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2022 ◽  
pp. 1-6
Author(s):  
Min Kyoung Kang ◽  
Jae-Kwan Cha ◽  
Dae-il Chang ◽  
Hyun Young Kim ◽  
Jong-Won Chung ◽  
...  

<b><i>Purpose:</i></b> The aim of this study is to investigate the effect of gradual dipyridamole titration and the incidence of dipyridamole-induced headache in patients with ischemic stroke or transient ischemic attack (TIA). <b><i>Methods:</i></b> A randomized, double-blind, double-placebo, parallel group, phase 4 clinical trial (KCT0005457) was conducted between July 1, 2019, and February 25, 2020, at 15 medical centers in South Korea. The study included patients aged &#x3e;19 years diagnosed with a noncardioembolic ischemic stroke or TIA within the previous 3 weeks. The participants were randomized 1:1:1 to receive Adinox® (aspirin 25 mg/dipyridamole 200 mg) and aspirin (100 mg) once daily for the first 2 weeks followed by Adinox® twice daily for 2 weeks (titration group), Adinox® twice daily for 4 weeks (standard group), and aspirin 100 mg once daily for 4 weeks (control group). The primary endpoint was incidence of headache over 4 weeks. The key secondary endpoint was mean cumulative headache. <b><i>Results:</i></b> Ninety-six patients were randomized into the titration (<i>n</i> = 31), standard (<i>n</i> = 32), and control (<i>n</i> = 33) groups. The titration and standard groups (74.1% vs. 74.2%, respectively) showed no difference in the primary endpoint. However, the mean cumulated headache was significantly lower in the titration group than in the standard group (0.31 ± 0.46 vs. 0.58 ± 0.51, <i>p</i> = 0.023). Further, adverse drug reactions were more common in the standard group than in the titration group (28.1% vs. 9.7%, respectively, <i>p</i> = 0.054), although not significantly different. <b><i>Conclusion:</i></b> The titration strategy was effective in lowering the incidence of cumulative dipyridamole-induced headache.


Author(s):  
Karl-Christian Bergmann ◽  
Jennifer Raab ◽  
Linda Krause ◽  
Sylvia Becker ◽  
Sebastian Kugler ◽  
...  

Summary Purpose The long-term effects of targeted micronutrition with the holoBLG lozenge in house dust mite (HDM) allergic rhinoconjunctivitis (ARC) patients were evaluated at a follow-up visit in an allergen exposure chamber (AEC). Methods Patients who were supplemented for 3‑months with the holoBLG lozenge in a previous study with two controlled HDM-AEC challenges [visits: V1, V3] were recruited for a third AEC challenge (V5) 7–8 months after cessation of supplementation. Symptoms (nose, conjunctival, bronchial, others), well-being, and lung function parameters were recorded exactly as in the previous study. Primary endpoint was change in median Total Nasal Symptom Score (TNSS) at V5 compared to V1. Secondary endpoints included e.g. change in median Total Symptom Score (TSS) and the exploratory analysis of temporal evolution of symptom scores using linear mixed effects models. Results Of the 32 patients included in the original study, 27 could be recruited for the follow-up visit with a third AEC challenge. An improvement of 20% (p = 0.15) in the primary endpoint TNSS [V1: 2.5 (interquartile range [IQR]: 1–4), V5: 2.0 (IQR: 1–3)] was observed; 40% (p = 0.04) improvement was seen for the TSS [V1: 5.0 (IQR: 3–9), V5: 3.0 (IQR: 2–5.5)]. Analysis of temporal evolution of all symptom scores, and the personal well-being revealed sustained, clinically meaningful improvement at V5 compared to V1. No relevant lung function parameter differences were observed. Conclusions Sustained long-term reduction of TNSS (primary endpoint) and sustained long-term improvement of secondary endpoints (temporal evolution of all symptom scores and well-being) were demonstrated 7–8 months after cessation of holoBLG supplementation, indicative of a long-lasting nature of immune resilience induced by holoBLG. Trial registration The study was registered at clinicaltrials.gov (NCT04872868).


2022 ◽  
Vol 13 (1) ◽  
Author(s):  
Earl Sands ◽  
Alan Kivitz ◽  
Wesley DeHaan ◽  
Sheldon S. Leung ◽  
Lloyd Johnston ◽  
...  

AbstractBiologic drugs have transformed the standard of care for many diseases. However, many biologics induce the formation of anti-drug antibodies (ADAs), which can compromise their safety and efficacy. Preclinical studies demonstrate that biodegradable nanoparticles-encapsulating rapamycin (ImmTOR), but not free rapamycin, mitigate the immunogenicity of co-administered biologic drugs. Here we report the outcomes from two clinical trials for ImmTOR. In the first ascending dose, open-label study (NCT02464605), pegadricase, an immunogenic, pegylated uricase enzyme derived from Candida utilis, is assessed for safety and tolerability (primary endpoint) as well as activity and immunogenicity (secondary endpoint); in the second single ascending dose Phase 1b trial (NCT02648269) composed of both a double-blind and open-label parts, we evaluate the safety of ImmTOR (primary endpoint) and its ability to prevent the formation of anti-drug antibodies against pegadricase and enhance its pharmacodynamic activity (secondary endpoint) in patients with hyperuricemia. The combination of ImmTOR and pegadricase is well tolerated. ImmTOR inhibits the development of uricase-specific ADAs in a dose-dependent manner, thus enabling sustained enzyme activity and reduction in serum uric acid levels. ImmTOR may thus represent a feasible approach for preventing the formation of ADAs to a broad range of immunogenic biologic therapies.


2022 ◽  
Vol 11 (2) ◽  
pp. 348
Author(s):  
Matteo Pagnesi ◽  
Luca Baldetti ◽  
Alberto Aimo ◽  
Riccardo Maria Inciardi ◽  
Daniela Tomasoni ◽  
...  

Background: The new heart failure (HF) therapies of sodium-glucose cotransporter 2 inhibitors (SGLT2i), vericiguat, and omecamtiv mecarbil do not act primarily through the neuro-hormonal blockade, but have shown clinical benefits in patients with HF with reduced ejection fraction (HFrEF). However, their respective efficacies remain unclear. Our aim was to evaluate the relative efficacy of new drugs for HFrEF. Methods: We performed a network meta-analysis (NMA) of randomized controlled trials (RCTs) comparing SGLT2i, vericiguat, omecamtiv mecarbil, and placebo in HFrEF patients. The primary endpoint was the composite of cardiovascular death (CVD) or HF hospitalization (CVD-HF); secondary endpoints were CVD, all-cause death, and HF hospitalization (HFH). Results: Twelve RCTs (n = 23,861 patients) were included. A significant reduction in CVD-HF was observed with SGLT2i compared with placebo (risk ratio (RR) 0.77, 95% confidence interval (CI) 0.71–0.83), vericiguat (RR 0.84, 95% CI 0.75–0.93), and omecamtiv mecarbil (RR 0.80, 95% CI 0.72–0.88). No significant difference was observed between vericiguat and omecamtiv mecarbil (RR 0.95, 95% CI 0.87–1.04). SGLT2i were superior to placebo and omecamtiv mecarbil for all individual secondary endpoints (CVD, all-cause death, and HFH), and also to vericiguat for HFH. SGLT2i ranked as the most effective therapy for all endpoints, and vericiguat, omecamtiv mecarbil, and placebo ranked as the second, third, and last options, respectively, for the primary endpoint. Conclusions: In patients with HFrEF on standard-of-care therapy, SGLT2i therapy was associated with a reduced risk of CVD-HF compared to placebo, vericiguat, and omecamtiv mecarbil. Furthermore, SGLT2i were superior to placebo and omecamtiv mecarbil for CVD, all-cause death, and HFH, and also to vericiguat for HFH.


2022 ◽  
Vol 22 (1) ◽  
Author(s):  
Tisungane Mvalo ◽  
Eric D. McCollum ◽  
Elizabeth Fitzgerald ◽  
Portia Kamthunzi ◽  
Robert H. Schmicker ◽  
...  

Abstract Background Pneumonia is the leading infectious cause of death in children aged under 5 years in low- and middle-income countries (LMICs). World Health Organization (WHO) pneumonia diagnosis guidelines rely on non-specific clinical features. We explore chest radiography (CXR) findings among select children in the Innovative Treatments in Pneumonia (ITIP) project in Malawi in relation to clinical outcomes. Methods When clinically indicated, CXRs were obtained from ITIP-enrolled children aged 2 to 59 months with community-acquired pneumonia hospitalized with treatment failure or relapse. ITIP1 (fast-breathing pneumonia) and ITIP2 (chest-indrawing pneumonia) trials enrolled children with non-severe pneumonia while ITIP3 enrolled children excluded from ITIP1 and ITIP2 with severe pneumonia and/or selected comorbidities. A panel of trained pediatricians classified the CXRs using the standardized WHO CXR research methodology. We analyzed the relationship between CXR classifications, enrollee characteristics, and outcomes. Results Between March 2016 and June 2018, of 114 CXRs obtained, 83 met analysis criteria with 62.7% (52/83) classified as having significant pathology per WHO standardized interpretation. ITIP3 (92.3%; 12/13) children had a higher proportion of CXRs with significant pathology compared to ITIP1 (57.1%, 12/21) and ITIP2 (57.1%, 28/49) (p-value = 0.008). The predominant pathological CXR reading was “other infiltrates only” in ITIP1 (83.3%, 10/12) and ITIP2 (71.4%, 20/28), while in ITIP3 it was “primary endpoint pneumonia”(66.7%, 8/12,; p-value = 0.008). The percent of CXRs with significant pathology among children clinically cured (60.6%, 40/66) vs those not clinically cured (70.6%, 12/17) at Day 14 was not significantly different (p-value = 0.58). Conclusions In this secondary analysis we observed that ITIP3 children with severe pneumonia and/or selected comorbidities had a higher frequency of CXRs with significant pathology, although these radiographic findings had limited relationship to Day 14 outcomes. The proportion of CXRs with “primary endpoint pneumonia” was low. These findings add to existing data that additional diagnostics and prognostics are important for improving the care of children with pneumonia in LMICs. Trial registration ITIP1, ITIP2, and ITIP3 were registered with ClinicalTrials.gov (NCT02760420, NCT02678195, and NCT02960919, respectively).


Angiology ◽  
2022 ◽  
pp. 000331972110626
Author(s):  
Andrew Xanthopoulos ◽  
Konstantinos Tryposkiadis ◽  
Grigorios Giamouzis ◽  
Apostolos Dimos ◽  
Angeliki Bourazana ◽  
...  

Coexisting morbidities (CM) are common in patients with heart failure (HF). This study evaluated the CM burden and its clinical significance in elderly hospitalized patients with new-onset (De-novo) HF (n = 84) and acutely decompensated chronic HF (ADCHF) (n = 122). All had HF symptoms associated with: (a) LVEF <50%, or, (b) left ventricular ejection fraction (LVEF) ≥50% and NT-proBNP ≥300 pg/mL. The primary endpoint was the composite of all-cause death/HF rehospitalization at 6 months. Age was similar between patients with new-onset HF and ADCHF [82 (12.5) vs 80 (11) years, respectively; P = .549]. The CM burden was high in both groups. However, the number of CM [3 (2) vs 4 (1.75)] and the prevalence of multimorbidity [CM ≥2; 65 (77.4%) vs 108 (88.5%)] were lower in new-onset HF ( P = .016 and P = .035, respectively). The survival probability without the primary endpoint was higher in new-onset HF than in ADCHF ( P = .001) driven by less rehospitalizations ( P = .001). In the total study population significant primary endpoint predictors were red blood cell distribution width (RDW), urea, and coronary artery disease (CAD) prevalence (AUC of the model =.7685), whereas significant death predictors were RDW, urea, and the number of CM (AUC = .7859), all higher in ADCHF. Thus, the higher CM burden in ADCHF than in new-onset HF most likely contributed to the worse outcome.


2022 ◽  
Vol 12 (1) ◽  
pp. 50
Author(s):  
Yusuke Yumita ◽  
Yuji Nagatomo ◽  
Makoto Takei ◽  
Mike Saji ◽  
Ayumi Goda ◽  
...  

The optimal heart rate (HR) in patients with heart failure with reduced ejection fraction (HFrEF) has been ill-defined. Recently, a formula was proposed for estimating the target heart rate (THR), which eliminates the overlap between the E and A wave (E-A overlap). We aim to validate its prognostic significance in the multicenter WET-HF registry. This study used data from 647 patients with HFrEF hospitalized for acute decompensated HF (ADHF). The patients were divided into the 2 groups by THR. The primary endpoint was defined as the composite of all-cause death and ADHF readmission. The THR successfully discriminated the incidence of the primary endpoint, whereas no significant difference was observed in the primary endpoint when dividing the patients by uniform cutoff 70 bpm. HR at discharge ≤ THR was inversely associated with the primary endpoint. Restricted cubic spline analysis demonstrated the difference between HR at discharge, and THR (ΔHR) from −10 to ±0 was associated with a lower risk of primary endpoint and ΔHR from ±0 to +15 was associated with a higher risk. THR discriminated long-term outcomes in patients with HFrEF more efficiently than the uniform cutoff, suggesting that it may aid in tailored HR reduction strategies.


2022 ◽  
Vol 12 (1) ◽  
pp. 21
Author(s):  
Chien-Boon Jong ◽  
Tsui-Shan Lu ◽  
Patrick Yan-Tyng Liu ◽  
Jeng-Wei Chen ◽  
Ching-Chang Huang ◽  
...  

Fractional flow reserve (FFR)-guided percutaneous coronary intervention has shown favorable long-term clinical outcomes. However, limited data exist evaluating the FFR assessment among the chronic kidney disease (CKD) population. The aim of this study was to evaluate the long-term clinical outcomes of FFR-guided coronary revascularization in patients with CKD. A total of 242 CKD patients who underwent FFR assessment were retrospectively analyzed. Patients were divided into two groups: revascularization (FFR ≤ 0.80) and non-revascularization (FFR > 0.80). The primary endpoint was the composite of cardiac death, non-fatal myocardial infarction, and target vessel failure (TVF). The key secondary endpoint was TVF. The Cox regression model was used for risk evaluation. With 91% of the ischemic vessels revascularized, the revascularization group had higher risks for both the primary endpoint (adjusted hazard ratio [aHR]: 2.06; 95% confidence interval [CI], 1.07–3.97; p = 0.030) and key secondary endpoint (aHR: 2.19, 95% CI: 1.10–4.37; p = 0.026), during a median follow-up of 2.9 years. This result was consistent among different CKD severities. In patients with CKD, functional ischemia in coronary artery stenosis was associated with poor clinical outcomes despite coronary revascularization.


2022 ◽  
Author(s):  
Ann-Cathrin Koschker ◽  
Bodo Warrings ◽  
Caroline Morbach ◽  
Florian Seyfried ◽  
Nicole Rickert ◽  
...  

Obesity is a rapidly emerging health problem and an established risk factor for cardiovascular diseases. Bariatric surgery profoundly reduces body weight and mitigates sequelae of obesity. The open, randomized controlled WAS trial compares the effects of Roux-en-Y gastric bypass (RYGB) versus psychotherapy-supported lifestyle modification in morbidly obese patients. The co-primary endpoint addresses 1-year changes in cardiovascular function (peak VO2 during cardiopulmonary exercise testing) and quality of life (Short-Form-36 physical functioning scale). Prior to randomization, all included patients underwent a multimodal anti-obesity treatment for 6-12 months. Thereafter, patients were randomized and followed through month 12 to collect primary endpoints. Afterwards, patients in the lifestyle group could opt for surgery, and final visit was scheduled for all patients 24 months after randomization. Sample size calculation suggested to enroll 90 patients in order to arrive at minimally 22 patients per group evaluable for the primary endpoint. Secondary objectives were to quantify changes in body weight, left ventricular hypertrophy, systolic and diastolic function (by echocardiography and cardiac magnet resonance imaging [MRI]), functional brain MRI, psychometric scales, endothelial and metabolic function. WAS enrolled 93 patients (72 women, median age 38 years, BMI 47.5 kg/m2) exhibiting a relevantly compromised exercise capacity (median peakVO2 18.3 ml/min/kg) and quality of life (median physical functioning scale 50). WAS is the first randomized controlled trial focusing on the effects of RYGB on cardiovascular function beyond hypertension. In addition, it will provide a wealth of high-quality data on cerebral, psychiatric, hepatic, and metabolic function in obese patients after RYGB. The trial is registered at ClinicalTrials.gov (NCT01352403).


2021 ◽  
Vol 8 ◽  
Author(s):  
Haruka Kameshima ◽  
Tokuhisa Uejima ◽  
Alan G. Fraser ◽  
Lisa Takahashi ◽  
Junyi Cho ◽  
...  

Background: Discriminating between different patterns of diastolic dysfunction in heart failure (HF) is still challenging. We tested the hypothesis that an unsupervised machine learning algorithm would detect heterogeneity in diastolic function and improve risk stratification compared with recommended consensus criteria.Methods: This study included 279 consecutive patients aged 24–97 years old with clinically stable HF referred for echocardiographic assessment, in whom diastolic variables were measured according to the current guidelines. Cluster analysis was undertaken to identify homogeneous groups of patients with similar profiles of the variables. Sequential Cox models were used to compare cluster-based classification with guidelines-based classification for predicting clinical outcomes. The primary endpoint was hospitalization for worsening HF.Results: The analysis identified three clusters with distinct properties of diastolic function that shared similarities with guidelines-based classification. The clusters were associated with brain natriuretic peptide level (p &lt; 0.001), hemoglobin concentration (p = 0.017) and estimated glomerular filtration rate (p = 0.001). During a mean follow-up period of 2.6 ± 2.0 years, 62 patients (22%) experienced the primary endpoint. Cluster-based classification predicted events with a hazard ratio 1.68 (p = 0.019) that was independent from and incremental to the Meta-analysis Global Group in Chronic Heart Failure (MAGGIC) risk score for HF, and from left ventricular end-diastolic volume and global longitudinal strain, whereas guidelines-based classification did not retain its independent prognostic value (hazard ratio = 1.25, p = 0.202).Conclusion: Machine learning can identify patterns of diastolic function that better stratify the risk for decompensation than the current consensus recommendations in HF. Integrating this data-driven phenotyping may help in refining prognostication and optimizing treatment.


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