scholarly journals Prehospital Transdermal Glyceryl Trinitrate for Ultra-Acute Intracerebral Hemorrhage

Stroke ◽  
2019 ◽  
Vol 50 (11) ◽  
pp. 3064-3071 ◽  
Author(s):  
Philip M. Bath ◽  
Lisa J. Woodhouse ◽  
Kailash Krishnan ◽  
Jason P. Appleton ◽  
Craig S. Anderson ◽  
...  
Keyword(s):  
Intracerebral Hemorrhage ◽  
Glyceryl Trinitrate ◽  
Global Analysis ◽  
Mass Effect ◽  
Modified Rankin Scale ◽  
Unique Identifier ◽  
Serious Adverse Events ◽  
Clinical Trial Registration ◽  
Prehospital Treatment ◽  
Acute Intracerebral Hemorrhage

Background and Purpose— Pilot trials suggest that glyceryl trinitrate (GTN; nitroglycerin) may improve outcome when administered early after stroke onset. Methods— We undertook a multicentre, paramedic-delivered, ambulance-based, prospective randomized, sham-controlled, blinded-end point trial in adults with presumed stroke within 4 hours of ictus. Participants received transdermal GTN (5 mg) or a sham dressing (1:1) in the ambulance and then daily for three days in hospital. The primary outcome was the 7-level modified Rankin Scale at 90 days assessed by central telephone treatment-blinded follow-up. This prespecified subgroup analysis focuses on participants with an intracerebral hemorrhage as their index event. Analyses are intention-to-treat. Results— Of 1149 participants with presumed stroke, 145 (13%; GTN, 74; sham, 71) had an intracerebral hemorrhage: time from onset to randomization median, 74 minutes (interquartile range, 45–110). By admission to hospital, blood pressure tended to be lower with GTN as compared with sham: mean, 4.4/3.5 mm Hg. The modified Rankin Scale score at 90 days was nonsignificantly higher in the GTN group: adjusted common odds ratio for poor outcome, 1.87 (95% CI, 0.98–3.57). A prespecified global analysis of 5 clinical outcomes (dependency, disability, cognition, quality of life, and mood) was worse with GTN; Mann-Whitney difference, 0.18 (95% CI, 0.01–0.35; Wei-Lachin test). GTN was associated with larger hematoma and growth, and more mass effect and midline shift on neuroimaging, and altered use of hospital resources. Death in hospital but not at day 90 was increased with GTN. There were no significant between-group differences in serious adverse events. Conclusions— Prehospital treatment with GTN worsened outcomes in patients with intracerebral hemorrhage. Since these results could relate to the play of chance, confounding, or a true effect of GTN, further randomized evidence on the use of vasodilators in ultra-acute intracerebral hemorrhage is needed. Clinical Trial Registration— URL: http://www.controlled-trials.com . Unique identifier: ISRCTN26986053.

Statistical analysis plan for pooled individual patient data from two landmark randomized trials (INTERACT2 and ATACH-II) of intensive blood pressure lowering treatment in acute intracerebral hemorrhage

2018 ◽  
Vol 14 (3) ◽  
pp. 321-328 ◽  
Author(s):  
Tom J Moullaali ◽  
Xia Wang ◽  
Renee' H Martin ◽  
Virginia B Shipes ◽  
Adnan I Qureshi ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Intracerebral Hemorrhage ◽  
Systolic Blood Pressure ◽  
Functional Recovery ◽  
Modified Rankin Scale ◽  
Blood Pressure Lowering ◽  
Safety Outcomes ◽  
Pressure Lowering ◽  
Acute Intracerebral Hemorrhage ◽  
Intensive Blood Pressure

Background There is persistent uncertainty over the benefits of early intensive systolic blood pressure lowering in acute intracerebral hemorrhage. In particular, over the timing, target, and intensity of systolic blood pressure control for optimum balance of potential benefits (i.e. functional recovery) and risks (e.g. cerebral ischemia). Aims To determine associations of early systolic blood pressure lowering parameters and outcomes in patients with a hypertensive response in acute intracerebral hemorrhage. Secondary aims are to identify the modifying effects of patient characteristics and an optimal systolic blood pressure lowering profile. Methods Individual participant data pooled analyses of two large, multicenter, randomized controlled trials specifically undertaken to assess the effects of early intensive systolic blood pressure reduction on clinical outcomes in acute intracerebral hemorrhage: the Intensive Blood Pressure in Acute Intracerebral Hemorrhage Trial (INTERACT2) and the Antihypertensive Treatment of Acute Cerebral Hemorrhage (ATACH-II) trial. Combined data will include baseline characteristics; systolic blood pressure in the first 24 h; process of care measures; and key efficacy and safety outcomes. Outcomes The primary outcome is functional recovery, defined by an ordinal distribution of scores on the modified Rankin scale at 90 days post-randomization. Secondary outcomes include various standard binary cut-points for disability-free survival on the modified Rankin scale, and health-related quality of life at 90 days. Safety outcomes include symptomatic hypotension requiring corrective therapy and early neurologic deterioration within 24 h, and deaths, any serious adverse event, and cardiac and renal serious adverse events, within 90 days. Discussion A pre-determined protocol was developed to facilitate successful collaboration and reduce analysis bias arising from prior knowledge of the findings. Clinical trial registration URL: http://www.clinicaltrials.gov . Unique identifiers for INTERACT2 (NCT00716079) and ATACH-II (NCT01176565).

scholarly journals Effect of Heart Rate Variabilities on Outcome After Acute Intracerebral Hemorrhage: A Post Hoc Analysis of ATACH‐2

2021 ◽  
Author(s):  
Kaori Miwa ◽  
Masatoshi Koga ◽  
Mayumi Fukuda‐Doi ◽  
Haruko Yamamoto ◽  
Kanata Tanaka ◽  
...  
Keyword(s):  
Heart Rate ◽  
Intracerebral Hemorrhage ◽  
Unfavorable Outcome ◽  
Hematoma Expansion ◽  
Unique Identifier ◽  
Therapeutic Implications ◽  
Acute Intracerebral Hemorrhage ◽  
Average Real Variability ◽  
Deviation Coefficient ◽  
Post Hoc

Background To explore how the clinical impact of heart rate (HR) and heart rate variabilities (HRV) during the initial 24 hours after acute intracerebral hemorrhage (ICH) contribute to worse clinical outcomes. Methods and Results In the ATACH‐2 (Antihypertensive Treatment in Intracerebral Hemorrhage 2) trial, the HR was recorded for every 15 minutes from baseline to 1 hour and hourly during the initial 24 hours post‐randomization. We calculated the following: mean, standard deviation, coefficient of variation, successive variation, and average real variability (ARV). Outcomes were hematoma expansion at 24 hours and unfavorable functional outcome, defined as modified Rankin Scale score 4 to 6 at 90 days. Of the 1000 subjects in ATACH‐2, 994 with available HR data were included in the analyses. Overall, 262 experienced hematoma expansion, and 362 had unfavorable outcomes. Increased mean HR was linearly associated with unfavorable outcome (per 10 bpm increase adjusted odds ratio [aOR], 1.31, 95% CI, 1.14–1.50) but not with hematoma expansion, while HR‐ARV was associated with hematoma expansion (aOR, 1.06, 95% CI, 1.01–1.12) and unfavorable outcome (aOR, 1.07, 95% CI, 1.01–1.3). Every 10‐bpm increase in mean HR increased the probability of unfavorable outcome by 4.3%, while every 1 increase in HR‐ARV increased the probability of hematoma expansion by 1.1% and unfavorable outcome by 1.3%. Conclusions Increased mean HR and HR‐ARV within the initial 24 hours were independently associated with unfavorable outcome in acute ICH. Moreover, HR‐ARV was associated with hematoma expansion at 24 hours. This may have future therapeutic implications to accommodate HR and HRV in acute ICH. Registration URL: https://www.clinicaltrials.gov ; Unique Identifier: NCT01176565.

scholarly journals Validation of the simplified modified Rankin scale for stroke trials: Experience from the ENCHANTED alteplase-dose arm

2020 ◽  
pp. 174749301989785 ◽  
Author(s):  
Xiaoying Chen ◽  
Jingwei Li ◽  
Craig S Anderson ◽  
Richard I Lindley ◽  
Maree L Hackett ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Logistic Regression ◽  
Outcome Measurement ◽  
Demographic Data ◽  
Weighted Kappa ◽  
Alternative Measure ◽  
Modified Rankin Scale ◽  
Unique Identifier ◽  
Clinical Trial Registration ◽  
Quality Of Life Scale

Background and aims The structured, simplified modified Rankin scale questionnaire (smRSq) may increase reliability over the interrogative approach to scoring the modified Rankin scale (mRS) in acute stroke research and practice. During the conduct of the alteplase-dose arm of the international ENhanced Control of Hypertension ANd Thrombolysis StrokE stuDy (ENCHANTED), we had an opportunity to compare each of these approaches to outcome measurement. Methods Baseline demographic data were recorded together with the National Institutes of Health Stroke Scale (NIHSS). Follow-up measures obtained at 90 days included mRS, smRSq, and the 5-Dimension European Quality of life scale (EQ-5D). Agreements between smRSq and mRS were assessed with the Kappa statistic. Multiple logistic regression was used to identify baseline predictors of Day 90 smRSq and mRS scores. Treatment effects, based on Day 90 smRSq/mRS scores, were tested in logistic and ordinal logistic regression models. Results SmRSq and mRS scores had good agreement (weighted Kappa 0.79, 95% confidence interval (CI) 0.78–0.81), while variables of age, atrial fibrillation, diabetes mellitus, pre-morbid mRS (1 vs. 0), baseline NIHSS scores, and imaging signs of cerebral ischemia, similarly predicted their scores. Odds ratios for death or disability, and ordinal shift, 90-day mRS scores using smRSq were 1.05 (95% CI 0.91–1.20; one-sided P = 0.23 for non-inferiority) and 0.98 (95% CI 0.87–1.11; P = 0.02 for non-inferiority), similar to those using mRS. Conclusions This study demonstrates the utility of the smRSq in a large, ethnically diverse clinical trial population. Scoring of the smRSq shows adequate agreement with the standard mRS, thus confirming it is a reliable, valid, and useful alternative measure of functional status after acute ischemic stroke. Clinical Trial registration URL: http://www.clinicaltrials.gov . Unique identifier: NCT01422616.

Serious Adverse Events and Their Impact on Functional Outcome in Acute Ischemic Stroke in the WAKE-UP Trial

Stroke ◽  
2021 ◽  
Author(s):  
Iris Lettow ◽  
Märit Jensen ◽  
Eckhard Schlemm ◽  
Florent Boutitie ◽  
Fanny Quandt ◽  
...  
Keyword(s):  
Regression Analysis ◽  
Ischemic Stroke ◽  
Adverse Events ◽  
Acute Ischemic Stroke ◽  
Functional Outcome ◽  
Fatal Outcome ◽  
Modified Rankin Scale ◽  
Unique Identifier ◽  
Serious Adverse Events ◽  
Link Type

Background and Purpose: During the first days and weeks after an acute ischemic stroke, patients are prone to complications that can influence further treatment, recovery, and functional outcome. In clinical trials, severe complications are recorded as serious adverse events (SAE). We analyzed the effect of SAE on functional outcome and predictors of SAE in the randomized controlled WAKE-UP trial (Efficacy and Safety of MRI-Based Thrombolysis in Wake-Up Stroke). Methods: We performed a post hoc analysis of WAKE-UP, a multicenter, randomized, placebo-controlled clinical trial of magnetic resonance imaging-guided intravenous thrombolysis with alteplase in patients with acute ischemic stroke and unknown time of onset. Functional outcome was assessed by the modified Rankin Scale 90 days after the stroke. SAE were reported to a central safety desk and recorded and categorized by organ system using Medical Dictionary for Regulatory Activities terminology. We used logistic regression analysis to determine the effect of SAE on functional outcome and linear multiple regression analysis to identify baseline predictors of SAE. Results: Among 503 patients randomized, 199 SAE were reported for n=110 (22%) patients. Of those patients who did suffer a SAE, 20 (10%) had a fatal outcome. Patients suffering from at least one SAE had a lower odds of reaching a favorable outcome (modified Rankin Scale score of 0–1) at 90 days (adjusted odds ratio, 0.36 [95% CI, 0.21–0.61], P <0.001). Higher age ( P =0.04) and male sex ( P =0.01) were predictors for the occurrence of SAE. Conclusions: SAEs were observed in about one in 5 patients, were more frequent in elderly and male patients and were associated with worse functional outcome. These results may help to assess the risk of SAE in future stroke trials and create awareness for severe complications after stroke in clinical practice. REGISTRATION: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT01525290 and https://eudract.ema.europa.eu ; Unique identifier: 2011-005906-32.

Asymmetry of Intracranial Hemodynamics as an Indicator of Mass Effect in Acute Intracerebral Hemorrhage

Stroke ◽  
1996 ◽  
Vol 27 (10) ◽  
pp. 1788-1792 ◽  
Author(s):  
Stephan A. Mayer ◽  
Carole E. Thomas ◽  
Beverly E. Diamond
Keyword(s):  
Intracerebral Hemorrhage ◽  
Mass Effect ◽  
Acute Intracerebral Hemorrhage

scholarly journals Tenecteplase Versus Alteplase Between 3 and 4.5 Hours in Low National Institutes of Health Stroke Scale

Stroke ◽  
2019 ◽  
Vol 50 (2) ◽  
pp. 498-500 ◽  
Author(s):  
Ole Morten Rønning ◽  
Nicola Logallo ◽  
Bente Thommessen ◽  
Håkon Tobro ◽  
Vojtech Novotny ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Functional Outcome ◽  
Scale Score ◽  
Odds Ratio ◽  
National Institutes Of Health ◽  
Modified Rankin Scale ◽  
Unique Identifier ◽  
Clinical Trial Registration ◽  
Intention To Treat ◽  
Good Functional Outcome

Background and Purpose— Thrombolysis with alteplase has beneficial effect on outcome and is safe within 4.5 hours. The present study compares the efficacy and safety of tenecteplase and alteplase in patients treated 3 to 4.5 hours after ischemic stroke. Methods— The data are from a prespecified substudy of patients included in The NOR-TEST (Norwegian Tenecteplase Stroke Trial), a randomized control trial comparing tenecteplase with alteplase. Results— The median admission National Institutes of Health Stroke Scale for this study population was 3 (interquartile range, 2–6). In the intention-to-treat analysis, 57% of patients that received tenecteplase and 53% of patients that received alteplase reached good functional outcome (modified Rankin Scale score of 0–1) at 3 months (odds ratio, 1.19; 95% CI, 0.68–2.10). The rates of intracranial hemorrhage in the first 48 hours were 5.7% in the tenecteplase group and 6.7% in the alteplase group (odds ratio, 0.84; 95% CI, 0.26–2.70). At 3 months, mortality was 5.7% and 4.5%, respectively. After excluding stroke mimics and patients with modified Rankin Scale score of >1 before stroke, the proportion of patients with good functional outcome was 61% in the tenecteplase group and 57% in the alteplase group (odds ratio, 1.24; 95% CI, 0.65–2.37). Conclusions— Tenecteplase is at least as effective as alteplase to achieve a good clinical outcome in patients with mild stroke treated between 3 and 4.5 hours after ischemic stroke. Clinical Trial Registration— URL: https://www.clinicaltrials.gov . Unique identifier: NCT01949948.

scholarly journals Glyceryl Trinitrate for Acute Intracerebral Hemorrhage

Stroke ◽  
2016 ◽  
Vol 47 (1) ◽  
pp. 44-52 ◽  
Author(s):  
Kailash Krishnan ◽  
Polly Scutt ◽  
Lisa Woodhouse ◽  
Alessandro Adami ◽  
Jennifer L. Becker ◽  
...  
Keyword(s):  
Intracerebral Hemorrhage ◽  
Glyceryl Trinitrate ◽  
Acute Intracerebral Hemorrhage

scholarly journals Ambulance-delivered transdermal glyceryl trinitrate versus sham for ultra-acute stroke: Rationale, design and protocol for the Rapid Intervention with Glyceryl trinitrate in Hypertensive stroke Trial-2 (RIGHT-2) trial (ISRCTN26986053)

2017 ◽  
Vol 14 (2) ◽  
pp. 191-206 ◽  
Author(s):  
Jason P Appleton ◽  
Polly Scutt ◽  
Mark Dixon ◽  
Harriet Howard ◽  
Lee Haywood ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Glyceryl Trinitrate ◽  
Acute Stroke ◽  
Sample Size ◽  
Modified Rankin Scale ◽  
Time Data ◽  
Serious Adverse Events ◽  
Discharge Disposition ◽  
Include Blood Pressure ◽  
Stroke Trial

Rationale Vascular nitric oxide levels are low in acute stroke and donors such as glyceryl trinitrate have shown promise when administered very early after stroke. Potential mechanisms of action include augmentation of cerebral reperfusion, thrombolysis and thrombectomy, lowering blood pressure, and cytoprotection. Aim To test the safety and efficacy of four days of transdermal glyceryl trinitrate (5 mg/day) versus sham in patients with ultra-acute presumed stroke who are recruited by paramedics prior to hospital presentation. Sample size estimates The sample size of 850 patients will allow a shift in the modified Rankin Scale with odds ratio 0.70 (glyceryl trinitrate versus sham, ordinal logistic regression) to be detected with 90% power at 5% significance (two-sided). Design The Rapid Intervention with Glyceryl trinitrate in Hypertensive stroke Trial-2 (RIGHT-2) is a multicentre UK prospective randomized sham-controlled outcome-blinded parallel-group trial in 850 patients with ultra-acute (≤4 h of onset) FAST-positive presumed stroke and systolic blood pressure ≥120 mmHg who present to the ambulance service following a 999 emergency call. Data collection is performed via a secure internet site with real-time data validation. Study outcomes The primary outcome is the modified Rankin Scale measured centrally by telephone at 90 days and masked to treatment. Secondary outcomes include: blood pressure, impairment, recurrence, dysphagia, neuroimaging markers of the acute lesion including vessel patency, discharge disposition, length of stay, death, cognition, quality of life, and mood. Neuroimaging and serious adverse events are adjudicated blinded to treatment. Discussion RIGHT-2 has recruited more than 500 participants from seven UK ambulance services. Status Trial is ongoing. Funding British Heart Foundation. Registration ISRCTN26986053.

Rapid Blood Pressure Lowering According to Recovery at Different Time Intervals after Acute Intracerebral Hemorrhage: Pooled Analysis of the INTERACT Studies

2015 ◽  
Vol 39 (3-4) ◽  
pp. 242-248 ◽  
Author(s):  
Xia Wang ◽  
Hisatomi Arima ◽  
Rustam Al-Shahi Salman ◽  
Mark Woodward ◽  
Emma Heeley ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Intracerebral Hemorrhage ◽  
Repeated Measures ◽  
Treatment Effects ◽  
Blood Pressure Reduction ◽  
Pooled Analysis ◽  
Clinical Trial Registration ◽  
Acute Intracerebral Hemorrhage ◽  
Time Periods ◽  
Intensive Blood Pressure

Background and Purpose: Early intensive blood pressure (BP) lowering has been shown to improve functional outcome in acute intracerebral hemorrhage (ICH), but the treatment effect is modest and without a clearly defined underlying explanatory mechanism. We aimed at more reliably quantifying the benefits of this treatment according to different time periods in the recovery of participants in the Intensive Blood Pressure Reduction in Acute Cerebral Hemorrhage Trial (INTERACT) studies. Methods: Pooled analysis of the pilot INTERACT1 (n = 404) and main INTERACT2 (n = 2,839) involving patients with spontaneous ICH (<6 h) and elevated systolic BP (SBP 150-220 mm Hg) who were randomized to intensive (target SBP <140 mm Hg) or guideline-recommended (target SBP <180 mm Hg) BP lowering treatment. Treatment effects were examined according to repeated measures analysis of an ordinal (‘shift') across all 7 levels of the modified Rankin Scale (mRS) assessed during follow-up at 7, 28, and 90 days, post-randomization. Clinical trial registration information: http://www.clinicaltrials.gov, NCT00226096 and NCT00716079. Results: Intensive BP lowering resulted in a significant favorable distribution of mRS scores for better functioning (odds ratio 1.13, 95% confidence interval 1.00-1.26; p = 0.042) over 7, 28 and 90 days, and the effect was consistency for early (7-28 days) and later (28-90 days) time periods (p homogeneity 0.353). Treatment effects were also consistent across several pre-specified patient characteristic subgroups, with trends favoring those randomized early, and with higher SBP and milder neurological severity at baseline. Conclusions: Intensive BP lowering provides beneficial effects on physical functioning that manifests consistently through the early and later phases of recovery from ICH.

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