359 Neo-Kidney Augment (NKA): Phase II Study of Percutaneous Renal Injection of Autologous Homologous NKA in Subjects with Type 2 Diabetes and CKD

Abstract INTRODUCTION Vascular endothelial growth factor receptor (VEGFR), platelet derived growth factor receptor (PDGFR), and c-KIT represent clinically and/or preclinically validated molecular targets in vestibular schwannomas. We conducted a single institution, prospective, open-label, two-stage phase II study (ClinicalTrials.gov identifier NCT02129647) to estimate the response rate to axitinib, an oral multi-receptor tyrosine kinase inhibitor targeting VEGFR, PDGFR and c-KIT, in neurofibromatosis type 2 (NF2) patients with progressive vestibular schwannomas (VS). METHODS NF2 patients older than 5 years with at least one volumetrically measurable, progressive VS were eligible. The primary endpoint was to estimate the objective volumetric response rates to axitinib. Axitinib was given continuously in 28-day cycles for up to of 12 cycles. Response was assessed every 3 months with MRI using 3-D volumetric tumor analysis and audiograms. Volumetric response and progression were defined as ≥20% decrease or increase in VS volume, respectively. RESULTS Twelve eligible patients (ages: 14–56 years) were enrolled on this study. Seven of twelve patients completed 12 cycles (range: 2 to 12 cycles). We observed two imaging and three hearing responses. Best volumetric response was -53.9% after nine months on axitinib. All patients experienced drug-related toxicities, the most common adverse events were diarrhea, hematuria and skin toxicity, not exceeding grade 2 and hypertension, not exceeding grade 3. CONCLUSIONS While axitinib has modest anti-tumor activity in NF2 patients, it is more toxic and appears to be less effective compared to bevacizumab. Based on these findings, further clinical development of axitinib for this indication does not appear warranted.

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Influence of Renin-Angiotensin System Inhibitors on Lower Respiratory Tract Infections in Type 2 Diabetes: The Fremantle Diabetes Study Phase II

10.2337/figshare.12398024 ◽

2020 ◽

Author(s):

Timothy M E Davis ◽

Wendy A Davis

Keyword(s):

Type 2 Diabetes ◽

Respiratory Tract ◽

Phase Ii ◽

Lower Respiratory Tract ◽

Respiratory Tract Infections ◽

Study Phase ◽

Lower Respiratory Tract Infections ◽

Tract Infections

Objective: To determine whether angiotensin converting enzyme inhibitors (ACEi) and angiotensin receptor blockers (ARB) protect against lower respiratory tract infections complicating type 2 diabetes. Research design and methods: Of 1,732 participants with diabetes recruited to the longitudinal observational Fremantle Diabetes Study Phase II (FDS2) between 2008 and 2011, 1,482 had confirmed type 2 diabetes (mean age of 65.8 years, 51.6% were males, median diabetes duration 9.0 years). All were followed for hospitalizations for/with, or deaths from, pneumonia/influenza ascertained from validated administrative data linkage from study entry to end-2016. Cox and competing risk regression were used to identify independent predictors of this outcome. Results: Two-thirds of participants (n=982) were taking an ACEi and/or ARB at study entry (498 (33.6%) ACEi, 408 (27.5%) ARB, 76 (5.1%) both). During 9,511 person-years of follow-up (mean 6.4±2.0 years), 174 participants had incident pneumonia/influenza (156 hospitalizations, 18 deaths without hospitalization). In Cox regression analysis, baseline ACEi/ARB use was independently associated with a reduced risk of incident pneumonia/influenza (cause-specific hazard ratio (HR) (95% confidence interval) 0.64 (0.45, 0.89), P=0.008). Allowing for the competing risk of death did not change this finding (subdistribution HR 0.67 (0.48, 0.95), P=0.024), and similar reductions were seen for ACEi, ARB alone, and ACEi/ARB combination therapy. There was no significant change in use of ACEi/ARB during follow-up (interaction with ln(time), P=0.70). Other significant predictors of incident pneumonia/influenza were previously reported, clinically plausible variables. Conclusions: ACEi/ARB reduce the risk of pneumonia/influenza in community-based people with type 2 diabetes.

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Influence of Renin-Angiotensin System Inhibitors on Lower Respiratory Tract Infections in Type 2 Diabetes: The Fremantle Diabetes Study Phase II

10.2337/figshare.12398024.v1 ◽

2020 ◽

Author(s):

Timothy M E Davis ◽

Wendy A Davis

Keyword(s):

Type 2 Diabetes ◽

Respiratory Tract ◽

Phase Ii ◽

Lower Respiratory Tract ◽

Respiratory Tract Infections ◽

Study Phase ◽

Lower Respiratory Tract Infections ◽

Tract Infections

Objective: To determine whether angiotensin converting enzyme inhibitors (ACEi) and angiotensin receptor blockers (ARB) protect against lower respiratory tract infections complicating type 2 diabetes. Research design and methods: Of 1,732 participants with diabetes recruited to the longitudinal observational Fremantle Diabetes Study Phase II (FDS2) between 2008 and 2011, 1,482 had confirmed type 2 diabetes (mean age of 65.8 years, 51.6% were males, median diabetes duration 9.0 years). All were followed for hospitalizations for/with, or deaths from, pneumonia/influenza ascertained from validated administrative data linkage from study entry to end-2016. Cox and competing risk regression were used to identify independent predictors of this outcome. Results: Two-thirds of participants (n=982) were taking an ACEi and/or ARB at study entry (498 (33.6%) ACEi, 408 (27.5%) ARB, 76 (5.1%) both). During 9,511 person-years of follow-up (mean 6.4±2.0 years), 174 participants had incident pneumonia/influenza (156 hospitalizations, 18 deaths without hospitalization). In Cox regression analysis, baseline ACEi/ARB use was independently associated with a reduced risk of incident pneumonia/influenza (cause-specific hazard ratio (HR) (95% confidence interval) 0.64 (0.45, 0.89), P=0.008). Allowing for the competing risk of death did not change this finding (subdistribution HR 0.67 (0.48, 0.95), P=0.024), and similar reductions were seen for ACEi, ARB alone, and ACEi/ARB combination therapy. There was no significant change in use of ACEi/ARB during follow-up (interaction with ln(time), P=0.70). Other significant predictors of incident pneumonia/influenza were previously reported, clinically plausible variables. Conclusions: ACEi/ARB reduce the risk of pneumonia/influenza in community-based people with type 2 diabetes.

Download Full-text