Primary Endpoint
Recently Published Documents





BMC Cancer ◽  
2021 ◽  
Vol 21 (1) ◽  
Yoshiki Arakawa ◽  
Keita Sasaki ◽  
Yohei Mineharu ◽  
Megumi Uto ◽  
Takashi Mizowaki ◽  

Abstract Background The current standard treatment for elderly patients with newly diagnosed glioblastoma is surgery followed by short-course radiotherapy with temozolomide. In recent studies, 40 Gy in 15 fractions vs. 60 Gy in 30 fractions, 34 Gy in 10 fractions vs. 60 Gy in 30 fractions, and 40 Gy in 15 fractions vs. 25 Gy in 5 fractions have been reported as non-inferior. The addition of temozolomide increased the survival benefit of radiotherapy with 40 Gy in 15 fractions. However, the optimal regimen for radiotherapy plus concomitant temozolomide remains unresolved. Methods This multi-institutional randomized phase III trial was commenced to confirm the non-inferiority of radiotherapy comprising 25 Gy in 5 fractions with concomitant (150 mg/m2/day, 5 days) and adjuvant temozolomide over 40 Gy in 15 fractions with concomitant (75 mg/m2/day, every day from first to last day of radiation) and adjuvant temozolomide in terms of overall survival (OS) in elderly patients with newly diagnosed glioblastoma. A total of 270 patients will be accrued from 51 Japanese institutions in 4 years and follow-up will last 2 years. Patients 71 years of age or older, or 71–75 years old with resection of less than 90% of the contrast-enhanced region, will be registered and randomly assigned to each group with 1:1 allocation. The primary endpoint is OS, and the secondary endpoints are progression-free survival, frequency of adverse events, proportion of Karnofsky performance status preservation, and proportion of health-related quality of life preservation. The Japan Clinical Oncology Group Protocol Review Committee approved this study protocol in April 2020. Ethics approval was granted by the National Cancer Center Hospital Certified Review Board. Patient enrollment began in August 2020. Discussion If the primary endpoint is met, short-course radiotherapy comprising 25 Gy in 5 fractions with concomitant and adjuvant temozolomide will be a standard of care for elderly patients with newly diagnosed glioblastoma. Trial registration Registry number: jRCTs031200099. Date of Registration: 27/Aug/2020. Date of First Participant Enrollment: 4/Sep/2020.

2021 ◽  
Vol 8 ◽  
Allison G. Hays ◽  
Michael Schär ◽  
Gabriele Bonanno ◽  
Shenghan Lai ◽  
Joseph Meyer ◽  

Aims: Inflammation plays a critical role in the pathogenesis of coronary artery disease (CAD), however the impact of anti-inflammatory therapies to reduce those processes which promote atherosclerosis in CAD patients is unknown. We aimed to test the hypothesis that anti-inflammatory approaches improve impaired coronary endothelial function (CEF), a driver of coronary atherosclerosis, in stable CAD patients.Methods and Results: We performed a single-center, randomized, placebo-controlled, double-blinded trial to assess whether low dose methotrexate (MTX), low dose colchicine (LDC), and/or their combination (MTX+LDC), improves CEF using non-invasive MRI measures in patients with stable CAD (N = 94). The primary endpoint was the MRI-detected change in coronary cross-sectional area from rest to isometric handgrip exercise (IHE), a predominantly nitric oxide-dependent endothelial dependent stressor. Coronary and systemic endothelial endpoints, and serum inflammatory markers, were collected at baseline, 8 and 24 weeks. Anti-inflammatory study drugs were well-tolerated. There were no significant differences in any of the CEF parameters among the four groups (MTX, LDC, MTX+LDC, placebo) at 8 or 24 weeks. Serum markers of inflammation and systemic endothelial function measures were also not significantly different among the groups.Conclusion: This is the first study to examine the effects of the anti-inflammatory approaches using MTX, LDC, and/or the combination in stable CAD patients on CEF, a marker of vascular health and the primary endpoint of the study. Although these anti-inflammatory approaches were relatively well-tolerated, they did not improve coronary endothelial function in patients with stable CAD.Clinical Trial, identifier: NCT02366091.

2021 ◽  
pp. 001857872110516
Alexandra Whiddon Tatara ◽  
Christine Ji ◽  
Susan Jacob ◽  
John Marshall

Introduction: Studies have shown that patients would like to receive more medication education while hospitalized. Higher patient satisfaction has been correlated with lower mortality and fewer hospital readmissions. Methods: This was a quasi-experimental study. Four Doctor of Pharmacy students were assigned 1 medicine inpatient unit to provide education on new medications during the study period, June to September. The primary endpoint was the change in HCAHPS scores for the medication communication domain composite for the intervention unit and a similar control unit that was not receiving the intervention from the pre-intervention to the intervention periods. Results: A total of 124 patients were educated during the intervention period, with an average age of 65 and 2.2 new medications. Average HCAHPS scores for the medication communication domain for the intervention unit increased from 68% pre-intervention to 91% during the intervention ( P = .389) while the control unit remained unchanged at 78% both pre- and during the intervention ( P = .13). Conclusion: An increase in the medication communication HCAHPS score for the intervention unit was observed, while the control unit remained stable. This study has the potential to drive change by implementing pharmacy students throughout inpatient units to educate patients on new medications thereby improving patient satisfaction.

2021 ◽  
Vol 12 (1) ◽  
Priscilla K. Brastianos ◽  
Matthew R. Strickland ◽  
Eudocia Quant Lee ◽  
Nancy Wang ◽  
Justine V. Cohen ◽  

AbstractLeptomeningeal disease (LMD) is a common complication from solid tumor malignancies with a poor prognosis and limited treatment options. We present a single arm Phase II study of 18 patients with LMD receiving combined ipilimumab and nivolumab until progression or unacceptable toxicity (NCT02939300). The primary end point is overall survival at 3 months (OS3). Secondary end points include toxicity, cumulative time-to-progression at 3 months, and progression-free survival. A Simon two-stage design is used to compare a null hypothesis OS3 of 18% against an alternative of 44%. Median follow up based on patients still alive is 8.0 months (range: 0.5 to 15.9 months). The study has met its primary endpoint as 8 of 18 (OS3 0.44; 90% CI: 0.24 to 0.66) patients are alive at three months. One third of patients have experienced one (or more) grade-3 or higher adverse events. Two patients have discontinued protocol treatment due to unacceptable toxicity (hepatitis and colitis, respectively). The most frequent adverse events include fatigue (N = 7), nausea (N = 6), fever (N = 6), anorexia (N = 6) and rash (N = 6). Combined ipilimumab and nivolumab has an acceptable safety profile and demonstrates promising activity in LMD patients. Larger, multicenter clinical trials are needed to validate these results.

2021 ◽  
Vol 11 (1) ◽  
Bruno M. L. Rocha ◽  
Gonçalo J. L. Cunha ◽  
Pedro Freitas ◽  
Pedro M. D. Lopes ◽  
Ana C. Santos ◽  

AbstractTo assess whether a simplified cardiac magnetic resonance (CMR)–derived lung water density (LWD) quantification predicted major events in Heart Failure (HF). Single-centre retrospective study of consecutive HF patients with left ventricular ejection fraction (LVEF) < 50% who underwent CMR. All measurements were performed on HASTE sequences in a parasagittal plane at the right midclavicular line. LWD was determined by the lung-to-liver signal ratio multiplied by 0.7. A cohort of 102 controls was used to derive the LWD upper limit of normal (21.2%). The primary endpoint was a composite of time to all-cause death or HF hospitalization. Overall, 290 patients (mean age 64 ± 12 years) were included. LWD measurements took on average 35 ± 4 s, with good inter-observer reproducibility. LWD was increased in 65 (22.4%) patients, who were more symptomatic (NYHA ≥ III 29.2 vs. 1.8%; p = 0.017) and had higher NT-proBNP levels [1973 (IQR: 809–3766) vs. 802 (IQR: 355–2157 pg/mL); p < 0.001]. During a median follow-up of 21 months, 20 patients died and 40 had ≥ 1 HF hospitalization. In multivariate analysis, NYHA (III–IV vs. I–II; HR: 2.40; 95%-CI: 1.30–4.43; p = 0.005), LVEF (HR per 1%: 0.97; 95%-CI: 0.94–0.99; p = 0.031), serum creatinine (HR per 1 mg/dL: 2.51; 95%-CI: 1.36–4.61; p = 0.003) and LWD (HR per 1%: 1.07; 95%-CI: 1.02–1.12; p = 0.007) were independent predictors of the primary endpoint. These findings were mainly driven by an association between LWD and HF hospitalization (p = 0.026). A CMR-derived LWD quantification was independently associated with an increased HF hospitalization risk in HF patients with LVEF < 50%. LWD is a simple, reproducible and straightforward measurement, with prognostic value in HF.

Biomedicines ◽  
2021 ◽  
Vol 9 (10) ◽  
pp. 1423
Olivier Chevallier ◽  
Patricia Fauque ◽  
Carole Poncelet ◽  
Kévin Guillen ◽  
Pierre-Olivier Comby ◽  

Surgical treatment or varicocele embolization (VE) with sclerosing or mechanical embolic agents have been shown to improve the semen parameters of infertile men. The aim of this study was to evaluate the impact of VE using N-butyl cyanoacrylate (NBCA) glue on semen parameters in infertile men. From January 2014 to June 2018, infertile adult patients with stage 3 varicocele and an initial semen analysis showing at least one abnormal semen parameter, and who were successfully embolized with NBCA Glubran®2 glue, were retrospectively recruited. The availability of a second semen analysis after VE was mandatory for patient inclusion. The primary endpoint was the change in total sperm number (TSN) after VE. The other parameters of interest were progressive and total sperm motilities (Smot) at 1 h (H1), sperm vitality (SV) and morphology (SMor). One hundred and two patients were included. Eight patients presented null TSN before and after VE. Among the remaining 94 patients, a significant improvement in the median TSN after VE was shown (31.79 × 106/ejaculate [IQR:11.10–127.40 × 106/ejaculate] versus 62.24 × 106/ejaculate [IQR:17.90–201.60 × 106/ejaculate], p= 0.0295). Significant improvement in TSN was found for the 60 oligo- or azoospermic patients (p = 0.0007), whereas no significant change was found for the 42 patients with normal initial TSN (p = 0.49). Other parameters, such as progressive and total SMot, SV and SMor, also significantly improved after VE (p = 0.0003, 0.0013, 0.0356 and 0.007, respectively). The use of NBCA glue as an embolic agent for VE in infertile men with stage 3 varicocele significantly improves the semen parameters.

Infection ◽  
2021 ◽  
Maximilian J. Schons ◽  
Amke Caliebe ◽  
Christoph D. Spinner ◽  
Annika Y. Classen ◽  
Lisa Pilgram ◽  

Abstract Purpose Reported antibiotic use in coronavirus disease 2019 (COVID-19) is far higher than the actual rate of reported bacterial co- and superinfection. A better understanding of antibiotic therapy in COVID-19 is necessary. Methods 6457 SARS-CoV-2-infected cases, documented from March 18, 2020, until February 16, 2021, in the LEOSS cohort were analyzed. As primary endpoint, the correlation between any antibiotic treatment and all-cause mortality/progression to the next more advanced phase of disease was calculated for adult patients in the complicated phase of disease and procalcitonin (PCT) ≤ 0.5 ng/ml. The analysis took the confounders gender, age, and comorbidities into account. Results Three thousand, six hundred twenty-seven cases matched all inclusion criteria for analyses. For the primary endpoint, antibiotic treatment was not correlated with lower all-cause mortality or progression to the next more advanced (critical) phase (n = 996) (both p > 0.05). For the secondary endpoints, patients in the uncomplicated phase (n = 1195), regardless of PCT level, had no lower all-cause mortality and did not progress less to the next more advanced (complicated) phase when treated with antibiotics (p > 0.05). Patients in the complicated phase with PCT > 0.5 ng/ml and antibiotic treatment (n = 286) had a significantly increased all-cause mortality (p = 0.029) but no significantly different probability of progression to the critical phase (p > 0.05). Conclusion In this cohort, antibiotics in SARS-CoV-2-infected patients were not associated with positive effects on all-cause mortality or disease progression. Additional studies are needed. Advice of local antibiotic stewardship- (ABS-) teams and local educational campaigns should be sought to improve rational antibiotic use in COVID-19 patients.

2021 ◽  
Vol 11 (1) ◽  
Aska Drljevic-Nielsen ◽  
Finn Rasmussen ◽  
Jill Rachel Mains ◽  
Kennet Thorup ◽  
Frede Donskov

AbstractRECIST v1.1 has limitations in evaluating progression. We assessed Dynamic Constrast Enhanced Computed Tomography (DCE-CT) identified Blood Volume (BV) for the evaluation of progressive disease (PD) in patients with metastatic renal cell carcinoma (mRCC). BV was quantified prospectively at baseline, after one month, then every three months until PD. Relative changes (ΔBV) were assessed at each timepoint compared with baseline values. The primary endpoint was Time to PD (TTP), the secondary endpoint was Time to the scan prior to PD (PDminus1). Cox proportional hazard models adjusted ΔBV for treatments and International mRCC Database Consortium factors. A total of 62 patients had analyzable scans at the PD timepoint. Median BV was 23.92 mL × 100 g−1 (range 4.40–399.04) at PD and 26.39 mL × 100 g−1 (range 8.70–77.44) at PDminus1. In the final multivariate analysis higher ΔBV was statistically significantly associated with shorter Time to PD, HR 1.11 (95% CI 1.07–1.15, P < 0.001). Also assessed at PDminus1, higher ΔBV was significantly associated with shorter time to PD, HR 1.14 (95% CI 1.01–1.28, P = 0.031). In conclusion, DCE-CT identified BV is a new image-based biomarker of therapy progression in patients with mRCC.

Umberto Ricardi ◽  
Mario Levis ◽  
Andrea Evangelista ◽  
Daniela Maria Gioia ◽  
Gian Mauro Sacchetti ◽  

The role of consolidation radiotherapy (RT) to bulky lesions is controversial for advanced-stage Hodgkin's lymphoma (HL) patients achieving complete metabolic response (CMR) after ABVD-based chemotherapy. Herein we present the final results of the Fondazione Italiana Linfomi HD0801 trial, investigating the potential benefit of RT in that particular setting. In this phase III randomized study, patients with a bulky lesion at baseline (mass with the largest diameter ≥5 cm) achieving CMR after 2 and 6 ABVD cycles were randomly assigned 1:1 to RT vs observation with a primary endpoint of event-free survival (EFS) at two years. The sample size was calculated estimating an EFS improvement for RT of 20% (from 60% to 80%). The secondary endpoint was progression-free survival (PFS). One-hundred and sixteen (116) patients met the inclusion criteria and were randomized. Intention-to-treat (ITT) analysis showed a 2-year EFS of 87.8% vs. 85.8% for RT vs. observation, respectively (HR:1.5, CI:0.6-3.5, p=0.34). Per-protocol (PP) analysis showed a 2-year EFS of 89.6% vs. 85.8%, respectively (HR:1.19, CI:0.47-3.02, p=0.71). At 2 years, ITT PFS was 91.3% vs. 85.8% (HR:1.2, CI:0.5-3, p=0.7), while PP PFS was 93.8% vs. 85.8% (HR:0.7, CI:0.2-2.1, p=0.52) for RT vs observation, respectively. Our study showed that patients in CMR randomized to observation have a very good outcome and the primary endpoint of a 20% benefit in EFS for RT was not met. However, the sample size was under-powered to detect a benefit of 10% or less, keeping open the question on potential, more limited, role of RT in this setting. This trial was registered at as # NCT00784537.

QJM ◽  
2021 ◽  
Vol 114 (Supplement_1) ◽  
Mohamad Gamaleldin Elewa ◽  
Shehab Adel Eletriby ◽  
Ahmed Shawky Elserafy

Abstract Background Primary PCI is the preferred reperfusion strategy for ST segment elevation myocardial infarction (STEMI); because it offers prompt and complete recanalization of an occluded infarct-related artery. However, inspite of successfully restored (Thrombolysis in Myocardial Infarction [TIMI] grade 3) epicardial blood flow, myocardial reperfusion is not regained in some patients. This phenomenon is referred to as coronary no reflow. Such patients with no reflow have higher incidence of resting segmental wall motion abnormalities (SWMA), myocardial free wall rupture, and death. Objective To compare the effect of 180 mg ticagrelor versus 600 mg clopidogrel loading doses, on the incidence of no-reflow in acute ST segment elevation myocardial infarction (STEMI) patients. Material and Methods This study was carried out on 100 patients, presented with acute STEMI to Ain Shams university hospitals, in the period between November 2018 and February 2019 who underwent primary percutaneous coronary intervention (PCI). All patients were subjected to history, clinical examination, ECG recording before and after primary PCI, blood samples before primary PCI for (creatinine, CKTotal, CKMB in addition to routine laboratory investigations), and echocardiography after primary PCI. Patients were divided into two groups, where 50 patients received a 600 mg loading dose of clopidogrel and the other 50 received a 180 mg loading dose of ticagrelor prior to primary PCI. The primary endpoint was the occurrence of no reflow defined as TIMI flow grades ≤ 2 and or MBG of 0 or 1. The secondary endpoint was the occurrence of major adverse cardiac events during hospital stay. Results The primary endpoint of no reflow occurred in 17 (34%) patients in the clopidogrel group versus 12 (24%) patients in the ticagrelor group. This difference was not statistically significant (P-value 0.271). There was no significant statistical difference in the occurrence of major adverse cardiac events either. Conclusion The incidence of no reflow does not seem to be affected by the type of P2Y12 inhibitor loading received in the setting of STEMI. Further large-scale multi-center studies are required to prove or disprove the current evidence on the superiority of ticagrelor over clopidogrel in STEMI patients.

Sign in / Sign up

Export Citation Format

Share Document