Primary Feasibility Endpoint Research Articles

Feasibility of low-dose dexmedetomidine for prevention of postoperative delirium after intracranial operations: a pilot randomized controlled trial

BackgroundClinical trials have shown that dexmedetomidine might decrease the occurrence of postoperative delirium after major surgery, but neurosurgical patients were excluded from these studies. We aimed to determine the feasibility of conducting a full-scale randomized controlled trial of the effect of prophylactic low-dose dexmedetomidine on postoperative delirium in patients after elective intracranial operation for brain tumors.MethodsIn this single-center, parallel-arm pilot randomized controlled trial, adult patients who underwent an elective intracranial operation for brain tumors were recruited. Dexmedetomidine (0.1 μg/kg/hour) or placebo was continuously infused from intensive care unit (ICU) admission on the day of surgery until 08:00 AM on postoperative day one. Adverse events during the study-drug administration were recorded. The primary feasibility endpoint was the occurrence of study-drug interruption. Delirium was assessed twice daily with the Confusion Assessment Method for the ICU during the first five postoperative days. The assessable rate of delirium evaluation was documented.ResultsSixty participants were randomly assigned to receive either dexmedetomidine (n = 30) or placebo (n = 30). The study-drug was stopped in two patients (6.7%) in the placebo group due to desaturation after new-onset unconsciousness and an unplanned reoperation for hematoma evacuation and in one patient (3.3%) in the dexmedetomidine group due to unplanned discharge from the ICU. The absolute difference (95% confidence interval) of study-drug interruption between the two groups was 3.3% (− 18.6 to 12.0%), with a noninferiority P value of 0.009. During the study-drug infusion, no bradycardia occurred, and hypotension occurred in one patient (3.3%) in the dexmedetomidine group. Dexmedetomidine tended to decrease the incidence of tachycardia (10.0% vs. 23.3%) and hypertension (3.3% vs. 23.3%). Respiratory depression, desaturation, and unconsciousness occurred in the same patient with study-drug interruption in the placebo group (3.3%). Delirium was evaluated 600 times, of which 590 (98.3%) attempts were assessable except in one patient in the placebo group who remained in a coma after an unplanned reoperation.ConclusionsThe low rate of study-drug interruption and high assessable rate of delirium evaluation supported a fully powered trial to determine the effectiveness of low-dose dexmedetomidine on postoperative delirium in patients after intracranial operation for brain tumors.Trial registrationThe trial was registered at ClinicalTrials.gov (NCT04494828) on 31/07/2020.

A pilot study of a low glycemic load diet in patients with stage I-III colorectal cancer.

Consumption of a diet with high glycemic indices has been associated with inferior cancer-specific outcomes in patients with early-stage colorectal cancer, but there is limited prospective evidence that alterations in dietary habits improves cancer outcomes. This study aimed to determine the feasibility and acceptability of following a low glycemic load (GL) diet in patients with stage I-III colorectal cancer. Patients with stage I-III colorectal cancer, who completed definitive therapy, and consumed an average daily GL >150 participated in a 12-week tailored face-to-face dietary intervention with a target GL. This study followed a 2-stage design, with 4 planned cohorts, each with an assigned GL target and dietary intervention intensity. The primary endpoint of feasibility was determined by participant compliance, defined as an individual following the assigned GL ≥75% of the time. Compliance was determined using 24-hour telephone recalls. A cohort was deemed feasible if at least 67% of participants were compliant. Secondary endpoints included acceptability of the diet, nutritional support resources necessary to follow the diet, and evaluation of the effect of the diet on physical measures and correlative laboratories. Only cohort 1 was required as the primary endpoint of feasibility was met (stringent GL target, low intensity dietary support). The majority of participants experienced a decrease in body mass index (BMI) and waist circumference, 29% experiencing meaningful weight loss (≥5%). The dietitian spent an average of 6.97 hours (SD 2.18) face-to-face time and 1.58 hours (SD 0.68) by phone with each participant. Significant decreases were seen in total cholesterol, very-low-density lipoprotein (VLDL) and triglycerides (all P<0.05). All participants liked the foods and were satisfied with the diet. All participants felt the in-person meetings were helpful, and 62% did not feel a virtual meeting (e.g., Skype, etc.) could replace in-person meetings. Patients with stage I-III colorectal cancer can follow a low GL diet with a 12-week in-person dietary intervention. Significant changes in physical and laboratory measures suggest relevant biologic effects of the dietary intervention. This study establishes feasibility, and warrants a larger scale prospective intervention trial to evaluate the impact of a low GL diet on cancer outcomes.

TCF-001 TRACK (Target Rare Cancer Knowledge): A national patient-centric precision oncology trial for rare cancers.

TPS3143 Background: Many rare cancers are understudied, and affected patients often have few if any standard treatment options and limited access to clinical trials. Comprehensive genomic profiling (CGP) is a robust tool to efficiently identify the genomic alterations of cancer and can be applied to study rare tumors. The promise of this technology is to simultaneously enhance our understanding of diverse rare tumors and find matched therapies to benefit the individual patient in real-time. The COVID19 pandemic has challenged the “trial-centric” clinical trial infrastructure. Novel “patient-centric” trials are needed, especially for rare cancers. TRACK is a decentralized, patient advocacy-initiated trial that aims to establish whether patients with rare tumors and cancer of unknown primary can benefit from matched molecular therapy as dictated by their CGP results. Methods: This is a national open label, non-randomized, multi-center (includes community and academic centers) pragmatic study in rare tumors (&lt;6 cases per 100,000 persons per year) and cancer of unknown primary. All participants will have tumor tissue and blood analyzed by CGP (FoundationOneCDx and FoundationOneLiquidCDx). A Virtual Molecular Tumor Board (VMTB) will convene to identify targeted treatment recommendations for participants with genomic alterations. Overall, 400 participants will be enrolled to achieve the goal of 100 patients matched to genomically informed treatment, utilizing remote consenting to ensure study access regardless of geographic location. The primary feasibility endpoint is the percent of participants who receive a molecularly matched treatment after recommendation from the VMTB. The primary efficacy endpoint is the progression-free survival (PFS) among participants who received the molecularly matched treatment. Secondary endpoints include the percent of participants with genomic alterations, overall response rate, response duration, overall survival, clinical benefit rate (SD &gt; 6 months; PR; CR), and high-grade toxicities (as available) of matched targeted therapy. Exploratory endpoints include matching rates; understanding genomic correlates of response; concordance rates between CGP from tissue and blood, time-to-treatment failure, and the impact of the cancer treatment from the patient perspective (via ESAS-FS, a validated patient-reported outcomes (PRO) instrument). All eligible and enrolled patients, regardless of whether receiving matched treatment or not, will be followed for a minimum of one year in a uniform way such that the treatment efficacy and outcomes can be assessed in standard formats. The study is open with six patients enrolled at time of submission. Clinical trial information: NCT04504604.

Pilot trial treating recurrent GBM patients with precision medicine regimens.

2045 Background: Recurrence of GBM after initial treatment with surgery, radiation, and chemotherapy is nearly universal. Salvage therapies have limited efficacy with median overall survival (OS) of approximately 9 months and 6-month-progression-free survival (PFS-6) of 10-25% for both targeted and traditional therapies. Given GBM’s molecular heterogeneity, targeting a single molecular abnormality in isolation has consistently failed as a strategy, and precision combination approaches are needed. Methods: The primary objective was to demonstrate the feasibility of implementing a personalized drug regimen for patients (pts) with surgically resectable recurrent GBM within 35 days of surgery. Secondary objectives included safety and efficacy. Eligible pts signed consent before surgery, and tumor tissue was analyzed using the CLIA-approved “UCSF500” next-generation sequencing panel with paired tumor/germline sequencing. A specialized genomic tumor board made individualized treatment recommendations incorporating sequencing results of the recurrent tumor and clinical history for each pt, using up to 4 FDA-approved drugs in combination (all drugs provided by study). Correlative studies will be reported separately. Results: 19 pts signed consent and 16 pts had surgery on trial, 1 with pathology showing treatment effect only. The remaining 15 pts were all genetically profiled and successfully started their individualized treatment within 35 days of surgery, meeting the primary feasibility endpoint. Conclusions: Implementation of an individualized treatment regimen was feasible in a timely fashion in surgically resectable recurrent GBM pts, with encouraging preliminary efficacy results. Further investigation is warranted, both to validate efficacy and to streamline this approach in larger pt populations. Clinical trial information: NCT03681028. [Table: see text]

Feasibility of integrating the Outcomes4Me smartphone navigation application into the care of breast cancer patients (FIONA).

1570 Background: Patients diagnosed with breast cancer (BC) face complex decisions about their care and many studies have shown that improved patient engagement results in increased satisfaction and better outcomes. Patient engagement includes education, treatment option selection, symptom tracking and reporting, and clinical trial opportunities. We conducted a pilot study to determine the feasibility of introducing the Outcomes4Me patient engagement app into the standard of care experience of BC patients. Methods: This was a pilot study (NCT04262518) conducted at an academic medical center. Eligible patients had any subtype of stage 1-4 BC and were on any type of chemo-, hormonal-, targeted-, or radiation-therapy for BC during the study period. Participants downloaded the app on their smartphone and their app usage was evaluated. Surveys were administered at baseline and end of study. Clinicians caring for patients using the app were surveyed at the end of the study. The primary endpoint was feasibility, defined as at least 40% of patients engaging with the app at least 3 times over the 12-week study period. Additional endpoints included usability, satisfaction, correlation of patient reported data with the EHR, clinical trial matching, and patient experience. Results: Between June 2020 and December 2020, 107 patients enrolled; results are reported for 90 patients with complete data as of 1/24/21. Baseline demographics: median age 53 (range: 27-77); 90% White, 4% Black, 3% Asian; 66% had hormone positive/HER2-, 20% HER2+, and 13% triple negative BC; 31% had stage 4 disease. At study entry, 93% had never used an app to help with their disease or treatment options. Over the 12 week study period, 58% of patients engaged with the app at least 3 times, meeting the primary feasibility endpoint. Patients engaged with the app on average 5.5 days (range: 0-40) with 20% engaging on more than 10 days during the study. The mean System Usability Score was 71 (median = 76) and was similar across age groups. The 5 app features deemed most (‘somewhat’ or ‘very’) helpful were: background about their BC (76%), information about treatment options (74%), newsfeed about their BC (70%), symptom tracking (65%), and clinical trial information (65%). 53% said that the app helped them keep track of symptoms and 33% said they are more likely to explore or enroll in a clinical trial after using the app. Conclusions: Integration of the Outcomes4Me app into the care management of BC patients is feasible with acceptable usability. Our results suggest that use of a patient smartphone app may be helpful for many aspects of patient education and engagement for patients with BC. The results also suggest that this type of intervention can help patients better track their symptoms and make them aware of clinical trials, potentially facilitating the management of side effects and accelerating clinical trials recruitment. Clinical trial information: NCT04262518.

A Mobile Patient-Facing App for Tracking Patient-Reported Outcomes in Head and Neck Cancer Survivors: Single-Arm Feasibility Study.

BackgroundPatients with head and neck cancer (HNC) frequently experience disease-related symptoms and treatment adverse effects that impact their overall quality of life. Cancer-specific mobile health apps for patient-related outcomes allow patients to communicate with their clinicians and proactively track their symptoms, which have been shown to improve clinical management and disease outcomes.ObjectiveThe purpose of this study was to evaluate the feasibility of LogPAL, a novel iPhone-based mobile health app designed to help HNC survivors track and manage their posttreatment symptoms.MethodsPatients who completed curative treatment for HNC in the preceding 24 months were recruited from 2 clinical sites within a single institution. Upon enrollment, participants completed a brief sociodemographic survey, downloaded the app onto their iPhone devices, and were asked to complete a series of biweekly questionnaires (based on the Patient-Reported Outcomes version of the Common Terminology Criteria for Adverse Events) via the app for an 8-week study period. The primary feasibility endpoints included retention (retaining >80% of the enrolled participants for the duration of the study period), adherence (>50% of the participants completing 100% of the questionnaires over the study period), and usability (a mean system usability scale [SUS] score >68). Additional postintervention questions were collected to assess perceived usefulness, acceptance, and overall satisfaction.ResultsBetween January and October 2019, 38 participants were enrolled in the study. Three participants dropped out, and 3 were classified as nonusers. The remaining 32 (87%) were eligible for analysis. Their mean age was 57.8 (SD 12.3) years (range 24-77 years, 81% [26/32] male). Overall, 375 of 512 (73.2%) questionnaires were completed, with 17 (53%) of the 32 participants adherent. Participant-reported usability was acceptable; the mean SUS score was 71.9 (95% CI 64.3-79.5) with high satisfaction of LogPAL usefulness and likelihood to recommend to other cancer survivors.ConclusionsThis single-arm prospective pilot study showed that LogPAL is a feasible, regularly used, accepted app for HNC survivors, justifying a full-scale pilot. Based on the findings from this study, future iterations will aim to improve usability and test intervention efficacy.

Online Quantitative Aortographic Assessment of Aortic Regurgitation AfterTAVR: Results of the OVAL Study.

The aim of this study was to investigate the online assessment feasibility of aortography using videodensitometry in the catheterization laboratory during transcatheter aortic valve replacement (TAVR). Quantitative assessment of regurgitation after TAVR through aortography using videodensitometry is simple, reproducible, and validated invitro, invivo, in clinical trials, and in "real-world" patients. However, thus far the assessment has been done offline. This was a single center, prospective, proof-of-principle, feasibility study. One hundred consecutive patients with aortic stenosis and indications to undergo TAVR were enrolled. All final aortograms were analyzed immediately after acquisition in the catheterization laboratory and were also sent to an independent core laboratory for blinded offline assessment. The primary endpoint of the study was the feasibility of the online assessment of regurgitation (percentage of analyzable cases). The secondary endpoint was the reproducibility of results between the online assessment and the offline analysis by the core laboratory. Patients' mean age was 81 ± 7 years, and 56% were men. The implanted valves were either SAPIEN 3 (97%) or SAPIEN 3 Ultra (3%). The primary endpoint of online feasibility of analysis was 92% (95% confidence interval [CI]: 86% to 97%) which was the same feasibility encountered by the core laboratory (92%; 95%CI: 86% to 97%). Reproducibility assessment showed a high correlation between online and core laboratory evaluations (R2=0.87, p<0.001), with an intraclass correlation coefficient of 0.962 (95%CI: 0.942 to 0.975; p<0.001). This study showed high feasibility of online quantitative assessment of regurgitation and high agreement between the online examiner and core laboratory. These results may pave the way for the application of videodensitometry in the catheterization laboratory after TAVR. (Online Videodensitometric Assessment of Aortic Regurgitation in the Cath-Lab [OVAL]; NCT04047082).

Designing a Pragmatic Intervention to Help Improve the Bladder Cancer Patient Experience.

Bladder cancer (BC) is the 10th most common malignancy worldwide and the patient experience is found to be worse than that for patients diagnosed with other cancer types. We aimed to develop a wellbeing intervention to help improve the bladder cancer patient experience by ameliorating their health-related Quality of Life (HRQoL). We followed the 3 phases of the modified Medical Research Council (MRC) Framework for development of complex interventions. Following a systematic review of the literature on mental, sexual, and physical wellbeing, we conducted discussion groups with patients and healthcare professionals on these 3 themes. A consultation phase was then conducted with all relevant stakeholders to co-design a wellbeing intervention as part of a feasibility study. A pragmatic wellbeing feasibility trial was designed based on the hypothesis that a wellbeing program will increase patient awareness and attendance to services available to them and will better support their needs to improve HRQoL. The primary feasibility endpoints are patient attendance to the services offered and changes in HRQoL. The principle of patient centered care has strengthened the commitment to provide a holistic approach to support BC patients. In this study, we developed a wellbeing intervention in collaboration with patients and healthcare professionals to meet an unmet need in terms of the BC patient experience.

High flow in children with respiratory failure: A randomised controlled pilot trial - A paediatric acute respiratory intervention study.

High-flow is increasingly used in children with acute hypoxaemic respiratory failure (AHRF), despite limited evidence. The primary feasibility endpoint for this pilot-study was the proportion of treatment failure, secondary outcomes being intensive care unit (ICU) admissions and proportion of patients requiring escalation of care. We measured duration of hospital stay, duration of oxygen therapy and rates of ICU admission. An open-labelled randomised controlled trial feasibility design was used in two tertiary children's hospitals in the emergency department and general wards. Children aged 0-16 years with AHRF were randomised (1:1) to either high-flow or standard-oxygen. Children on standard-oxygen received rescue high-flow in general wards if failure criteria were met. Of 563 randomised, 283 received high-flow and 280 standard-oxygen with no adverse events. The proportion of children who failed treatment and receiving escalation of care was 11.7% (32/283 children) on high-flow and 18.1% (50/280 infants) on standard-oxygen (odds ratio 0.68, 95% confidence interval 0.38-1.00). In children with obstructive airway disease, 9.7% on high-flow and 17.4% on standard-oxygen required escalation (risk-difference -7.7% percentage points; 95% confidence interval -14.3, -1.1); in children with non-obstructive disease no difference was observed. Neither difference in ICU admissions nor any difference in length of hospital stay was observed. Sixty percent of children who failed standard-oxygen responded to rescue high-flow. High-flow outside ICU appears to be feasible in children with AHRF and the required proportion of escalation was lower compared to standard-oxygen. The trial design can be applied in a future large randomised controlled trial.

Safety and feasibility evaluation of planning and execution of surgical revascularisation solely based on coronary CTA and FFRCT in patients with complex coronary artery disease: study protocol of the FASTTRACK CABG study

IntroductionThe previously published SYNTAX III REVOLUTION trial demonstrated that clinical decision-making between coronary artery bypass graft (CABG) and percutaneous coronary intervention based on coronary CT angiography (CCTA) had a very...

A novel decision aid for acute myeloid leukemia: a feasibility and preliminary efficacy trial.

Acute myeloid leukemia (AML) is a hematologic malignancy characterized by a poor prognosis but also a paradoxical possibility of cure. This renders decision-making complex and imminent. Unfortunately, many patients with AML misestimate their prognosis and treatment risk. While decision aids can improve illness understanding and reduce decisional conflict, there are no validated decision aids for AML. We developed and tested a novel AML decision aid (NCT03442452). Patients (n = 20) were recruited at Duke University from May 2018 to February 2019. Participants completed assessments of AML knowledge and decisional conflict, before and after using the electronic decision aid. The primary endpoint was feasibility (endpoint met if > 80% of study participants completed all study components). Secondary analyses of efficacy were conducted using paired t tests for dependent pre-/post-samples. The primary endpoint of feasibility was met (100% of participants completed all study components). Secondary analyses showed improved knowledge and reduced decisional conflict after using the decision aid. Knowledge scores improved from a mean of 11.8 (out of 18) correct items at baseline to 15.1 correct items after using the decision aid (mean difference 3.35; p < 0.0001). Decisional conflict scores reduced significantly from baseline to post-test as well (mean difference - 6.5; p = 0.02). These findings suggest that our AML decision aid is a useful tool to improve the patient experience and promote shared decision-making in AML. A randomized efficacy trial is planned.

A Pilot Study of Brentuximab Vedotin, Rituximab and Dose Attenuated CHP in Patients 75 Years and Older with Diffuse Large B-Cell Lymphoma

Older patients with hematologic malignancies are underrepresented on prospective clinical trials relative to the incidence of disease in this group (Kanapuru et al, 2020). There are few studies in diffuse large B-cell lymphoma (DLBCL) focused specifically on older patients. Rituximab and dose attenuated cyclophosphamide, doxorubicin, vincristine, and prednisone (R-miniCHOP) has been studied on a prospective trial in fit patients aged 80 years and older. Seventy-two percent of patients on this study completed 6 cycles of R-miniCHOP. The overall response rate (ORR) was 73%, and the 2-year progression free survival (PFS) was 47% (Peyrade et al, 2011). Novel regimens are needed to improve upon the efficacy of therapy while preserving tolerability. Brentuximab vedotin (BV) has demonstrated activity in relapsed and refractory DLBCL (Jacobsen et al, 2015) as well as in combination with chemoimmunotherapy (Svoboda, 2020). This study evaluates the feasibility of BV with dose attenuated chemoimmunotherapy. Methods: Patients with both CD30 positive (cut off 1%) and CD30 negative DLBCL aged 75 years and older were enrolled on the study. Patients received six, 3-week cycles of BV 1.8 mg/kg, cyclophosphamide 400 mg/m2, doxorubicin 25 mg/m2, vincristine 1 mg and prednisone 40 mg/m2 days 1-5 (BV R-miniCHP). For the first cycle patients received BV and prednisone as a prephase starting one week prior to cycle 1. All patients received pegfilgrastim. All patients underwent geriatric assessments at screening, following prephase and at the end of treatment. The primary endpoint was feasibility of this regimen in older patients. The regimen was considered feasible if 71% of patients completed 6 cycles of treatment with a 90% confidence interval (CI)=(58.0, 90.6%). Secondary endpoints included toxicity, ORR and complete response (CR) evaluated by positron emission tomography, PFS and overall survival (OS). Response assessments used the Lugano Criteria (Cheson et al, 2014). PFS and OS were estimated using the Kaplan-Meier method. Results: Twenty-two patients were enrolled and started prephase with BV and prednisone. Their baseline characteristics are summarized in the table. Seventy-seven percent (17/22) of patients completed 6 cycles of BV R-miniCHP. Reasons for not completing treatment included progressive disease in 2 patients, myocardial infarction, fatigue, and an unrelated injury in 1 patient each. Twenty-one patients were evaluable for response. ORR was 86% (18/21) in all patients, with 67% (14/21) achieving CR. In CD30 positive patients the ORR was 80% (8/10) and the CR rate was 70% (7/10). In CD30 negative patients the ORR was 91% (10/11) and the CR rate was 64% (7/11). With a median follow up of 23 months, median OS and PFS (figure) were not reached. The 2-year PFS was 60.6%, 90% CI=(40.0%, 76.1%), and the 2-year OS was 73.9%, 90% CI=(52.4%, 86.8%). The most common adverse events (AEs) were fatigue (82%), anemia (50%), diarrhea (50%), dysgeusia (45%) and peripheral sensory neuropathy (45%). Grade ≥3 AEs seen in more than 2 patients included neutropenia (23%), fatigue (18%), pneumonia (18%), hypoxia (14%), thrombocytopenia (9%) and thromboembolism (9%). Grade ≥3 peripheral sensory neuropathy was seen in 9% of patients. There were two deaths in patients receiving study treatment. These included a myocardial infarction related to treatment, and a bowel obstruction secondary to disease progression. Three other patients have died in follow up with 2 secondary to disease progression and 1 due to an unrelated event. Conclusions: The study met its primary feasibility endpoint with 77% of patients completing 6 cycles of therapy. This regimen was delivered safely in this population and toxicities were consistent with those reported in larger prospective studies with R-miniCHOP or ofatumumab and miniCHOP (Peyrade et al, 2011; Peyrade et al 2017). Peripheral neuropathy is a key AE of interest given the inclusion of BV and while nearly half of patients experienced some peripheral neuropathy, it was severe in only 9% of pts. The ORR and CR rate, as well as the 2-year PFS compare favorably to other prospective studies in a population that included patients with high clinical risk, histologic transformation, and double hit lymphoma. BV and R-miniCHP may be a feasible regimen in older patients, and warrants further study based on these preliminary data demonstrating clinical activity and tolerability. Figure 1 Disclosures Reagan: Seattle Genetics: Research Funding; Curis: Consultancy; Kite, a Gilead Company: Consultancy. Portell:Xencor: Research Funding; Roche/Genentech: Consultancy, Research Funding; Infinity: Research Funding; TG Therapeutics: Research Funding; AbbVie: Research Funding; Pharmacyclics: Consultancy; Janssen: Consultancy; Amgen: Consultancy; Bayer: Consultancy; BeiGene: Consultancy, Research Funding; Kite: Consultancy, Research Funding; Acerta/AstraZeneca: Research Funding. Barr:Gilead: Consultancy; Verastem: Consultancy; Abbvie/Pharmacyclics: Consultancy, Research Funding; Genentech: Consultancy; AstraZeneca: Consultancy, Research Funding; Janssen: Consultancy; Seattle Genetics: Consultancy; Celgene: Consultancy; Morphosys: Consultancy; TG therapeutics: Consultancy, Research Funding; Merck: Consultancy. Friedberg:Acerta Pharma - A member of the AstraZeneca Group, Bayer HealthCare Pharmaceuticals.: Other; Roche: Other: Travel expenses; Kite Pharmaceuticals: Research Funding; Seattle Genetics: Research Funding; Portola Pharmaceuticals: Consultancy; Astellas: Consultancy; Bayer: Consultancy.

Primary Palliative Care for Patients with Advanced Hematologic Malignancies: A Pilot Trial of the SHARE Intervention.

Objective: Develop and pilot-test a nurse-led primary palliative care intervention for patients with advanced hematologic malignancies. Background: Nurse-led primary palliative care interventions may improve outpatient palliative care provision for patients with advanced hematologic malignancies. Methods: This two-phase, single-arm pilot study involved patients with recurrent or resistant hematologic malignancies, their caregivers, and oncology clinicians at two US-based urban, university-affiliated oncology clinics. Measurements included feasibility (enrollment rates, intervention fidelity, and outcome assessment rates) and acceptability (patient, caregiver, and clinician surveys). Results: In Phase 1 we developed and implemented an oncology nurse-led primary palliative care intervention for patients with recurrent or resistant hematologic malignancies and their caregivers. In Phase 2, we tested feasibility and acceptability. Twenty-six patient participants enrolled. Consent-to-approach rate was 78% and enrolled-to-consent rate was 84%. All enrolled participants received the intervention per protocol. Sixty-nine percent of patients and 100% of caregivers reported that the intervention helped them better understand the patient's illness and cope. Seventy-five percent of oncologists reported that the intervention improved their patients' quality of care, and 25% reported that it helped them take better care of patients. Conclusions: Although our pilot of oncology nurse-led primary palliative care for patients with advanced hematologic malignancies met some of its secondary feasibility endpoints, it did not meet its primary feasibility endpoint (enrollment) and acceptability was mixed. Protecting nursing staff time, increasing patient and clinician involvement in intervention development, and identifying patients with highest supportive needs may improve feasibility and acceptability of future primary palliative care in hematologic malignancy trials.

Subarachnoid Hemorrhage "Fast Track": A Health Economics and Health Care Redesign Approach for Early Selected Hospital Discharge.

ObjectiveTo determine whether earlier hospital discharge is feasible and safe in selected patients with subarachnoid hemorrhage (SAH) using an outpatient “fast-track” protocol.Patients and MethodsWe conducted a prospective quality improvement cohort study with the primary feasibility end point of patients with SAH deemed safe for discharge by treating team consensus. All patients received detailed education and outpatient transcranial Doppler monitoring; caregivers could contact the on-call team 24-7. Primary safety end points were adverse events after discharge and hospital readmission.ResultsFrom January 1, 2010, to January 1, 2015, our center had 377 SAH diagnoses, of which 200 were included in the final cohort, 36 qualifying for fast-track early discharge. The 30-day readmission rate for fast-track patients was 11.0% (4 of 36) compared with 11.4% (18 of 164) for non–fast-track patients. The rate of delayed cerebral ischemia and stroke was 3% (1 of 36) in the fast-track group vs 25.0% (41 of 164) for the non–fast-track group. Adverse events occurred in 11.0% (4 of 36) of the fast-track group compared with 26.0% (43 of 164) in the non–fast-track group. The mean length of stay was reduced 60% from 15 days to 6.6 days in the fast-track group.ConclusionAlthough our fast-track group was relatively small, data suggested early feasibility and safety in a carefully selected group of patients with SAH. Direct and indirect financial benefits of early discharge over a 5-year period were an estimated savings at least $864,000 in overall costs. A comparative effectiveness study is planned to replicate and validate these results using a larger multicenter design.

Lipid microsphere bound oxycodone for pain management in patients receiving radiotherapy for head and neck cancer

Wax microsphere bound oxycodone was developed as an abuse-deterrent opioid and maintains a similar pharmacokinetic profile whether administered with or without an intact capsule. We hypothesized that microsphere oxycodone could be utilized for extended release analgesia in patients undergoing radiation (RT) for head-and-neck cancer (HNC) and would not need to be discontinued due to dysphagia or gastrostomy tube dependence. We performed a prospective trial that enrolled participants > 18years with histologically confirmed HNC who were scheduled to receive RT. Analgesia was prescribed in accordance with the WHO pain ladder. Microsphere oxycodone was initiated when total daily opioid dose exceeded 30mg of morphine sulfate equivalent and was titrated weekly during RT. Pain level and effect on quality of life were assessed using the Brief Pain Inventory. The primary feasibility endpoint was frequency of microsphere oxycodone discontinuation within 3months of RT for reasons other than pain resolution. Twenty-six eligible patients were enrolled. Microsphere oxycodone was initiated in 16 (61.5%) patients. Six (23.1%) patients utilized a gastrostomy tube to administer microsphere oxycodone during all or part of RT. Microsphere oxycodone was discontinued in 1 (7.6%) patient due to perceived inefficacy. No patients were discontinued due to toxicity or difficulty with administration. Ratings for average pain was 3.1 (± 3.4) at enrollment, 4.0 (± 2.4) at week 6 of RT, and 1.8 (± 2.2) at 3-month follow-up. These results support the feasibility and safety of microsphere oxycodone for extended release analgesia among patients with HNC undergoing RT.

Randomised, double-blind, multicentre, mixed-methods, dose-escalation feasibility trial of mirtazapine for better treatment of severe breathlessness in advanced lung disease (BETTER-B feasibility)

New treatments are required for severe breathlessness in advanced disease. We conducted a randomised feasibility trial of mirtazapine over 28 days in adults with a modified medical research council breathlessness...

Microsphere oxycodone for pain management in head and neck cancer (HNC) patients receiving radiotherapy.

123 Background: Pain is a common adverse effect of RT in patients with HNC, and extended release analgesic options are limited due to high rates of dysphagia. Wax microsphere bound oxycodone was developed as an abuse-deterrent opioid and maintains a similar pharmacokinetic profile whether administered with or without an intact capsule. We hypothesized that microsphere oxycodone could be used for extended release analgesia in patients undergoing RT for HNC and would not need to be discontinued due to dysphagia or gastrostomy tube dependence. Methods: We performed an open-label prospective clinical trial (NCT03317730) to assess the feasibility of microsphere oxycodone for extended release analgesia during RT for HNC. Participants were &gt; 18y, had histologically confirmed HNC, and were to receive &gt; 50 Gy of RT. Analgesia was prescribed in accordance with the World Health Organization pain ladder. Non-opioid and immediate release opioids were used at the discretion of the treating physicians. Microsphere oxycodone was initiated when total daily opioid dose exceeded 30mg morphine sulfate equivalent and was titrated weekly during RT. The primary feasibility endpoint was frequency of microsphere oxycodone discontinuation within 3 months of RT for reasons other than pain resolution. Secondary endpoints included pain level during RT. Results: Twenty-six eligible patients were enrolled between June and November, 2018. Microsphere oxycodone was initiated in 13 (50%) patients at a median of 5 weeks after beginning RT (range: 0 – 7 weeks). The mean Brief Pain Index Severity composite score at time of microsphere oxycodone initiation was 5.4 (SD ±2.0) and was 4.8 (SD ±1.5) during the final week of RT ( p= 0.21). Six patients utilized a gastrostomy tube to administer microsphere oxycodone for all or part of RT. Microsphere oxycodone was discontinued in 1 (7.6%) patient due to perceived inefficacy, 0 patients due to toxicity, and 0 patients due to difficulty with administration. Conclusions: These results support the feasibility and safety of microsphere oxycodone for extended release analgesia in patients with HNC undergoing RT. Future research should compare microsphere oxycodone and transdermal fentanyl in this population. Clinical trial information: NCT03317730.

P4490Safety and feasibility of non invasive transthoracic pulsed cavitational ultrasound therapy (PCUT) on a swine aortic valve model

Abstract Background Aortic valve stenosis is associated with age and comorbidities, which require exploring less invasive therapeutic approach to improve patient outcome. We previously demonstrated in vitro and in vivo that pulsed cavitational ultrasound therapy (PCUT) can improve calcified bioprosthesis stenosis by softening leaflets remotely. To apply this technique noninvasively we aim to test PCUT transthoracicalyin a swine model targeting aortic valve. Because calcified aortic valve model doesn't exist, we tested this technique on a normal valve. Objective Primary objective was to estimate the feasibility and safety of PCUT. Secondary objectiveswere to evaluate occurrence, severity and evolution of cardiovascular side effects during therapy and within follow-up period (30±5 days) with and without double antithrombotic treatment. Methods All the experiments were performed on normal aortic valves (n=19) of swine. The system was composed of a high-power multi-element transducer with electronic steering and 2D echocardiographic probe embedded in the center. Swine were divided in three groups: one with PCUT and no anti thrombotic treatment (n=10), a second with PCUT and one-month treatment of aspirin and clopidogrel (n=5) and third group sham (n=4). All groups were followed up after 30 days. Results The primary feasibility endpoint was successful in 100% of tests performed (n=16). A maximal amplitude of 70 MPa and −19 MPa respectively for positive and negative peak pressure was found at the focus point. Survival at 30 days was 100% and no life-threatening arrhythmia was recorded and no sustained ventricular arrhythmia (SVT &gt;30 s) was noticed. For the secondary safety objectives,we recorded acutely, at the time of procedure, NSVT in 7 pigs which corresponded to a cumulated duration of 2.1 out of the 485.3 min of the total US delivery (0.4% of time). Mean cycle of NSVT was slow 428.9 ms in average (139.6 bpm). The interruption or decrease of power of US delivery allowed immediate cessation of cardiac arrhythmia in all cases. There was no evidence of damage to the valve and no observation of impairment of valvular function by echocardiography. Only one animal showed side effects (RV dilatation) and the RV returned to normal after cessation of the therapy with no sequelae at follow up. At follow up no significant findings biology disturbance or valve thrombosis was observed (creatinine, CK MB, hemoglobin, hematocrit, haptoglobin or red blood cell numbers). Antithrombotic treatment didn't demonstrate any advantage at follow up. Conclusion We demonstrated in vivo feasibility and safety of transthoracic PCUT targeting aortic valve without any serious adverse event and no significant histopathology damage. We hope that this first-time transthoracic delivery of very focused ultrasound at high power will pave the way to new non invasive approach of valve softening in case of human aortic valve calcified stenosis.

Sustained High-dose Thiamine Supplementation in High-risk Cardiac Patients Undergoing Cardiopulmonary Bypass: A Pilot Feasibility Study (The APPLY trial)

To test the feasibility and investigate possible cardiovascular effects of a sustained high-dose intravenous thiamine protocol in patients undergoing combined valvular and coronary artery bypass graft surgery. Randomized, placebo-controlled, pilot feasibility trial. Cardiac surgery department of a tertiary hospital. Forty patients undergoing combined valvular and coronary artery bypass surgery. Intravenous thiamine (600 mg on the day of surgery, and 400 mg/day on postoperative days 1, 2, and 3) or placebo. The primary feasibility endpoints were recruitment rate and protocol compliance. Secondary endpoints included markers of possible biological and physiological effects. The mean recruitment rate was 8 patients per month and protocol compliance was 97.5%. There were no differences in median peak postoperative lactate (2.7 mmol/L [interquartile range [IQR] 1.4-4.6] for thiamine v 2.5 mmol/L [IQR 1.4-3.6] for placebo; p = 0.53), median peak postoperative creatinine (104 µmol/L [IQR 92.5-129] for thiamine v 99 µmol/L [IQR 86.5-109.5] for placebo; p = 0.53), median nadir postoperative cardiac index (1.8 L/min/m2 [IQR 1.5-2.1] for thiamine v 2.2 L/min/m2 [IQR 1.5-2.5] for placebo; p = 0.25), or the number of patients on vasopressor/inotropic agents (thiamine, 12 [63%]; placebo, 12 [60%]; p = 0.80), or in the total inotrope/vasopressor dose 0.14 µg/kg for thiamine v 0.12 µg/kg for placebo; p = 0.88). A double-blind trial of sustained high-dose intravenous thiamine supplementation in higher-risk cardiac surgery patients was feasible and appeared to be safe. However, such treatment did not demonstrate evidence of biological or physiological effects.

Initiating resuscitation before umbilical cord clamping in infants with congenital diaphragmatic hernia: a pilot feasibility trial

BackgroundInfants with congenital diaphragmatic hernia (CDH) often experience hypoxaemia with acidosis immediately after birth. The traditional approach in the delivery room is immediate cord clamping followed by intubation. Initiating resuscitation...