Determining the Feasibility of Ambulance-Based Randomised Controlled Trials in Patients with Ultra-Acute Stroke: Study Protocol for the "Rapid Intervention with GTN in Hypertensive Stroke Trial" (RIGHT, ISRCTN66434824).
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SUBMITTER: Ankolekar S
PROVIDER: S-EPMC3480012 | biostudies-literature | 2012
REPOSITORIES: biostudies-literature
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Determining the Feasibility of Ambulance-Based Randomised Controlled Trials in Patients with Ultra-Acute Stroke: Study Protocol for the "Rapid Intervention with GTN in Hypertensive Stroke Trial" (RIGHT, ISRCTN66434824).
Ankolekar Sandeep S Sare Gillian G Geeganage Chamila C Fuller Michael M Stokes Lynn L Sprigg Nikola N Parry Ruth R Siriwardena A Niroshan AN Bath Philip M W PM
Stroke research and treatment 20121016
Background. Time from acute stroke to enrolment in clinical trials needs to be reduced to improve the chances of finding effective treatments. No completed randomised controlled trials of ambulance-based treatment for acute stroke have been reported in the UK, and the practicalities of recruiting, consenting, and treating patients are unknown. Methods. RIGHT is an ambulance based, single-blind, randomised controlled trial with blinded-outcome assessment. The trial will assess feasibility of usin ...[more]
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Project description:BackgroundHigh blood pressure is common in acute stroke and is a predictor of poor outcome; however, large trials of lowering blood pressure have given variable results, and the management of high blood pressure in ultra-acute stroke remains unclear. We investigated whether transdermal glyceryl trinitrate (GTN; also known as nitroglycerin), a nitric oxide donor, might improve outcome when administered very early after stroke onset.MethodsWe did a multicentre, paramedic-delivered, ambulance-based, prospective, randomised, sham-controlled, blinded-endpoint, phase 3 trial in adults with presumed stroke within 4 h of onset, face-arm-speech-time score of 2 or 3, and systolic blood pressure 120 mm Hg or higher. Participants were randomly assigned (1:1) to receive transdermal GTN (5 mg once daily for 4 days; the GTN group) or a similar sham dressing (the sham group) in UK-based ambulances by paramedics, with treatment continued in hospital. Paramedics were unmasked to treatment, whereas participants were masked. The primary outcome was the 7-level modified Rankin Scale (mRS; a measure of functional outcome) at 90 days, assessed by central telephone follow-up with masking to treatment. Analysis was hierarchical, first in participants with a confirmed stroke or transient ischaemic attack (cohort 1), and then in all participants who were randomly assigned (intention to treat, cohort 2) according to the statistical analysis plan. This trial is registered with ISRCTN, number ISRCTN26986053.FindingsBetween Oct 22, 2015, and May 23, 2018, 516 paramedics from eight UK ambulance services recruited 1149 participants (n=568 in the GTN group, n=581 in the sham group). The median time to randomisation was 71 min (IQR 45-116). 597 (52%) patients had ischaemic stroke, 145 (13%) had intracerebral haemorrhage, 109 (9%) had transient ischaemic attack, and 297 (26%) had a non-stroke mimic at the final diagnosis of the index event. In the GTN group, participants' systolic blood pressure was lowered by 5·8 mm Hg compared with the sham group (p<0·0001), and diastolic blood pressure was lowered by 2·6 mm Hg (p=0·0026) at hospital admission. We found no difference in mRS between the groups in participants with a final diagnosis of stroke or transient ischaemic stroke (cohort 1): 3 (IQR 2-5; n=420) in the GTN group versus 3 (2-5; n=408) in the sham group, adjusted common odds ratio for poor outcome 1·25 (95% CI 0·97-1·60; p=0·083); we also found no difference in mRS between all patients (cohort 2: 3 [2-5]; n=544, in the GTN group vs 3 [2-5]; n=558, in the sham group; 1·04 [0·84-1·29]; p=0·69). We found no difference in secondary outcomes, death (treatment-related deaths: 36 in the GTN group vs 23 in the sham group [p=0·091]), or serious adverse events (188 in the GTN group vs 170 in the sham group [p=0·16]) between treatment groups.InterpretationPrehospital treatment with transdermal GTN does not seem to improve functional outcome in patients with presumed stroke. It is feasible for UK paramedics to obtain consent and treat patients with stroke in the ultra-acute prehospital setting.FundingBritish Heart Foundation.
| S-EPMC6497986 | biostudies-literature
Project description:BackgroundPrehospital stroke trials will inevitably recruit patients with non-stroke conditions, so called stroke mimics. We undertook a pre-specified analysis to determine outcomes in patients with mimics in the second Rapid Intervention with Glyceryl trinitrate in Hypertensive stroke Trial (RIGHT-2).MethodsRIGHT-2 was a prospective, multicentre, paramedic-delivered, ambulance-based, sham-controlled, participant-and outcome-blinded, randomised-controlled trial of transdermal glyceryl trinitrate (GTN) in adults with ultra-acute presumed stroke in the UK. Final diagnosis (intracerebral haemorrhage, ischaemic stroke, transient ischaemic attack, mimic) was determined by the hospital investigator. This pre-specified subgroup analysis assessed the safety and efficacy of transdermal GTN (5 mg daily for 4 days) versus sham patch among stroke mimic patients. The primary outcome was the 7-level modified Rankin Scale (mRS) at 90 days.ResultsAmong 1149 participants in RIGHT-2, 297 (26%) had a final diagnosis of mimic (GTN 134, sham 163). The mimic group were younger, mean age 67 (SD: 18) vs 75 (SD: 13) years, had a longer interval from symptom onset to randomisation, median 75 [95% CI: 47,126] vs 70 [95% CI:45,108] minutes, less atrial fibrillation and a lower systolic blood pressure and Face-Arm-Speech-Time tool score than the stroke group. The three most common mimic diagnoses were seizure (17%), migraine or primary headache disorder (17%) and functional disorders (14%). At 90 days, the GTN group had a better mRS score as compared to the sham group (adjusted common odds ratio 0.54; 95% confidence intervals 0.34, 0.85; p = 0.008), a difference that persisted at 365 days. There was no difference in the proportion of patients who died in hospital, were discharged to a residential care facility, or suffered a serious adverse event.ConclusionsOne-quarter of patients suspected by paramedics to have an ultra-acute stroke were subsequently diagnosed with a non-stroke condition. GTN was associated with unexplained improved functional outcome observed at 90 days and one year, a finding that may represent an undetected baseline imbalance, chance, or real efficacy. GTN was not associated with harm.Trial registrationThis trial is registered with International Standard Randomised Controlled Trials Number ISRCTN 26986053 .
| S-EPMC8744321 | biostudies-literature
Project description:Background and purposePrehospital evaluation using telemedicine may accelerate acute stroke treatment with tissue-type plasminogen activator. We explored the feasibility and reliability of using telemedicine in the field and ambulance to help evaluate acute stroke patients.MethodsTen unique, scripted stroke scenarios, each conducted 4 times, were portrayed by trained actors retrieved and transported by Houston Fire Department emergency medical technicians to our stroke center. The vascular neurologists performed remote assessments in real time, obtaining clinical data points and National Institutes of Health (NIH) Stroke Scale, using the In-Touch RP-Xpress telemedicine device. Each scripted scenario was recorded for a subsequent evaluation by a second blinded vascular neurologist. Study feasibility was defined by the ability to conduct 80% of the sessions without major technological limitations. Reliability of video interpretation was defined by a 90% concordance between the data derived during the real-time sessions and those from the scripted scenarios.ResultsIn 34 of 40 (85%) scenarios, the teleconsultation was conducted without major technical complication. The absolute agreement for intraclass correlation was 0.997 (95% confidence interval, 0.992-0.999) for the NIH Stroke Scale obtained during the real-time sessions and 0.993 (95% confidence interval, 0.975-0.999) for the recorded sessions. Inter-rater agreement using κ-statistics showed that for live-raters, 10 of 15 items on the NIH Stroke Scale showed excellent agreement and 5 of 15 showed moderate agreement. Matching of real-time assessments occurred for 88% (30/34) of NIH Stroke Scale scores by ±2 points and 96% of the clinical information.ConclusionsMobile telemedicine is reliable and feasible in assessing actors simulating acute stroke in the prehospital setting.
| S-EPMC4116449 | biostudies-literature
Project description:Telemedicine is currently mainly applied as an in-hospital service, but this technology also holds potential to improve emergency care in the prehospital arena. We report on the safety, feasibility and reliability of in-ambulance teleconsultation using a telemedicine system of the third generation.A routine ambulance was equipped with a system for real-time bidirectional audio-video communication, automated transmission of vital parameters, glycemia and electronic patient identification. All patients ( ? 18 years) transported during emergency missions by a Prehospital Intervention Team of the Universitair Ziekenhuis Brussel were eligible for inclusion. To guarantee mobility and to facilitate 24/7 availability, the teleconsultants used lightweight laptop computers to access a dedicated telemedicine platform, which also provided functionalities for neurological assessment, electronic reporting and prehospital notification of the in-hospital team. Key registrations included any safety issue, mobile connectivity, communication of patient information, audiovisual quality, user-friendliness and accuracy of the prehospital diagnosis.Prehospital teleconsultation was obtained in 41 out of 43 cases (95.3%). The success rates for communication of blood pressure, heart rate, blood oxygen saturation, glycemia, and electronic patient identification were 78.7%, 84.8%, 80.6%, 64.0%, and 84.2%. A preliminary prehospital diagnosis was formulated in 90.2%, with satisfactory agreement with final in-hospital diagnoses. Communication of a prehospital report to the in-hospital team was successful in 94.7% and prenotification of the in-hospital team via SMS in 90.2%. Failures resulted mainly from limited mobile connectivity and to a lesser extent from software, hardware or human error. The user acceptance was high.Ambulance-based telemedicine of the third generation is safe, feasible and reliable but further research and development, especially with regard to high speed broadband access, is needed before this approach can be implemented in daily practice.
| S-EPMC4208882 | biostudies-literature
Project description:The Consolidated Standards of Reporting Trials (CONSORT) statement is a guideline designed to improve the transparency and quality of the reporting of randomised controlled trials (RCTs). In this article we present an extension to that statement for randomised pilot and feasibility trials conducted in advance of a future definitive RCT. The checklist applies to any randomised study in which a future definitive RCT, or part of it, is conducted on a smaller scale, regardless of its design (eg, cluster, factorial, crossover) or the terms used by authors to describe the study (eg, pilot, feasibility, trial, study). The extension does not directly apply to internal pilot studies built into the design of a main trial, non-randomised pilot and feasibility studies, or phase II studies, but these studies all have some similarities to randomised pilot and feasibility studies and so many of the principles might also apply. The development of the extension was motivated by the growing number of studies described as feasibility or pilot studies and by research that has identified weaknesses in their reporting and conduct. We followed recommended good practice to develop the extension, including carrying out a Delphi survey, holding a consensus meeting and research team meetings, and piloting the checklist. The aims and objectives of pilot and feasibility randomised studies differ from those of other randomised trials. Consequently, although much of the information to be reported in these trials is similar to those in randomised controlled trials (RCTs) assessing effectiveness and efficacy, there are some key differences in the type of information and in the appropriate interpretation of standard CONSORT reporting items. We have retained some of the original CONSORT statement items, but most have been adapted, some removed, and new items added. The new items cover how participants were identified and consent obtained; if applicable, the prespecified criteria used to judge whether or how to proceed with a future definitive RCT; if relevant, other important unintended consequences; implications for progression from pilot to future definitive RCT, including any proposed amendments; and ethical approval or approval by a research review committee confirmed with a reference number. This article includes the 26 item checklist, a separate checklist for the abstract, a template for a CONSORT flowchart for these studies, and an explanation of the changes made and supporting examples. We believe that routine use of this proposed extension to the CONSORT statement will result in improvements in the reporting of pilot trials. Editor's note: In order to encourage its wide dissemination this article is freely accessible on the BMJ and Pilot and Feasibility Studies journal websites.
| S-EPMC5154046 | biostudies-literature
Project description:BACKGROUND:Some studies have suggested that transdermal administration of glyceryl trinitrate (GTN; nitroglycerin) in the first few hours after symptom onset increases the chance of a favourable outcome after ischaemic stroke or intracerebral haemorrhage, possibly through an increase in intracranial collateral blood flow and a reduction in blood pressure. The Multicentre Randomised trial of Acute Stroke treatment in the Ambulance with a nitroglycerin Patch (MR ASAP) aims to assess the effect of transdermal GTN, started within 3 h after stroke onset in the prehospital setting, on functional outcome at 90?days in patients with acute ischaemic stroke or intracerebral haemorrhage. METHODS:MR ASAP is a phase III, multicentre, randomised, open-label clinical trial with a blinded outcome assessment. A total of 1400 adult patients with suspected stroke and a systolic blood pressure???140?mmHg will be randomised to transdermal GTN (5?mg/day), administered as a transdermal patch by paramedics in the prehospital setting within 3?h of stroke onset and continued for 24?h or to standard care. The primary outcome is the score on the modified Rankin Scale (mRS) at 90?days, analysed with ordinal logistic regression. Secondary outcomes include blood pressure and collateral circulation at hospital admission, neurological deficit measured with the National Institutes of Health Stroke Scale at 24?h, and mortality and poor outcome (mRS score 3 to 6) at 90?days. This trial will be conducted in the Netherlands and will use a deferred consent procedure. The trial is part of the Collaboration for New Treatments of Acute Stroke (CONTRAST) programme. DISCUSSION:MR ASAP will assess whether very early administration of GTN improves outcome after stroke in a setting where rates of intravenous thrombolysis and endovascular treatment for acute ischaemic stroke are high. The deferred consent procedure facilitates prompt GTN treatment and will prevent delay to revascularisation therapies. If early transdermal GTN treatment proves to be effective, this low-cost treatment can be readily implemented into daily clinical practice. TRIAL REGISTRATION:ISRCTN Registry, ISRCTN99503308 . Registered on 2 January 2018.
| S-EPMC6595565 | biostudies-literature
Project description:Background:The Regaining Confidence after Stroke (RCAS) course was designed to facilitate adjustment for people with stroke discharged from rehabilitation. The aim of the trial was to evaluate the feasibility of conducting a randomised trial to compare a RCAS course with usual care. The rates feasibility of screening and recruitment, rates of consent and retention, acceptability of outcome measures and the acceptability and fidelity of the intervention were evaluated. Methods:Participants with stroke were recruited from hospital databases and community services and randomly assigned to the Regaining Confidence after Stroke (RCAS) course or usual care. The course comprised 11 weekly 2-h sessions with six-eight participants, delivered by two rehabilitation assistants. Carers were invited to attend three of the sessions. Sessions were video recorded. A six-item checklist was developed from the manual content. Each item was rated as met, partially met or not met. Fidelity was assumed if >?75% of the criteria were met. Outcomes were assessed three and six months after randomisation. Semi-structured interviews were conducted using open-ended questions to assess the acceptability of the intervention. Results:Of 47 participants (mean age 66.9?years [SD 14.9]; 26 men), 22 were randomly allocated to the intervention and 25 to usual care. Participants attended a mean of 8.2 [SD 2.6] out of 11 sessions. Fidelity outcomes suggested that the content corresponded to the manual but further training of the therapist was needed. Interview findings indicated the intervention was acceptable and considered beneficial. At three months, 35 (78%) participants returned questionnaires and 30 (67%) at six months, but only 38(42%) were fully completed. Conclusion:The results support the feasibility of conducting a randomised trial to evaluate the effectiveness of a RCAS course compared to usual care. Trial registration:ISRCTN 36330958.
| S-EPMC6657106 | biostudies-literature
Project description:RationaleGlyceryl trinitrate, a nitric oxide donor, is a candidate treatment for acute stroke; it lowers blood pressure, does not alter cerebral blood flow or platelet function and is neuroprotective in experimental stroke. The ongoing rapid intervention with glyceryl trinitrate in hypertensive stroke trial-2 trial aims to assess the safety and efficacy of paramedic-delivered glyceryl trinitrate in patients with ultra-acute stroke.Aims and design: The rapid intervention with glyceryl trinitrate in hypertensive stroke trial-2 trial is a multicentre UK-based prospective randomised sham-controlled outcome-blinded parallel-group trial in patients with presumed stroke who present to the ambulance service following a 999 emergency call. The primary outcome is the modified Rankin scale measured by central telephone follow-up at 90 days.ResultsThis paper describes the statistical analysis plan for the rapid intervention with glyceryl trinitrate in hypertensive stroke trial-2 trial and was developed prior to unblinding to treatment allocation. The statistical analysis plan includes details of methods for analyses and unpopulated tables and figures to be included in the primary and other secondary publications.DiscussionStatistical analysis plan details what analyses will be done prior to unblinding to treatment allocation to avoid bias in the findings. Rapid intervention with glyceryl trinitrate in hypertensive stroke trial-2 trial will determine whether glyceryl trinitrate administered ultra-acutely can improve outcome after stroke. The rapid intervention with glyceryl trinitrate in hypertensive stroke trial-2 trial is registered as ISRCTN26986053.
| S-EPMC6460414 | biostudies-literature
Project description:BackgroundLess than 50% of stroke patients in Norway reach hospital within 4 h of symptom onset. Early prehospital identification of stroke and triage to the right level of care may result in more patients receiving acute treatment. Quality of communication between paramedics and the stroke centre directly affects prehospital on-scene time, emphasising this as a key factor to reduce prehospital delay. Prehospital stroke scales are developed for quick and easy identification of stroke, but have poor sensitivity and specificity compared to an in-hospital assessment with the National Institutes of Health Stroke Scale (NIHSS). The aim of the Paramedic Norwegian Acute Stroke Prehospital Project (ParaNASPP) is to assess whether a structured learning program, prehospital NIHSS and a mobile application facilitating communication with the stroke physician may improve triage of acute stroke patients.MethodsA stepped wedge cluster randomised controlled intervention design will be used in this trial in Oslo, Norway. Paramedics at five ambulance stations will enrol adult patients with suspected stroke within 24 h of symptom onset. All paramedics will begin in a control phase with standard procedures. Through an e-learning program and practical training, a random and sequential switch to the intervention phase takes place. A mobile application for NIHSS scoring, including vital patient information for treatment decisions, transferring data from paramedics to the on-call stroke physician at the Stroke Unit at Oslo University Hospital, will be provided for the intervention. The primary outcome measure is positive predictive value (PPV) for prehospital identification of patients with acute stroke defined as the proportion of patients accepted for stroke evaluation and discharged with a final stroke diagnosis. One thousand three hundred patients provide a 50% surplus to the 808 patients needed for 80% power to detect a 10% increase in PPV.DiscussionStructured and digital communication using a common scale like NIHSS may result in increased probability for better identification of stroke patients and less stroke mimics delivered to a stroke team for acute diagnostics and treatment in our population.Trial registrationClinicalTrials.gov NCT04137874 . Registered on October 24, 2019.
| S-EPMC8814805 | biostudies-literature
Project description:BACKGROUND:The value of cardiac rehabilitation (CR) after a transient ischaemic attack (TIA) or minor stroke is untested despite these conditions sharing similar pathology and risk factors to coronary heart disease. We aimed to evaluate the feasibility of conducting a trial of an adapted home-based CR programme, 'The Healthy Brain Rehabilitation Manual', for patients following a TIA/minor stroke, participants' views on the intervention and, to identify the behaviour change techniques (BCTs) used. METHODS:Clinicians were asked to identify patients attending the Ulster Hospital, Belfast within 4 weeks of a first TIA or minor stroke. Those who agreed to participate underwent assessments of physical fitness, cardiovascular risk, quality of life and mental health, before random allocation to: Group (1) standard/usual care; (2) rehabilitation manual or (3) manual plus pedometer. All participants received telephone support at 1 and 4 weeks, reassessment at 6 weeks and an invitation to a focus group exploring views regarding the study. Two trained review authors independently assessed the manual to identify the BCTs used. RESULTS:Twenty-eight patients were invited to participate, with 15 (10 men, 5 women; 9 TIA, 6 minor stroke; mean age 69 years) consenting and completing the study. Mean time to enrolment from the TIA/stroke was 20.5 days. Participants completed all assessment measures except VO2max testing, which all declined. The manual and telephone contact were viewed positively, as credible sources of advice. Pedometers were valued highly, particularly for goal-setting. Overall, 36 individual BCTs were used, the commonest being centred around setting goals and planning as well as social support. CONCLUSION:Recruitment and retention rates suggest that a trial to evaluate the effectiveness of a novel home-based CR programme, implemented within 4 weeks of a first TIA/minor stroke is feasible. The commonest BCTs used within the manual revolve around goals, planning and social support, in keeping with UK national guidelines. The findings from this feasibility work have been used to further refine the next stage of the intervention's development, a pilot study. TRIAL REGISTRATION:ClinicalTrials.gov Identifier: NCT02712385 . This study was registered prospectively on 18/03/2016.
| S-EPMC5727948 | biostudies-literature