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

2015 ◽  
Vol 33 (3_suppl) ◽  
pp. 390-390 ◽  
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.

scholarly journals Effect of Low-dose ColchiciNe on the InciDence of Atrial Fibrillation in Open Heart Surgery Patients: END-AF Low Dose Trial

2020 ◽  
Vol 48 (7) ◽  
pp. 030006052093983
Author(s):  
Ramzi A. Tabbalat ◽  
Imad Alhaddad ◽  
Ayman Hammoudeh ◽  
Yousef S. Khader ◽  
Hassan Abu Khalaf ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Side Effects ◽  
Low Dose ◽  
Heart Surgery ◽  
Small Sample Size ◽  
Open Heart Surgery ◽  
Small Sample ◽  
Controlled Study ◽  
Unique Identifier ◽  
Double Blind

Background Studies using 1 mg of colchicine to prevent postoperative atrial fibrillation (POAF) reported conflicting results. Moreover, colchicine was associated with significant gastrointestinal (GI) side effects. This study examined whether low-dose colchicine effectively prevents POAF and whether low-dose therapy is associated with lower rates of colchicine-induced GI side effects. Methods In this prospective, randomized, double-blind, placebo-controlled study, consecutive adult patients admitted for elective cardiac surgeries randomly received a 1-mg dose of colchicine (n = 81) or placebo (n = 71) orally 12 to 24 hours before surgery followed by a daily dose of 0.5 mg until hospital discharge. The primary efficacy endpoint was the development of at least one episode of POAF of ≥5 minutes. The primary safety endpoint was the development of adverse events, especially diarrhea. Results The in-hospital mortality rate was 3.9%. POAF occurred in 13 patients (16.1%) in the colchicine group and 13 patients (18.3%) in the placebo group (odds ratio 0.85 [95% Confidence Interval = 0.37−1.99]). Diarrhea occurred in two patients in each group and necessitated treatment discontinuation in one patient in each group. Conclusion Low-dose colchicine did not prevent POAF in patients undergoing cardiac surgery. These results should be interpreted cautiously because of the small sample size and early study termination. ClinicalTrials.gov Unique Identifier number: NCT03015831

Valpromide increases amplitude of heart rate circadian rhythm in remitted bipolar and unipolar disorders.A placebo-controlled study

2000 ◽  
Vol 15 (7) ◽  
pp. 424-432 ◽  
Author(s):  
P Lemoine ◽  
J Fondarai ◽  
T Faivre
Keyword(s):  
Heart Rate ◽  
Circadian Rhythm ◽  
Rating Scale ◽  
Small Sample Size ◽  
Bipolar Disorders ◽  
Small Sample ◽  
Sleep Diary ◽  
Controlled Study ◽  
Double Blind ◽  
Sleep Study

The aim of this study was to investigate for the effects of valpromide on heart rate circadian rhythm in remitted recurrent unipolar and bipolar disorders (DSM-III-R). It consisted of a comparative, randomized, double-blind, repeated cross-over study of valpromide versus placebo over four four-week periods. The primary evaluation criteria was heart rate (HR). Secondary criteria comprised motor activity (MA) and the Bech and Rafaelsen mania assessment scale, Horne and Ostberg questionnaire, Montgomery and Asberg depression rating scale, Spiegel questionnaire, a sleep diary, and Clinical Global Impression. Fifteen patients were included, giving 60 one-month periods (30 valpromide periods and 30 placebo periods).Cosinor analysis of HR and MA data revealed a difference in amplitude (P = 0.037, analysis of variance, one-tailed test).The clinical sleep study shows that the duration of sleep was greater with valpromide than with placebo (P = 0.007, one-tailed test). Similarly, evaluation of the quality of sleep by patients themselves showed valpromide to be superior to placebo (P = 0.045, one-tailed test). The results of analysis of the Spiegel questionnaire also confirm the superiority of valpromide over placebo. Safety and compliance were comparable for the active drug and the placebo.In conclusion, the relatively small sample size requires cautious interpretation of this study. Nevertheless, these initial results show a definite effect of valpromide on a biological rhythm that leads one to suppose that it may be effective through a ‘synchronizing’ effect.

Safety and Tolerability of Ganoderma lucidum in Healthy Subjects: A Double-Blind Randomized Placebo-Controlled Trial

2007 ◽  
Vol 35 (03) ◽  
pp. 407-414 ◽  
Author(s):  
Sheila M. Wicks ◽  
Robin Tong ◽  
Chong-Zhi Wang ◽  
Michael O'Connor ◽  
Theodore Karrison ◽  
...  
Keyword(s):  
Ganoderma Lucidum ◽  
Small Sample Size ◽  
Controlled Trial ◽  
Statistical Significance ◽  
Blood Chemistry ◽  
Small Sample ◽  
Controlled Study ◽  
Double Blind ◽  
Human Volunteers ◽  
Complete Blood Counts

Ganoderma lucidum is a herbal medicine commonly used in oriental countries as a remedy for treating various medical conditions. In this controlled study, we evaluated the safety and tolerance of oral administration of Ganoderma lucidum in 16 human volunteers who received 2 grams of the extract or placebo twice daily for 10 consecutive days. During the study, information from subjective questionnaires were obtained, electrocardiograms, complete blood counts, blood chemistry analysis and urinalysis were performed. In addition, blood tests reflecting immunity were done. Our data showed that compared to placebo group, no adverse effects were observed after the extract intake. Although there were no obvious changes in CD4, CD8, and CD19 levels after the extract, CD56 cell count increased during the study and returned to baseline 10 days after the herbal intake. However, due to relatively high variability and small sample size, this CD56 increase did not achieve statistical significance, and remains to be re-evaluated in the future. It appears that an additional long-term safety and tolerance trial with herbal dose-escalating design is warranted.

FC 049A RANDOMISED DOSE RANGING, PLACEBO-CONTROLLED, PHASE II STUDY ASSESSING THE EFFICACY AND SAFETY OF BI 655064, AN ANTAGONISTIC ANTI-CD40 ANTIBODY, IN PATIENTS WITH LUPUS NEPHRITIS

2021 ◽  
Vol 36 (Supplement_1) ◽  
Author(s):  
David Jayne ◽  
Richard Furie ◽  
Juanita Romero-Diaz ◽  
Hirofumi Amano ◽  
Kajohnsak Noppakun ◽  
...  
Keyword(s):  
B Cells ◽  
Lupus Nephritis ◽  
Small Sample Size ◽  
Safety Data ◽  
Placebo Response ◽  
Small Sample ◽  
Efficacy And Safety ◽  
Class Iii ◽  
Serious Adverse Events ◽  
Double Blind

Abstract Background and Aims In patients (pts) with SLE, activation of the CD40–CD40L pathway results in stimulation and proliferation of B cells and other inflammatory cell types. The subsequent generation of autoantibodies and their deposition in the kidney, as well as activation of myeloid and resident kidney cells, result in local inflammation and eventually, kidney injury. Thus, CD40 is an appealing therapeutic target in lupus nephritis (LN). BI 655064 is a humanised anti-CD40 monoclonal antibody that blocks the CD40 pathway in a nanomolar range and downregulates activated B cells. This study assessed the efficacy and safety over 52 weeks (wks) of three doses of subcutaneous BI 655064 compared with placebo, as add-on to mycophenolate and steroids, in pts with active proliferative LN (ClinicalTrials.gov number: NCT02770170). Method Overall, 121 pts with LN were randomised, double blind, in a 2:1:1:2 ratio to placebo or BI 655064 120 mg, 180 mg or 240 mg, and received a weekly loading dose for the first 3 wks, followed by dosing every 2 wks for the 120 and 180 mg doses, and weekly (120 mg) for the 240 mg group. Key inclusion criteria included an active ISN/RPS class III or IV (±V) renal biopsy within 3 months prior to screening and a screening protein/creatinine ratio of ≥1 mg/mg. Randomisation was stratified based on race (Asian vs non-Asian) and screening protein/creatine (UP/UC) ratio (<3 vs ≥3). The primary efficacy endpoint was complete renal response (CRR), defined as 24 h proteinuria <0.5 g/day and stable eGFR at Wk 52. Results The placebo response in this trial was higher than expected (48.3%; Table 1); none of the  BI 655064 doses increased rates of CRR at Wk 52 compared with placebo. However, CRR at Wk 52 based on creatinine-adjusted proteinuria, assessed using spot urine, showed a better response in the 180 mg group (50%) vs placebo (42.5%), and the 180 mg dose showed a greater change from baseline over time vs placebo from Wk 4. Time to CRR was shorter in the 180 mg group (17.3 wks) vs placebo (20.4 wks). The 180 mg group also showed improvement vs placebo in total SLEDAI (SELENA) and its subscores. The unexpected high placebo response prompted a post hoc analysis evaluating confirmed CRR (cCRR), whereby confirmation of the endpoint was required at both Wks 46 (penultimate visit on treatment) and 52. A 15.2% higher cCRR in the 180 mg group (44.3%) vs placebo (29.1%) was observed (p=0.26). While based on a small sample size, there were more reports of infection-related severe and serious adverse events and neutropenia in the 240 mg group compared with placebo. Of note, in those who experienced neutropenia, a clinical impact (e.g. increase in infections) was not established. Aside from these observations, safety data were comparable across treatment groups. Larger decreases from baseline were observed in the percentage of CD27−IgD−CD95+, CD27−IgD+CD95+, CD27+IgD+CD95+ and CD27+IgD−CD95+ B-cell subsets in the 180 and 240 mg groups compared with placebo. Treatment-emergent anti-drug antibodies (ADAs) were detected in five pts treated with BI 655054, all at low titre, and in one who received placebo; ADAs had no impact on pharmacokinetics or safety. Conclusion The trial did not meet its primary CRR endpoint. However, when confirmation of CRR was required at both Wks 46 and 52, the resultant decrease in the placebo response generated an effect size of 15.2% and 9.1% in favour of 180 mg and 240 mg BI 655064, respectively.

A randomized, double-blind, placebo-controlled study of polyunsaturated fatty acids efficacy in adolescents with anorexia nervosa

2020 ◽  
Vol 36 (2) ◽  
pp. 95-106
Author(s):  
Agnieszka M. Piróg-Balcerzak ◽  
Anna K. Bażyńska ◽  
Katarzyna Biernacka ◽  
Joanna Brągoszewska ◽  
Lidia Popek ◽  
...  
Keyword(s):  
Fatty Acids ◽  
Anorexia Nervosa ◽  
Polyunsaturated Fatty Acids ◽  
Small Sample Size ◽  
Small Sample ◽  
Female Adolescent ◽  
Eating Attitude ◽  
Controlled Study ◽  
Omega 3 ◽  
Eat 26

Objective. Omega–3 polyunsaturated fatty acids (PUFAs) were tested in adolescent depression and in several neurodevelopmental disorders with partial success. Anorexia nervosa (AN) is characterised by deficiencies in fatty food intake and frequent comorbidity, including depressive and cognitive symptoms. Thus supplementation with PUFAs may be beneficial in this group of patients. The aim of the study was to assess whether PUFAs as an add-on treatment is associated with better improvement of body mass index (BMI) and psychopathological symptoms than placebo in patients with AN. Method. 61 female adolescent inpatients with AN were randomly allocated to omega–3 PUFAs supplementation or placebo for 10 weeks. Patients also participated in the behavioural programme and eclectic psychotherapy (treatment as usual, TAU). At baseline and follow-up visits, patients’ BMI and psychopathology were assessed with Clinical Global Impression Scale (CGI), Patient Global Impression Scale (PGI), and Eating Attitude Test (EAT-26). Results. After 10 weeks, both groups showed improvement in all parameters. Improvement in CGI scores was observed greater in placebo vs. PUFA-s group (p = 0.015) while other differences were not statistically significant. Omega–3 PUFAs supplementation appears not to be effective as an add-on treatment in inpatient adolescent girls with anorexia nervosa. Conclusions. The results should be analysed with caution due to small sample size and heterogeneity in TAU. As the TAU turned out to be highly effective, additional therapeutic effect of PUFA might not be visible. Nevertheless, that does not explain the tendency for better improvement in the placebo group.

Comparative Efficacy of Once Daily Loratadine versus Terfenadine in the Treatment of Allergic Rhinitis

1989 ◽  
Vol 17 (2) ◽  
pp. 150-156 ◽  
Author(s):  
C. H. Banov
Keyword(s):  
Allergic Rhinitis ◽  
Initial Dose ◽  
Small Sample Size ◽  
Small Sample ◽  
Double Blind ◽  
Once Daily ◽  
Excellent Response ◽  
Parallel Group ◽  
Parallel Group Trial ◽  
Group Trial

This 1 week study compared the efficacy of once daily administration of 10 mg loratadine with 120 mg terfenadine in out-patients with seasonal allergic rhinitis. It focussed on the efficacy of treatment at the end of the 24 h period following a daily dose. The study was designed as a double-blind, randomized, parallel-group trial, and 41 patients were enrolled and evaluated for efficacy. Patients took an initial dose at the study site and returned on days 2 and 8. At day 2 (24 h after the initial dose), according to the physician's evaluation 57% of loratadine-treated patients had a good or excellent response, compared to 50% of those given terfenadine. At day 8, 24 h after the final dose, 71% of the loratadine-treated patients and 35% of the terfenadine-treated patients had a good or excellent response ( P = 0.03). At days 2 and 8, reductions in mean symptom scores measured 22, 23 and 24 h after the initial and final doses showed an indication of being greater with loratadine than with terfenadine (non-significant due to small sample size). The incidence of sedation was similar in both groups. It is concluded that 10 mg loratadine, administered once daily, controls the symptoms of rhinitis more effectively than 120 mg terfenadine given once daily in the last few hours of the 24 h dosing period.

scholarly journals Review of the Studies in the Use of Biofeedback Therapy in Rehabilitation and Physiatrics of Neurological Patients

Doctor Ru ◽  
2021 ◽  
Vol 20 (9) ◽  
pp. 43-47
Author(s):  
E.Yu. Mozheyko ◽  
◽  
O.V. Petryaeva ◽  
◽  
◽  
...  
Keyword(s):  
Large Scale ◽  
Small Sample Size ◽  
Small Sample ◽  
Healthy Population ◽  
Biofeedback Therapy ◽  
Level Of Evidence ◽  
Double Blind ◽  
Key Points ◽  
Neurological Patients ◽  
Drug Free

Objective of the Review: To collect information, analyse and evaluate previous studies in the use of biofeedback in neurological patients. Key Points. Despite the wide practical application and a lot of available publications, the level of evidence of this method is low because of a small sample size and the challenges with biofeedback mechanism description. A review of various types of biocontrol, its mechanisms and developments shows that drug-free therapy using only patient’s resources (organic, psychological, emotional and volitional) can activate the mechanisms of neuroplasticity, which are poorly studied. Still, it does not prevent from using biocontrol for the therapy of patients and/or prevention of various diseases in healthy population. Conclusion. Biofeedback therapy has proven to be a safe, relatively efficient and easy-to-use method. However, organisation of a large-scale double blind randomized trial is one of the predominant directions in the future. Keywords: biofeedback, biocontrol, neurofeedback, biofeedback therapy.

scholarly journals Efficacy and Safety of 0.625% and 1.25% Capsaicin Patch in Peripheral Neuropathic Pain: Multi-Center, Randomized, and Semi-Double Blind Controlled Study

2017 ◽  
Vol 2 (20;2) ◽  
pp. 27-35
Author(s):  
PyungBok Lee
Keyword(s):  
Neuropathic Pain ◽  
Peripheral Neuropathy ◽  
College Teaching ◽  
Small Sample ◽  
Controlled Study ◽  
Efficacy And Safety ◽  
High Concentration ◽  
Double Blind ◽  
Peripheral Neuropathic Pain ◽  
Topical Capsaicin

Background: Topical capsaicin therapy may be of benefit in providing pain relief in patients with peripheral neuropathy. Objectives: To investigate the efficacy and safety of 0.625% (50 µg/cm2 ) and 1.25% (100 µg/cm2 ) capsaicin patches (CPs) compared to conventional 0.075% capsaicin cream or placebo patches in patients suffering from peripheral neuropathy. Study Design: Early Phase II, multi-center, randomized, semi-double-blind, and placebocontrolled clinical trial. Setting: Two medical college teaching hospitals. Methods: Sixty patients were randomized to the 0.625% CP, 1.25% CP, placebo-controlled patch, or 0.075% capsaicin cream. The primary efficacy endpoint was the mean difference in the change of daily numerical rating scale (NRS) pain score. Secondary endpoints included values for the Daily Sleep Interference Scale, the percentage of patients achieving a ≥ 30% or ≥ 50% reduction in pain, and data for Global Impression Change (GIC) and EQ-5D. Results: Patients treated with the 0.625% CP and 0.075% capsaicin cream showed statistically significant improvements in pain after 6-weeks of test drug application. Daily sleep disorder scores were improved only for those patients applying the 0.075% capsaicin cream. For patient-derived GIC scores, the majority (11 of 12) of patients in the 0.625% CP group reported that their pain was improved. For the safety evaluation, 2 severe adverse events were reported for the 0.075% capsaicin cream group only. Repetitive patch application was related to minor skin problems such as a burning sensation, erythema, pruritus, and vesicles in 28 patients (46.67%). Limitations: The small sample size and relatively high dropout rates. Conclusion: Our data indicate that the 0.625% CP may prove to be an effective and safe alternative with which to treat patients with peripheral neuropathy and could replace the high concentration (8%) CP. Further studies are now needed to definitively establish efficacy. Key words: Capsaicin, patch, CP, topical capsaicin, neuropathic pain, peripheral neuropathic pain, PNP, high concentration CP

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

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

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

2016 ◽  
Vol 43 (2) ◽  
pp. 284-290 ◽  
Author(s):  
Michel Prud’homme ◽  
François Mathieu ◽  
Nicolas Marcotte ◽  
Sylvine Cottin
Keyword(s):  
Conservative Treatment ◽  
Adverse Events ◽  
Small Sample Size ◽  
Chronic Subdural Hematoma ◽  
Symptomatic Patient ◽  
Placebo Treatment ◽  
Small Sample ◽  
Chi Square ◽  
Serious Adverse Events ◽  
Before And After

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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