scholarly journals P119: Pain free laceration repairs using intra-nasal ketamine: DosINK 1- A dose escalation clinical trial

CJEM ◽  
2018 ◽  
Vol 20 (S1) ◽  
pp. S99-S99
Author(s):  
S. Rached-dastous ◽  
B. Bailey ◽  
C. Marquis ◽  
M. Desjardins ◽  
D. Lebel ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Adverse Event ◽  
Dose Escalation ◽  
Optimal Dose ◽  
Dose Finding ◽  
Procedural Sedation ◽  
Secondary Outcome ◽  
Finding Study ◽  
Baseline Status ◽  
Set Up

Introduction: Laceration is common in children presenting to the emergency department (ED). They are often uncooperative related to pain and distressed during repair. Currently, there are wide variations regarding sedation and analgesia practices when sutures are required. There is a growing interest in the intranasal (IN) route for procedural sedation and pain control because of its effectiveness potential and ease of administration. Few studies have evaluated IN ketamine for procedural sedation in children with reported doses ranging from 3 to 9 mg/kg. The objective is to evaluate the optimal IN ketamine dose for effective and safe procedural sedation for laceration repair in children aged 1 to 12 years. Methods: A dose escalation clinical trial with an initial dose of 3 mg/kg of IN ketamine up to a maximum dose of 9 mg/kg in children 1 to 12 years old, using a 3+3 trial design. For each tested dose, 3 patients are enrolled. Escalation to the next dose is permitted if sedation is unsuccessful in at least one patient without serious adverse event (SAE). Regression to prior dose is warranted in the occurrence of two or more SEAs. This process is repeated until effective sedation for 6 patients at two consecutive doses is achieved with a maximum of 1 SAE or if regression occurs. The primary outcome is the optimal dose for successful procedural sedation as per the PERC/PECARN consensus criteria. Secondary outcome, namely, pain and anxiety levels, parent, patient and provider satisfaction, recovery time, length of stay in the ED, side effects and adverse event are recorded. Results: Nine patients have been recruited from March to December 2017 with median age of 2.9 years-old and with laceration length of 2 to 5 cm and with facial involvement in 55% of cases, respectively. Sedation was successful in 1/3, 1/3 and 3/3 of patients at doses of 3, 4, 5 mg/kg respectively, without any SAE. Median time from ketamine administration to return to baseline status and discharge were 35 and 98 min, respectively. We expect to complete patient recruitment in March 2018. Conclusion: The results from our trial is a groundwork for future dose-finding study. Pending study completion, a multicentric dose validation trial, is set up to further validate the optimal dose from dosINK1 trial. IN ketamine has the potential to improve the field of procedural sedation for children by introducing an effective IN agent with respiratory stability but without the need for an IV line insertion not otherwise needed.

scholarly journals Optimal dose-finding study of antithrombin III for the treatment of acute DIC

2008 ◽  
Vol 19 (11) ◽  
pp. 1011-1022
Author(s):  
Masahiro Okashiro ◽  
Takahisa Kawashima ◽  
Noboru Ishii ◽  
Yusuke Itagaki ◽  
Yukiko Watanabe ◽  
...  
Keyword(s):  
Antithrombin Iii ◽  
Optimal Dose ◽  
Dose Finding ◽  
Finding Study ◽  
Dose Finding Study

scholarly journals LO50: Pain free laceration repairs using intra-nasal ketamine: DosINK 2 clinical trial

CJEM ◽  
2020 ◽  
Vol 22 (S1) ◽  
pp. S25-S25
Author(s):  
S. Rached-Dastous ◽  
E. D. Trottier ◽  
Y. Finkelstein ◽  
B. Bailey ◽  
C. Marquis ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Procedural Sedation ◽  
Convenience Sample ◽  
Serious Adverse Event ◽  
Dental Procedures ◽  
Baseline Status ◽  
The Face ◽  
Repeated Doses ◽  
Prior Administration ◽  
Sedative Agents

Introduction: Lacerations are common in children presenting to the emergency department (ED). They are often uncooperative when sutures are needed and may require procedural sedation. Few studies have evaluated intranasal (IN) ketamine for procedural sedation in children, with doses from 3 to 9 mg/kg used mostly for dental procedures. In a previous dose escalation trial, DosINK-1, 6 mg/kg was found to be the optimal IN ketamine dose for procedural sedation for sutures in children. In this trial, we aim to further evaluate the efficacy of this dose. Methods: We conducted a multicentre single-arm clinical trial. A convenience sample of 30 uncooperative children between 1 and 12 years (10 to 30 kg) with no cardiac or kidney disease, active respiratory infection, prior administration of opioid or sedative agents received 6 mg/kg of IN ketamine using an atomizer for their laceration repair with sutures in the ED. The primary outcome was defined as the proportion (95% CI) of patients who achieved an adequate procedural sedation evaluated with the PERC/PECARN consensus criteria. Results: Thirty patients were recruited from April 2018 to November 2019 in 2 pediatric ED. The median age was 3.2 (interquartile range(IQR), 1.9 to 4.7) years-old with laceration of more than 2 cm in 20 (67%) patients and in the face in 21 (70%) cases. Sedation was effective in 18 out of 30 children 60% (95%CI, 45 to 80), was suboptimal in 6 patients (20%) with a procedure completed with minimal difficulties, and unsuccessful in the remaining 6 (20%), all without serious adverse event. Similarly, 21/30 (70%) physicians were willing to reuse IN ketamine at the same doses and 25 parents (83%) would agree to the same sedation in the future. Median time to return to baseline status was 58 min (IQR, 33 to 73). One patient desaturated during the procedure and required transitory oxygen and repositioning. After the procedure, 1 (3%) patient had headache, 1 (3%) patient had nausea, and 2 (7%) patients vomited. Conclusion: A single dose of 6 mg/kg of IN Ketamine for laceration repair with sutures in uncooperative children is safe and facilitated the procedure in 60% (95%CI, 45 to 80) of patients, was suboptimal in 20% and unsuccessful in 20% of patients. As seen with IV ketamine, an available additional dose of IN ketamine for some children if needed could potentially increase proportion of successful sedation. However, the safety and efficacy of repeated doses needs to be addressed.

scholarly journals Brivaracetam: a newly approved medication for epilepsy

2019 ◽  
Vol 14 (3) ◽  
pp. FNL23
Author(s):  
Joel M Oster
Keyword(s):  
Clinical Trial ◽  
Adverse Event ◽  
Dose Finding ◽  
Adjunctive Treatment ◽  
Adverse Event Profile ◽  
Focal Seizures ◽  
The Usa ◽  
Clinical Trial Program ◽  
The Eu

Brivaracetam (BRV) in both the USA and EU was developed as a novel molecule for the adjunctive treatment of partial-onset (focal) seizures in patients ≥16 years of age and as of September 2017 was approved for use as monotherapy in the USA uniquely as an antiseizure medication that may be prescribed without a dose finding uptitration. This article reviews BRV's pharmacology, efficacy, safety and adverse event profiles, along with the relevant and noted regulatory hurdles in the USA and the EU. Available postmarketing data will also be summarized. Approximately 3000 patients were studied over about 9 years in the clinical trial program illustrating that BRV has efficacy at 50–200 mg/day with an acceptable adverse event profile.

Hierarchical models for sharing information across populations in phase I dose-escalation studies

2017 ◽  
Vol 27 (11) ◽  
pp. 3447-3459 ◽  
Author(s):  
Kristen M Cunanan ◽  
Joseph S Koopmeiners
Keyword(s):  
Clinical Trial ◽  
Phase I ◽  
Dose Escalation ◽  
Hierarchical Models ◽  
Hierarchical Modeling ◽  
Maximum Tolerated Dose ◽  
Phase I Clinical Trial ◽  
Dose Finding ◽  
Novel Treatment ◽  
Number Of Patients

The primary goal of a phase I clinical trial in oncology is to evaluate the safety of a novel treatment and identify the maximum tolerated dose, defined as the maximum dose with a toxicity rate below some pre-specified threshold. Researchers are often interested in evaluating the performance of a novel treatment in multiple patient populations, which may require multiple phase I trials if the treatment is to be used with background standard-of-care that varies by population. An alternate approach is to run parallel trials but combine the data through a hierarchical model that allows for a different maximum tolerated dose in each population but shares information across populations to achieve a more accurate estimate of the maximum tolerated dose. In this manuscript, we discuss hierarchical extensions of three commonly used models for the dose–toxicity relationship in phase I oncology trials. We then propose three dose-finding guidelines for phase I oncology trials using hierarchical modeling. The proposed guidelines allow us to fully realize the benefits of hierarchical modeling while achieving a similar toxicity profile to standard phase I designs. Finally, we evaluate the operating characteristics of a phase I clinical trial using the proposed hierarchical models and dose-finding guidelines by simulation. Our simulation results suggest that incorporating hierarchical modeling in phase I dose-escalation studies will increase the probability of correctly identifying the maximum tolerated dose and the number of patients treated at the maximum tolerated dose, while decreasing the rate of dose-limiting toxicities and number of patients treated above the maximum tolerated dose, in most cases.

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