Dataset Information

Adjusting perioperative methadone dose for elderly and fragile hip fracture patients (MetaHip-trial) - A statistical analysis plan for an adaptive dose-finding trial.

ABSTRACT:

Background

The elderly population is expanding globally. This gives numerous challenges especially regarding hip fracture patients. In the US alone over 300.000 hip fracture patients are treated each year, and a large amount of those develop opoid addiction. Hip fractures require surgical intervention within 24 h and is associated with significant pain even at rest. Postoperative analgesic treatment need to be optimized to ensure adequate pain relief and to prevent subsequent opioid addiction. Previous studies have shown that methadone effectively decreases post-operative opioid consumption but the studies focused on younger patients undergoing elective surgery. This study focus on the use of methadone on the elderly, fragile patients undergoing acute surgery, by first determining the maximal tolerable dose.The hypothesis is the maximal tolerable doses of these hip-fracture patients lies between 0.10 mg/kg and 0.20 mg/kg. This trial aims to estimate the maximum tolerable dose of methadone when administered to elderly patients undergoing surgery for a hip fracture.

Method

This project is an adaptive dose-finding trial. The continuous reassessment method will estimate the maximum tolerable dose of methadone. The primary outcome will be respiratory depression. The statistical analysis plan will be published a priori to the closure of patient recruitment and statistical analysis of database results.

Conclusion

The results of this study will give valuable information about the maximally tolerated dose of methadone for postoperative pain relief for elderly patients with hip fractures and potential adverse events.This trial is registered on clinicaltrials.gov with trial registration: NCT05581901. Registered 17 October 2022, https://www.clinicaltrials.gov/ct2/show/NCT05581901?term=methadone&cond = hip&draw = 2&rank = 1.

SUBMITTER: Pedersen AK

PROVIDER: S-EPMC10689264 | biostudies-literature | 2023 Dec

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Adjusting perioperative methadone dose for elderly and fragile hip fracture patients (MetaHip-trial) - A statistical analysis plan for an adaptive dose-finding trial.

Pedersen Andreas Kristian AK Nygaard Kevin Heebøll KH Petersen Sofie Ronja SR Specht Kirsten K Strøm Thomas T Moos Caroline Margaret CM Skjøt-Arkil Helene H Schønnemann Jesper Ougaard JO

Contemporary clinical trials communications 20231114

<h4>Background</h4>The elderly population is expanding globally. This gives numerous challenges especially regarding hip fracture patients. In the US alone over 300.000 hip fracture patients are treated each year, and a large amount of those develop opoid addiction. Hip fractures require surgical intervention within 24 h and is associated with significant pain even at rest. Postoperative analgesic treatment need to be optimized to ensure adequate pain relief and to prevent subsequent opioid addi ...[more]

PMID: 38047142

Similar Datasets

Project description:BackgroundAcute gastroenteritis is a leading cause of emergency department visits and hospitalizations among children in North America. Oral-rehydration therapy is recommended for children with mild-to-moderate dehydration, but children who present with vomiting are frequently offered intravenous rehydration in the emergency department (ED). Recent studies have demonstrated that the anti-emetic ondansetron can reduce vomiting, intravenous rehydration, and hospitalization when administered in the ED to children with dehydration. However, there is little evidence of additional benefit from prescribing ondansetron beyond the initial ED dose. Moreover, repeat dosing may increase the frequency of diarrhea. Despite the lack of evidence and potential adverse side effects, many physicians across North America provide multiple doses of ondansetron to be taken following ED disposition. Thus, the Multi-Dose Oral Ondansetron for Pediatric Gastroenteritis (DOSE-AGE) trial will evaluate the effectiveness of prescribing multiple doses of ondansetron to treat acute gastroenteritis-associated vomiting. This article specifies the statistical analysis plan (SAP) for the DOSE-AGE trial and was submitted before the outcomes of the study were available for analysis.Methods/designThe DOSE-AGE study is a phase III, 6-center, placebo-controlled, double-blind, parallel design randomized controlled trial designed to determine whether participants who are prescribed multiple doses of oral ondansetron to administer, as needed, following their ED visit have a lower incidence of experiencing moderate-to-severe gastroenteritis, as measured by the Modified Vesikari Scale score, compared with a placebo. To assess safety, the DOSE-AGE trial will investigate the frequency and maximum number of diarrheal episodes following ED disposition, and the occurrence of palpitations, pre-syncope/syncope, chest pain, arrhythmias, and serious adverse events. For the secondary outcomes, the DOSE-AGE trial will investigate the individual elements of the Modified Vesikari Scale score and caregiver satisfaction with the therapy.DiscussionThe DOSE-AGE trial will provide evidence on the effectiveness of multiple doses of oral ondansetron, taken as needed, following an initial ED dose in children with acute gastroenteritis-associated vomiting. The data from the DOSE-AGE trial will be analyzed using this SAP. This will reduce the risk of producing data-driven results and bias in our reported outcomes. The DOSE-AGE study was registered on ClinicalTrials.gov on February 22, 2019.Trial registrationClinicalTrials.gov NCT03851835 . Registered on 22 February 2019.

Project description:BackgroundTransforaminal epidural injections with steroids (TESI) are used increasingly for patients with sciatica. However, their safety, effectiveness, and cost-effectiveness are still a matter of debate. This a priori statistical analysis plan describes the methodology of the analysis for the STAR trial that assesses the (cost-)effectiveness of TESI during the acute stage of sciatica (< 8 weeks).MethodsThe STAR trial is a multicentre, randomized controlled, prospective trial (RCT) investigating the (cost-)effectiveness of TESI by making a three-group comparison among patients with acute sciatica due to a herniated lumbar disc (< 8 weeks): (1) TESI combined with levobupivacaine added to oral pain medication (intervention group 1) versus oral pain medication alone (control group), (2) intervention group 1 versus transforaminal epidural injection with levobupivacaine and saline solution added to oral pain medication (intervention group 2), and (3) intervention group 2 versus control group. Co-primary outcomes were physical functioning (Roland Morris Disability Questionnaire), pain intensity (10-point numerical rating scale), and global perceived recovery (7-point Likert scale, dichotomized into 'recovered' and 'not recovered'). For all three comparisons, we defined the following minimal clinically relevant between-group differences: two points for pain intensity (range 0-10), four points for physical functioning (range 0-24) and a 20% difference in recovery rate. Secondary outcomes are health-related quality of life (EQ-5D-5L) and patient satisfaction (7-point Likert scale) and surgery rate. We also collected resource use data to perform an economic evaluation. Analyses will be conducted by intention-to-treat with p < 0.05 (two-tailed) for all three comparisons. Effects will be estimated using mixed models by maximum likelihood. For each comparison, mean differences, or difference in proportions, between groups will be tested per time point and an overall mean difference, or difference in proportions, between groups during the complete duration of follow-up (6 months) will be estimated. In the economic evaluation, Multivariate Imputation by Chained Equations will be used to handle missing data. Cost and effect differences will be estimated using seemingly unrelated regression, and uncertainty will be estimated using bootstrapping techniques.DiscussionThis statistical analysis plan provides detailed information on the intended analysis of the STAR trial, which aims to deliver evidence about the (cost-)effectiveness of TESI during the acute phase of sciatica (< 8 weeks).Trial registrationDutch National trial register NTR4457 (6 March 2014).

Project description:BackgroundContemporary perioperative practice seeks to use less intraoperative opioid, diminish postoperative pain and opioid use, and enable less postdischarge opioid prescribing. For inpatient surgery, anesthesia with intraoperative methadone, compared with short-duration opioids, results in less pain, less postoperative opioid use, and greater patient satisfaction. This pilot investigation aimed to determine single-dose intraoperative methadone feasibility for next-day discharge outpatient surgery, determine an optimally analgesic and well-tolerated dose, and explore whether methadone would result in less postoperative opioid use compared with conventional short-duration opioids.MethodsThis double-blind, randomized, dose-escalation feasibility and pilot study in next-day discharge surgery compared intraoperative single-dose IV methadone (0.1 then 0.2, 0.25 and 0.3 mg/kg ideal body weight) versus as-needed short-duration opioid (fentanyl, hydromorphone) controls. Perioperative opioid use, pain, and side effects were assessed before discharge. Patients recorded pain, opioid use, and side effects for 30 days postoperatively using take-home diaries. Primary clinical outcome was in-hospital (intraoperative and postoperative) opioid use. Secondary outcomes were 30-day opioid consumption, pain, opioid side effects, and leftover opioid counts.ResultsMedian (interquartile range) intraoperative methadone doses were 6 (5 to 7), 11 (10 to 12), 14 (13 to 16), and 18 (15 to 19) mg in 0.1, 0.2, 0.25, and 0.3 mg/kg ideal body weight groups, respectively. Anesthesia with single-dose methadone and propofol or volatile anesthetic was effective. Total in-hospital opioid use (IV milligram morphine equivalents [MME]) was 25 (20 to 37), 20 (13 to 30), 27 (18 to 32), and 25 (20 to 36) mg, respectively, in patients receiving 0.1, 0.2, 0.25 and 0.3 mg/kg methadone, compared to 46 (33 to 59) mg in short-duration opioid controls. Opioid-related side effects were not numerically different. Home pain and opioid use were numerically lower in patients receiving methadone.ConclusionsThe most effective and well-tolerated single intraoperative induction dose of methadone for next-day discharge surgery was 0.25 mg/kg ideal body weight (median, 14 mg). Single-dose intraoperative methadone was analgesic and opioid-sparing in next-day discharge outpatient surgery.Editor’s perspective

Dataset Information

Adjusting perioperative methadone dose for elderly and fragile hip fracture patients (MetaHip-trial) - A statistical analysis plan for an adaptive dose-finding trial.

Background

Method

Conclusion

Publications

Adjusting perioperative methadone dose for elderly and fragile hip fracture patients (MetaHip-trial) - A statistical analysis plan for an adaptive dose-finding trial.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets