7 research outputs found
RESTART Extended Follow Up Dataset
No full textAnalysis dataset used for the RESTART extended follow up results paper in 2021 (doi:10.1001/jamaneurol.2021.2956). This dataset contains the data dictionary and statistical analysis plan form the RESTART extended follow up. It also contains the Data sharing description and Request form that should be used to obtain a copy of the data. Additional information about the data (trial protocol, annotated CRFs) can be found with the RESTART main results dataset ( https://doi.org/10.1016/S0140-6736(19)30840-2 ).Salman, Rustam Al-Shahi; Rodriguez Carbonell, Aryelly; Stephen, Jacqueline; Drever, Jonathan. (2022). RESTART Extended Follow Up Dataset, [dataset]. University of Edinburgh. Deanery of Clinical Sciences. Centre for Clinical Brain Sciences. https://doi.org/10.7488/ds/3399
RESTART Extended Follow Up Dataset
No full textAnalysis dataset used for the RESTART extended follow up results paper in 2021 (doi:10.1001/jamaneurol.2021.2956).
This dataset contains the data dictionary and statistical analysis plan form the RESTART extended follow up. It also contains the Data sharing description and Request form that should be used to obtain a copy of the data.
Additional information about the data (trial protocol, annotated CRFs) can be found with the RESTART main results dataset ( https://doi.org/10.1016/S0140-6736(19)30840-2 ).SOP, Data dictionary, request form, data sharing process.
Annotated CRFs are available via RESTART trail main results dataset
Hypothermia for Intracranial Hypertension after Traumatic Brain Injury
Full text linkBackground In patients with traumatic brain injury, hypothermia can reduce intracranial hypertension. The benefit of hypothermia on functional outcome is unclear. Methods We randomly assigned adults with an intracranial pressure of more than 20 mm Hg despite stage 1 treatments (including mechanical ventilation and sedation management) to standard care (control group) or hypothermia (32 to 35°C) plus standard care. In the control group, stage 2 treatments (e.g., osmotherapy) were added as needed to control intracranial pressure. In the hypothermia group, stage 2 treatments were added only if hypothermia failed to control intracranial pressure. In both groups, stage 3 treatments (barbiturates and decompressive craniectomy) were used if all stage 2 treatments failed to control intracranial pressure. The primary outcome was the score on the Extended Glasgow Outcome Scale (GOS-E; range, 1 to 8, with lower scores indicating a worse functional outcome) at 6 months. The treatment effect was estimated with ordinal logistic regression adjusted for prespecified prognostic factors and expressed as a common odds ratio (with an odds ratio <1.0 favoring hypothermia). Results We enrolled 387 patients at 47 centers in 18 countries from November 2009 through October 2014, at which time recruitment was suspended owing to safety concerns. Stage 3 treatments were required to control intracranial pressure in 54% of the patients in the control group and in 44% of the patients in the hypothermia group. The adjusted common odds ratio for the GOS-E score was 1.53 (95% confidence interval, 1.02 to 2.30; P=0.04), indicating a worse outcome in the hypothermia group than in the control group. A favorable outcome (GOS-E score of 5 to 8, indicating moderate disability or good recovery) occurred in 26% of the patients in the hypothermia group and in 37% of the patients in the control group (P=0.03). Conclusions In patients with an intracranial pressure of more than 20 mm Hg after traumatic brain injury, therapeutic hypothermia plus standard care to reduce intracranial pressure did not result in outcomes better than those with standard care alone. (Funded by the National Institute for Health Research Health Technology Assessment program; Current Controlled Trials number, ISRCTN34555414 .).</p
Statistical analysis plans (SAPS) for academic clinical trials at the edinburgh clinical trials unit: what should they contain?
Full text linkBronchiolitis of infancy discharge study (BIDS): a multicentre, parallel-group, double-blind, randomised controlled, equivalence trial with economic evaluation
Full text linkBackground
There are no randomised trials of peripheral capillary oxygen saturation (SpO2) targets in acute respiratory infection. Two national guidelines recommended different targets for the management of acute viral bronchiolitis.
Objectives
To compare the American Academy of Pediatrics guideline target of SpO2 ≥ 90% with the Scottish Intercollegiate Guidelines Network target of SpO2 ≥ 94%.
Design
A multicentre, parallel-group, double-blind, randomised controlled, equivalence trial with economic evaluation.
Setting
Eight paediatric hospital departments in the UK.
Participants
Infants 6 weeks and ≤ 12 months of age (corrected for prematurity) with physician-diagnosed bronchiolitis admitted to hospital from a paediatric emergency assessment area. Follow-up for 6 months by standardised telephone contacts.
Intervention
Infants were randomised to a target oxygen saturation of ≥ 94% (standard care) or ≥ 90% (modified care) displayed by a pulse saturation oximeter (Masimo Corporation Limited, CA, USA).
Routine care
All infants received routine care in addition to the study intervention. Infants were eligible for discharge when they exhibited a SpO2 of ≥ 94% in room air for 4 hours including a period of sleep and were also feeding adequately (≥ 75% usual volume).
Primary outcome
A total of 615 infants were recruited, of whom 308 were allocated to the standard care group and 307 to the modified care group. The primary outcome was time to cough resolution. There was equivalence at the prespecified variance of ± 2 days [time to cough resolution: standard care group, 15 days; modified care group, 15 days; median difference 1 day (benefit modified), 95% confidence interval (CI) –1 to 2 days].
Secondary results
Return to adequate feeding occurred sooner in infants in the modified care group than in those in the standard care group (19.5 vs. 24.1 hours). This difference was non-equivalent [median difference 2.7 hours (95% CI –0.3 to 7.0 hours) versus prespecified ± 4 hours; post-hoc hazard ratio 1.22 (95% CI 1.04 to 1.44 (p-value = 0.015)]. Parent perspective of the time taken to return to normal was not equivalent, being 12 days in the standard care group compared with 11 days in the modified care group [median difference 1.0 day (95% CI 0.0 to 3.0 days) versus prespecified ± 2 days; post-hoc hazard ratio 1.19 (95% CI 1.00 to 1.41); p-value = 0.043]. At 28 days, SpO2 was equivalent [mean difference 0.11% (95% CI –0.35% to 0.57%), within the 1% prespecified]. The modified care group (55.6%) required oxygen less than the standard care group (73.1%), and for a shorter period (5.7 hours vs. 27.6 hours). Infants in the modified care group were fit for discharge (30.2 hours vs. 44.2 hours, hazard ratio 1.46, 95% CI 1.23 to 1.73; p-value < 0.001) and were discharged (40.9 hours vs. 50.9 hours; hazard ratio 1.28, 95% CI 1.06 to 1.50; p-value < 0.003) sooner than those in the standard care group. There were 35 serious adverse events in the standard care group, compared with 25 in the modified care group. Eight infants in the standard care group and 12 in the modified care group were admitted to a high-dependency unit. By 28 days, 23 infants had been readmitted to hospital in the standard care group and 12 infants in the modified care group. Parents of infants in the modified care group did not experience higher levels of anxiety and, by 14 days, had lost 28% fewer hours to usual activities. NHS costs were £290 lower in the modified care group than in the standard care group, with additional societal costs also being lower in the modified care group.
Conclusions
Management of infants to a SpO2 target of ≥ 90% is as clinically effective as ≥ 94%, gives rise to no additional safety concerns, and appears to be cost-effective. Future work could focus on the safety and effectiveness of using intermittent oxygen saturation monitoring in secondary care, and to consider what are safe and effective oxygen saturation targets for children with bronchiolitis managed in primary care
Mortality Risk Stratification After Traumatic Brain Injury and Hazard of Death With Titrated Hypothermia in the Eurotherm3235Trial
Full text linkObjective: Hypothermia reduces intracranial hypertension in patients with traumatic brain injury (TBI) but was associated with harm in the Eurotherm3235trial. We stratified trial patients by IMPACT extended model sum scores (IEMSS) to determine where the balance of risks lay with the intervention.Design: The Eurotherm3235Trial was a randomized controlled trial, with standardized and blinded outcome assessment. Patients in the trial were split into risk tertiles by IEMSS. A proportional hazard analysis for death between randomisation and 6 months was performed by intervention and IEMSS tertiles in both the intention-to-treat (ITT) and the per-protocol (PP) populations of the Eurotherm3235 Trial.Setting: Forty seven Neurological Critical Care units in 18 countries.Patients: Adult traumatic brain injury patients admitted to intensive care who had suffered a primary, closed traumatic brain injury; had increased intracranial pressure; an initial head injury less than 10days earlier; a core temperature at least 36°C and an abnormal brain CT.Measurements and Main results: 386 patients were available for analysis in the ITT and 257 in the PP population. The proportional hazard analysis (ITT and PP populations) showed that the treatment effect behaves similarly across all risk stratums. However, there is a trend that indicates that patients in the low-risk group could be at greater risk of suffering harm due to hypothermia.Conclusion: Hypothermia as a first line measure to reduce ICP to less than 20mmHg is harmful in patients with a lower severity of injury and no clear benefit exists in patients with more severe injuries
Does metformin reduce excess birthweight in offspring of obese pregnant women? A randomised controlled trial of efficacy, exploration of mechanisms and evaluation of other pregnancy complications
Full text linkBackgroundMaternal obesity is associated with high birthweight, obesity and premature mortality in adult offspring, probably as a result of maternal hyperglycaemia and insulin resistance. We present the results of a trial designed to test the hypothesis that metformin will improve insulin sensitivity in obese pregnant women, thereby reducing the incidence of high-birthweight babies.ObjectiveTo determine the efficacy of metformin (up to 2500 mg daily) given to obese pregnant women in reducing the gestational age-, parity- and sex-adjusted birthweight centile of the baby.DesignDouble-blind, placebo-controlled, randomised controlled trial with embedded substudies.SettingFifteen NHS hospitals in the UK.ParticipantsPregnant women aged ≥ 16 years with a singleton fetus and a body mass index of ≥ 30 kg/m2.InterventionMetformin tablets (or placebo) administered between 12 and 16 weeks’ gestation until delivery of the baby.Main outcome measuresThe primary outcome measure was z-score corresponding to the gestational age-, parity- and sex-adjusted birthweight centile of live-born babies delivered at ≥ 24 weeks’ gestation. The main secondary outcome was maternal insulin resistance at 36 weeks’ gestation. Embedded substudies were included to assess the effect of metformin on insulin sensitivity using the hyperinsulinaemic–euglycaemic clamp; endothelial function; maternal and fetal fat distribution using magnetic resonance imaging; placental expression of 11β-hydroxysteroid dehydrogenase types 1 and 2 and glucocorticoid receptor; and myometrial contractility and glycogen storage.ResultsWe randomised 449 women to either placebo (n = 223) or metformin (n = 226), of whom 434 were included in the final intention-to-treat analysis. Mean birthweight at delivery was 3463 g [standard deviation (SD) 660 g] in the placebo group and 3462 g (SD 548 g) in the metformin group. The estimated effect size of metformin on the primary outcome was non-significant [adjusted mean difference in z-score –0.029, 95% confidence interval (CI) –0.217 to 0.158; p = 0.7597]. There was no evidence of a reduction in the main secondary outcome of homeostatic model assessment – insulin resistance (HOMA-IR) at 36 weeks’ gestation (mean HOMA-IR 5.98 and 6.30 molar units in the placebo and metformin groups, respectively; adjusted mean ratio 0.974, 95% CI 0.865 to 1.097). Metformin had no effect on the combined adverse outcome of miscarriage, termination of pregnancy, stillbirth or neonatal death. Subjects taking metformin demonstrated increased insulin sensitivity [glucose disposal per unit plasma insulin difference between means during high-dose insulin 0.02 mg/kg, 95% CI 0.001 to 0.03 mg/kg (fat-free mass)/minute/µIU/l; p = 0.04] compared with those taking placebo and enhanced endogenous glucose production [difference between means 0.54 mg/kg, 95% CI 0.08 to 1.00 mg/kg (fat-free mass)/minute; p = 0.02]. There were no differences in endothelial function, maternal or fetal body fat distribution, placental expression of 11β-hydroxysteroid dehydrogenase types 1 and 2 and glucocorticoid receptor, or myometrial contractility and glycogen storage.ConclusionsMetformin has no clinically significant effect on birthweight centile in obese pregnant women. Follow-up studies of the children born to participants in the trial are required to determine whether or not there are any longer-term benefits or harms of maternal metformin for offspring weight, fat mass or metabolism.Trial registrationCurrent Controlled Trials ISRCTN51279843.FundingThis project was funded by the Efficacy and Mechanism Evaluation programme, a Medical Research Council and National Institute for Health Research partnership
