The SHINE trial (a multicentre, randomised trial of stabilisation with nasal high flow during neonatal endotracheal intubation): statistical analysis plan

Abstract Endotracheal intubation is an essential but potentially destabilising procedure for neonates. With an increased focus on avoiding mechanical ventilation, particularly in preterm infants, there are fewer opportunities for clinicians to gain proficiency in this important emergency skill. Rates of successful intubation at the first attempt are relatively low, and adverse event rates including desaturation and bradycardia are high, when compared with intubations in paediatric and adult populations. Interventions to improve operator success and patient stability during neonatal endotracheal intubations are needed. Using nasal high flow therapy during apnoea extends the safe apnoea time of adults undergoing upper airway surgery and during endotracheal intubation [1]. This technique is untested in neonates.

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Statistical analysis plan for the Dex-CSDH trial: a randomised, double-blind, placebo-controlled trial of a 2-week course of dexamethasone for adult patients with a symptomatic chronic subdural haematoma

Trials ◽

10.1186/s13063-019-3866-6 ◽

2019 ◽

Vol 20 (1) ◽

Cited By ~ 2

Author(s):

Annabel Allison ◽

Ellie Edlmann ◽

Angelos G. Kolias ◽

Carol Davis-Wilkie ◽

Harry Mee ◽

...

Keyword(s):

Statistical Analysis ◽

Subdural Haematoma ◽

Controlled Trial ◽

Randomised Trial ◽

Statistical Analysis Plan ◽

Chronic Subdural Haematoma ◽

Double Blind ◽

Additional Material ◽

Parallel Group ◽

The Uk

Abstract Background The incidence of chronic subdural haematoma (CSDH) is increasing. Although surgery remains the mainstay of management for symptomatic patients, uncertainty remains regarding the role of steroids. Hence, the Dex-CSDH trial was launched in the UK in 2015 aiming to determine whether, compared to placebo, dexamethasone can improve the 6-month functional outcome of patients with symptomatic CSDH by reducing the rate of surgical intervention and recurrence rate. Methods and design Dex-CSDH is a multi-centre, pragmatic, parallel group, double-blind, randomised trial assessing the clinical utility of a 2-week course of dexamethasone following a CSDH. Seven hundred fifty patients were randomised to either dexamethasone or placebo. The primary outcome is the modified Rankin Scale at 6 months which is dichotomised to favourable (a score of 0–3) versus unfavourable (a score of 4–6). Conclusions This paper and the accompanying additional material describe the statistical analysis plan for the trial. Trial registration ISRCTN, ISRCTN80782810. Registered on 7 November 2014. http://www.isrctn.com/ISRCTN80782810. EudraCT, 2014-004948-35. Registered on 20 March 2015.

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A nested randomised trial of the effect of tranexamic acid on intracranial haemorrhage and infarction in traumatic brain injury (CRASH-3 trial intracranial bleeding mechanistic study): Statistical analysis plan

Wellcome Open Research ◽

10.12688/wellcomeopenres.14731.2 ◽

2019 ◽

Vol 3 ◽

pp. 99

Author(s):

Abda Mahmood ◽

Ian Roberts ◽

Haleema Shakur-Still

Keyword(s):

Traumatic Brain Injury ◽

Statistical Analysis ◽

Brain Injury ◽

Primary Outcome ◽

Randomised Trial ◽

Statistical Analysis Plan ◽

Intracranial Bleeding ◽

Mechanistic Study ◽

Cerebral Infarcts ◽

Post Randomisation

Background: The CRASH-3 trial is a randomised trial on the effect of tranexamic acid (TXA) on death and disability in traumatic brain injury (TBI). The CRASH-3 intracranial bleeding mechanistic study (IBMS) is a randomised trial nested within the CRASH-3 trial to examine the effect of TXA on intracranial bleeding and infarction. Methods: Patients eligible for the CRASH-3 trial, with a GCS of 12 or less or intracranial bleeding on a pre-randomisation CT scan are eligible for the IBMS. The occurrence of intracranial bleeding, infarction, haemorrhagic oedematous lesions, mass effect and haemorrhage evacuation is examined within 28 days of randomisation using routinely collected brain scans. The primary outcome is the volume of intra-parenchymal bleeding in patients randomised within three hours of injury (adjusted for prognostic covariates). Secondary outcomes include a composite “poor” outcome, progressive and new intracranial bleeding, intracranial bleeding after neurosurgery and cerebral infarcts seen up to 28 days post-randomisation. All outcomes will be compared between treatment groups. Statistical analyses: The primary outcome will be analysed using a covariate adjusted linear mixed model. The same analysis will be done separately for patients who undergo haemorrhage evacuation post-randomisation. We will express the effect of TXA on the composite outcome, new and progressive bleeding using relative risks and 95% CIs, and on cerebral infarcts using hazard ratios and 95% CIs. We will conduct sensitivity analyses assuming missing data are MCAR or MNAR. Conclusion: The IBMS will provide information on the mechanism of action of TXA in TBI. This pre-specified statistical analysis plan is a technical extension of the published protocol. Trial registration: The CRASH-3 trial was prospectively registered at the International Standard Randomised Controlled Trials registry (19 July 2011) and ClinicalTrials.gov (25 July 2011). The registries were updated with details for the IBMS on 20 December 2016.

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Statistical Analysis Plan for the MSK DI AF trial

10.31219/osf.io/prnd2 ◽

2021 ◽

Author(s):

Laurent Billot ◽

Denise O'Connor ◽

Brigit Maguire ◽

Dina Schram ◽

Robert Ma ◽

...

Keyword(s):

Statistical Analysis ◽

Diagnostic Imaging ◽

Randomised Trial ◽

Statistical Analysis Plan ◽

Primary Objective ◽

Audit And Feedback ◽

Cluster Randomised Trial ◽

Cluster Randomised ◽

Trial Testing ◽

Australian General Practice

The primary objective of the MSK DI AF trial is to estimate the effectiveness of audit and feedback for reducing diagnostic imaging requests for 11 musculoskeletal imaging services in high requesting GPs in Australia compared with control. It is a 5-arm partial 2 x 2 factorial cluster randomised trial testing variations in the design and delivery of audit and feedback for reducing musculoskeletal diagnostic imaging requests in Australian general practice. This statistical analysis plan pre-specifies all analyses and was prepared while blinded to the randomised allocation.

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Statistical analysis plan for the Maximizing the Efficacy of Sedation and Reducing Neurological Dysfunction and Mortality in Septic Patients with Acute Respiratory Failure trial

Critical Care and Resuscitation ◽

10.51893/2020.1.oa7 ◽

2020 ◽

Vol 22 (1) ◽

pp. 63-71

Author(s):

Rameela Chandrasekhar ◽

◽

Christopher G Hughes ◽

Brenda T Pun ◽

Onur M Orun ◽

...

Keyword(s):

Statistical Analysis ◽

Randomised Trial ◽

Randomised Clinical Trial ◽

Statistical Analysis Plan ◽

Brain Dysfunction ◽

Neurological Dysfunction ◽

Long Term Effects ◽

Double Blind ◽

Mechanically Ventilated

BACKGROUND: The best sedative medication to reduce delirium, mortality and long term brain dysfunction in mechanically ventilated septic patients is unclear. This multicentre, double-blind, randomised trial investigates the short term and long term effects of dexmedetomidine versus propofol for sedation in mechanically ventilated severely septic patients. OBJECTIVES: To describe the statistical analysis plan for this randomised clinical trial comprehensively and place it in the public domain before unblinding. METHODS: To ensure that analyses are not selectively reported, we developed a comprehensive statistical analysis plan before unblinding. This trial has an enrolment target of 420 severely septic and mechanically ventilated adult patients, randomly assigned to dexmedetomidine or propofol in a 1:1 ratio. Enrolment was completed in January 2019, and the study was estimated to be completed in September 2019. The primary endpoint is days alive without delirium or coma during first 14 study days. Secondary outcomes include 28-day ventilator-free days, 90-day all-cause mortality and cognitive function at 180 days. Time frames all begin on the day of randomisation. All analyses will be conducted on an intention-to-treat basis. CONCLUSION: This study will compare the effects of two sedatives in mechanically ventilated severely septic patients. In keeping with the guidance on statistical principles for clinical trials, we have developed a comprehensive statistical analysis plan by which we will adhere, as this will avoid bias and support transparency and reproducibility. TRIAL REGISTRATION: ClinicalTrials.gov (NCT01739933).

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A nested randomised trial of the effect of tranexamic acid on intracranial haemorrhage and infarction in traumatic brain injury (CRASH-3 trial intracranial bleeding mechanistic study): Statistical analysis plan

Wellcome Open Research ◽

10.12688/wellcomeopenres.14731.1 ◽

2018 ◽

Vol 3 ◽

pp. 99 ◽

Cited By ~ 2

Author(s):

Abda Mahmood ◽

Ian Roberts ◽

Haleema Shakur-Still

Keyword(s):

Traumatic Brain Injury ◽

Statistical Analysis ◽

Brain Injury ◽

Primary Outcome ◽

Randomised Trial ◽

Statistical Analysis Plan ◽

Intracranial Bleeding ◽

Mechanistic Study ◽

Cerebral Infarcts ◽

Post Randomisation

Background: The CRASH-3 trial is a randomised trial on the effect of tranexamic acid (TXA) on death and disability in traumatic brain injury (TBI). The CRASH-3 intracranial bleeding mechanistic study (IBMS) is a randomised trial nested within the CRASH-3 trial to examine the effect of TXA on intracranial bleeding and infarction. Methods: Patients eligible for the CRASH-3 trial, with a GCS of 12 or less or intracranial bleeding on a pre-randomisation CT scan are eligible for the IBMS. The occurrence of intracranial bleeding, infarction, haemorrhagic oedematous lesions, mass effect and haemorrhage evacuation is examined within 28 days of randomisation using routinely collected brain scans. The primary outcome is the volume of intracranial bleeding in patients randomised within three hours of injury (adjusted for prognostic covariates). Secondary outcomes include progressive and new intracranial bleeding, intracranial bleeding after neurosurgery and new cerebral infarcts up to 28 days post-randomisation. All outcomes will be compared between treatment groups. Statistical analyses: The primary outcome will be analysed using absolute measures (ANCOVA) and relative measures (ratios). The same analysis will be done separately for patients who undergo haemorrhage evacuation post-randomisation. We will express the effect of TXA on new and progressive bleeding using relative risks and 95% CIs, and on cerebral infarcts using hazard ratios and 95% CIs. If any missing post-randomisation scans appear to be missing not at random, we will conduct sensitivity analyses to explore the implications. Conclusion: The IBMS will provide information on the mechanism of action of TXA in TBI. This pre-specified statistical analysis plan is a technical extension of the published protocol. Trial registration: The CRASH-3 trial was prospectively registered at the International Standard Randomised Controlled Trials registry (19 July 2011) and ClinicalTrials.gov (25 July 2011). The registries were updated with details for the IBMS on 20 December 2016.

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A multicentre, randomised trial of stabilisation with nasal high flow during neonatal endotracheal intubation (the SHINE trial): a study protocol

BMJ Open ◽

10.1136/bmjopen-2020-039230 ◽

2020 ◽

Vol 10 (10) ◽

pp. e039230

Author(s):

Kate A Hodgson ◽

Louise S Owen ◽

Camille Omar Kamlin ◽

Calum T Roberts ◽

Susan M Donath ◽

...

Keyword(s):

Endotracheal Intubation ◽

Controlled Trial ◽

Randomised Trial ◽

Upper Airway ◽

Ethics Committees ◽

High Flow ◽

Successful Intubation ◽

Peripheral Oxygen Saturation ◽

Human Research Ethics ◽

Randomised Controlled

IntroductionNeonatal endotracheal intubation is an essential but potentially destabilising procedure. With an increased focus on avoiding mechanical ventilation, particularly in preterm infants, there are fewer opportunities for clinicians to gain proficiency in this important emergency skill. Rates of successful intubation at the first attempt are relatively low, and adverse event rates are high, when compared with intubations in paediatric and adult populations. Interventions to improve operator success and patient stability during neonatal endotracheal intubations are needed. Using nasal high flow therapy extends the safe apnoea time of adults undergoing upper airway surgery and during endotracheal intubation. This technique is untested in neonates.Methods and analysisThe Stabilisation with nasal High flow during Intubation of NEonates (SHINE) trial is a multicentre, randomised controlled trial comparing the use of nasal high flow during neonatal intubation with standard care (no nasal high flow). Intubations are randomised individually, and stratified by site, use of premedications, and postmenstrual age (<28 weeks’ gestation; ≥28 weeks’ gestation). The primary outcome is the incidence of successful intubation on the first attempt without physiological instability of the infant. Physiological instability is defined as an absolute decrease in peripheral oxygen saturation >20% from preintubation baseline and/or bradycardia (<100 beats per minute).Ethics and disseminationThe SHINE trial received ethical approval from the Human Research Ethics Committees of The Royal Women’s Hospital, Melbourne, Australia and Monash Health, Melbourne, Australia. The trial is currently recruiting in these two sites. The findings of this study will be disseminated via peer-reviewed journals and presented at national and international conferences.Trial registration numberACTRN12618001498280.

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Promoting Recruitment using Information Management Efficiently (PRIME): statistical analysis plan for a stepped wedge cluster randomised trial within the REstart or STop Antithrombotics Randomised Trial (RESTART)

Trials ◽

10.1186/s13063-017-1840-8 ◽

2017 ◽

Vol 18 (1) ◽

Cited By ~ 4

Author(s):

Richard A. Parker ◽

Christopher J. Weir ◽

Amy E. Maxwell ◽

Rustam Al-Shahi Salman

Keyword(s):

Statistical Analysis ◽

Information Management ◽

Randomised Trial ◽

Statistical Analysis Plan ◽

Cluster Randomised Trial ◽

Stepped Wedge ◽

Cluster Randomised

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The REstart or STop Antithrombotics Randomised Trial (RESTART) after stroke due to intracerebral haemorrhage: statistical analysis plan for a randomised controlled trial

10.21203/rs.2.56/v2 ◽

2019 ◽

Author(s):

Rustam Al-Shahi Salman ◽

Gordon D. Murray ◽

Martin S. Dennis ◽

David E. Newby ◽

Peter A.G. Sandercock ◽

...

Keyword(s):

Statistical Analysis ◽

Intracerebral Haemorrhage ◽

Controlled Trial ◽

Randomised Trial ◽

Statistical Analysis Plan ◽

Antiplatelet Drugs ◽

Antiplatelet Drug ◽

Health Board ◽

Vascular Events ◽

Travel Fellowship

Abstract Background: For adults surviving stroke due to spontaneous (non-traumatic) intracerebral haemorrhage (ICH) who had taken an antithrombotic (i.e. anticoagulant or antiplatelet) drug for the prevention of vaso-occlusive disease before the ICH, it is unclear whether starting antiplatelet drugs modifies the risks of recurrent ICH, haemorrhagic events, vaso-occlusive events, or a composite of all serious vascular events compared to avoiding antiplatelet drugs. Methods/design: The REstart or STop Antithrombotics Randomised Trial (RESTART) is an investigator-led, parallel group, open, assessor-blind, randomised trial comparing starting versus avoiding antiplatelet drugs for adults surviving antithrombotic-associated ICH. Recruitment began on 22 May 2013 and ended on 31 May 2018. Follow-up ended on 30 November 2018. This update to the protocol describes the statistical analysis plan (version 1.7, finalised on 25 January 2019). Database lock and un-blinding occured on 29 January 2019, after which the un-blinded trial statistician conducted the final analyses according to this statistical analysis plan. Discussion: Final results of RESTART will be analysed and disseminated in May 2019. Trial registration: ISRCTN registry 71907627. Prospectively registered on 25 April 2013. The trial is funded by a British Heart Foundation special project grant (SP/12/2/29422) and a travel fellowship (FS/13/72/30531). The trial sponsor is the Academic and Clinical Central Office for Research and Development (ACCORD), which is a partnership between the University of Edinburgh and NHS Lothian Health Board.

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A nested randomised trial of the effect of tranexamic acid on intracranial haemorrhage and infarction in traumatic brain injury (CRASH-3 trial intracranial bleeding mechanistic study): Statistical analysis plan

Wellcome Open Research ◽

10.12688/wellcomeopenres.14731.3 ◽

2019 ◽

Vol 3 ◽

pp. 99

Author(s):

Abda Mahmood ◽

Ian Roberts ◽

Haleema Shakur-Still

Keyword(s):

Traumatic Brain Injury ◽

Statistical Analysis ◽

Brain Injury ◽

Primary Outcome ◽

Randomised Trial ◽

Statistical Analysis Plan ◽

Intracranial Bleeding ◽

Mechanistic Study ◽

Cerebral Infarcts ◽

Post Randomisation

Background: The CRASH-3 trial is a randomised trial on the effect of tranexamic acid (TXA) versus placebo on death and disability in traumatic brain injury (TBI). The CRASH-3 intracranial bleeding mechanistic study (IBMS) is a randomised trial nested within the CRASH-3 trial to examine the effect of TXA versus placebo on intracranial bleeding and infarction. Methods: Patients eligible for the CRASH-3 trial, with a GCS of 12 or less or intracranial bleeding on a pre-randomisation CT scan are eligible for the IBMS. The occurrence of intracranial bleeding, infarction, haemorrhagic oedematous lesions, mass effect and haemorrhage evacuation is examined within 28 days of randomisation using routinely collected brain scans. The primary outcome is the volume of intra-parenchymal bleeding in patients randomised within three hours of injury (adjusted for prognostic covariates). Secondary outcomes include a composite “poor” outcome, progressive and new intracranial bleeding, intracranial bleeding after neurosurgery and cerebral infarcts seen up to 28 days post-randomisation. All outcomes will be compared between treatment groups. Statistical analyses: The primary outcome will be analysed using a covariate adjusted linear mixed model. The same analysis will be done separately for patients who undergo haemorrhage evacuation post-randomisation. We will express the effect of TXA on the composite outcome, new and progressive bleeding using relative risks and 95% CIs, and on cerebral infarcts using hazard ratios and 95% CIs. We will conduct sensitivity analyses assuming missing data are MCAR or MNAR. Conclusion: The IBMS will provide information on the mechanism of action of TXA in TBI. This pre-specified statistical analysis plan is a technical extension of the published protocol. Trial registration: The CRASH-3 trial was prospectively registered at the International Standard Randomised Controlled Trials registry (19 July 2011) and ClinicalTrials.gov (25 July 2011). The registries were updated with details for the IBMS on 20 December 2016.

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