Pub Date : 2026-01-01Epub Date: 2025-12-04DOI: 10.1016/j.clinthera.2025.10.011
Hitesh Pandya MBChB, MD , Mehul Patel MBBS, PhD, FRCP , Michael Gillen BS, PhD , Jitendar Reddy MPharm , Artur Bednarczyk MD , Marek Kokot MD, MBA , Yubo Tan MSc , Maria Heijer MSc , Magdalena Andersson MSc, MSBA , David Petullo MSc , Mandeep Jassal MD
Purpose
Hydrofluoroalkane-134a (HFA-134a), the propellant in the marketed budesonide/glycopyrronium/formoterol fumarate dihydrate (BGF) formulation, has a global warming potential (GWP) that falls above environmental regulation thresholds and therefore will be phased out. With global efforts to minimize carbon emissions, the hydrofluoroolefin-1234ze (HFO-1234ze) propellant, with a >99% lower GWP than HFA-134a, is in development for pressurized metered-dose inhalers (pMDIs). Spacers support drug delivery in patients with poor pMDI inhalation technique, but it is unknown if BGF exposure with HFO-1234ze exceeds that observed with HFA-134a when using a spacer.
Methods
This Phase I study assessed systemic BGF component exposure with HFO-1234ze versus HFA-134a when using a spacer, and for HFO-1234ze with and without a spacer. Participants (N = 42) were randomized to BGF with HFA-134a with a spacer (reference), HFO-1234ze with a spacer (test), and HFO-1234ze without a spacer (descriptive treatment) over 3 treatment periods in 1 of 6 sequences. As spacer devices help to increase exposure, the upper limit of the 90% confidence interval (CI) of geometric mean ratios (GMRs) was of interest, and bioequivalence was not included as a study objective.
Findings
Analyses demonstrated the upper 90% CI of the GMRs for maximum observed plasma concentration (Cmax) and area under the plasma concentration curve from time zero to the time of the last quantifiable concentration (AUClast) were <125% for all BGF components for HFO-1234ze versus HFA-134a when using a spacer, indicating exposure with HFO-1234ze did not exceed exposure with HFA-134a. Additionally, Cmax was increased for all BGF components with HFO-1234ze when using versus not using a spacer, with the largest increases observed among participants with the lowest exposure when not using a spacer, likely due to poor inhalation technique. No new safety findings, and no deaths or serious adverse events, occurred during the study.
Implications
These findings provide evidence that may help to support the future use of HFO-1234ze propellant in BGF pMDIs.
{"title":"Exposure to Budesonide, Glycopyrronium, and Formoterol With a Next-Generation Propellant Does Not Exceed Exposure With Hydrofluoroalkane-134a Propellant When Administered Via Pressurized Metered-Dose Inhaler With a Spacer","authors":"Hitesh Pandya MBChB, MD , Mehul Patel MBBS, PhD, FRCP , Michael Gillen BS, PhD , Jitendar Reddy MPharm , Artur Bednarczyk MD , Marek Kokot MD, MBA , Yubo Tan MSc , Maria Heijer MSc , Magdalena Andersson MSc, MSBA , David Petullo MSc , Mandeep Jassal MD","doi":"10.1016/j.clinthera.2025.10.011","DOIUrl":"10.1016/j.clinthera.2025.10.011","url":null,"abstract":"<div><h3>Purpose</h3><div>Hydrofluoroalkane-134a (HFA-134a), the propellant in the marketed budesonide/glycopyrronium/formoterol fumarate dihydrate (BGF) formulation, has a global warming potential (GWP) that falls above environmental regulation thresholds and therefore will be phased out. With global efforts to minimize carbon emissions, the hydrofluoroolefin-1234ze (HFO-1234ze) propellant, with a >99% lower GWP than HFA-134a, is in development for pressurized metered-dose inhalers (pMDIs). Spacers support drug delivery in patients with poor pMDI inhalation technique, but it is unknown if BGF exposure with HFO-1234ze exceeds that observed with HFA-134a when using a spacer.</div></div><div><h3>Methods</h3><div>This Phase I study assessed systemic BGF component exposure with HFO-1234ze versus HFA-134a when using a spacer, and for HFO-1234ze with and without a spacer. Participants (<em>N</em> = 42) were randomized to BGF with HFA-134a with a spacer (reference), HFO-1234ze with a spacer (test), and HFO-1234ze without a spacer (descriptive treatment) over 3 treatment periods in 1 of 6 sequences. As spacer devices help to increase exposure, the upper limit of the 90% confidence interval (CI) of geometric mean ratios (GMRs) was of interest, and bioequivalence was not included as a study objective.</div></div><div><h3>Findings</h3><div>Analyses demonstrated the upper 90% CI of the GMRs for maximum observed plasma concentration (Cmax) and area under the plasma concentration curve from time zero to the time of the last quantifiable concentration (AUClast) were <125% for all BGF components for HFO-1234ze versus HFA-134a when using a spacer, indicating exposure with HFO-1234ze did not exceed exposure with HFA-134a. Additionally, Cmax was increased for all BGF components with HFO-1234ze when using versus not using a spacer, with the largest increases observed among participants with the lowest exposure when not using a spacer, likely due to poor inhalation technique. No new safety findings, and no deaths or serious adverse events, occurred during the study.</div></div><div><h3>Implications</h3><div>These findings provide evidence that may help to support the future use of HFO-1234ze propellant in BGF pMDIs.</div></div>","PeriodicalId":10699,"journal":{"name":"Clinical therapeutics","volume":"48 1","pages":"Pages 73-80"},"PeriodicalIF":3.6,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145676351","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-01-01Epub Date: 2025-12-11DOI: 10.1016/j.clinthera.2025.11.004
Manan M. Nayak PhD, MA , Peter R. Chai MD, MS , Stephanie Tung MD , Anna Revette PhD , Ilana M. Braun MD
Purpose
Medical cannabis (MC) is used by 1 in 3 patients with cancer. Scientific work suggests a disconnect between patients’ cannabis therapeutics practices and oncologists’ clinical preferences. This qualitative study explores the preferences of patients with cancer as they relate to MC formulations, administration routes, and dosing.
Methods
Semistructured interviews were conducted with patients with cancer consuming MC in 8 states and examined using thematic analysis.
Findings
Among study participants (N = 24), the mean age was 54 years, 67% were female, and 51% had metastatic disease. A powerful theme identified across interviews was of myriad MC dispensary product formulations, triggering astonishment and burden. Common strategies among participants included purchasing and sampling multiple store-bought formulations, modifying dispensary products, and altering intended routes of administration. Preferred dispensary products were not consistently available. Top-cited modes of administration included oral, followed by topical, sublingual, vaporization, combustion, and rectal suppository. Three-quarters of participants alternated between modes. Medical cannabis dosing imprecision represented another powerful theme due to the lack of dispensary quality assurance and accuracy in home measurements.
Implications
This investigation suggests that MC preparations, dosing, and administration routes vary among patients with cancer, and that common consumption patterns (for instance, reliance on multiple routes of cannabis administration) are not rooted in science. Although these findings should be further interrogated, they suggest a need for lay-facing cannabis therapeutics education and standardization of dispensary products to strengthen cannabis-related care.
{"title":"Medical Cannabis Formulations, Administration Routes, and Dosing: Perspectives of Patients With Cancer Who Consume","authors":"Manan M. Nayak PhD, MA , Peter R. Chai MD, MS , Stephanie Tung MD , Anna Revette PhD , Ilana M. Braun MD","doi":"10.1016/j.clinthera.2025.11.004","DOIUrl":"10.1016/j.clinthera.2025.11.004","url":null,"abstract":"<div><h3>Purpose</h3><div>Medical cannabis (MC) is used by 1 in 3 patients with cancer. Scientific work suggests a disconnect between patients’ cannabis therapeutics practices and oncologists’ clinical preferences. This qualitative study explores the preferences of patients with cancer as they relate to MC formulations, administration routes, and dosing.</div></div><div><h3>Methods</h3><div>Semistructured interviews were conducted with patients with cancer consuming MC in 8 states and examined using thematic analysis.</div></div><div><h3>Findings</h3><div>Among study participants (N = 24), the mean age was 54 years, 67% were female, and 51% had metastatic disease. A powerful theme identified across interviews was of myriad MC dispensary product formulations, triggering astonishment and burden. Common strategies among participants included purchasing and sampling multiple store-bought formulations, modifying dispensary products, and altering intended routes of administration. Preferred dispensary products were not consistently available. Top-cited modes of administration included oral, followed by topical, sublingual, vaporization, combustion, and rectal suppository. Three-quarters of participants alternated between modes. Medical cannabis dosing imprecision represented another powerful theme due to the lack of dispensary quality assurance and accuracy in home measurements.</div></div><div><h3>Implications</h3><div>This investigation suggests that MC preparations, dosing, and administration routes vary among patients with cancer, and that common consumption patterns (for instance, reliance on multiple routes of cannabis administration) are not rooted in science. Although these findings should be further interrogated, they suggest a need for lay-facing cannabis therapeutics education and standardization of dispensary products to strengthen cannabis-related care.</div></div>","PeriodicalId":10699,"journal":{"name":"Clinical therapeutics","volume":"48 1","pages":"Pages 51-56"},"PeriodicalIF":3.6,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145741435","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-01-01Epub Date: 2025-12-15DOI: 10.1016/j.clinthera.2025.11.011
Jinho Shin MD, PhD , Seong Hwan Kim MD, PhD , Ki Hoon Han MD, PhD , Moo Hyun Kim MD, PhD , Young Keun Ahn MD, PhD , Il Suk Sohn MD, PhD , Kwang Il Kim MD, PhD , Dong Hun Cha MD, PhD , Soon Jun Hong MD, PhD , Eun Joo Cho MD, PhD , Hae Young Lee MD, PhD , Wook Bum Pyun MD, PhD , Ho Joong Youn MD, PhD , Woo Shik Kim MD, PhD , Moo Yong Rhee MD, PhD , Jun Hee Lee MD, PhD , Jong Won Ha MD, PhD , Ji Yong Choi MD, PhD , Byung Su Yoo MD, PhD , Jin Ok Jeong MD, PhD , Chong Jin Kim MD, PhD
{"title":"Corrigendum to “Multicenter, Randomized, Double-Blind, Parallel, Phase 2 Clinical Trial to Compare and Evaluate the Efficacy and Safety of SPC1001 and Monotherapy in Patients With Essential Hypertension” (Clin Ther. 2025 Oct 28. [Epub ahead of print])","authors":"Jinho Shin MD, PhD , Seong Hwan Kim MD, PhD , Ki Hoon Han MD, PhD , Moo Hyun Kim MD, PhD , Young Keun Ahn MD, PhD , Il Suk Sohn MD, PhD , Kwang Il Kim MD, PhD , Dong Hun Cha MD, PhD , Soon Jun Hong MD, PhD , Eun Joo Cho MD, PhD , Hae Young Lee MD, PhD , Wook Bum Pyun MD, PhD , Ho Joong Youn MD, PhD , Woo Shik Kim MD, PhD , Moo Yong Rhee MD, PhD , Jun Hee Lee MD, PhD , Jong Won Ha MD, PhD , Ji Yong Choi MD, PhD , Byung Su Yoo MD, PhD , Jin Ok Jeong MD, PhD , Chong Jin Kim MD, PhD","doi":"10.1016/j.clinthera.2025.11.011","DOIUrl":"10.1016/j.clinthera.2025.11.011","url":null,"abstract":"","PeriodicalId":10699,"journal":{"name":"Clinical therapeutics","volume":"48 1","pages":"Page 131"},"PeriodicalIF":3.6,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145767421","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Letter to The Editor, Regarding “Indirect Comparison of Maralixibat and Odevixibat for the Treatment of Progressive Familial Intrahepatic Cholestasis” Recently Published by Lacey and Colleagues","authors":"Emmanuelle Kaltenbach PharmD, MSc , Virginie Jacquemin PhD , Luis Briseño-Roa PhD , Andres Gomez-Lievano PhD , Marie-Cécile Fournier PhD , Fatine Elaraki MD","doi":"10.1016/j.clinthera.2025.10.014","DOIUrl":"10.1016/j.clinthera.2025.10.014","url":null,"abstract":"","PeriodicalId":10699,"journal":{"name":"Clinical therapeutics","volume":"48 1","pages":"Pages 127-128"},"PeriodicalIF":3.6,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145631082","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-01-01Epub Date: 2025-11-24DOI: 10.1016/j.clinthera.2025.10.008
Sara Youssif Ibrahim PhD , Yara Ali BSc , Zohra Abdelfattah BSc , Amany Gad BSc , Nada Mohamed BSc , Nancy Mortada BSc , Omar Ahmed BSc , Ahmed Nabil BSc , Mahmoud Refay BSc , Ahmed Mohamed BSc , Mohamed Goda BSc , Ahmed Essam Abou Warda PhD , Salwa Selim Abougalambou PhD , Hadeer Ehab Barakat PhD
Purpose
Multidrug-resistant (MDR) microorganisms has emerged as a significant global health crisis leading to higher rates of morbidity. Antimicrobial resistance (AMR) presents a serious challenge in intensive care units (ICUs), where infections caused by MDR pathogens are common. Thus, implementation of antimicrobial stewardship programs (ASPs) ensures prudent antibiotic use and decreases AMR. Therefore, the current study evaluates the impact of ASP applications on empirical antibiotic prescribing practices and AMR through a Point Prevalence Survey (PPS) in ICU settings.
Methods
A prospective, multicentric, quasi-experimental study was conducted in various departments over a period of 12 weeks. Inpatients receiving antibiotics were surveyed before and after the implementation of ASP. These interventions included customizing ASP guidelines, training healthcare team, and auditing prescribing behaviors. Data was analyzed using SPSS, and outcomes evaluated included adherence to guidelines, prevalence of antibiotic use, and appropriateness of prescriptions.
Results
Of the 174 patients were surveyed across PPS. Escherichia coli showed the highest prevalence in PPS-1 (26%), while Klebsiella pneumoniae and Staphylococcus aureus showed the highest in PPS-2 (18%). Carbapenem-resistant Enterobacteriaceae decreased from 25% in PPS-1 to 8% in PPS-2. Guideline-inappropriate prescriptions and missing documentation of preparation or administration method declined from 27.3% to 5.2% (P = 0.000042) and from 78.5% to 56.2% (P = 0.002) respectively, reflecting improved prescribing quality and record-keeping. Although the proportion of prescriptions with improper antibiotic duration increased from 32.1% to 42.7% (P = 0.145), this trend may reflect evolving clinical decision-making rather than a decline in care quality.
Conclusion
The study suggests that ASP interventions were associated with improved antibiotic prescribing practices and adherence to guidelines in ICU settings, contributing to the fight against AMR. Given the study design and sample size, findings are exploratory and suggestive. Future work includes expanding ASP monitoring and education strategies with solutions focusing on antibiotic duration.
{"title":"Evaluation of the Application of Antimicrobial Stewardship on the Rational Use of Antibiotics and Overcoming Antimicrobial Resistance in Tertiary Hospitals: A Point Prevalence Survey","authors":"Sara Youssif Ibrahim PhD , Yara Ali BSc , Zohra Abdelfattah BSc , Amany Gad BSc , Nada Mohamed BSc , Nancy Mortada BSc , Omar Ahmed BSc , Ahmed Nabil BSc , Mahmoud Refay BSc , Ahmed Mohamed BSc , Mohamed Goda BSc , Ahmed Essam Abou Warda PhD , Salwa Selim Abougalambou PhD , Hadeer Ehab Barakat PhD","doi":"10.1016/j.clinthera.2025.10.008","DOIUrl":"10.1016/j.clinthera.2025.10.008","url":null,"abstract":"<div><h3>Purpose</h3><div>Multidrug-resistant (MDR) microorganisms has emerged as a significant global health crisis leading to higher rates of morbidity. Antimicrobial resistance (AMR) presents a serious challenge in intensive care units (ICUs), where infections caused by MDR pathogens are common. Thus, implementation of antimicrobial stewardship programs (ASPs) ensures prudent antibiotic use and decreases AMR. Therefore, the current study evaluates the impact of ASP applications on empirical antibiotic prescribing practices and AMR through a Point Prevalence Survey (PPS) in ICU settings.</div></div><div><h3>Methods</h3><div>A prospective, multicentric, quasi-experimental study was conducted in various departments over a period of 12 weeks. Inpatients receiving antibiotics were surveyed before and after the implementation of ASP. These interventions included customizing ASP guidelines, training healthcare team, and auditing prescribing behaviors. Data was analyzed using SPSS, and outcomes evaluated included adherence to guidelines, prevalence of antibiotic use, and appropriateness of prescriptions.</div></div><div><h3>Results</h3><div>Of the 174 patients were surveyed across PPS. <em>Escherichia coli</em> showed the highest prevalence in PPS-1 (26%), while <em>Klebsiella pneumoniae</em> and <em>Staphylococcus aureus</em> showed the highest in PPS-2 (18%). Carbapenem-resistant Enterobacteriaceae decreased from 25% in PPS-1 to 8% in PPS-2. Guideline-inappropriate prescriptions and missing documentation of preparation or administration method declined from 27.3% to 5.2% (<em>P</em> = 0.000042) and from 78.5% to 56.2% (<em>P</em> = 0.002) respectively, reflecting improved prescribing quality and record-keeping. Although the proportion of prescriptions with improper antibiotic duration increased from 32.1% to 42.7% (<em>P</em> = 0.145), this trend may reflect evolving clinical decision-making rather than a decline in care quality.</div></div><div><h3>Conclusion</h3><div>The study suggests that ASP interventions were associated with improved antibiotic prescribing practices and adherence to guidelines in ICU settings, contributing to the fight against AMR. Given the study design and sample size, findings are exploratory and suggestive. Future work includes expanding ASP monitoring and education strategies with solutions focusing on antibiotic duration.</div></div>","PeriodicalId":10699,"journal":{"name":"Clinical therapeutics","volume":"48 1","pages":"Pages e1-e9"},"PeriodicalIF":3.6,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145602763","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-01-01Epub Date: 2025-11-21DOI: 10.1016/j.clinthera.2025.10.012
Jing Li MM , Caiyun Xu MM , Zhe Huang MM , Lan Yao MM , Huayun Liu MM , Fuxing Deng MD , Can Zhu MM , Qinjuan Jiang MM
Purpose
This study aims to evaluate how the timing of continuous renal replacement therapy (CRRT) initiation influences survival outcomes in oliguric patients with sepsis-associated acute kidney injury (S-AKI) admitted to the intensive care unit (ICU).
Methods
Using the MIMIC-IV database, we conducted a retrospective analysis of 2,131 ICU patients with oliguric S-AKI who had CRRT records. Patients were categorized into 2 groups according to the timing of CRRT initiation: early initiation within 48 hours (n = 1,222) and delayed initiation after 48 hours (n = 909) following the onset of oliguria. Propensity score matching (PSM) and inverse probability of treatment weighting (IPTW) were applied to adjust for confounding factors. Baseline characteristics, physiological parameters, and laboratory findings were compared between the 2 groups. Survival outcomes were analyzed using Kaplan-Meier curves and log-rank tests, with a primary focus on 90-day mortality.
Findings
Patients who initiated CRRT more than 48 hours after oliguria onset had significantly longer ICU stays compared to those who received early CRRT (17.6 vs. 11.5 days, P < 0.001) and exhibited higher SOFA scores (11.5 vs. 9.14, P < 0.001). After PSM, delayed CRRT was associated with decreased 90-day survival among patients with oliguria, as demonstrated by Kaplan-Meier analysis (P < 0.05). Causal inference showed a 10% increase in the 90-day mortality rate for patients who started CRRT after 48 hours (ATE 0.11, 95% CI: 0.02 - 0.19, P = 0.01).
Implications
Early initiation of CRRT, within 48 hours of oliguria onset, in S-AKI patients is associated with improved 90-day survival. These findings suggest that earlier CRRT initiation may be beneficial for improving survival outcomes in this patient population.
{"title":"Impact of CRRT Timing on Mortality in Oliguric Sepsis-Associated Acute Kidney Injury: A Propensity Score Matching Cohort Study","authors":"Jing Li MM , Caiyun Xu MM , Zhe Huang MM , Lan Yao MM , Huayun Liu MM , Fuxing Deng MD , Can Zhu MM , Qinjuan Jiang MM","doi":"10.1016/j.clinthera.2025.10.012","DOIUrl":"10.1016/j.clinthera.2025.10.012","url":null,"abstract":"<div><h3>Purpose</h3><div>This study aims to evaluate how the timing of continuous renal replacement therapy (CRRT) initiation influences survival outcomes in oliguric patients with sepsis-associated acute kidney injury (S-AKI) admitted to the intensive care unit (ICU).</div></div><div><h3>Methods</h3><div>Using the MIMIC-IV database, we conducted a retrospective analysis of 2,131 ICU patients with oliguric S-AKI who had CRRT records. Patients were categorized into 2 groups according to the timing of CRRT initiation: early initiation within 48 hours (<em>n</em> = 1,222) and delayed initiation after 48 hours (<em>n</em> = 909) following the onset of oliguria. Propensity score matching (PSM) and inverse probability of treatment weighting (IPTW) were applied to adjust for confounding factors. Baseline characteristics, physiological parameters, and laboratory findings were compared between the 2 groups. Survival outcomes were analyzed using Kaplan-Meier curves and log-rank tests, with a primary focus on 90-day mortality.</div></div><div><h3>Findings</h3><div>Patients who initiated CRRT more than 48 hours after oliguria onset had significantly longer ICU stays compared to those who received early CRRT (17.6 vs. 11.5 days, <em>P</em> < 0.001) and exhibited higher SOFA scores (11.5 vs. 9.14, <em>P</em> < 0.001). After PSM, delayed CRRT was associated with decreased 90-day survival among patients with oliguria, as demonstrated by Kaplan-Meier analysis (<em>P</em> < 0.05). Causal inference showed a 10% increase in the 90-day mortality rate for patients who started CRRT after 48 hours (ATE 0.11, 95% CI: 0.02 - 0.19, <em>P</em> = 0.01).</div></div><div><h3>Implications</h3><div>Early initiation of CRRT, within 48 hours of oliguria onset, in S-AKI patients is associated with improved 90-day survival. These findings suggest that earlier CRRT initiation may be beneficial for improving survival outcomes in this patient population.</div></div>","PeriodicalId":10699,"journal":{"name":"Clinical therapeutics","volume":"48 1","pages":"Pages 65-72"},"PeriodicalIF":3.6,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145573429","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-12-01Epub Date: 2025-10-04DOI: 10.1016/j.clinthera.2025.09.005
Anastasia Uster MD , Nihar Desai MD , Sankar D. Navaneethan MD , Egon Pfarr MSc , Anna Rita Mazo MD
Purpose
Chronic kidney disease (CKD) increases hospitalization risk. In the randomized, phase III, EMPA-KIDNEY trial, empagliflozin significantly reduced risk of all-cause hospitalizations (ACH; first and recurrent) vs placebo. This post hoc analysis of the EMPA-KIDNEY trial examines the burden of ACH in CKD and the effects of empagliflozin on ACH.
Methods
Participants with CKD (n = 6609) were randomized to empagliflozin 10 mg or placebo. Reasons for hospitalizations were derived from adverse events leading to hospitalization, assessed by system organ class.
Findings
Overall, 1995 participants (1035 placebo, 960 empagliflozin) had ≥1 ACH (1895 ACH in placebo and 1611 in the empagliflozin 10-mg groups). The estimated mortality rate after first hospitalization in participants with ≥1 hospitalization was 12% after 1 year and 18% after 2 years, and risk of death was ∼10 times higher vs those without (hazard ratio [HR] 9.53; 95% confidence interval [CI], 7.18–12.64; P < 0.0001). The most common reasons for hospitalization were infections and infestations, surgical and medical procedures, investigations, cardiac disorders, renal and urinary disorders, and metabolic disorders. Risk of ACH was significantly reduced for empagliflozin vs placebo (HR: 0.86, 95% CI, 0.78–0.95, P = 0.003). This was consistent regardless of baseline diabetes status, estimated glomerular filtration rate, or urinary albumin-to-creatinine ratio. Mean cumulative incidence of ACH in empagliflozin and placebo groups diverged shortly after randomization and separated further over time. Risk of hospital admissions from cardiovascular (CV), renal, or metabolic conditions was significantly lower with empagliflozin vs placebo (P < 0.05).
Implications
Treatment with empagliflozin significantly reduced risk of ACH, including those attributed to CV, renal, or metabolic conditions.
{"title":"Empagliflozin Reduces Risk of Hospitalization in Patients With Chronic Kidney Disease in the EMPA-KIDNEY Trial","authors":"Anastasia Uster MD , Nihar Desai MD , Sankar D. Navaneethan MD , Egon Pfarr MSc , Anna Rita Mazo MD","doi":"10.1016/j.clinthera.2025.09.005","DOIUrl":"10.1016/j.clinthera.2025.09.005","url":null,"abstract":"<div><h3>Purpose</h3><div>Chronic kidney disease (CKD) increases hospitalization risk. In the randomized, phase III, EMPA-KIDNEY trial, empagliflozin significantly reduced risk of all-cause hospitalizations (ACH; first and recurrent) vs placebo. This post hoc analysis of the EMPA-KIDNEY trial examines the burden of ACH in CKD and the effects of empagliflozin on ACH.</div></div><div><h3>Methods</h3><div>Participants with CKD (n = 6609) were randomized to empagliflozin 10 mg or placebo. Reasons for hospitalizations were derived from adverse events leading to hospitalization, assessed by system organ class.</div></div><div><h3>Findings</h3><div>Overall, 1995 participants (1035 placebo, 960 empagliflozin) had ≥1 ACH (1895 ACH in placebo and 1611 in the empagliflozin 10-mg groups). The estimated mortality rate after first hospitalization in participants with ≥1 hospitalization was 12% after 1 year and 18% after 2 years, and risk of death was ∼10 times higher vs those without (hazard ratio [HR] 9.53; 95% confidence interval [CI], 7.18–12.64; <em>P</em> < 0.0001). The most common reasons for hospitalization were infections and infestations, surgical and medical procedures, investigations, cardiac disorders, renal and urinary disorders, and metabolic disorders. Risk of ACH was significantly reduced for empagliflozin vs placebo (HR: 0.86, 95% CI, 0.78–0.95, <em>P</em> = 0.003). This was consistent regardless of baseline diabetes status, estimated glomerular filtration rate, or urinary albumin-to-creatinine ratio. Mean cumulative incidence of ACH in empagliflozin and placebo groups diverged shortly after randomization and separated further over time. Risk of hospital admissions from cardiovascular (CV), renal, or metabolic conditions was significantly lower with empagliflozin vs placebo (<em>P</em> < 0.05).</div></div><div><h3>Implications</h3><div>Treatment with empagliflozin significantly reduced risk of ACH, including those attributed to CV, renal, or metabolic conditions.</div></div><div><h3>ClinicalTrials.gov number</h3><div>NCT03594110</div></div>","PeriodicalId":10699,"journal":{"name":"Clinical therapeutics","volume":"47 12","pages":"Pages 1091-1096"},"PeriodicalIF":3.6,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145231496","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-12-01Epub Date: 2025-10-28DOI: 10.1016/j.clinthera.2025.10.001
Jinho Shin MD, PhD , SeongHwan Kim MD, PhD , KiHoon Han MD, PhD , MooHyun Kim MD, PhD , YoungKeun Ahn MD, PhD , IlSuk Sohn MD, PhD , KwangIl Kim MD, PhD , DongHun Cha MD, PhD , SoonJun Hong MD, PhD , EunJoo Cho MD, PhD , HaeYoung Lee MD, PhD , WookBum Pyun MD, PhD , HoJoong Youn MD, PhD , WooShik Kim MD, PhD , MooYong Rhee MD, PhD , JunHee Lee MD, PhD , JongWon Ha MD, PhD , JiYong Choi MD, PhD , ByungSu Yoo MD, PhD , JinOk Jeong MD, PhD , ChongJin Kim MD, PhD
<div><h3>Purpose</h3><div>Hypertension poses challenges for many patients in achieving adequate blood pressure control, despite using monotherapy or standard treatment regimens. A low-dose triple combination drug has recently been considered for initial hypertension therapy; however, its safety, efficacy, and dose-response relationship remain unclear. We evaluated these aspects for patients with hypertension to determine the optimal combination dose.</div></div><div><h3>Methods</h3><div>A multicenter, randomized, double-blind, parallel, phase 2 clinical trial was conducted in South Korea. Following a two-week placebo run-in period, 253 patients of SPC1001 were randomized into the High, Mid1, Mid2, and Low groups, which consisted of a fixed-dose triple combination of candesartan, amlodipine, and indapamide at varying doses. The dosages were SPC1001 High (4/2.5/1.25 mg), SPC1001 Mid1 (2.67/1.67/0.83 mg), SPC1001 Mid2 (4/1.25/1.25 mg), SPC1001 Low (2/1.25/0.625 mg), SPC3001 (candesartan 8 mg), SPC4001 (amlodipine 5 mg), SPC4002 (amlodipine 10 mg), and placebo, with the number of participants in the groups at a 1:1:1:1:1:1:1:1 ratio. Participants who had been using antihypertensive medication during the screening visit were required to discontinue it at least 4 weeks before the run-in period. The primary endpoint was determined by evaluating how mean sitting systolic blood pressure (MSSBP) varied between the baseline measurement and week 8. Treatment emergent adverse events and clinically significant changes on physical examination, including the assessment of ankle edema, laboratory tests, vital signs, and 12-lead electrocardiography, were also evaluated.</div></div><div><h3>Findings</h3><div>SPC1001 High and SPC1001 Mid2 were identified as the two groups with the most effective dosages. The least square mean difference (LSMD) of SPC1001 High compared to SPC3001, SPC4001, SPC4002, and placebo was –7.50, −7.68, 0.03, and −16.97 mm Hg, respectively (<em>P</em>-values for ANCOVA were 0.04, 0.0473, 0.9929, and <0.0001). The LSMD of SPC 1001 Mid2 compared with that of SPC3001, SPC4001, SPC4002, and placebo was −8.72, −8.72, −1.85, and −18.02 mm Hg, respectively (<em>P-values</em> for ANCOVA were 0.0075, 0.0119, 0.5704, and <0.0001). The LSMD of SPC 1001 Mid1 compared to that of SPC3001, SPC4001, SPC4002, and placebo was −4.90, −5.21, 3.03, and −14.44 mm Hg, respectively (<em>P</em>-values for ANCOVA were 0.1178, 0.1205, 0.3347, and <0.0001). The LSMD of SPC1001 Low compared to that of SPC3001, SPC4001, SPC4002, and placebo was −0.51, −0.87, 7.30, and −9.88 mm Hg, respectively (<em>P-values</em> for ANCOVA were 0.8799, 0.8088, 0.0284, and <0.0047). There were two serious adverse events recorded, in SPC1001 High and SPC3001.</div></div><div><h3>Implications</h3><div>Low-dose triple combination therapies may be effective for treating hypertension.</div></div><div><h3>Trial Registration</h3><div>ClinicalTrials.gov identifier: NCT06212648.</div></
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Pub Date : 2025-12-01Epub Date: 2025-10-10DOI: 10.1016/j.clinthera.2025.09.010
Li Wang PhD, Xiangyun Jin MS, YanChun Li MS
Purpose
To investigate whether fenofibrate use is associated with an increased risk of renal and urinary adverse events based on the U.S. Food and Drug Administration Adverse Event Reporting System (FAERS).
Methods
This retrospective pharmacovigilance study utilized data from the FAERS between January 1st, 2019, and December 31st, 2023. Reports listing fenofibrate as the primary suspect drug were extracted, and renal and urinary adverse events were identified based on preferred terms (PTs) in the MedDRA dictionary. Disproportionality analysis was conducted using four standard algorithms—reporting odds ratio (ROR), proportional reporting ratio (PRR), bayesian confidence propagation neural network (BCPNN), and multi-item gamma poisson shrinker (MGPS)—to detect safety signals. The PTs exhibiting positive signals were clinically prioritized, and bivariate logistic regression analysis was performed to identify demographic risk factors associated with serious clinical outcomes.
Findings
Between 1 January 2019 and 31 December 2023, a total of 2,810 adverse event reports related to fenofibrate were identified, of which 443 (15.77%) were classified as renal and urinary adverse events. The mean age of affected patients was 57.89 years, with a higher proportion of males (n = 183, 27.94%). Signal detection showed a significant association between fenofibrate and renal and urinary adverse events: ROR = 2.23 (95% CI:2.07–2.41), PRR = 2.18 (χ² = 428.29), IC = 1.12 (IC025 = 1.01), EBGM = 2.18 (EBGM05 = 2.04). Adverse events reported with high frequency included acute kidney injury (n = 149, 22.29%), haematuria (n = 88, 13.44%), and urinary tract disorder (n = 82, 12.52%), with acute kidney injury and anuria identified as key clinical priority events. Bivariate logistic regression analysis demonstrated that individuals aged above 65 years had a significantly higher likelihood of experiencing serious clinical outcomes (OR = 2.046, 95% CI: 1.579–3.665; P < 0.001), males have a lower risk (OR = 0.656, 95% CI: 0.444–0.968, P = 0.034).
Implications
This study suggests a possible significant association between fenofibrate and renal and urinary adverse events. Safety monitoring and individualized risk assessment of patients using fenofibrate should be enhanced to reduce the risk of potential adverse outcomes.
{"title":"Characterizing Fenofibrate-Related Renal and Urinary Adverse Events: A Comprehensive Analysis of FDA Adverse Event Reporting System Database","authors":"Li Wang PhD, Xiangyun Jin MS, YanChun Li MS","doi":"10.1016/j.clinthera.2025.09.010","DOIUrl":"10.1016/j.clinthera.2025.09.010","url":null,"abstract":"<div><h3>Purpose</h3><div>To investigate whether fenofibrate use is associated with an increased risk of renal and urinary adverse events based on the U.S. Food and Drug Administration Adverse Event Reporting System (FAERS).</div></div><div><h3>Methods</h3><div>This retrospective pharmacovigilance study utilized data from the FAERS between January 1st, 2019, and December 31st, 2023. Reports listing fenofibrate as the primary suspect drug were extracted, and renal and urinary adverse events were identified based on preferred terms (PTs) in the MedDRA dictionary. Disproportionality analysis was conducted using four standard algorithms—reporting odds ratio (ROR), proportional reporting ratio (PRR), bayesian confidence propagation neural network (BCPNN), and multi-item gamma poisson shrinker (MGPS)—to detect safety signals. The PTs exhibiting positive signals were clinically prioritized, and bivariate logistic regression analysis was performed to identify demographic risk factors associated with serious clinical outcomes.</div></div><div><h3>Findings</h3><div>Between 1 January 2019 and 31 December 2023, a total of 2,810 adverse event reports related to fenofibrate were identified, of which 443 (15.77%) were classified as renal and urinary adverse events. The mean age of affected patients was 57.89 years, with a higher proportion of males (n = 183, 27.94%). Signal detection showed a significant association between fenofibrate and renal and urinary adverse events: ROR = 2.23 (95% CI:2.07–2.41), PRR = 2.18 (χ² = 428.29), IC = 1.12 (IC<sub>025</sub> = 1.01), EBGM = 2.18 (EBGM05 = 2.04). Adverse events reported with high frequency included acute kidney injury (n = 149, 22.29%), haematuria (n = 88, 13.44%), and urinary tract disorder (n = 82, 12.52%), with acute kidney injury and anuria identified as key clinical priority events. Bivariate logistic regression analysis demonstrated that individuals aged above 65 years had a significantly higher likelihood of experiencing serious clinical outcomes (OR = 2.046, 95% CI: 1.579–3.665; <em>P < 0.</em>001), males have a lower risk (OR = 0.656, 95% CI: 0.444–0.968, <em>P = 0.</em>034).</div></div><div><h3>Implications</h3><div>This study suggests a possible significant association between fenofibrate and renal and urinary adverse events. Safety monitoring and individualized risk assessment of patients using fenofibrate should be enhanced to reduce the risk of potential adverse outcomes.</div></div>","PeriodicalId":10699,"journal":{"name":"Clinical therapeutics","volume":"47 12","pages":"Pages 1149-1154"},"PeriodicalIF":3.6,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145274013","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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