Clinical Trial Protocol for BEACH: A Phase 2a Study of MW189 in Patients with Acute Nontraumatic Intracerebral Hemorrhage.

Patients with acute spontaneous intracerebral hemorrhage (ICH) develop secondary neuroinflammation and cerebral edema that can further damage the brain and lead to increased risk of neurologic complications. Preclinical studies in animal models of acute brain injury have shown that a novel small-molecule drug candidate, MW01-6-189WH (MW189), decreases neuroinflammation and cerebral edema and improves functional outcomes. MW189 was also safe and well tolerated in phase 1 studies in healthy adults.

Decentralized clinical trials in the trial innovation network: Value, strategies, and lessons learned.

New technologies and disruptions related to Coronavirus disease-2019 have led to expansion of decentralized approaches to clinical trials. Remote tools and methods hold promise for increasing trial efficiency and reducing burdens and barriers by facilitating participation outside of traditional clinical settings and taking studies directly to participants. The Trial Innovation Network, established in 2016 by the National Center for Advancing Clinical and Translational Science to address critical roadblocks in clinical research and accelerate the translational research process, has consulted on over 400 research study proposals to date.

Mechanisms to expedite pediatric clinical trial site activation: The DOSE trial experience.

Background: Timely trial start-up is a key determinant of trial success; however, delays during start-up are common and costly. Moreover, data on start-up metrics in pediatric clinical trials are sparse. To expedite trial start-up, the Trial Innovation Network piloted three novel mechanisms in the trial titled Dexmedetomidine Opioid Sparing Effect in Mechanically Ventilated Children (DOSE), a multi-site, randomized, double-blind, placebo-controlled trial in the pediatric intensive care setting.

Design and Protocol of the Renal Anhydramnios Fetal Therapy (RAFT) Trial.

Purpose: Anhydramnios secondary to anuria before 22 weeks of gestational age and congenital bilateral renal agenesis before 26 weeks of gestational age are collectively referred to as early-pregnancy renal anhydramnios. Early-pregnancy renal anhydramnios occurs in at least 1 in 2000 pregnancies and is considered universally fatal when left untreated because of severe pulmonary hypoplasia precluding ex utero survival The Renal Anhydramnios Fetal Therapy (RAFT) trial is a nonrandomized, nonblinded, multicenter clinical trial designed to assess the efficacy, safety, and feasibility of amnioinfusions for patients with pregnancies complicated by early-pregnancy renal anhydramnios. The primary objective of this study is to determine the proportion of neonates surviving to successful dialysis, defined as use of a dialysis catheter for ≥14 days.

Bayesian deep learning outperforms clinical trial estimators of intracerebral and intraventricular hemorrhage volume.

Background And Purpose: Intracerebral hemorrhage (ICH) and intraventricular hemorrhage (IVH) clinical trials rely on manual linear and semi-quantitative (LSQ) estimators like the ABC/2, modified Graeb and IVH scores for timely volumetric estimation from CT. Deep learning (DL) volumetrics of ICH have recently approached the accuracy of gold-standard planimetry. However, DL and LSQ strategies have been limited by unquantified uncertainty, in particular when ICH and IVH estimates intersect.

Post-Trial Enhanced Deployment and Technical Performance with the MISTIE Procedure per Lessons Learned.

Objective: We hypothesize that procedure deployment rates and technical performance with minimally invasive surgery and thrombolysis for intracerebral hemorrhage (ICH) evacuation (MISTIE) can be enhanced in post-trial clinical practice, per Phase III trial results and lessons learned.

Materials And Methods: We identified ICH patients and those who underwent MISTIE procedure between 2017-2021 at a single site, after completed enrollments in the Phase III trial. Deployment rates, complications and technical outcomes were compared to those observed in the trial.

Intracerebral Hemorrhage Volume Reduction and Timing of Intervention Versus Functional Benefit and Survival in the MISTIE III and STICH Trials.

Background: The extent of intracerebral hemorrhage (ICH) removal conferred survival and functional benefits in the minimally invasive surgery with thrombolysis in intracerebral hemorrhage evacuation (MISTIE) III trial. It is unclear whether this similarly impacts outcome with craniotomy (open surgery) or whether timing from ictus to intervention influences outcome with either procedure.

Objective: To compare volume evacuation and timing of surgery in relation to outcomes in the MISTIE III and STICH (Surgical Trial in Intracerebral Hemorrhage) trials.

3D Deep Neural Network Segmentation of Intracerebral Hemorrhage: Development and Validation for Clinical Trials.

Intracranial hemorrhage (ICH) occurs when a blood vessel ruptures in the brain. This leads to significant morbidity and mortality, the likelihood of which is predicated on the size of the bleeding event. X-ray computed tomography (CT) scans allow clinicians and researchers to qualitatively and quantitatively diagnose hemorrhagic stroke, guide interventions and determine inclusion criteria of patients in clinical trials.

Haptoglobin is associated with increased early perihematoma edema progression in spontaneous intracranial hemorrhage.

Introduction: Perihematomal edema in intracranial hemorrhage is influenced by free hemoglobin clearance and inflammation. Serum Haptoglobin (Hp) binds free hemoglobin, affecting heme clearance and free radical production. Of the three Hp phenotypes, Hp 1-1 has the greatest effect on free hemoglobin clearance.

Primary intraventricular hemorrhage outcomes in the CLEAR III trial.

Background: Intraventricular hemorrhage occurs due to intracerebral hemorrhage with intraventricular extension or without apparent parenchymal involvement, known as primary intraventricular hemorrhage.

Aims: We evaluated the prognosis of primary intraventricular hemorrhage patients in the CLEAR III trial (Clot Lysis: Evaluating Accelerated Resolution of Intraventricular Hemorrhage).

Methods: In patients with primary intraventricular hemorrhage versus those with secondary intraventricular hemorrhage, we compared intraventricular alteplase response and outcomes including modified Rankin Scale, Barthel Index, National Institutes of Health Stroke Scale (NIHSS), and extended Glasgow Outcome Scale (eGOS) at 30, 180, and 365 days.

Efficacy and safety of minimally invasive surgery with thrombolysis in intracerebral haemorrhage evacuation (MISTIE III): a randomised, controlled, open-label, blinded endpoint phase 3 trial.

Background: Acute stroke due to supratentorial intracerebral haemorrhage is associated with high morbidity and mortality. Open craniotomy haematoma evacuation has not been found to have any benefit in large randomised trials. We assessed whether minimally invasive catheter evacuation followed by thrombolysis (MISTIE), with the aim of decreasing clot size to 15 mL or less, would improve functional outcome in patients with intracerebral haemorrhage.

Retrospective Methods Analysis of Semiautomated Intracerebral Hemorrhage Volume Quantification From a Selection of the STICH II Cohort (Early Surgery Versus Initial Conservative Treatment in Patients With Spontaneous Supratentorial Lobar Intracerebral Haematomas).

Background And Purpose: The ABC/2 method for calculating intracerebral hemorrhage (ICH) volume has been well validated. However, the formula, derived from the volume of an ellipse, assumes the shape of ICH is elliptical. We sought to compare the agreement of the ABC/2 formula with other methods through retrospective analysis of a selection of the STICH II cohort (Early Surgery Versus Initial Conservative Treatment in Patients With Spontaneous Supratentorial Lobar Intracerebral Haematomas).

The Incidence of Catheter Tract Hemorrhage and Catheter Placement Accuracy in the CLEAR III Trial.

Background: Incidence of catheter tract hemorrhage (CTH) after initial ventriculostomy placement ranges from 10 to 34%. We investigated CTH incidence in the Clot Lysis: Evaluation of Accelerated Resolution of Intraventricular Hemorrhage Phase III trial.

Methods: Prospective observational analysis of 1000 computer tomography (CT) scans from all 500 patients enrolled in the trial.

Symptomatic Hemorrhagic Complications in Clot Lysis: Evaluation of Accelerated Resolution of Intraventricular Hemorrhage Phase III Clinical Trial (CLEAR III): A Posthoc Root-Cause Analysis.

Background: As intraventricular thrombolysis for intraventricular hemorrhage (IVH) has developed over the last 2 decades, hemorrhagic complications have remained a concern despite general validation of its safety in controlled trials in the Clot Lysis: Evaluation of Accelerated Resolution of Intraventricular Hemorrhage Phase III (CLEAR-IVH) program.

Objective: To analyze factors associated with symptomatic bleeding following IVH with and without thrombolysis in conjunction with the recently completed CLEAR III trial.

Methods: We reviewed safety reports on symptomatic bleeding events reported during the first year after randomization among subjects enrolled in the CLEAR III trial.

Fibrinolytic for treatment of intraventricular hemorrhage: A meta-analysis and systematic review.

Background Intraventricular hemorrhage is a significant cause of mortality and morbidity worldwide. Treating intraventricular hemorrhage with intraventricular fibrinolytic therapy via a catheter is becoming an increasingly utilized intervention. Aims This meta-analysis aimed to investigate the role of intraventricular fibrinolytic treatment in hypertensive intraventricular hemorrhage patients and evaluate the effect sizes for survival as well as level of function at differing time points.

Surgical Performance in Minimally Invasive Surgery Plus Recombinant Tissue Plasminogen Activator for Intracerebral Hemorrhage Evacuation Phase III Clinical Trial.

Background: Minimally invasive thrombolytic evacuation of intracerebral hematoma is being investigated in the ongoing phase III clinical trial of Minimally Invasive Surgery plus recombinant Tissue plasminogen activator for Intracerebral hemorrhage Evacuation (MISTIE III).

Objective: To assess the accuracy of catheter placement and efficacy of hematoma evacuation in relation to surgical approach and surgeon experience.

Methods: We performed a trial midpoint interim assessment of 123 cases that underwent the surgical procedure.

Thrombolytic removal of intraventricular haemorrhage in treatment of severe stroke: results of the randomised, multicentre, multiregion, placebo-controlled CLEAR III trial.

Background: Intraventricular haemorrhage is a subtype of intracerebral haemorrhage, with 50% mortality and serious disability for survivors. We aimed to test whether attempting to remove intraventricular haemorrhage with alteplase versus saline irrigation improved functional outcome.

Methods: In this randomised, double-blinded, placebo-controlled, multiregional trial (CLEAR III), participants with a routinely placed extraventricular drain, in the intensive care unit with stable, non-traumatic intracerebral haemorrhage volume less than 30 mL, intraventricular haemorrhage obstructing the 3rd or 4th ventricles, and no underlying pathology were adaptively randomly assigned (1:1), via a web-based system to receive up to 12 doses, 8 h apart of 1 mg of alteplase or 0·9% saline via the extraventricular drain.

Safety and efficacy of minimally invasive surgery plus alteplase in intracerebral haemorrhage evacuation (MISTIE): a randomised, controlled, open-label, phase 2 trial.

Background: Craniotomy, according to the results from trials, does not improve functional outcome after intracerebral haemorrhage. Whether minimally invasive catheter evacuation followed by thrombolysis for clot removal is safe and can achieve a good functional outcome is not known. We investigated the safety and efficacy of alteplase, a recombinant tissue plasminogen activator, in combination with minimally invasive surgery (MIS) in patients with intracerebral haemorrhage.

Validated automatic brain extraction of head CT images.

Background: X-ray computed tomography (CT) imaging of the brain is commonly used in diagnostic settings. Although CT scans are primarily used in clinical practice, they are increasingly used in research. A fundamental processing step in brain imaging research is brain extraction - the process of separating the brain tissue from all other tissues.

Identification of hematomas in mild traumatic brain injury using an index of quantitative brain electrical activity.

Rapid identification of traumatic intracranial hematomas following closed head injury represents a significant health care need because of the potentially life-threatening risk they present. This study demonstrates the clinical utility of an index of brain electrical activity used to identify intracranial hematomas in traumatic brain injury (TBI) presenting to the emergency department (ED). Brain electrical activity was recorded from a limited montage located on the forehead of 394 closed head injured patients who were referred for CT scans as part of their standard ED assessment.

Use of brain electrical activity for the identification of hematomas in mild traumatic brain injury.

This study investigates the potential clinical utility in the emergency department (ED) of an index of brain electrical activity to identify intracranial hematomas. The relationship between this index and depth, size, and type of hematoma was explored. Ten minutes of brain electrical activity was recorded from a limited montage in 38 adult patients with traumatic hematomas (CT scan positive) and 38 mild head injured controls (CT scan negative) in the ED.

Minimally invasive surgery plus recombinant tissue-type plasminogen activator for intracerebral hemorrhage evacuation decreases perihematomal edema.

Background And Purpose: Perihematomal edema (PHE) can worsen outcomes after intracerebral hemorrhage (ICH). Reports suggest that blood degradation products lead to PHE. We hypothesized that hematoma evacuation will reduce PHE volume and that treatment with recombinant tissue-type plasminogen activator (rt-PA) will not exacerbate it.

Improved ELISA for thyroid microsomal auto-antibodies. Comparison with haemagglutination and immunofluorescent techniques.

Thyroid microsomal antibodies (TMA) and thyroglobulin antibodies (TGA) are strongly associated with auto-immune thyroid disease. TMA and TGA have been mostly detected by means of either immunofluorescence (IF), tanned red cell haemagglutination (TRCH), or radio-immunoassay (RIA) until the recent development of the enzyme-linked immunosorbent assay (ELISA). The ELISA has not been as extensively used in TMA detection as in the assay for TGA.