Design of a prospective, dose-escalation study evaluating the Safety of Pioglitazone for Hematoma Resolution in Intracerebral Hemorrhage (SHRINC).

RATIONALE : Preclinical work demonstrates that the transcription factor peroxisome proliferator-activated receptor gamma plays an important role in augmenting phagocytosis while modulating oxidative stress and inflammation. We propose that targeted stimulation of phagocytosis to promote efficient removal of the hematoma without harming surrounding brain cells may be a therapeutic option for intracerebral hemorrhage. AIMS : The primary objective is to assess the safety of the peroxisome proliferator-activated receptor gamma agonist, pioglitazone, in increasing doses for three-days followed by a maintenance dose, when administered to patients with spontaneous intracerebral hemorrhage within 24 h of symptom onset compared with standard care. We will determine the maximum tolerated dose of pioglitazone. STUDY DESIGN : This is a prospective, randomized, blinded, placebo-controlled, dose-escalation safety trial in which patients with spontaneous intracerebral hemorrhage are randomly allocated to placebo or treatment. The Continual Reassessment Method for dose finding is used to determine the maximum tolerated dose of pioglitazone. Hematoma and edema resolution is evaluated with serial magnetic resonance imaging (MRI) at specified time points. Functional outcome will be evaluated at three- and six-months. OUTCOMES : The primary safety outcome is mortality at discharge. Secondary safety outcomes include mortality at three-months and six-months, symptomatic cerebral edema, clinically significant congestive heart failure, edema, hypoglycemia, anemia, and hepatotoxicity. Radiographic outcomes will explore the time frame for resolution of 25%, 50%, and 75% of the hematoma. Clinical outcomes are measured by the National Institutes of Health Stroke Scale (NIHSS), the Barthel Index, modified Rankin Scale, Stroke Impact Scale-16, and EuroQol at three- and six-months.

No consensus on definition criteria for stroke registry common data elements.

BACKGROUND: Stroke registries contribute to the conduct of clinical research and to the assessment of health care quality control. Efforts to compare clinical outcomes and quality indicators between centers are dependent on standardized data elements, but it is unknown how stroke physicians define common data elements, such as hypertension or diabetes, when collecting data for registries at their centers. METHODS: We conducted an internet-based survey of 91 centers affiliated with a university to assess their definitions of common data elements (CDEs) and compared their responses with standardized definitions, including those from the American College of Cardiology (ACC). RESULTS: More than half (52%) of centers completed the survey. There was only modest agreement among respondents regarding definitions of CDEs in the survey and even less agreement on how the respondents' definitions compared to ACC standards. CONCLUSIONS: Surveyed respondents do not agree on the definitions of CDEs, making comparisons between centers problematic. Standardized definitions of CDEs are needed to improve data collection for patient care and clinical research.

Is the drip-and-ship approach to delivering thrombolysis for acute ischemic stroke safe?

BACKGROUND: The drip-and-ship method of treating stroke patients may increase the use of tissue plasminogen activator (t-PA) in community hospitals. OBJECTIVE: The safety and early outcomes of patients treated with t-PA for acute ischemic stroke (AIS) by the drip-and-ship method were compared to patients directly treated at a stroke center. METHODS: The charts of all patients who were treated with intravenous (i.v.) t-PA at outside hospitals under the remote guidance of our stroke team and were then transferred to our facility were reviewed. Baseline NIHSS (National Institutes of Health Stroke Scale) scores, onset-to-treatment (OTT), and arrival-to-treatment (ATT) times were abstracted. The rates of in-hospital mortality, symptomatic hemorrhage (sICH), early excellent outcome (modified Rankin Scale [mRS] ≤ 1), and early good outcome (discharge home or to inpatient rehabilitation) were determined. RESULTS: One hundred sixteen patients met inclusion criteria. Eighty-four (72.4%) were treated within 3 h of symptom onset. The median estimated NIHSS score was 9.5 (range 3-27). The median OTT time was 150 min, and the median ATT was 85 min. These patients had an in-hospital mortality rate of 10.7% and sICH rate of 6%. Thirty percent of patients had an early excellent outcome and 75% were discharged to home or inpatient rehabilitation. When these outcome rates were compared with those observed in patients treated directly at our stroke center, there were no statistical differences. CONCLUSIONS: In this small retrospective study, drip-and-ship management of delivering i.v. t-PA for AIS patients did not seem to compromise safety. However, a large prospective study comparing drip-and-ship management to routine care is needed to validate the safety of this approach to treatment.