Open Blinded Endpoint Research Articles

Safety and efficacy of fluoxetine in post-stroke anxiety-A pilot prospective randomized open blinded endpoint (PROBE) study.

The prevalence of post-stroke anxiety (PSA) is reported to be 20%-25%. There is insufficient evidence on the efficacy of antidepressants for treating anxiety in such patients. This Prospective Randomized Open Blinded Endpoint (PROBE) study was designed to assess the safety and efficacy of fluoxetine in PSA. In this single-center pilot study conducted in India, post-stroke patients (between 1 to 6months) were randomized to fluoxetine (intervention group: 20mg/day for 12weeks) or standard medical care (control group). The primary outcome was improvement in the Hamilton Anxiety Rating Scale (HAM-A) at 12weeks. The secondary outcomes were anxiety remission (>50% improvement in HAM-A), modified Rankin Scale (mRS), Barthel Index (BI), quality of life (SF-36), and Hamilton Depression Rating Scale (HAM-D). A linear regression analysis was done for determinants of HAM-A to account for baseline differences in the intervention and control groups. A total of 60 patients were randomized: (30: intervention, 30: control). The overall prevalence of post-stroke anxiety among participants in the study was 50.8%, and 31.5% experienced both anxiety and depression. The average HAM-A score at baseline was 11, and average follow-up score at study conclusion was 4. There was similar improvement in the HAM-A score at 12weeks post-randomization in the intervention and control groups [fluoxetine: -8.0 (95% CI = -11.0 to -4.0); control: -7.0 (95% CI = -9.5 to -4.0); P = 0.91]. Likewise, there was no significant difference between intervention and control groups at 12weeks post-randomization on the mRS, BI, SF-36, or HAM-D. There were no serious adverse events in either group during the study. Fluoxetine and standard medical care had comparable improvement in HAM-A in post-stroke patients with mild anxiety at 12weeks. Further study of the pharmacological treatment of post-stroke patients with more severe anxiety is needed. CTRI/2018/12/016568.

ChatGPT-4 and wearable device assisted Intelligent Exercise Therapy for co-existing Sarcopenia and Osteoarthritis (GAISO): a feasibility study and design for a randomized controlled PROBE non-inferiority trial.

Sarcopenia and osteoarthritis are prevalent age-related diseases that mutually exacerbate each other, creating a vicious cycle that worsens both conditions. Exercise is key to breaking this detrimental cycle. Facing increasing demand for rehabilitation services within this patient demographic, ChatGPT-4 and wearable device may increase the availability, efficiency and personalization of such health care. To evaluate the clinical efficacy and cost-effectiveness of a rehabilitation system implemented on mobile platforms, utilizing the integration of ChatGPT-4 and wearable devices. The study design is a prospective randomized open blinded end-point (PROBE) non-inferiority trial. 278 patients diagnosed with osteoarthritis and sarcopenia will be recruited and randomly assigned to the intervention group and the control group. In the intervention group patients receive mobile phone-based rehabilitation service where ChatGPT-4 generates personalized exercise therapy, and wearable device guides and monitor the patient to implement the exercise therapy. Traditional clinic based face-to-face exercise therapy will be prescribed and implemented in the control group. All patients will receive three-months exercise therapies following the frequency, intensity, type, time, volume and progression (FITT-VP) principle. The patients will be assessed at baseline, one month, three months, and six months after initiation. Outcome measures will include ROM, gait patterns, Visual Analogue Scale (VAS) for pain assessment, Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), Knee Injury and Osteoarthritis Outcome Score (KOOS) for functional assessment, Short-Form Health Survey 12 (SF-12) for quality of life, Minimal Clinically Important Difference (MCID), Patient Acceptable Symptom State (PASS), and Substantial Clinical Benefit (SCB) for clinically significant measures. A rehabilitation system combining the capabilities of ChatGPT-4 and wearable devices potentially enhance the availability and efficiency of professional rehabilitation services, thus enhancing the therapeutic outcomes for a substantial population concurrently afflicted with sarcopenia and osteoarthritis.

Abstract 26: An Effective mHealth Intervention to Close the Guideline-to-Practice Gap in Hypertension Treatment: mGlide RCT

Background: Suboptimal HTN control is a widespread problem particularly among minorities and socioeconomically disadvantaged groups. Objective: To determine if a mobile health (mHealth) intervention facilitating an active partnership between inter-professional care teams (including pharmacists) and patients improves HTN control in patients with uncontrolled HTN. Methods: mGlide is an NIH-funded, 2-arm RCT evaluating HTN control between a mHealth intervention (mGlide) vs. state-of-clinical-care (comparison) groups using a PROBE (Prospective Randomized Open Blinded End-point) design. Table 1 shows intervention components. High CVD risk patients with uncontrolled HTN identified by EHR query were randomized 1:1 to either mGlide or to comparison for a 6-month intervention followed by a 6-month observation period. Recruitment sites include primary care clinics and specialty stroke service in an integrated health system, community clinics (CC) and federally qualified health centers (FQHC). The FQHC and CC serve low income and minority (Hmong and Latino) patients. The primary aim tested clinical effectiveness of mGlide in reducing SBP at 6 months. Secondary outcomes include resource utilization, adverse events and medication side-effects. Results: Recruitment started in 2019. N=395 participants enrolled by August 2023. The pandemic impacted enrollment; however enrollment recovered after vaccine availability (Figure). Primary outcome was available in March 2024 on everyone except in those lost to follow-up (n=38; 9.6%). We used multiple imputation for those missing 6 month SBP. Baseline mean SBP was 143.2 vs. 143.6 mm Hg in mGlide vs. comparison. The intervention led to better HTN control (Table 2). Mean 6-month SBP was 128.1 (mGlide) vs. 134 mm Hg (comparison). Adjusting for baseline SBP and study strata, 6-month mean SBP was 5.7 mm Hg (95% CI 2.9-8.4; p = 0.0001) lower in mGlide vs. comparison. The odds of HTN control defined as “alive and SBP < 130 mm Hg”, was 60% higher in the mGlide arm (OR 1.6; 95% CI 1.03-2.48; p=0.035). There was one death in each study arm. The mGlide arm had fewer ER visits (16% vs. 25%; p=0.024), fewer hospitalizations (7% vs. 13%; p=0.044) and more medication side effects (39% vs. 26%, p=0.008). Conclusions: An inexpensive mHealth intervention that used the patient’s own phone (Table 1) was implemented in diverse health systems and significantly reduced SBP and was associated with less resource utilization at 6 months (Table 2).

Extended Computed Tomography Angiography for the Successful Diagnosis of Cardioaortic Thrombus in Acute Ischemic Stroke and TIA: Study Protocol for a Randomized Controlled Trial.

Cardiac imaging is one of the main components of the etiological investigation of ischemic strokes. However, basic and advanced cardiac imaging remain underused in most stroke centers globally. Computed tomography angiography (CTA) of the supra-aortic and intracranial arteries is the most frequent imaging modality applied during the evaluation of patients with acute ischemic stroke to identify the presence of a large vessel occlusion. Recent evidence from retrospective observational studies has shown a high detection of cardiac thrombi, ranging from 6.6 to 17.4%, by extending a CTA a few cm below the carina to capture cardiac images. However, this approach has never been prospectively compared against usual care in a randomized controlled trial. The Extended Computed Tomography Angiography for the Successful Screening of Cardioaortic Thrombus in Acute Ischemic Stroke and TIA (DAYLIGHT) prospective, randomized, controlled trial evaluates whether an extended CTA (eCTA) + standard-of-care stroke workup results in higher detection rates of cardiac and aortic source of embolism compared to standard-of-care CTA (sCTA) + standard-of-care stroke workup. DAYLIGHT is a single-center, prospective, randomized, open-blinded endpoint trial, aiming to recruit 830 patients with suspected acute ischemic stroke or transient ischemic attack (TIA) being assessed under acute code stroke at the emergency department or at a dedicated urgent stroke prevention clinic. Patients are randomized 1:1 to eCTA versus sCTA. The eCTA expands image acquisition caudally, 6 cm below the carina. All patients receive standard-of-care cardiac imaging and diagnostic stroke workup. The primary efficacy endpoint is the diagnosis of a cardioaortic thrombus after at least 30 days of follow-up. The primary safety endpoint is door-to-CTA completion time. The diagnosis of a qualifying ischemic stroke or TIA is independently adjudicated by a stroke neurologist, blinded to the study arm allocation. Patients without an adjudicated ischemic stroke or TIA are excluded from the analysis. The primary outcome events are adjudicated by a board-certified radiologist with subspecialty training in cardiothoracic radiology and a cardiologist with formal training in cardiac imaging. The primary analysis is performed according to the modified intention-to-diagnose principle and without adjustment by logistic regression models. Results are presented with odds ratios and 95% confidence intervals. The DAYLIGHT trial will provide evidence on whether extending a CTA to include the heart results in an increased detection of cardioaortic thrombi compared to standard-of-care stroke workup.

Gait pattern after electromechanically-assisted gait training with the Hybrid Assistive Limb and conventional gait training in sub-acute stroke rehabilitation-A subsample from a randomized controlled trial.

Electromechanically-assisted gait training has been introduced in stroke rehabilitation as a means to enable gait training with a large number of reproducible and symmetrical task repetitions, i.e. steps. However, few studies have evaluated its impact on gait pattern functions. This study includes persons with no independent ambulation function at the start of a 4-week neurorehabilitation period in the sub-acute phase after stroke. The primary aim of the study was to evaluate whether the addition of electromechanically-assisted gait training to conventional training resulted in better gait pattern function than conventional training alone. The secondary aim was to identify correlations between overall gait quality and standardized clinical assessments. Seventeen patients with no independent ambulation function who participated in a Prospective Randomized Open Blinded End-point study in the sub-acute phase after stroke were randomized into two groups; one group (n = 7) to undergo conventional training only (CONV group) and the other group (n = 10) to undergo conventional training with additional electromechanically-assisted gait training (HAL group). All patients were assessed with 3D gait analysis and clinical assessments after the 4-week intervention period. Overall gait quality as per the Gait Profile Score (GPS), as well as kinematic, and kinetic and other spatiotemporal metrics were collected and compared between intervention groups. Correlations between biomechanical and clinical outcomes were evaluated. Both the CONV and HAL groups exhibited similar gait patterns with no significant differences between groups in any kinematic, kinetic parameters or other spatiotemporal metrics. The GPS for the paretic limb had a median (IQR) of 12.9° (7.8°) and 13.4° (4.3°) for the CONV and HAL groups, respectively (p = 0.887). Overall gait quality was correlated with independence in walking, walking speed, movement function and balance. We found no added benefit in gait pattern function from the electromechanically-assisted gait training compared to the conventional training alone. This finding raises new questions about how to best design effective and optimal post-stroke rehabilitation programs in patients with moderate to severe gait impairments to achieve both independent walking and optimal gait pattern function, and about which patients should be in focus in further studies on the efficacy of electromechanically-assisted gait training. The study was retrospectively registered at ClinicalTrials.gov, identifier (NCT02410915) on April 2015.

Effect of Individualized Versus Standardized Blood Pressure Management During Endovascular Stroke Treatment on Clinical Outcome: A Randomized Clinical Trial.

Optimal blood pressure (BP) management during endovascular stroke treatment is not well established. We studied whether an individualized approach for managing BP during endovascular stroke treatment gives a better clinical outcome than an approach with standardized systolic BP targets. The INDIVIDUATE study (Individualized Blood Pressure Management During Endovascular Treatment of Acute Ischemic Stroke Under Procedural Sedation) is a randomized clinical trial with a prospective randomized open blinded end point (PROBE) design. Patients were recruited between October 1, 2020 and July 7, 2022 at a single center at a tertiary care university hospital. Patients were eligible, when they were suffering from acute ischemic stroke of the anterior circulation with occlusions of the internal carotid artery and middle cerebral artery and a National Institutes of Health Stroke Scale score of ≥8 receiving endovascular stroke treatment in procedural sedation. The intervention consists of an individualized BP management strategy, where preinterventional baseline systolic BP (SBP) values are used as intraprocedural BP targets. As a control, the standard treatment aims to maintain the intraprocedural SBP between 140 and 180 mm Hg. The main prespecified outcome is the proportion of favorable functional outcomes 90 days after stroke, defined as a modified Rankin Scale score of 0 to 2. Two hundred fifty patients were enrolled and included in the analysis, mean (SD) age was 77 (12) years, 142 (57%) patients were women, and mean (SD) National Institutes of Health Stroke Scale score on admission was 17 (5.2). In all, 123 (49%) patients were treated with individualized and 127 (51%) with standard BP management. Mean (SD) intraprocedural SBP was similar in the individualized versus standard BP management group (157 [19] versus 154 [18] mm Hg; P=0.16). The rate of favorable functional outcome after 3 months was not significantly different between the individualized versus the standard BP management group (25% versus 24%; adjusted odds ratio, 0.81 [95% CI, 0.41-1.61]; P=0.56). Among patients treated with endovascular stroke treatment due to an acute ischemic stroke of the anterior circulation, no significant difference was seen between the individualized BP management strategy, where intraprocedural SBP was targeted to baseline values, and the standardized regimen of targeting SBP between 140 and 180 mm Hg. URL: https://www. gov; Unique identifier: NCT04578288.

Tenecteplase to Replace Alteplase? Comparing Thrombolytic Therapies for Acute Ischemic Stroke: June 2023 Annals of Emergency Medicine Journal Club.

Tenecteplase to Replace Alteplase? Comparing Thrombolytic Therapies for Acute Ischemic Stroke: June 2023 Annals of Emergency Medicine Journal Club.

Efficacy and Safety of Automated Antiseptic Lavage and Suctioning of Oral, Oropharyngeal, and Subglottic Secretions (Vapcare) Among Ventilated Patients with COVID-19 Developing VentilatorAssociated Events During Hospitalization: A Prospective Randomized Open Blinded End-Point Study

Background: Globally, invasive mechanical ventilation is one of the many methods relied on by intensivists to treat patients diagnosed with COVID-19. In this population, substandard oral care and secretion management permit the colonization of pathogens in the oral cavity and aspiration of these microbeladen secretions is the leading cause of ventilator-associated pneumonia (VAP). This study was conducted to analyze the effects of VapCare, an automated and intelligent secretion clearance and oral hygiene management system for VAP prevention, compared to the manual process.

Abstract 156: Main Results Of The Take Off Pounds After Stroke Trial

Objective: To test the effectiveness of a 12-week partial meal replacement (PMR) intervention for achieving meaningful weight loss in overweight or obese patients with a recent ischemic stroke. Methods: Take Off Pounds After Stroke (TOPS) was a prospective randomized open blinded endpoint trial. Eligible patients had an ischemic stroke within the past 90 days, were ≥18 years of age, with BMI 27 to 49.9 kg/m 2 , maximum weight ≤350 pounds (limit of home scale we provided), and were able to stand on a scale unassisted, meet all nutritional needs by oral intake, and ready to undergo behavioral change. Patients were excluded if they required dialysis, had a contra-indication to a weight loss diet, had lost ≥12 lbs in the prior 3 months, were allergic to soy, did not speak English or were pregnant, breast feeding, or desired to become pregnant. Patients were randomized to a PMR (OPTAVIA® Optimal Weight 4&2&1 Plan™) or enhanced standard care (SC). The PMR program is commercially available and consists of daily intake of four meal replacements, two “lean and green” meals and one healthy snack (1,100 to 1,300 calories per day). Enhanced standard care consisted of one instructional session on a healthy diet advocated by the US Department of Agriculture (and provision of a manual). The primary outcome was achievement of at least 5% weight loss at 12 weeks. Results: From 1 2/2019 to 2/2021, a total of 38 patients were enrolled from two sites. Two patients in each arm did not complete the study. At 12 weeks, 9 of 17 patients in the PMR group and 2 of 17 patients in the SC group achieved at least 5% weight loss (52.9% v. 11.9%; Fisher’s exact p=.02). Mean percent weight loss in the PMR group was 3.0% (SD 13.7) compared with 2.6% (SD 3.4) in the SC group (Wilcoxon rank sum p=.17). Patients in the PMR group had a mean change in waist circumference of -5.0 cms (SD 9.8) compared to -4.7 cms (SD 6.3) in the standard advice group (ANOVA p=.94). Changes in blood pressure and modified Rankin Scale did not differ between groups. No adverse outcomes were associated with the study intervention. Conclusion: A dietary intervention for weight loss implemented soon after ischemic stroke is feasible, safe and effective for weight loss.

Penile Hemodynamic Response to Phosphodiesterase Type V Inhibitors after Cavernosal Sparing Inflatable Penile Prosthesis Implantation: A Prospective Randomized Open-Blinded End-Point (PROBE) Study.

Forceful corporal dilatation amidst penile prosthesis implantation may injure cavernosal arteries compromising penile vasculature. In this study, we aimed to compare the conventional and cavernosal sparing techniques regarding cavernosal artery preservation. Overall, 33 patients underwent inflatable penile prosthesis implantation with Coloplast Titan Touch® three-piece inflatable penile implants. 16 patients had conventional implantations with serial vigorous dilatations, while 17 patients were implanted with the cavernosal sparing technique, consisting of a single minimal corporal dilatation after an intraoperative intracavernosal injection (ICI) of Alprostadil. Postoperatively, a penile duplex Doppler ultrasound study was performed. Whenever a cavernosal artery was spared and thus successfully probed, its hemodynamics were studied before and after an oral administration of a phosphodiesterase type 5 inhibitor (PDE5i). A cavernosal artery was successfully probed in 16/17 (94%) of patients in the cavernosal sparing group compared to 5/16 (31%) of patients in the conventional group with a significant statistical difference (P=0.001). This demonstrated that the cavernosal sparing technique was superior to the conventional approach in preserving the cavernosal artery (odds ratio 35.2, 95% IC 3.5–344.2; P=0.0022). Whenever a cavernosal artery could be probed, its hemodynamic responsiveness was also preserved. This trial is registered with NCT03733860.

The beneficial effect over 3 years by pictorial information to patients and their physician about subclinical atherosclerosis and cardiovascular risk: Results from the VIPVIZA randomized clinical trial

ObjectiveNon-adherence to guidelines and preventive measures is a major challenge, particularly so to obtain long-term adherence to lifestyle changes and recommended medication. The objective was to investigate if pictorial information regarding subclinical carotid atherosclerosis provided to individuals and physicians gave sustained effects on cardiovascular risk beyond the previously reported effect after 1 year and up to 3 years. MethodsA Prospective Randomized Open Blinded End-point (PROBE) trial. Within a CVD prevention program in Västerbotten County, Sweden, 3532 healthy individuals aged 40, 50 or 60 years were enrolled and 1:1 randomized to intervention (n = 1749; pictorial information with additional prevention materials to participants and physicians) or control group (n = 1783; no pictorial information to participants and physicians). Preventive measures were managed within primary care. Participants were investigated at baseline during 2013–2016 and at follow-up after 1 and 3 years. ResultsA beneficial effect on cardiovascular risk was observed at 3-year follow-up; Framingham Risk Score (FRS) was 13.38 for the intervention group and 14.08 for the control group (p = 0.047) and SCORE was 1.69 vs. 1.82 (p = 0.022). The effect observed at 1-year was sustained over 3 years after adjustment for sex and education and more pronounced among participants with a severe atherosclerotic picture at baseline. ConclusionsThis study provides evidence of sustained beneficial effects on the adherence to prevention guidelines over 3 years of pictorial information about subclinical carotid atherosclerosis, resulting in lower cardiovascular risk regardless of sex and educational level. Direct visualization of the underlying still subclinical atherosclerotic disease, rather than just indirect information about risk factors and statistical risk of future myocardial infarction, stroke and death, is one way to tackle the problem of non-adherence to prevention of cardiovascular diseases.

Thromboprophylaxis with rivaroxaban in patients with malignancy and central venous lines (TRIM‐Line): A two‐center open‐label pilot randomized controlled trial

BackgroundCentral venous catheter (CVC) insertion is an important risk factor for venous thromboembolism (VTE) among patients with cancer. Routine use of primary thromboprophylaxis in this patient population is not currently recommended. We sought to assess the feasibility of conducting a randomized controlled trial (RCT) assessing the safety and efficacy of rivaroxaban (10 mg daily) to prevent VTE complications in this patient population. MethodsThis is a two‐center prospective, randomized, open blinded end point pilot trial including patients with active cancer and a newly inserted CVC. Patients were randomly assigned 1:1 to rivaroxaban or observation for 90 days. The primary feasibility outcome of this pilot study was the number of participants recruited per month. Secondary clinical outcomes included thrombotic complications, major VTE, and major bleeding episodes. ResultsOverall, 105 patients were enrolled over 11 months. The average enrollment rates were 7.5 and 2 patients per month at the two participating centers, respectively. Overall, thrombotic complications occurred in 3 patients in the rivaroxaban group (5.8%; 95% confidence interval [CI], 1.2‐16.0) compared with 5 patients in the control group (9.4%; 95% CI, 3.1‐20.7) (HR, 0.58; 95% CI, 0.14‐2.5). Major VTE occurred in 2 (3.9%; 95% CI, 0.5‐13.2) and 3 (5.7%; 95% CI, 1.2‐15.7) patients in the rivaroxaban and control group, respectively (HR, 0.66; 95% CI, 0.11‐3.9). One patient (1.9%) receiving rivaroxaban had a major bleeding event. ConclusionsThrombotic complications are common in patients with cancer and a newly inserted CVC. The pilot trial achieved its enrollment targets and supports that a large multicenter RCT is feasible in this area. ClinicalTrials.gov (NCT03506815).

The first data on international multicenter clinical study RheoSTAT-CP0698 on the efficacy and safety of Rheosorbilact® infusion in therapy of pneumonia

ABSTRACT. Adequate and effective treatment of severe pneumonia is especially relevant in present situation. The most problematic issue is infusion therapy. The current evidence and guidelines recommend balanced crystalloid infusion for patients with severe pneumonia and sepsis. The composition of Rheosorbilact® provides significant benefits in patients with severe infections, including respiratory infections. According to the results of the randomized open blinded end-point RheoSTAT-CP0698 study, administration of Rheosorbilact® to patients with pneumonia (intravenous infusion at a dose of 200-400 ml/day for 3 days) effectively improves the clinical condition, reduces the manifestations of (multi-) organ failure and endogenous intoxication. Small-volume infusion therapy promotes rapid normalization of circulating blood volume, stabilization of hemodynamics, acid-base, electrolyte and gas composition of the blood, significantly improves saturation and reduces tachypnea. The positive effect of therapy on renal function and inflammation has also been established. This therapy had a favorable safety profile (e. g., it did not lead to fluid overload, pulmonary edema, pleural effusion or other serious side effects, and was not associated with a clinically significant increase in endogenous serum lactate level). The RheoSTAT-CP0698 study substantiates the feasibility of using Rheosorbilact® in the complex treatment of pneumonia.

Impact of Fever Prevention in Brain-Injured Patients (INTREPID): Study Protocol for a Randomized Controlled Trial

Multiple studies demonstrate that fever/elevated temperature is associated with poor outcomes in patients with vascular brain injury; however, there are no conclusive studies that demonstrate that fever prevention/controlled normothermia is associated with better outcomes. The primary objective of the INTREPID (Impact of Fever Prevention in Brain-Injured Patients) trial is to test the hypothesis that fever prevention is superior to standard temperature management in patients with acute vascular brain injury. INTREPID is a prospective randomized open blinded endpoint study of fever prevention versus usual care in patients with ischemic or hemorrhagic stroke. The fever prevention intervention utilizes the Arctic Sun System and will be compared to standard care patients in whom fever may spontaneously develop. Ischemic stroke, intracerebral hemorrhage or subarachnoid hemorrhage patients will be included within disease-specific time-windows. Both awake and sedated patients will be included, and treatment is initiated immediately upon enrollment. Eligible patients are expected to require intensive care for at least 72h post-injury, will not be deemed unlikely to survive without severe disability, and will be treated for up to 14days, or until deemed ready for discharge from the ICU, whichever comes first. Fifty sites in the USA and worldwide will participate, with a target enrollment of 1176 patients (1000 evaluable). The target temperature is 37.0°C. The primary efficacy outcome is the total fever burden by °C-h, defined as the area under the temperature curve above 37.9°C. The primary secondary outcome, on which the sample size is based, is the modified Rankin Scale Score at 3months. All efficacy analyses including the primary and key secondary endpoints will be primarily based on an intention-to-treat population. Analysis of the as-treated and per protocol populations will also be performed on the primary and key secondary endpoints as sensitivity analyses. The INTREPID trial will provide the first results of the impact of a pivotal fever prevention intervention in patients with acute stroke ( www.clinicaltrials.gov ; NCT02996266; registered prospectively 05DEC2016).

Feasibility trial of metformin XR in people with pre-diabetes and stroke (MIPPS)-randomised open blinded endpoint controlled trial

AimsPre-diabetes is a common condition that affects about 16.4% of Australian adults. Hyperglycaemia is a strong risk factor for the development of stroke. Metformin XR is an approved medication to treat type 2 diabetes in Australia but not pre-diabetes. Additionally, whether it is tolerated following a stroke is unclear. In this pilot study, we aimed to assess the feasibility of Metformin XR in people with stroke and pre-diabetes. MethodsIn this PROBE design trial, people who had recent stroke (within 3 months) with pre-diabetes were randomized to either the active arm (n = 13) receiving usual care plus Metformin XR (500 mg daily increased to a total daily dose of 1500 mg) or the control group receiving only usual care (n = 13). At baseline & after four months of intervention, clinical and biomedical characteristics, cardiovascular risk factors and medication data were recorded. At one month and 2.5 months into the study, compliance rateandside effects were determined. ResultsThis trial showed that it is feasible to recruit, retain and monitor participants. However, the compliance rate was low. Adherence to metformin XR was 52% (IQR:42% to 61%) based on the remaining tablets in the container after 4 months of intervention. None of the reported side effects were deemed to be related to the study treatment and no significant differences were observed between the metformin XR and the control group. ConclusionTreatment with Metformin XR in participants admitted with stroke and with pre-diabetes is feasible and safe. Strategies are needed to improve adherence in future trials.

A randomized ablation-based atrial fibrillation rhythm control versus rate control trial in patients with heart failure and high burden atrial fibrillation: The RAFT-AF trial rationale and design

Heart failure (HF) and atrial fibrillation (AF) are 2 cardiac conditions that are increasing in prevalence and incidence. The 2 conditions frequently coexist, and are associated with increased morbidity and mortality. Catheter ablation of AF has been successfully performed in patients with HF, with an improvement in HF and AF, when compared to amiodarone, but further data is required to compare this to rate control. ObjectivesThe primary objective is to determine whether AF treated by catheter ablation, with or without antiarrhythmic drugs reduces all-cause mortality and hospitalizations for HF as compared with rate control in patients with HF and a high burden AF. MethodsThis is a multi-center prospective randomized open blinded endpoint (PROBE) study. Patients with NYHA class II-III HF (HF with reduced ejection fraction (<35%) or HF with preserved ejection fraction), and high burden AF are included in the trial. Patients are randomized to either rate control or catheter ablation-based AF rhythm control in a 1:1 ratio. Patients in the rate control group receive optimal HF therapy and rate control measures to achieve a resting hazard ratio (HR) < 80 bpm and 6-minute walk HR < 110 bpm. Patients randomized to catheter ablation-based AF rhythm control group receive optimal HF therapy and one or more aggressive catheter ablation, which include PV antral ablation and LA substrate ablation with or without adjunctive antiarrhythmic drug. The primary outcome is a composite of all-cause mortality and hospitalization for heart failure defined as an admission to a health care facility. The sample size is 600. Enrolment has been completed.

Quality of life measured in first-line therapy during the Cryo-FIRST study: a comparison between cryoballoon catheter ablation versus antiarrhythmic drug therapy

Abstract Background By consensus statements, catheter ablation is a recommended treatment for patients with symptomatic drug-refractory paroxysmal atrial fibrillation (AF), as patients try to alleviate the burdensome AF symptoms that reduce the Quality of Life (QoL). Yet, first-line treatment of symptomatic patients via catheter ablation prior to initiation of antiarrhythmic drugs (AADs) is only a reasonable alternative (Class IIa). Clearly, more clinical data is necessary that compares catheter ablation to AAD therapy in treatment naïve patients. Purpose The Cryo-FIRST trial was designed to compare AAD treatment against pulmonary vein isolation (PVI) while using a cryoballoon catheter (Arctic Front Advance; Medtronic, Inc.). This current data analysis examines the QoL endpoints when comparing AADs to cryoballoon ablation in patients with symptomatic treatment naïve paroxysmal AF. Methods This randomized multicenter trial enrolled 220 patients from 18 sites in 9 countries (Europe, Australia, and Latin America) in a prospective open-blinded endpoint study design. Patients had not been administered a class I or III AAD for longer than 48 hours for inclusion into the study. Subjects were randomized (1:1) into a cohort that was administered AAD therapy or a cohort that received PVI via cryoablation. The prespecified QoL endpoint at 12 months was measured using the Atrial Fibrillation Effect on Quality of Life (AFEQT) scores, and QoL recordings were taken at baseline, 1, 3, 6, 9, and 12 months following the index treatment. Results Of the 218 patients randomized (age 52±13 years, 68% male) 86% completed the 12-month follow-up. Crossovers occurred in 9% of subjects (N=20), including: 1 subject in the cryoablation arm and 19 subjects in the AAD arm. At 12 months, 86.5% of the patients in the cryoablation arm and 70.4% of the patients in the AAD arm where without symptoms (EHRA score 1). The mean AFEQT summary score was more favorable in the catheter ablation group compared to the drug therapy group at 12 months (88.9 vs. 78.1 points, respectively). The adjusted difference was 9.9 points (95% CI: 5.5–14.2; P&amp;lt;0.0001). Conclusions Cryoballoon ablation resulted in a significant improvement in QoL at 12 months compared to AAD therapy in treatment naïve patients with first-line symptomatic paroxysmal AF. Funding Acknowledgement Type of funding source: Private company. Main funding source(s): Medtronic International Trading Sàrl

Effect of rectus sheath block vs. spinal anaesthesia on time-to-readiness for hospital discharge after trans-peritoneal hand-assisted laparoscopic live donor nephrectomy: A randomised trial.

The role of spinal anaesthesia in patients having a transperitoneal hand-assisted laparoscopic donor nephrectomy in an enhanced recovery setting has never been investigated. We explored whether substituting a rectus sheath block (RSB) with spinal anaesthesia, as an adjunct to a general anaesthetic technique, influenced time-to-readiness for discharge in patients undergoing hand-assisted laparoscopic donor nephrectomy. Prospective randomised open blinded end-point (PROBE) study with two parallel groups. Tertiary University Hospital. Ninety-seven patients undergoing a trans-peritoneal hand-assisted laparoscopic donor nephrectomy. Patients (n=52) were randomly assigned to receive a general anaesthetic and a surgical RSB with 2 mg kg-1 of levobupivacaine at the time of surgical closure or a spinal anaesthetic with hyperbaric bupivacaine 12.5 mg and diamorphine 0.5 mg (n=45) before general anaesthesia. The primary outcome was the time-to-readiness for discharge following surgery. Median [IQR] times-to-readiness for discharge were 75 [56 to 83] and 79 [67 to 101] h for RSB and spinal anaesthesia and there was no significant difference in times-to-readiness for discharge (median difference 4 (95% CI, 0 to 20h; P = 0.07)). There were no significant differences in pain scores at rest (P = 0.91) or on movement (P = 0.66). Median 24-h oxycodone consumptions were similar (P = 0.80). Nausea and vomiting scores were similar (P = 0.57) and urinary retention occurred in one vs. four patients with RSB and spinal anaesthesia, respectively (P = 0.077). Substitution of RSB with spinal anaesthesia using 12.5 mg hyperbaric bupivacaine and 0.5 mg diamorphine, together with a general anaesthetic failed to confer any benefit on time-to-discharge readiness following transperitoneal hand-assisted laparoscopic donor nephrectomy. RSB provided similar analgesia in the immediate postoperative period with a low frequency of side-effects in this cohort. ClinicalTrial.gov identifier: NCT02700217.

Non-invasive brain stimulation in Stroke patients (NIBS): A prospective randomized open blinded end-point (PROBE) feasibility trial using transcranial direct current stimulation (tDCS) in post-stroke hemispatial neglect

ABSTRACT Up to 80% of people who experience a right-hemisphere stroke suffer from hemispatial neglect. This syndrome is debilitating and impedes rehabilitation. We carried out a clinical feasibility trial of transcranial direct current stimulation (tDCS) and a behavioural rehabilitation programme, alone or in combination, in patients with neglect. Patients >4 weeks post right hemisphere stroke were randomized to 10 sessions of tDCS, 10 sessions of a behavioural intervention, combined intervention, or a control task. Primary outcomes were recruitment and retention rates, with secondary outcomes effect sizes on measures of neglect and quality of life, assessed directly after the interventions, and at 6 months follow up. Of 288 confirmed stroke cases referred (representing 7% of confirmed strokes), we randomized 8% (0.6% of stroke cases overall). The largest number of exclusions (91/288 (34%)) were due to medical comorbidities that prevented patients from undergoing 10 intervention sessions. We recruited 24 patients over 29 months, with 87% completing immediate post-intervention and 67% 6 month evaluations. We established poor feasibility of a clinical trial requiring repeated hospital-based tDCS within a UK hospital healthcare setting, either with or without behavioural training, over a sustained time period. Future trials should consider intensity, duration and location of tDCS neglect interventions. Trial registration: ClinicalTrials.gov identifier: NCT02401724.

Effect of Probucol and/or Cilostazol on Carotid Intima Media Thickness in Patients with Coronary Heart Disease: A Randomized, Multicenter, Multinational Study.

Aim: In a prospective randomized multinational open blinded endpoint study, the long-term effects of probucol or probucol and cilostazol with statin on carotid mean intima media thickness (IMT) were evaluated for the first time.Methods: Hypercholesterolemic patients with coronary artery disease were randomized to three groups and received study drugs for 3 years: the control with statin alone; the probucol group with statin and probucol; and the combo group with statin, probucol, and cilostazol. Primary efficacy endpoint was changes of mean carotid IMT at 3 years. Biomarkers, major adverse cerebro-cardiovascular events (MACCEs) and safety were secondary endpoints.Results: Two hundred eighty-one patients were randomized into three groups. All three groups showed significant regression of carotid IMT at 3 years compared with baseline. Decrease in mean carotid IMT was significantly greater in the combo group than in the control group at 1 year. However, there were no significant differences in changes of mean carotid IMT between groups at 3 years (control; −0.12 ± 0.36 mm vs. probucol; −0.11 ± 0.32 mm vs. combo; −0.16 ± 0.38 mm). MACCEs were frequent in the control group, but the difference was not significant (control; 10.8% vs. probucol; 4.4% vs. combo; 6.9%, p = 0.35). Probucol and cilostazol were well tolerated in long-term treatment without serious drug-related adverse reactions.Conclusion: Probucol or probucol and cilostazol with statin did not reduce carotid IMT in comparison with statin alone in this study. However, the clinical outcome of probucol-based treatment with current standard statin treatment may need further studies.