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Intravitreal dexamethasone implant one month before versus concomitant with cataract surgery in patients with diabetic macular oedema: the dexcat study.
Fallico, M, Avitabile, T, Castellino, N, Longo, A, Russo, A, Bonfiglio, V, Parisi, F, Furino, C, Panozzo, G, Scorcia, V, et al
Acta ophthalmologica. 2021;(1):e74-e80
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Abstract
PURPOSE To report clinical outcomes of two different timings of intravitreal dexamethasone (DEX) implant administration for prevention of diabetic macular oedema (DME) worsening following cataract surgery. METHODS This multicentre, retrospective study included patients with DME who received an intravitreal DEX implant 1 month before cataract surgery, 'precataract DEX' group, or at the time of cataract surgery, 'concomitant treatments' group. Inclusion criteria were a follow-up ≥3 months and ophthalmological examination with optical coherence tomography (OCT) imaging at baseline (cataract surgery) and throughout follow-up. Anatomical improvement was considered to be a decrease in OCT central subfield (CSF) thickness ≥20% compared to baseline. The primary outcomes were anatomical and functional results at 3 months. RESULTS Two hundred twenty-one patients were included: 136 in the 'precataract DEX' group and 85 in the 'concomitant treatments' group. At 3 months, a reduction of CSF thickness ≥ 20% was found in 7.3% of eyes in the 'precataract DEX group' and in 83.7% of eyes in the 'concomitant treatments' group (p < 0.001), with mean CSF thickness lower in the latter group (371 ± 52 µm versus 325 ± 57 µm, p < 0.001). At 3 months, mean best-corrected visual acuity had improved from baseline in both groups (p < 0.001), with no difference between groups (p = 0. 20). No serious systemic adverse events were reported. CONCLUSION Both approaches prevented a worsening of DME, showing a comparable visual outcome. Dexamethasone (DEX) implant given at the same time as cataract surgery provided a better anatomical outcome.
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Daratumumab, lenalidomide, and dexamethasone versus lenalidomide and dexamethasone alone in newly diagnosed multiple myeloma (MAIA): overall survival results from a randomised, open-label, phase 3 trial.
Facon, T, Kumar, SK, Plesner, T, Orlowski, RZ, Moreau, P, Bahlis, N, Basu, S, Nahi, H, Hulin, C, Quach, H, et al
The Lancet. Oncology. 2021;(11):1582-1596
Abstract
BACKGROUND In the primary analysis of the phase 3 MAIA trial (median follow-up 28·0 months), a significant improvement in progression-free survival was observed with daratumumab plus lenalidomide and dexamethasone versus lenalidomide and dexamethasone alone in transplantation-ineligible patients with newly diagnosed multiple myeloma. Here, we report the updated efficacy and safety results from a prespecified interim analysis for overall survival. METHODS MAIA is an ongoing, multicentre, randomised, open-label, phase 3 trial that enrolled patients at 176 hospitals in 14 countries across North America, Europe, the Middle East, and the Asia-Pacific region. Eligible patients were aged 18 years or older, had newly diagnosed multiple myeloma, had an Eastern Cooperative Oncology Group performance status score of 0-2, and were ineligible for high-dose chemotherapy with autologous stem-cell transplantation because of their age (≥65 years) or comorbidities. Patients were randomly assigned (1:1) using randomly permuted blocks (block size 4) by an interactive web response system to receive 28-day cycles of intravenous daratumumab (16 mg/kg, once per week during cycles 1-2, once every 2 weeks in cycles 3-6, and once every 4 weeks thereafter) plus oral lenalidomide (25 mg on days 1-21 of each cycle) and oral dexamethasone (40 mg on days 1, 8, 15, and 22 of each cycle; daratumumab group) or lenalidomide and dexamethasone alone (control group). Randomisation was stratified by International Staging System disease stage, geographical region, and age. Neither patients nor investigators were masked to treatment assignment. The primary endpoint was progression-free survival, which was centrally assessed, and a secondary endpoint was overall survival (both assessed in the intention-to-treat population). The safety population included patients who received at least one dose of the study treatment. The results presented here are from a prespecified interim analysis for overall survival, for which the prespecified stopping boundary was p=0·0414. This trial is registered with ClinicalTrials.gov, NCT02252172. FINDINGS Between March 18, 2015, and Jan 15, 2017, 952 patients were assessed for eligibility, of whom 737 patients were enrolled and randomly assigned to the daratumumab group (n=368) or the control group (n=369). At a median follow-up of 56·2 months (IQR 52·7-59·9), median progression-free survival was not reached (95% CI 54·8-not reached) in the daratumumab group versus 34·4 months (29·6-39·2) in the control group (hazard ratio [HR] 0·53 [95% CI 0·43-0·66]; p<0·0001). Median overall survival was not reached in either group (daratumumab group, 95% CI not reached-not reached; control group, 95% CI 55·7-not reached; HR 0·68 [95% CI 0·53-0·86]; p=0·0013). The most common (>15%) grade 3 or higher treatment-emergent adverse events were neutropenia (197 [54%] patients in the daratumumab group vs 135 [37%] patients in the control group), pneumonia (70 [19%] vs 39 [11%]), anaemia (61 [17%] vs 79 [22%]), and lymphopenia (60 [16%] vs 41 [11%]). Serious adverse events occurred in 281 (77%) patients in the daratumumab group and 257 (70%) patients in the control group. Treatment-related deaths occurred in 13 (4%) patients in the daratumumab group and ten (3%) patients in the control group. INTERPRETATION Daratumumab plus lenalidomide and dexamethasone increased overall survival and progression-free survival in patients ineligible for stem-cell transplantation with newly diagnosed multiple myeloma. There were no new safety concerns. Our results support the frontline use of daratumumab plus lenalidomide and dexamethasone for patients with multiple myeloma who are ineligible for transplantation. FUNDING Janssen Research & Development.
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All-trans retinoic acid plus high-dose dexamethasone as first-line treatment for patients with newly diagnosed immune thrombocytopenia: a multicentre, open-label, randomised, controlled, phase 2 trial.
Huang, QS, Liu, Y, Wang, JB, Peng, J, Hou, M, Liu, H, Feng, R, Wang, JW, Xu, LP, Wang, Y, et al
The Lancet. Haematology. 2021;(10):e688-e699
Abstract
BACKGROUND High-dose dexamethasone is the standard initial treatment for patients with immune thrombocytopenia, but many patients still relapse and require further treatments. All-trans retinoic acid has been shown to exert immunomodulatory effects and promote thrombopoiesis, and so we aimed to assess the activity and safety of all-trans retinoic acid plus high-dose dexamethasone as a first-line treatment for newly diagnosed patients with immune thrombocytopenia. METHODS This multicentre, open-label, randomised, controlled, phase 2 trial was done at six different tertiary medical centres in China. Eligible participants were adults (aged >18 years) with treatment-naive, newly diagnosed, primary immune thrombocytopenia who had either a platelet count of less than 30 × 109 platelets per L or a platelet count of less than 50 × 109 platelets per L and clinically significant bleeding. We randomly assigned (1:1) participants to receive either all-trans retinoic acid (10 mg orally twice daily for 12 weeks) plus high-dose dexamethasone (40 mg/day intravenously for 4 consecutive days) or high-dose dexamethasone alone using a central, web-based randomisation system. If patients did not respond by day 14, the 4-day course of dexamethasone was repeated. The primary endpoint was 6-month sustained response, defined as the maintenance of a platelet count of at least 30 × 109 platelets per L and at least 2-times higher than the baseline count and the absence of bleeding, with no need for rescue medication at this time. The primary endpoint was analysed by intention-to-treat and safety was assessed in all participants who received at least one dose of the study drug. This trial is registered with ClinicalTrials.gov, NCT04217148, and is now completed. FINDINGS Between Jan 1, 2020, and June 30, 2020, 132 patients were randomly assigned to either all-trans retinoic acid plus high-dose dexamethasone (n=66) or high-dose dexamethasone alone (n=66). Three patients did not receive their allocated treatment, leaving 129 in the safety analysis set. At 6 months, a significantly higher proportion of participants in the all-trans retinoic acid plus high-dose dexamethasone group (45 [68%] of 66) than in the high-dose dexamethasone monotherapy group (27 [41%] of 66) had a sustained response (OR 3·095, 95% CI 1·516-6·318; p=0·0017). The most common adverse events were dry skin (31 [48%] of 64 patients), headaches (12 [19%]), and insomnia (12 [19%]) in the combination group, and insomnia (ten [15%] of 65 patients) and anxiety or mood disorders (eight [12%]) in the monotherapy group. Both treatments were well tolerated and no grade 4 or worse adverse events occurred. There were no treatment-related deaths. INTERPRETATION The combination of all-trans retinoic acid and high-dose dexamethasone was safe and active in newly diagnosed patients with primary immune thrombocytopenia, providing a sustained response. This regimen represents a potential first-line treatment in this setting, but further studies are needed to validate its efficacy and safety. FUNDING The Beijing Municipal Science and Technology Commission, the National Natural Science Foundation of China, the Beijing Natural Science Foundation, the National Key Research and Development Program of China, and the Foundation for Innovative Research Groups of the National Natural Science Foundation of China.
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A Prospective, Randomized Trial of Povidone-Iodine 0.6% and Dexamethasone 0.1% Ophthalmic Suspension for Acute Bacterial Conjunctivitis.
Ta, CN, Raizman, MB, Gross, RD, Joshi, S, Mallick, S, Wang, Y, Segal, B
American journal of ophthalmology. 2020;:56-65
Abstract
PURPOSE To evaluate the efficacy and safety of a topical ophthalmic suspension combination of povidone-iodine 0.6% (PVP-I) and dexamethasone 0.1% (DEX) for infectious and inflammatory components of bacterial conjunctivitis. DESIGN Randomized, double-masked, multicenter, phase 3 clinical trial. METHODS Subjects of all ages (those <3 months had to be full-term) with a diagnosis of bacterial conjunctivitis were randomized 3:1:3 to either PVP-I/DEX, PVP-I alone, or placebo. The primary endpoint was clinical resolution in the study eye, and the key secondary efficacy endpoint was bacterial eradication, both at the day 5 visit. Adverse events (AEs) were documented at all visits. RESULTS Overall, 753 subjects were randomized (intent-to-treat [ITT] population; PVP-I/DEX [n = 324]; PVP-I [n = 108]; placebo [n = 321]); mean and standard deviation (SD) age was 44.3 (22.9) years, and most were female (61.2%) and white (78.1%). In all treatment groups, mean treatment compliance was >98%. The modified ITT population for the efficacy analysis comprised 526 subjects. In the study eye at the day 5 visit, clinical resolution was achieved by 50.5% (111/220) subjects in the PVP-I/DEX group vs 42.8% (95/222) in the placebo group (P = .127), and bacterial eradication was achieved by 43.3% (94/217) and 46.8% (102/218), respectively (P = .500). Treatment-emergent AEs were experienced by 32.8% (106/323), 39.8% (43/108), and 19.0% (61/321) of subjects in the safety population treated with PVP-I/DEX, PVP-I, and placebo, respectively (most mild in severity). CONCLUSION In this study, PVP-I/DEX did not demonstrate additional benefit in clinical efficacy compared with placebo in subjects with bacterial conjunctivitis.
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Optimizing DME Treatment With Decreased Injection Frequency Using Long-Term Steroid Implants.
Mantopoulos, D, Zhang, R, Roth, DB
Ophthalmic surgery, lasers & imaging retina. 2020;(4):S22-S29
Abstract
BACKGROUND AND OBJECTIVE Anti-vascular endothelial growth factor (VEGF) agents are the first-line treatment for diabetic macular edema (DME) based on randomized, control trials from the early 2000s. However, the efficacy of anti-VEGF is limited in clinical practice because its monthly injection schedule is logistically challenging for most working-age patients. PATIENTS AND METHODS Recent large-scale, randomized, control trials have demonstrated that intravitreal corticosteroid implants provide efficacious long-term treatment for DME. RESULTS Intravitreal corticosteroid implants block a wide spectrum of inflammatory factors involved in DME pathogenesis, with each implant lasting from months to years. Intravitreal corticosteroid implants also have the pharmacokinetic advantage over anti-VEGF agents in vitrectomized eyes. CONCLUSIONS Although anti-VEGF agents have lower bioavailability in vitrectomized eyes due to rapid clearance, intravitreal corticosteroid implants are not significantly affected by vitrectomy in bioavailability or efficacy. Side effects of intravitreal corticosteroid implants include cataract formation and ocular hypertension, both of which are manageable with appropriate monitoring. Taken together, intravitreal corticosteroid implants serve as a convenient, efficacious, and long-term treatment for patients with DME. [Ophthalmic Surg Lasers Imaging Retina. 2020;51:S22-S29.].
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Study protocol for efficacy and safety of steroid-containing mouthwash to prevent chemotherapy-induced stomatitis in women with breast cancer: a multicentre, open-label, randomised phase 2 study.
Kuba, S, Yamanouchi, K, Matsumoto, M, Maeda, S, Hatachi, T, Sakiko, S, Kawashita, Y, Morita, M, Sakimura, C, Inamasu, E, et al
BMJ open. 2020;(2):e033446
Abstract
INTRODUCTION Stomatitis is a frequent adverse event in patients undergoing chemotherapy for breast cancer. Stomatitis can hamper oral nutrition resulting in malnutrition, reduce quality of life and introduce the need for dose reductions and interruption of chemotherapy; however, there is currently no standard approach for preventing chemotherapy-induced stomatitis. We aimed to assess the safety and efficacy of a dexamethasone-based elixir mouthwash for preventing chemotherapy-induced stomatitis in patients with early breast cancer. METHODS AND ANALYSIS In this multicenter, randomised, controlled phase 2 trial, we will randomly assign 120 women with early breast cancer undergoing chemotherapy to use of a dexamethasone-based elixir or standard oral care, to compare their preventive effects on chemotherapy-induced stomatitis. Patients will be assigned in a 1:1 ratio. Patients in the intervention group will receive chemotherapy, oral care and a dexamethasone-based elixir (10 mL 0.1 mg/mL; swish for 2 min and spit, four times daily for 9 weeks), and patients in the control group will receive chemotherapy and oral care. The primary endpoint is the difference in incidence of stomatitis between the two groups. The sample size allows for the detection of a minimum difference of 20% in the incidence of stomatitis between the two groups. Secondary endpoints are severity of stomatitis, duration of stomatitis, completion rate of chemotherapy and adverse events. ETHICS AND DISSEMINATION All participants signed a written consent form, and the study protocol has been reviewed and approved by the Clinical Research Review Board of Nagasaki University (CRB7180001). TRIAL REGISTRATION NUMBER UMIN Clinical Trials Registry (UMIN000030489).
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The World Health Organization ACTION-I (Antenatal CorTicosteroids for Improving Outcomes in preterm Newborns) Trial: a multi-country, multi-centre, two-arm, parallel, double-blind, placebo-controlled, individually randomized trial of antenatal corticosteroids for women at risk of imminent birth in the early preterm period in hospitals in low-resource countries.
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Trials. 2019;(1):507
Abstract
BACKGROUND Antenatal corticosteroids (ACS) have long been regarded as a cornerstone intervention in mitigating the adverse effects of a preterm birth. However, the safety and efficacy of ACS in hospitals in low-resource countries has not been established in an efficacy trial despite their widespread use. Findings of a large cluster-randomized trial in six low- and middle-income countries showed that efforts to scale up ACS use in low-resource settings can lead to harm. There is equipoise regarding the benefits and harms of ACS use in hospitals in low-resource countries. This randomized controlled trial aims to determine whether ACS are safe and efficacious when given to women at risk of imminent birth in the early preterm period, in hospitals in low-resource countries. METHODS/DESIGN The trial design is a parallel, two-arm, double-blind, individually randomized, placebo-controlled trial of ACS (dexamethasone) for women at risk of imminent preterm birth. The trial will recruit 6018 women in participating hospitals across five low-resource countries (Bangladesh, India, Kenya, Nigeria and Pakistan). The primary objectives are to compare the efficacy of dexamethasone with placebo on survival of the baby and maternal infectious morbidity. The primary outcomes are: 1) neonatal death (to 28 completed days of life); 2) any baby death (any stillbirth postrandomization or neonatal death); and 3) a composite outcome to assess possible maternal bacterial infections. The trial will recruit eligible, consenting pregnant women from 26 weeks 0 days to 33 weeks 6 days gestation with confirmed live fetuses, in whom birth is planned or expected within 48 h. The intervention comprises a regimen of intramuscular dexamethasone sodium phosphate. The comparison is an identical placebo regimen (normal saline). A total of 6018 women will be recruited to detect a reduction of 15% or more in neonatal deaths in a two-sided 5% significance test with 90% power (including 10% loss to follow-up). DISCUSSION Findings of this trial will guide clinicians, programme managers and policymakers on the safety and efficacy of ACS in hospitals in low-resource countries. The trial findings will inform updating of the World Health Organization's global recommendations on ACS use. TRIAL REGISTRATION ACTRN12617000476336 . Registered on 31 March 2017.
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Effectiveness and Safety of Intravitreal Dexamethasone Implant (Ozurdex) in Patients with Diabetic Macular Edema: A Real-World Experience.
Mello Filho, P, Andrade, G, Maia, A, Maia, M, Biccas Neto, L, Muralha Neto, A, Moura Brasil, O, Minelli, E, Dalloul, C, Iglicki, M
Ophthalmologica. Journal international d'ophtalmologie. International journal of ophthalmology. Zeitschrift fur Augenheilkunde. 2019;(1):9-16
Abstract
INTRODUCTION There are few real-life studies on the intravitreal 0.7-mg dexamethasone implant for the treatment of diabetic macular edema (DME) conducted in Latin America. We aimed to assess the effectiveness and safety of this implant in clinical practice. METHODS Twenty-seven centers from Brazil and one from Argentina provided information on patients with DME treated with Ozurdex. The efficacy outcome variables were best-corrected visual acuity (BCVA) in Snellen and central retinal thickness (CRT). Safety was assessed by the elevation in intraocular pressure (IOP), occurrence of cataracts, and adverse events. RESULTS A total of 329 eyes (both treated cases and naïve eyes) from 282 patients underwent treatment. The time since diagnosis of DME ranged from 1 to 156 months. The median BCVA was 0.7 logMAR/50 letters at baseline and 0.3 logMAR/70 letters after treatment (both p < 0.001). Median CRT values decreased from 425 µm at baseline to 270 µm after treatment (p < 0.001). Increases in IOP of at least 10 mm Hg were observed in 7.4% of eyes, and 4% of eyes had cataract evolution. No cases of endophthalmitis were reported. CONCLUSION These real-life results suggest that the intravitreal dexamethasone implant is effective and safe for eyes with DME.
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Natural history of diabetic macular edema and factors predicting outcomes in sham-treated patients (MEAD study).
Yoon, YH, Boyer, DS, Maturi, RK, Bandello, F, Belfort, R, Augustin, AJ, Li, XY, Bai, Z, Hashad, Y, ,
Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie. 2019;(12):2639-2653
Abstract
PURPOSE To describe the natural history of diabetic macular edema (DME) with respect to best-corrected visual acuity (BCVA) and central retinal thickness (CRT) outcomes and to identify baseline patient characteristics and systemic factors associated with improvement or worsening of outcomes in sham-treated patients. METHODS The study population was sham-treated patients (n = 350) in the 3-year MEAD registration study of dexamethasone intravitreal implant for treatment of DME. Patients had center-involved DME and received sham intravitreal injections in the study eye at ≥ 6-month intervals. Potential prognostic factors for outcomes were evaluated using multiple linear regression analysis. RESULTS Visual and anatomic outcomes were poorer in patients who left the study early (n = 198) than in study completers (n = 152). Mean change in BCVA from baseline at the last visit with available data was + 0.9 letters; 37.5% of patients had no change in BCVA, 23.2% had gained > 10 letters, and 16.0% had lost > 10 letters. Older age and baseline diabetic retinopathy score > 6 were associated with worse BCVA outcomes; thicker baseline CRT and larger number of hypertension medications used were associated with larger reductions in CRT during the study. CONCLUSIONS BCVA and CRT outcomes were variable in this population of DME patients with generally good glycemic control. In DME patients without active treatment, older age and baseline diabetic retinopathy score > 6 were associated with less improvement in BCVA; thicker baseline CRT and a larger number of antihypertensive medications used predicted better improvement in CRT. TRIAL REGISTRATION The MEAD study trials are registered at ClinicalTrials.gov with the identifiers NCT00168337 and NCT00168389.
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Real-World Assessment of Dexamethasone Intravitreal Implant in DME: Findings of the Prospective, Multicenter REINFORCE Study.
Singer, MA, Dugel, PU, Fine, HF, Capone, A, Maltman, J
Ophthalmic surgery, lasers & imaging retina. 2018;(6):425-435
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Abstract
BACKGROUND AND OBJECTIVE Dexamethasone intravitreal implant (DEX) (Ozurdex; Allergan plc, Dublin, Ireland) is approved for the treatment of diabetic macular edema (DME). This study assessed the real-world effectiveness, safety, and reinjection interval of DEX in adult patients with DME. PATIENTS AND METHODS This was a phase 4, prospective, multicenter (18 U.S. sites), observational study. RESULTS The study population comprised 177 patients (180 eyes; 93.8% previously treated). Baseline mean best-corrected visual acuity (BCVA) and central retinal thickness (CRT) were 54.4 letters and 424.6 μm, respectively. DEX was administered as monotherapy or with other DME therapy (55%/45%). The mean reinjection interval was 5.0 months. Mean maximum BCVA change from baseline after the first three DEX injections was +9.1 letters, +7.7 letters, and +7.0 letters, respectively (P < .001); 36.0% of eyes achieved 15-letter or greater BCVA improvement. Mean maximum CRT change from baseline was -137.7 μm (P < .001). CONCLUSION DEX used alone or with other DME therapy improved visual and anatomic outcomes in DME patients in clinical practice, with no new safety concerns. [Ophthalmic Surg Lasers Imaging Retina. 2018;49:425-435.].