https://www.pure.ed.ac.uk/ws/files/64211283/1_s2.0_S014067361831033X_main.pdf

Tranexamic acid for hyperacute primary IntraCerebral Haemorrhage (TICH-2): an international randomised, placebo-controlled, phase 3 superiority trial

Background and Purpose The goal of the present study was to prospectively determine how frequently early growth of intracerebral hemorrhage occurs and whether this early growth is related to early neurological deterioration. Methods We performed a prospective observational study of patients with intracerebral hemorrhage within 3 hours of onset. Patients had a neurological evaluation and CT scan performed at baseline, 1 hour after baseline, and 20 hours after baseline. Results Substantial growth in the volume of parenchymal hemorrhage occurred in 26% of the 103 study patients between the baseline and 1-hour CT scans. An additional 12% of patients had substantial growth between the 1- and 20-hour CT scans. Hemorrhage growth between the baseline and 1-hour CT scans was significantly associated with clinical deterioration, as measured by the change between the baseline and 1-hour Glasgow Coma Scale and National Institutes of Health Stroke Scale scores. No baseline clinical or CT prediction of hemorrhage growt...

Early Hemorrhage Growth in Patients With Intracerebral Hemorrhage

https://archive-ouverte.unige.ch/unige:125919/ATTACHMENT01

Effect of treatment delay on the effectiveness and safety of antifibrinolytics in acute severe haemorrhage: a meta-analysis of individual patient-level data from 40 138 bleeding patients

Background and Purpose Standard radiographic criteria for hematoma enlargement have not been established. We undertook this investigation to assess the incidence and time course of hematoma growth using objective cutoff values. Methods We reviewed the clinical records of 204 patients with spontaneous intracerebral hemorrhage treated nonsurgically who underwent initial computed tomography (CT) within 48 hours and repeat CT within 120 hours of the onset of symptoms. The consensus of five observers reading the CT films was considered the “gold standard” for hematoma enlargement. The discriminant values of the difference (V2−V1) or the ratio (V2/V1) of the hematoma volume on the initial (V1) and second (V2) CT scans were determined by use of receiver operating characteristic curves. We chose the cutpoint that had the highest sensitivity and specificity for identifying hematoma expansion. Results The cutpoint for hematoma enlargement was determined as V2−V1=12.5 cm3 or V2/V1=1.4 (sensitivity=94.4%, specificity...

Enlargement of Spontaneous Intracerebral Hemorrhage

Few things are duller Than feeling unspecifically off-color, Yes, you feel like the fulfillment of a dismal prophecy, And you don't feel either exercisey or officey... Ogden Nash At any time of year, when a person ails vaguely in the head or the belly, or aches for no apparent reason and feels somewhat feverish, and mentions his symptoms to a friend or an acquaintance, the afflicted one is likely to hear, "Oh yes, there's a lot of that going around just now." The "that" remains as undefined as the sufferer's symptoms are ill-defined. The statement usually is made convincingly and consolingly, in an effort to reassure or with belief in the adage, "Misery loves company." Often, "that," offered as the sole diagnosis, does reassure and works wonders therapeutically when swallowed with a couple of aspirin tablets or the patient's favorite brand of sedative. Other times, "that" is not enough. For

Diagnosis of That

Post-stroke dysphagia (a difficulty in swallowing after a stroke) is a common and expensive complication of acute stroke and is associated with increased mortality, morbidity, and institutionalization due in part to aspiration, pneumonia, and malnutrition. Although most patients recover swallowing spontaneously, a significant minority still have dysphagia at six months. Although multiple advances have been made in the hyperacute treatment of stroke and secondary prevention, the management of dysphagia post-stroke remains a neglected area of research, and its optimal management, including diagnosis, investigation and treatment, have still to be defined.

https://journals.sagepub.com/doi/pdf/10.1177/1747493016639057

Post-stroke dysphagia: A review and design considerations for future trials:

Rationale: Outcome after intracerebral hemorrhage remains poor. Tranexamic acid is easy to administer, readily available, inexpensive, and effective in other hemorrhagic conditions.

Aim: This randomized trial aims to test the hypothesis that intravenous tranexamic acid given within 8 h of spontaneous intracerebral hemorrhage reduces death or dependency.

Design: Phase III prospective double-blind randomized placebo-controlled trial. Participants within 8 h of spontaneous intracerebral hemorrhage are randomized to receive either intravenous tranexamic acid 1 g 10 min bolus followed by 1 g 8 h infusion, or placebo.

Sample size estimates: A trial of 2000 participants (300 from start-up phase and 1700 from main phase) will have 90% power to detect an ordinal shift of the modified Rankin Scale with odds ratio 0.79.

Study outcomes: The primary outcome is death or dependency measured by ordinal shift analysis of the 7 level mRS at day 90. Secondary outcomes are neurological impairment at day 7 and disability, quality of life, cognition, and mood at day 90. Safety outcomes are death, serious adverse events, thromboembolic events, and seizures. Cost outcomes are length of stay in hospital, readmission, and institutionalization.

Discussion: This pragmatic trial is assessing efficacy of tranexamic acid after spontaneous intracerebral hemorrhage. Recruitment started in 2013; as of 15th January 2016 1355 participants have been enrolled, from 95 centers in seven countries. Recruitment is due to end in 2017. TICH-2 Trial is registered as ISRCTN93732214.

/pdf/intravenous-tranexamic-acid-for-hyperacute-primary-16h93ox0c1.pdf

Intravenous tranexamic acid for hyperacute primary intracerebral hemorrhage: Protocol for a randomized, placebo-controlled trial.

Rationale: Antiplatelet agents such as aspirin, clopidogrel and dipyridamole are effective in reducing the risk of recurrence after a stroke. Importantly, the risk of recurrence is highest immediately after the index event while antiplatelets cause bleeding.
Aims and/or hypothesis: The ‘Triple Antiplatelets for Reducing Dependency after Ischaemic Stroke’ (TARDIS) trial is testing whether short-term intensive antiplatelet therapy is safe and effective in reducing the early risk of recurrence as compared with standard guideline-based therapy.
Design: TARDIS is an international multi-center prospective randomized open-label blinded–end-point trial, with funding from the UK Health Technology Assessment program. Patients with acute ischemic stroke or transient ischemic attack are randomized within 48 h to intensive/triple antiplatelet therapy or guideline antiplatelets taken for one-month. Patients or relatives give written informed (proxy) consent and all sites have research ethics approval. Analyses will be done by intention-to-treat.
Study Outcome: The primary outcome is shift in stroke recurrent events and their severity, assessed using the modified Rankin Scale, at three-months.
Discussion: This paper and attachment describe the trial’s statistical analysis plan, as developed from the protocol during recruitment and prior to unblinding of data. The statistical analysis plan contains design and methods for analyses, and unpopulated tables and figures for the primary and baseline publications. The data from the trial will provide the first large-scale randomized evidence for the use of intensive antiplatelet therapy for preventing recurrence after acute stroke and transient ischemic attack.

/pdf/statistical-analysis-plan-for-the-triple-antiplatelets-for-524uwdsvvp.pdf

Katie Robson

Papers

Post-stroke dysphagia: A review and design considerations for future trials:

Intravenous tranexamic acid for hyperacute primary intracerebral hemorrhage: Protocol for a randomized, placebo-controlled trial.

Statistical analysis plan for the ‘Triple Antiplatelets for Reducing Dependency after Ischaemic Stroke’ (TARDIS) trial