A Pilot Placebo Controlled Randomized Trial of Dexamethasone for Chronic Subdural Hematoma

AbstractBackground: Current opinions regarding the use of dexamethasone in the treatment of chronic subdural hematomas (CSDH) are only based on observational studies. Moreover, the use of corticosteroids in asymptomatic or minimally symptomatic patient with this condition remains controversial. Here, we present data from a prospective randomized pilot study of CSDH patients treated with dexamethasone or placebo. Methods: Twenty patients with imaging-confirmed CSDH were recruited from a single center and randomized to receive dexamethasone (12 mg/day for 3 weeks followed by tapering) or placebo as a conservative treatment. Patients were followed for 6 months and the rate of success of conservative treatment with dexamethasone versus placebo was measured. Parameters such as hematoma thickness and clinical changes were also compared before and after treatment with chi-square tests. Adverse events and complications were documented. Results: During the 6-month follow-up, one of ten patients treated with corticosteroids had to undergo surgical drainage and three of ten patients were treated surgically after placebo treatment. At the end of the study, all remaining patients had complete radiological resolution. No significant differences were observed in terms of hematoma thickness profile and impression of change; however, patients experienced more severe side effects when treated with steroids as compared with placebo. Dexamethasone contributed to many serious adverse events. Conclusions: Given the small sample size, these preliminary results have not shown a clear beneficial effect of dexamethasone against placebo in our patients. However, the number of secondary effects reported was much greater for corticosteroids, and dexamethasone treatment was responsible for significant complications.

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Impact of the Oncology Care Model (OCM) on pain management: A retrospective cohort analysis.

Journal of Clinical Oncology ◽

10.1200/jco.2019.37.31_suppl.86 ◽

2019 ◽

Vol 37 (31_suppl) ◽

pp. 86-86

Author(s):

Aaron Ciner ◽

Jacqueline Norrell ◽

Renee Kurz ◽

Ann W. Silk

Keyword(s):

Pain Score ◽

Small Sample Size ◽

Performance Status ◽

Cohort Analysis ◽

Small Sample ◽

Common Symptom ◽

Chi Square ◽

Pain Scores ◽

Before And After ◽

Pain Intervention

86 Background: Pain is a common symptom among patients with cancer and impacts performance status and quality of life. The OCM was implemented at Rutgers Cancer Institute of New Jersey (RCINJ) in July 2016 with the goal of improving many quality metrics in cancer care including documentation of pain and a plan of care for pain. Hypothesis: Documentation of pain and a plan of care for pain improved after implementation of the OCM at RCINJ. Improved documentation would correlate with a decrease in reported quantitative pain scores. Methods: Data from patients enrolled in OCM during its first year of implementation (post OCM) was compared to data from a control cohort the preceding year (pre OCM). The initial progress note and EMR flowsheet in each year were reviewed to determine pain documentation. For patients reporting a pain score ≥ 1 on a 0-10 scale, the association between documentation of a plan of care and improvement in quantitative pain score on a subsequent visit was analyzed using Chi square testing. Results: A total of 260 patient charts were analyzed. A quantitative pain score was documented in 99% of patients in the pre OCM group and 100% in the post OCM group. For those with a pain score ≥ 1, documentation of a plan of care increased from 43% to 55% after OCM implementation. Patients whose charts contained documented plans of care for pain were less likely to have decreased pain scores at a subsequent visit (51% vs 76%). Conclusions: (1) Documentation of a quantitative pain score was completed in nearly all patients before and after the implementation of OCM. (2) There was a non-statistically significant increase in documentation of plan of care for pain after OCM implementation. (3) Documentation of a plan of care was not associated with a decreased pain score at a subsequent visit. This may be the result of small sample size or related to progressive cancer-related pain or inadequate pain intervention. [Table: see text]

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Immune related adverse events in NSCLC patients treated with immune checkpoint therapy who received the influenza vaccination versus no vaccination.

Journal of Clinical Oncology ◽

10.1200/jco.2019.37.15_suppl.e20657 ◽

2019 ◽

Vol 37 (15_suppl) ◽

pp. e20657-e20657

Author(s):

Haritha G. Reddy ◽

Taylor Mai Weis ◽

Shannon Hough ◽

Stephanie Daignault ◽

Bryan J. Schneider

Keyword(s):

Adverse Events ◽

Influenza Vaccine ◽

Influenza Vaccination ◽

Immune Checkpoint ◽

Checkpoint Inhibitors ◽

Small Sample Size ◽

Performance Status ◽

Small Sample ◽

Ecog Performance Status ◽

Chi Square

e20657 Background: Influenza vaccination is recommended by the CDC for cancer patients to reduce the risk of influenza-related complications. There is concern that the incidence of immune-related adverse events (irAEs) may be greater in vaccinated patients receiving immune checkpoint inhibitors (ICPI). We sought to interrogate if influenza vaccination in patients with NSCLC receiving ICPI therapy had an increased incidence of irAEs compared to non-vaccinated patients. Methods: We conducted a single-center retrospective analysis of patients with advanced NSCLC who received PD-1 or PD-L1 inhibitor monotherapy between 3/2015 – 12/2018. Influenza immunization records from both institutional and state-wide registries were obtained from 2014 -2019. Comparisons of adverse event incidence between flu vaccinated and control patients were tested using chi-square statistics. Results: 117 patients were included in our analysis, 33 (28%) were vaccinated during ICPI therapy, 19 (58%) received quadrivalent influenza vaccine, 13 (39%) received trivalent influenza vaccine and 1 (3%) was undetermined. 22 (67%) vaccinated patients had an irAE vs 53 (63%) patients who were not vaccinated during ICPI therapy (p = 0.720). 8 (24%) vaccinated patients had an irAE leading to discontinuation of therapy vs 12 (14%) patients who were not vaccinated during ICPI therapy (p = 0.198). The most frequent irAE in both groups was fatigue 16 (48%) vs 28 (33%) (p = 0.128). Notable irAEs included colitis (0 vs 1), pneumonitis (3 vs 3), hepatitis (1 vs 4) in vaccinated patients vs without vaccine, respectively. There were no statistically significant differences in baseline demographics between both groups including age, race, gender, tumor histology or ECOG performance status. Conclusions: Our study suggests that irAEs are not significantly increased with vaccination for influenza during ICPI therapy. However, there is a slight trend toward increased incidence of irAE warranting ICPI discontinuation for which further investigation is needed. Limitations of this study include a small sample size and inability to grade irAE retrospectively.

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Participant Reactions to Suicide-Focused Research

Crisis ◽

10.1027/0227-5910/a000650 ◽

2020 ◽

Vol 41 (5) ◽

pp. 367-374

Author(s):

Sarah P. Carter ◽

Brooke A. Ammerman ◽

Heather M. Gebhardt ◽

Jonathan Buchholz ◽

Mark A. Reger

Keyword(s):

Medical Records ◽

Research Study ◽

Small Sample Size ◽

Psychiatric Inpatient ◽

Small Sample ◽

Inpatient Unit ◽

Online Laboratory ◽

Psychiatric Inpatient Unit ◽

Before And After ◽

Participant Reactions

Abstract. Background: Concerns exist regarding the perceived risks of conducting suicide-focused research among an acutely distressed population. Aims: The current study assessed changes in participant distress before and after participation in a suicide-focused research study conducted on a psychiatric inpatient unit. Method: Participants included 37 veterans who were receiving treatment on a psychiatric inpatient unit and completed a survey-based research study focused on suicide-related behaviors and experiences. Results: Participants reported no significant changes in self-reported distress. The majority of participants reported unchanged or decreased distress. Reviews of electronic medical records revealed no behavioral dysregulation and minimal use of as-needed medications or changes in mood following participation. Limitations: The study's small sample size and veteran population may limit generalizability. Conclusion: Findings add to research conducted across a variety of settings (i.e., outpatient, online, laboratory), indicating that participating in suicide-focused research is not significantly associated with increased distress or suicide risk.

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Safety of meningococcal group B vaccination in hospitalised premature infants

Archives of Disease in Childhood - Fetal and Neonatal Edition ◽

10.1136/archdischild-2017-314152 ◽

2018 ◽

Vol 104 (2) ◽

pp. F171-F175 ◽

Cited By ~ 6

Author(s):

Alison Kent ◽

Kazim Beebeejaun ◽

Serena Braccio ◽

Seilesh Kadambari ◽

Paul Clarke ◽

...

Keyword(s):

Adverse Events ◽

Premature Infants ◽

Antibiotic Use ◽

Neurological Status ◽

Serious Adverse Events ◽

Historical Cohort ◽

Protein Levels ◽

Reactive Protein ◽

Before And After ◽

Group B

ObjectivesTo assess the risk of significant adverse events in premature infants receiving the novel 4-component group B meningococcal vaccine (4CMenB) with their routine immunisations at 2 months of age.Participants, design and settingIn December 2015, Public Health England requested neonatal units across England to voluntarily participate in a national audit; 19 units agreed to participate. Anonymised questionnaires were completed for infants receiving 4CMenB alongside their routine immunisations. For comparison, a historical cohort of premature infants receiving their primary immunisations without 4CMenB or paracetamol prophylaxis was used.Main outcome measuresParacetamol use; temperature, cardiovascular, respiratory and neurological status before and after vaccination; and management and investigations postvaccination, including serum C reactive protein levels, infection screens and antibiotic use.ResultsComplete questionnaires were returned for 133 premature infants (<35 weeks’ gestation) who received their first dose of 4CMenB at 8 weeks of age, including 108 who received prophylactic paracetamol according to national recommendations. Overall, 7% (8/108) of infants receiving 4CMenB with paracetamol had fever (>38°C) after vaccination compared with 20% (5/25) of those receiving 4CMenB without paracetamol (P=0.06) and none of those in the historical cohort. There were no significant differences between cohorts in the proportion of infants with apnoea, bradycardia, desaturation and receiving respiratory support after vaccination.Conclusions4CMenB does not increase the risk of serious adverse events in hospitalised premature infants. This audit supports the current national recommendations to offer 4CMenB with other routine vaccinations and prophylactic paracetamol to premature infants at their chronological age.

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O-225 Effects of SARS-Corona virus 2 on IVF treatment parameters: A cohort study of post COVID-19 patients

Human Reproduction ◽

10.1093/humrep/deab128.049 ◽

2021 ◽

Vol 36 (Supplement_1) ◽

Author(s):

Y Kabalkin ◽

M Gil ◽

E Lifshitz ◽

A Moav ◽

M Kabessa ◽

...

Keyword(s):

Cohort Study ◽

Virus Disease ◽

Small Sample Size ◽

Sperm Concentration ◽

Small Sample ◽

Cycle Performance ◽

Ang Ii ◽

P Values ◽

Corona Virus ◽

Before And After

Abstract Study question Does recovery from SARS–Corona virus 2 (SARS–CoV-2) infection negatively effect IVF cycle parameters? Summary answer Female IVF treatment parameters were comparable to the pre-Covid-19 infection cycle performance. Sperm concentration and motility demonstrated lower mean counts following Covid-19 infection. What is known already Corona-virus disease-19 (Covid-19) is a global pandemic caused by SARS–Corona virus 2 (SARS–CoV-2). The virus primarily affects the respiratory system, but other systemic and immune mediated effects have been reported. The spikes of SARS-CoV-2 have strong affinity for the Angiotensin converting enzyme (ACE) 2 receptor, leading to an increased Angiotensin II (Ang II) mediated pro-inflammatory response. ACE2 receptors exist in the human reproductive tract (more in males) and pose a regulatory role together with Ang II. So far, reports have been inconsistent regarding testicular effects. Other implications involving fertility and fertility treatment post infection are scarce. Study design, size, duration In this retrospective cohort study, IVF cycle performance was compared before and after Corona-virus disease-19. Patients were included only in cases where an IVF cycle was initiated within 3 months of Covid-19 recovery, between March 2020-December 2020. Participants/materials, setting, methods The study was conducted in a University affiliated IVF unit. Post Covid- 19 cycle parameters were compared to previous cycles of the same individual prior to infection. If previous cycles were not available, parameters were compared to non-exposed patients of same age, same treatment and identical indication. Sperm concentration and motility were compared before and after infection. Non exposure was defined by a lack of past Covid-19 diagnosis and a negative PCR throughout the treatment. Main results and the role of chance All together, including the matched cycles, we compared 40 cycles which started within 3 months of recovery: 26 fresh stimulation cycles and 14 frozen thawed transfer cycles. In 28 of these cycles the patient could serve as its own control. Mean age for the female partner was 33.2 years ±6.5 years. Eight male partners presented post infection and provided fresh samples for a cycle involving fertilization. We compared stimulation parameters including maximal Estradiol level, stimulation length, FSH dosage, number of oocytes retrieved, fertilization rates, number of embryos created, high quality embryo number and endometrial thickness. All of these were comparable to non-exposed cycles (generalized estimating equations, p values >0.1). No complications were recorded, specifically no thromboembolic events or respiratory complications. A total of 8 patients conceived: 1 was a chemical pregnancy, 1 extra-uterine pregnancy, 3 miscarriages and 3 ongoing, of those 1 was complicated by early bleeding. Male sperm analyses showed a trend towards lower post disease parameters, not reaching a statistical significance: 23mil/ml compared to 13.6 and 20.7% progressive motility compared to 12.3% (p values 0.09 and 0.17, respectively). Limitations, reasons for caution Current results are based on a small sample size, still insufficient for deducing definite conclusions or guidelines. Pregnancy outcome following IVF treatment in Covid-19 recoverees should further be studied. By the time of the conference, the number of cases is expected to be significantly higher. Wider implications of the findings This study provides preliminary data regarding the effects of SARS-COV-2 infection on IVF treatment outcomes. Despite the small sample size, treatment parameters seem unaffected, however, sperm performance seems to be compromised. Health policy and patients’ decisions regarding whether or not to postpone IVF procedures necessitates additional data. Trial registration number Not applicable - retrospective

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Randomized Double-blind Placebo-controlled Proof-of-concept Trial of Resveratrol for Outpatient Treatment of Mild Coronavirus Disease (COVID-19)

10.21203/rs.3.rs-861831/v1 ◽

2021 ◽

Author(s):

Marvin R. McCreary ◽

Patrick M. Schnell ◽

Dale A. Rhoda

Keyword(s):

Pulmonary Embolism ◽

Adverse Events ◽

Small Sample Size ◽

Primary Outcome Measure ◽

Small Sample ◽

Double Blind ◽

Phase 2 Study ◽

Clinically Significant ◽

Low Incidence ◽

To Receive

Abstract Resveratrol is a polyphenol that has been well studied and has demonstrated anti-viral and anti-inflammatory properties that might mitigate the effects of COVID-19. Outpatients (N=105) were recruited from central Ohio in late 2020. Participants were randomly assigned to receive placebo or resveratrol. Both groups received a single dose of Vitamin D3 which was used as an adjunct. The primary outcome measure was hospitalization within 21 days of symptom onset; secondary measures were ER visits, incidence of pneumonia and pulmonary embolism. Five patients chose not to participate after randomization. Twenty-one day outcome was determined of all one hundred participants (mean [SD] age 55.6 [8.8] years; 61% female) (or their surrogates). There were no clinically significant adverse events attributed to resveratrol. Outpatients in this phase 2 study treated with resveratrol had a lower incidence compared to placebo of: hospitalization (2% vs. 6%, RR 0.33, 95% CI 0.04-3.10), COVID-related ER visits (8% vs. 14%, RR 0.57, 95% CI 0.18-1.83), and pneumonia (8% vs. 16%, RR 0.5, 95% CI 0.16-1.55). One patient (2%) in each group developed pulmonary embolism (RR 1.00, 95% CI: 0.06-15.55). This underpowered study was limited by small sample size and low incidence of primary adverse events. A larger trial could determine efficacy.TRIAL REGISTRATIONS: ClinicalTrials.gov NCT04400890 26/05/2020; FDA IND #150033 05/05/2020

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Three-year results of phase I retinal gene therapy trial for CNGA3-mutated achromatopsia: results of a non randomised controlled trial

British Journal of Ophthalmology ◽

10.1136/bjophthalmol-2021-319067 ◽

2021 ◽

pp. bjophthalmol-2021-319067

Author(s):

Felix Friedrich Reichel ◽

Stylianos Michalakis ◽

Barbara Wilhelm ◽

Ditta Zobor ◽

Regine Muehlfriedel ◽

...

Keyword(s):

Gene Therapy ◽

Primary Endpoint ◽

Statistical Power ◽

Small Sample Size ◽

Controlled Trial ◽

Statistical Significance ◽

Small Sample ◽

Functional Improvement ◽

Limiting Factor ◽

Serious Adverse Events

AimsTo determine long-term safety and efficacy outcomes of a subretinal gene therapy for CNGA3-associated achromatopsia. We present data from an open-label, nonrandomised controlled trial (NCT02610582).MethodsDetails of the study design have been previously described. Briefly, nine patients were treated in three escalating dose groups with subretinal AAV8.CNGA3 gene therapy between November 2015 and October 2016. After the first year, patients were seen on a yearly basis. Safety assessment constituted the primary endpoint. On a secondary level, multiple functional tests were carried out to determine efficacy of the therapy.ResultsNo adverse or serious adverse events deemed related to the study drug occurred after year 1. Safety of the therapy, as the primary endpoint of this trial, can, therefore, be confirmed. The functional benefits that were noted in the treated eye at year 1 were persistent throughout the following visits at years 2 and 3. While functional improvement in the treated eye reached statistical significance for some secondary endpoints, for most endpoints, this was not the case when the treated eye was compared with the untreated fellow eye.ConclusionThe results demonstrate a very good safety profile of the therapy even at the highest dose administered. The small sample size limits the statistical power of efficacy analyses. However, trial results inform on the most promising design and endpoints for future clinical trials. Such trials have to determine whether treatment of younger patients results in greater functional gains by avoiding amblyopia as a potential limiting factor.

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Abstract 13215: Gender-affirming Hormones Are Associated With Increased Risk of QT Prolongation in Transgender Females

Circulation ◽

10.1161/circ.142.suppl_3.13215 ◽

2020 ◽

Vol 142 (Suppl_3) ◽

Author(s):

Daniel Antwi Amoabeng ◽

Ahmed Hanfy ◽

Munadel Awad ◽

Bryce D Beutler ◽

Amneet Rai ◽

...

Keyword(s):

Qt Interval ◽

Small Sample Size ◽

Qt Prolongation ◽

Small Sample ◽

Rank Test ◽

Qt Interval Prolongation ◽

Northern Nevada ◽

Increased Risk ◽

Before And After ◽

Signed Rank Test

Introduction: Women have a longer QT interval than men. This sex-specific difference is attributed to hormones associated with the biological female sex. Male-to-female transgender individuals often take antiandrogens such as spironolactone or goserelin in addition to estrogens to suppress testosterone effects while increasing feminine features. Effects of gender-affirming hormone therapy (GHT) on the QT interval in these individuals remains to be elucidated. Hypothesis: We assessed the hypothesis that the use of GHT is associated with an increased risk for QT interval prolongation in transgender females. Methods: We identified 46 transgender females through a search of the electronic medical records of a Veterans Administration hospital in Northern Nevada. Patients with a diagnosis of congenital long QT syndrome were excluded. Of these, 13 patients had ECGs before and after initiation of GHT and were included. We adapted the Tisdale score using the auto-calculated corrected QT interval (QTc) to estimate the risk of QT prolongation. Age, QTc, and Tisdale scores before and after GHT initiation were compared using the Wilcoxon signed-rank test. All tests were performed as two-tailed at a 5% level of significance. Results: All 13 study patients were taking estrogens. Of these, 3 (23.1%) were taking goserelin and 9 (69.2%) were taking spironolactone. Mean ± SEM age at ECG acquisition was 45.0 ± 4.4 and 47.7 ± 4.7 years before and after the initiation of GHT respectively. Mean ± SEM QTc after initiation of GHT was significantly higher compared to the baseline (467.5 ± 12.8 ms vs. 428.2 ± 7.1 ms) (Figure 1A). The average baseline Tisdale score was significantly smaller on follow-up (1-point vs. 3 points) (Figure 1B). Conclusions: GHT appears to be associated with increased QTc in transgender women. This needs to be interpreted with caution owing to the very small sample size in this study. Further studies to investigate the strength of this association, if it exists, are warranted.

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A Study of Adherence to Restrictive RBC Transfusion and 30 Day Patient Outcomes

Blood ◽

10.1182/blood.v128.22.5037.5037 ◽

2016 ◽

Vol 128 (22) ◽

pp. 5037-5037

Author(s):

Zhen Wang ◽

Elaine Zhai ◽

Aleksic Sandra ◽

Kibola Adam ◽

Richard May ◽

...

Keyword(s):

Cardiovascular Events ◽

Small Sample Size ◽

Small Sample ◽

University Hospital ◽

Red Blood Cell Transfusion ◽

Current Guideline ◽

Chi Square ◽

Exact Test ◽

Medicine Service ◽

Rbc Transfusion

Abstract Background: The American Association of Blood Banks (AABB) 2012 Guidelines recommend a restrictive transfusion strategy of 7 g/dL to 8 g/dL in asymptomatic, hemodynamically stable patients (pts) and for Hgb less than 8 g/dL in pts with preexisting cardiovascular disease. [1] Additional recommendations based on expert opinion include transfusion at threshold Hgb of 7 g/dL for hemodynamically stable ICU pts and Hgb less than 10 g/dL in pts with symptomatic anemia. We examined adherence to these guidelines and for differences in outcomes between restrictive and non-restrictive approaches at an academic hospital. Methods: We performed an IRB-approved retrospective review of all pts admitted to the Internal Medicine Service at University Hospital in Newark, New Jersey from July 1st to November 30th 2015 who received RBC transfusions. Charts were abstracted for demographic information, past medical history, indication for transfusion, presence of signs or symptoms of anemia (chest pain, orthostatic hypotension or tachycardia unresponsive to fluid resuscitation, or congestive heart failure), pre-transfusion Hgb, number of units transfused, and post-transfusion hgb. Outcomes were defined as requirement for additional transfusions, infections, cardiovascular events, adverse transfusion reactions, and death within 30 days of transfusion. Each transfusion was categorized as either adherent or non-adherent to the guidelines. Difference in outcomes between groups (adherent vs non-adherent) was tested using chi-square and Fisher's exact test with SAS studio version 3.4 (Cary, NC). Results: We reviewed 318 RBC transfusion records for 210 pts (median age: 55±17 years) with 157 (49%) transfusions in male and 161 (51%) in female pts. Site was ICU for 86 and the ward for 232 transfusions. The leading indication was acute bleeding (121 or 38%; pre-transfusion Hgb 6.9±1.3g/dL), followed by asymptomatic anemia (107 or 33%; pre-transfusion Hgb 6.8±0.8g/dL), and symptomatic anemia (91 or 29%; pre-transfusion Hgb 6.6±0.8g/dL). Of the 107 pts with asymptomatic anemia, 37 had pre-existing heart disease. Within this group, 35 were transfused at Hgb < 8g/dL (adherence of 95%). Seventy of the 107 transfusions were performed in pts without pre-existing cardiac disease. Fifty-nine were transfused at hgb < 7g/dL with an adherence of 84%. In the ICU, 21 of the 27 transfusions occurred for hgb < 7 g/dL in hemodynamically stable pts with an adherence of 78%. There were 91 transfusions for symptomatic anemia and all were adherent (100%). Regarding 30 day post-transfusion outcomes, there were 140 (44%) with subsequent transfusions; 54 (14%) infections; 7 (2.2%) cardiovascular events; 8 (2.5%) transfusion adverse reactions; 27(8%) deaths. No difference was detected for 30 day outcomes between the adherent group and the non-adherent group. (Table 1) Transfusion of at least 2unitsRBC in asymptomatic, symptomatic, and active bleeding pts were 25% (27/107), 44% (40/91), 57% (69/120) respectively. No difference in outcomes was found for the group receiving only 1 unit RBC (restrictive) compared to the group receiving 2 or more units RBC (non-restrictive). (Table 1) Conclusion: The majority of transfusions (92%) performed adhered to current guideline. While the restrictive approach was not associated with more complications or mortality, this study is limited by the small sample size and further work is being done. Acknowledgment: The authors are grateful to Dr. Koshy, Director of Blood Bank at University Hospital, for assistance. Reference: 1. Carson, J. L. et al. Red blood cell transfusion: a clinical practice guideline from the AABB. Ann Intern Med 157, 49-58 (2012). Disclosures Chang: Johnson and Johnson: Other: Stock; Amgen: Other: Research; Boehringer Ingelheim: Other: Research.

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Effect of coadministration of propranolol and etodolac (VT-122) plus sorafenib for patients with advanced hepatocellular carcinoma (HCC).

Journal of Clinical Oncology ◽

10.1200/jco.2015.33.3_suppl.390 ◽

2015 ◽

Vol 33 (3_suppl) ◽

pp. 390-390 ◽

Cited By ~ 1

Author(s):

Andrew N de la Torre ◽

Ismael Castaneda ◽

Aram F. Hezel ◽

Newell F. Bascomb ◽

Gouri Shankar Bhattacharyya ◽

...

Keyword(s):

Hepatitis Virus ◽

Small Sample Size ◽

Small Sample ◽

Controlled Study ◽

Advanced Hepatocellular Carcinoma ◽

Separate Study ◽

Serious Adverse Events ◽

Double Blind ◽

Duration Of Therapy ◽

Significant Efficacy

390 Background: Propranolol and etodolac (designated VT-122) target the adrenergic and prostaglandin stress systems activated in HCC. These stress-induced systems are proposed to induce changes in the tumor microenvironment and immune system leading to tumor promotion and immune tolerance. In a separate study, administration of VT-122 prior to sorafenib showed an increase in median overall survival (OS) of 21 months when VT-122 is administered before sorafenib compared to 10 months OS for sorafenib alone. The aim of the current study was to evaluate the effect of administering VT-122 at least 30 days after starting sorafenib. Methods: Patients with HCC receiving sorafenib for at least 30 days were eligible for this double-blind, placebo-controlled study. Patients were randomized to receive sorafenib with either VT-122 or placebo. Patients received therapy for up to 12 months or until treatment failure. VT-122 was administered twice daily. The primary endpoint was duration of therapy (DoT) and the secondary endpoint was OS. Results: Twenty patients were randomized, 11 and 9 patients to the VT122 and placebo arm, respectively. Each arm was balanced with regards to age (mean of 60.4 years), Child Pugh status (9 Child Pugh A, 11 Child Pugh B7), hepatitis virus status (6 HBV and 1 HCV positive) and C-reactive protein (CRP) (20.4 mg/L). VT122 with sorafenib was well tolerated with no unexpected serious adverse events reported. Mean OS was 13.9 months and 9.6 months in the VT-122 and placebo arms, respectively. Mean DoT (unvalidated) was 10.1 months and 7.5 months in the VT-122 and placebo arms, respectively. Conclusions: Co-administration of VT-122 with sorafenib was well tolerated and showed an increase in duration of therapy and OS versus sorafenib alone. The small sample size and number of events precludes the ability to make any significant efficacy conclusions. The increase in survival was not as great as that seen in a separate study in which VT122 was started prior to sorafenib. A further Phase 3 study of VT122 administered prior to sorafenib in patients with HCC is warranted. Clinical trial information: NCT01265576.

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