Final results of MRC CRASH, a randomised placebo-controlled trial of intravenous corticosteroid in adults with head injury—outcomes at 6 months

Edwards, Phil; Arango, Miguel; Balica, Laura; Cottingham, Rowland; El-Sayed, Hesham; Farrell, Barbara; Fernandes, Janice; Gogichaisvili, Tamar; Golden, Nyoman; Hartzenberg, Bennie H.; Husain, Mazhar; Ulloa, Mario Izurieta; Jerbi, Z; Khamis, Hussein; Komolafe, E O; Laloë, Véronique; Lomas, Gabrielle; Ludwig, Sabine; Mazairac, Guy; Sanchéz, Maria de los Angeles Muñoz; Nasi, Luis; Olldashi, Fatos; Plunkett, Patrick K.; Roberts, Ian; Sandercock, Peter; Shakur, Haleema; Soler, C. Rafael Trinchet; Stocker, Reto; Svoboda, Petr; Trenkler, Stefan; Venkataramana, N. K.; Wasserberg, Jonathan; Yates, David; Yutthakasemsunt, Surakrant

doi:10.1016/s0140-6736(05)66552-x

Cited by 655 publications

(118 citation statements)

References 5 publications

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“…89,90 Intensive insulin therapy (80–120 mg/dl) in TBI patients has been associated with less infectious complications and shorter ICU length of stay compared with a less aggressive strategy (<220 mg/dl), but was associated with more hypoglycemia and similar outcomes and infectious complications and has not generated strong clinical enthusiasm. 91 In two large multicenter randomized clinical trials, administration of intravenous progesterone also failed to show a clinical benefit in humans.…”

Section: Icu Management: Other Therapiesmentioning

confidence: 99%

Acute Management of Traumatic Brain Injury

Vella

Crandall

Patel

2017

Surgical Clinics of North America

255

141

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Synopsis Traumatic brain injury (TBI) is a leading cause of death and disability in trauma patients. As the primary injury cannot be undone, management strategies must therefore focus on preventing secondary injury by avoiding hypotension and hypoxia and maintaining appropriate cerebral perfusion pressure (CPP), which is a surrogate for cerebral blood flow (CBF). Cerebral perfusion pressure can be maintained by increasing mean arterial pressure (MAP), decreasing intracranial pressure (ICP), or both. MAP can be increased through a combination of pressors in the euvolemic state, although the ideal fluid in TBI patients is unknown. The goal should be euvolemia and avoidance of hypotension. Elevated intracranial pressure can be treated through an algorithmic approach utilization simple bedside maneuvers, hyperosmolar therapy, cerebral spinal fluid (CSF) drainage as well as pentobarbital coma and decompressive craniectomy in refractory cases. Mass lesions may require operative evacuation depending on size, exam findings, and ICP measurements. Although CPP may not be an ideal surrogate for cerebral blood flow and metabolic delivery, other modalities have not gained widespread use due to paucity of strong data. Other factors that deserve important consideration in the acute management of TBI patients are venous thromboembolism, stress ulcer, and seizure prophylaxis as well as nutritional and metabolic optimization.

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Section: Icu Management: Other Therapiesmentioning

confidence: 99%

Acute Management of Traumatic Brain Injury

Vella

Crandall

Patel

2017

Surgical Clinics of North America

255

141

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“…21,22 Given that TBI victims are known to be at risk for AI from injury to the pituitary gland [23][24][25] and from other causes, 26,27 the additional AI that could result from using etomidate might increase TBI mortality and morbidity. Given that high-dose corticosteroids have been shown to increase TBI mortality, 28,29 corticosteroids are avoided in this population. This decrease in the use of corticosteroids offers an opportunity to better determine the length of etomidate-induced AI and to assess the deleterious effects of etomidate-induced AI in TBI victims.…”

Section: Importance Of the Questionmentioning

confidence: 99%

Adrenal inhibition following a single dose of etomidate in intubated traumatic brain injury victims

Archambault

Dionne

Lortie

et al. 2012

CJEM

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Background: Etomidate is frequently used to intubate traumatic brain injury (TBI) victims, even though it has been linked to adrenal insufficiency (AI) in some populations. Few studies have explored the risk of prolonged etomidateinduced AI among TBI victims. Objective: To determine the risk and the length of AI induced by etomidate in patients intubated for moderate and severe TBI. Methods: Participants in this observational study were moderate to severe intubated TBI victims aged $ 16 years. The anesthetic used (etomidate versus others) was determined solely by the treating emergency physician. Adrenocorticotropic hormone (ACTH) stimulation tests (250 mg) were performed 24, 48, and 168 hours after intubation. AI was defined as an increase in serum cortisol 1 hour post-ACTH test (delta cortisol) of less than 248.4 nmol/L. Results: Forty subjects (participation 42.6%) underwent ACTH testing. Fifteen received etomidate, and 25 received another anesthetic. There were no statistically significant differences between groups as to the cumulative incidence of AI at any measurement time. However, at 24 hours, exploratory post hoc analyses showed a significant decrease in delta cortisol (adjusted means: etomidate group: 305.1 nmol/L, 95% CI 214.7-384.8 versus other anesthetics: 500.5 nmol/L, 95% CI 441.8-565.7). This decrease was not present at 48 and 168 hours. Conclusion: In TBI victims, although a single dose of etomidate does not increase the cumulative incidence of AI as defined, it seems to decrease the adrenal response to an

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“…This analysis can be complex as a trial’s target market may consist of several segments, to whom trial participation needs to be sold. A trial may need to be sold to trial participants themselves, as with txt2stop, or in other cases, to their legal representatives [24]. Further, market analysis is used to provide insights into other stakeholders whose involvement can be vital to a trial’s effectiveness, including its promotion.…”

Section: Resultsmentioning

confidence: 99%

Using marketing theory to inform strategies for recruitment: a recruitment optimisation model and the txt2stop experience

Leandro

Knight

Robertson

et al. 2014

Trials

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BackgroundRecruitment is a major challenge for many trials; just over half reach their targets and almost a third resort to grant extensions. The economic and societal implications of this shortcoming are significant. Yet, we have a limited understanding of the processes that increase the probability that recruitment targets will be achieved. Accordingly, there is an urgent need to bring analytical rigour to the task of improving recruitment, thereby increasing the likelihood that trials reach their recruitment targets. This paper presents a conceptual framework that can be used to improve recruitment to clinical trials.MethodsUsing a case-study approach, we reviewed the range of initiatives that had been undertaken to improve recruitment in the txt2stop trial using qualitative (semi-structured interviews with the principal investigator) and quantitative (recruitment) data analysis. Later, the txt2stop recruitment practices were compared to a previous model of marketing a trial and to key constructs in social marketing theory.ResultsPost hoc, we developed a recruitment optimisation model to serve as a conceptual framework to improve recruitment to clinical trials. A core premise of the model is that improving recruitment needs to be an iterative, learning process. The model describes three essential activities: i) recruitment phase monitoring, ii) marketing research, and iii) the evaluation of current performance. We describe the initiatives undertaken by the txt2stop trial and the results achieved, as an example of the use of the model.ConclusionsFurther research should explore the impact of adopting the recruitment optimisation model when applied to other trials.

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Final results of MRC CRASH, a randomised placebo-controlled trial of intravenous corticosteroid in adults with head injury—outcomes at 6 months

Cited by 655 publications

References 5 publications

Acute Management of Traumatic Brain Injury

Acute Management of Traumatic Brain Injury

Adrenal inhibition following a single dose of etomidate in intubated traumatic brain injury victims

Using marketing theory to inform strategies for recruitment: a recruitment optimisation model and the txt2stop experience

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