg-1 groups. Taken together, the results of the present study suggested that conscious sedation with intranasal dexmedetomidine and local anesthesia may be an effective anesthetic for breast lumpectomy surgery, and that the optimal dose for intranasal dexmedetomidine administration may be 1.5 µg.kg-1, as it resulted in good sedation and patient satisfaction without adverse effects.

Project description:BackgroundUncooperative children may need to receive dental treatment under sedation, which is indicated when nonpharmacological behavior guidance is unsuccessful. There are randomized controlled trials (RCTs) comparing different sedative protocols for dental procedures; however, the evidence for superiority of one form over another is weak. The primary aim of this study is to investigate the efficacy of intranasally administered ketamine plus midazolam for the dental treatment of children.MethodsWe have designed a three-armed, parallel RCT to assess intranasal sedation using ketamine/midazolam in terms of the following measures: efficacy, safety, and cost-effectiveness. Two- to 6-year-old healthy children, referred for dental treatment in a dental sedation center in Brazil due to uncooperative behavior and requiring restorative dental procedures, will be recruited. Each child will be randomly assigned to one of the three groups: A - Intranasal administration of ketamine (4.0 mg/kg, maximum 100 mg) and midazolam (0.2 mg/kg, maximum 5.0 mg); B - Oral administration of ketamine (4.0 mg/kg, maximum 100 mg) and midazolam (0.5 mg/kg, maximum 20 mg); and C - Oral administration of midazolam (1.0 mg/kg, maximum 20 mg). The primary outcome is the child's behavior assessed through an observational scale using digital videos of the restorative dental treatment under sedation. The secondary outcomes are as follows: acceptance of sedative administration; memory of intraoperative events; the child's stress; adverse events; the child's pain during the procedure; the parent's, dentists', and child's perceptions of sedation; and economic analysis. Measures will be taken at baseline and drug administration and during and after the dental procedure. The necessary sample size was estimated to be 84 children after a blinded interim analysis of the first 30 cases.DiscussionThis study will provide data that can substantially add to science and pediatric dentistry as it examines the effect of sedative regimes from different perspectives (outcomes).Trial registrationClinicalTrials.gov, identifier: NCT02447289 . Registered on 11 May 2015, named "Midazolam and Ketamine Effect Administered Through the Nose for Sedation of Children for Dental Treatment (NASO)."

Dataset Information

Adaptive randomised controlled non-inferiority multicentre trial (the Ketodex Trial) on intranasal dexmedetomidine plus ketamine for procedural sedation in children: study protocol.

Introduction

Methods and analysis

Ethics and dissemination

Trial registration number

Publications

Adaptive randomised controlled non-inferiority multicentre trial (the Ketodex Trial) on intranasal dexmedetomidine plus ketamine for procedural sedation in children: study protocol.

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