|By PR Newswire||
|September 9, 2013 02:01 AM EDT||
CHERTSEY, England, September 9, 2013 /PRNewswire/ --
In liver transplant patients, late renal failure is a significant cause of morbidity and is associated with premature mortality,,
Invasive fungal infections affect between 8.4%-17.7% of liver transplant patients and are associated with a high mortality rate,,,
New data presented at the 16th Congress of the European Society for Organ Transplantation (ESOT) demonstrate that in liver transplant patients, initiating ADVAGRAF™ prolonged-release capsules (tacrolimus) therapy immediately post transplant, at a dose 25% lower than the upper recommended limit, in combination with basiliximab, results in significantly better renal function and a lower incidence of acute organ rejection when compared with standard dose ADVAGRAF therapy. Furthermore, delaying the introduction of ADVAGRAF post transplant gives no additional advantage in terms of renal function.
In a separate study and the largest of its kind, MYCAMINE[TM] (micafungin) was found to be non-inferior to standard of care in preventing fungal infections in liver transplant patients and showed similar safety outcomes.
Results from the DIAMOND (ADVAGRAF studied In combinAtion with MycOphenolate mofetil aND basiliximab in liver transplantation) study show that an initial dose of prolonged-release tacrolimus (0.15-0.175mg/kg/day) plus MMF and induction therapy (without maintenance steroids) resulted in better renal function and a significantly lower incidence of acute rejection over 24 weeks compared to the other regimens; tacrolimus (initial dose: 0.2mg/kg/day) vs tacrolimus (0.2mg/kg/day delayed to day 5) plus basiliximab.
"These data provide new insights and considerations for immunosuppressive treatment in the immediate post-operative period," comments Dr. Ayad Abdulahad, Senior Vice President Medical Affairs and Health Economics, Astellas Pharma Europe Ltd. "Renal function is a vital predictor of long-term transplant success; the DIAMOND study suggests potential for balancing the risk of rejection, whilst minimising the risk of renal damage and potentially reducing the risk of long-term complications. This study shows that lower dose tacrolimus, given immediately post-transplantation, offers the potential advantages of an immunosuppressive regimen which minimises risk of graft rejection whilst preserving renal function without the need for maintenance steroids."
Infections are one of the major complications after transplantation and the incidence of infections in liver transplant patients is higher compared with recipients of other organs. Between 8.4% and 17.7% of liver transplant patients can be affected by fungal infections and these are associated with organ rejection, increased mortality and prolonged stay in the Intensive Care Unit.,,,
In the TENPIN (Liver Transplant EuropeaN Study Into the Prevention of Fungal INfection) study, the first randomised controlled trial of an echinocandin in this setting and the largest study of its kind, micafungin proved to be at least as effective as centre-specific standard of care (fluconazole, liposomal amphotericin B or caspofungin) in the prevention of invasive fungal infections in liver transplant patients. Current guidelines recommend either fluconazole or liposomal amphotericin B for prevention of invasive candidiasis in liver transplantation, and either lipid formulations of amphotericin B or an echinocandin for prevention of invasive aspergillosis. In addition, liver and renal safety of micafungin was also similar to study standard of care.
The TENPIN study included more than 340 liver transplant patients at high-risk of fungal infection, who were randomised to micafungin 100mg (2mg/kg in patients ≤40kg) once daily (n=173) or centre-specific standard of care (fluconazole 200-400mg; liposomal amphotericin B 1-3mg/kg/day; or caspofungin 70mg loading, 50mg maintenance) once daily (n=172). At the end of treatment, 98.6% of patients on micafungin in the Per Protocol population (n=140) were free of invasive fungal infections and had no need for further antifungals compared to 99.3% for standard of care (n=137).
"The low incidence of invasive fungal infections seen in this study clearly demonstrates the value of prophylactic antifungal treatment in high risk liver transplant patients," comments Professor Saliba, Associate Professor in Hepatology and Gastroenterology,Hôpital Paul Brousse Villejuif, France. "With current guideline-recommended treatments having their limitations, with risk of both resistance and drug interactions, micafungin looks to be a welcome and much needed additional treatment option."
NOTES FOR EDITORS
About ADVAGRAF™ and tacrolimus
Tacrolimus is a leading immunosuppressive drug used for the prevention of transplant allograft rejection after organ transplantation. It is available worldwide as a twice-a-day formulation (PROGRAF™) and as a prolonged-release formulation (ADVAGRAF™) which provides the convenience of once-daily dosing with more consistent tacrolimus exposure. Tacrolimus levels require careful management to maintain a minimum exposure of tacrolimus for the prevention of transplant allograft rejection, whilst avoiding excessive levels which may increase the risk of serious side effects. The prolonged-release formulation of ADVAGRAF allows tacrolimus to be available for absorption over a greater proportion of the gastrointestinal tract. This alteration in release profile provides the potential for reduced variability in tacrolimus exposure, achieving and maintaining consistent target trough levels with a reduced requirement for dose adjustments, and improved medication adherence as a single, morning dose., Emerging data indicate that these properties of ADVAGRAF may favourably influence clinical outcomes.
DIAMOND is a multicentre, randomised study involving 901 patients designed to investigate renal function with ADVAGRAF prolonged-release capsules (tacrolimus). Patients received either prolonged-release tacrolimus (0.15-0.175mg/kg/day) and Basiliximab induction therapy; tacrolimus (initial dose: 0.2mg/kg/day) or tacrolimus (0.2mg/kg/day delayed to day 5) plus basiliximab. All patients received MMF and maintenance steroids were not used.
In the study, patients on a lower dose of tacrolimus (0.15-0.175mg/kg/day) plus MMF and induction therapy (without maintenance steroids) had a higher eGFR than those treated with tacrolimus (0.2mg/kg/day) vs tacrolimus (0.2mg/kg/day delayed to day 5) plus basiliximab (76.4 vs 67.4 vs 73.3mL/min/1.73m2). Patients on the lower dose tacrolimus regimen also had a significantly better rejection free survival when compared with other regimens (85.7% vs 79.9% vs 79.6%). Adverse events were comparable between all treatment regimens.
Mycamine is an antifungal of the echinocandin class. In Europe, the indications for adults, adolescents 16 years of age and older, and the elderly are: treatment of invasive candidiasis, treatment of oesophageal candidiasis in patients for whom intravenous therapy is appropriate, and prophylaxis of Candida infection in patients undergoing allogeneic haematopoietic stem cell transplantation or patients who are expected to have neutropenia (absolute neutrophil count <500 cells/mcL) for 10 or more days.
For children (including neonates) and adolescents younger than 16 years of age, micafungin is indicated for treatment of invasive candidiasis and prophylaxis of Candida infection in patients undergoing allogeneic haematopoietic stem cell transplantation or patients who are expected to have neutropenia (absolute neutrophil count <500 cells/mcL) for 10 or more days.
TENPIN is an open-label, randomised, multicentre trial involving 345 liver transplant patients. The study was designed to investigate the efficacy and safety of micafungin compared with site-approved standard of care prophylaxis in liver transplant patients at high risk of invasive fungal disease. After transplant, patients were randomised to iv micafungin 100mg once daily (n=173) or iv standard of care according to centre-specific standard protocols (fluconazole 200-400mg once daily or liposomal amphotericin B 1-3mg/kg/day or caspofungin 70mg loading, 50mg maintenance once daily; n=172).
At end of prophylaxis (mean drug duration 17 days), clinical success was 98.6% for micafungin (n=140) and 99.3% for standard of care (n=137) in the Per Protocol population (primary efficacy endpoint). In the Full Analysis population clinical success was 96.5% for micafungin (n=172) and 93.6% for standard of care (n=172). Incidences of drug-related adverse events for micafungin and standard of care were 11.6% and 16.3%, leading to discontinuation in 6.4% and 11.6% of cases, respectively. Liver and renal function were similar between groups.
About Astellas Pharma Europe Ltd.
Astellas Pharma Europe Ltd., located in the UK, is the European headquarters of Tokyo-based Astellas Pharma Inc. Astellas is a pharmaceutical company dedicated to improving the health of people around the world through the provision of innovative and reliable pharmaceuticals. The organisation is committed to becoming a global company by combining outstanding R&D and marketing capabilities and continuing to grow in the world pharmaceutical market. Astellas Pharma Europe Ltd. is responsible for 21 affiliate offices located across Europe, the Middle East and Africa, an R&D site and three manufacturing plants. The company employs approximately 4,300 staff across these regions. For more information about Astellas Pharma Europe Ltd., please visit http://www.astellas.eu.
1. Cohen AJ, et al. Chronic Renal Dysfunction Late After Liver Transplantation. Liver Transpl. 2002 Vol 8, No 10 (October): pp 916-921.
2. Fisher NC, et al. Chronic Renal Failure Following Liver Transplantation. Transplantation. 1998; 66:59-66.
3. Ojo AO, et al. Chronic Renal Failure after Transplantation of a Nonrenal Organ. N Engl J Med. 2003; 349:931-40.
4. Vera A, et al. Incidence and risk factors for infections after liver transplant: single-center experience at the University Hospital Fundación Santa Fe de Bogotá, Colombia. Transpl Infect Dis. 2011 Dec;13(6):608-15. doi: 10.1111/j.1399-3062.2011.00640.x.
5. Zhou T, et al. Invasive fungal infection after liver transplantation: risk factors and significance of immune cell function monitoring. J Dig Dis. 2011 Dec;12(6):467-75. doi: 10.1111/j.1751-2980.2011.00542.x.
6. Pacholczyk M, et al. Invasive fungal infections following liver transplantation - risk factors, incidence and outcome. Ann Transplant. 2011 Jul-Sep;16(3):14-6.
7. Raghuram A, et al. Invasive fungal infections following liver transplantation: incidence, risk factors, survival, and impact of fluconazole-resistant Candida parapsilosis (2003-2007). Liver Transpl. 2012 Sep;18(9):1100-9. doi: 10.1002/lt.23467.
8. European Public Assessment Report (EPAR). Advagraf. Available at http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Summary_for_the_public/human/000712/WC500022235.pdf. Last accessed August 2013.
9. Trunecka P et al. Preserving Renal Function with Prolonged-Release Tacrolimus-Baesd Immunosuppression in De Novo Liver Tranplantation: Initial Results from the DIAMOND Study. 16th Congress of the European Society for Organ Transplantation; Vienna, Austria, 8-11 September 2013. [Abstract No: LB02].
10. Saliba F, et al. Micafungin as Antifungal Prophylaxis in High-Risk Liver Transplantation: Randomised Multicentre Trial. 16th Congress of the European Society for Organ Transplantation; Vienna, Austria, 8-11 September 2013. [Abstract No: P217].
11. Pappas PG et al. Guidelines for Treatment of Candidiasis. Clin Infect Dis. 2004;38:161-89.
12. Singh N et al. Invasive Aspergillosis in Solid Organ Transplant Recipients. Am J Transpl. 2009;9(4):S180-S191.
13. Abrams et al. Role of tacrolimus prolonged release in the prevention of allograft rejection. Transpl Research and Risk Management, 2010:2 65-70.
14. Valente G, et al. Conversion From Twice-Daily to Once-Daily Tacrolimus in Stable Liver Transplant Patients: Effectiveness in a Real-World Setting. Transplantation Proceedings, 45, 1273-1275 (2013).
15. Mycamine Summary of Product Characteristics. Available at http://www.medicines.org.uk/emc/medicine/20997/SPC/Mycamine+50mg+and+100mg+powder+for+solution+for+infusion/#INDICATIONS. Last accessed August 2013.
Building a cross-cloud operational model can be a daunting task. Per-cloud silos are not the answer, but neither is a fully generic abstraction plane that strips out capabilities unique to a particular provider. In his session at 20th Cloud Expo, Chris Wolf, VP & Chief Technology Officer, Global Field & Industry at VMware, will discuss how successful organizations approach cloud operations and management, with insights into where operations should be centralized and when it’s best to decentraliz...
Apr. 30, 2017 08:45 PM EDT Reads: 1,153
DevOps is often described as a combination of technology and culture. Without both, DevOps isn't complete. However, applying the culture to outdated technology is a recipe for disaster; as response times grow and connections between teams are delayed by technology, the culture will die. A Nutanix Enterprise Cloud has many benefits that provide the needed base for a true DevOps paradigm.
Apr. 30, 2017 08:30 PM EDT Reads: 1,442
20th Cloud Expo, taking place June 6-8, 2017, at the Javits Center in New York City, NY, will feature technical sessions from a rock star conference faculty and the leading industry players in the world. Cloud computing is now being embraced by a majority of enterprises of all sizes. Yesterday's debate about public vs. private has transformed into the reality of hybrid cloud: a recent survey shows that 74% of enterprises have a hybrid cloud strategy.
Apr. 30, 2017 08:15 PM EDT Reads: 3,467
With major technology companies and startups seriously embracing IoT strategies, now is the perfect time to attend @ThingsExpo 2016 in New York. Learn what is going on, contribute to the discussions, and ensure that your enterprise is as "IoT-Ready" as it can be! Internet of @ThingsExpo, taking place June 6-8, 2017, at the Javits Center in New York City, New York, is co-located with 20th Cloud Expo and will feature technical sessions from a rock star conference faculty and the leading industry p...
Apr. 30, 2017 08:00 PM EDT Reads: 1,746
Today we can collect lots and lots of performance data. We build beautiful dashboards and even have fancy query languages to access and transform the data. Still performance data is a secret language only a couple of people understand. The more business becomes digital the more stakeholders are interested in this data including how it relates to business. Some of these people have never used a monitoring tool before. They have a question on their mind like “How is my application doing” but no id...
Apr. 30, 2017 07:45 PM EDT Reads: 7,466
With major technology companies and startups seriously embracing Cloud strategies, now is the perfect time to attend @CloudExpo | @ThingsExpo, June 6-8, 2017, at the Javits Center in New York City, NY and October 31 - November 2, 2017, Santa Clara Convention Center, CA. Learn what is going on, contribute to the discussions, and ensure that your enterprise is on the right path to Digital Transformation.
Apr. 30, 2017 07:30 PM EDT Reads: 1,760
@GonzalezCarmen has been ranked the Number One Influencer and @ThingsExpo has been named the Number One Brand in the “M2M 2016: Top 100 Influencers and Brands” by Analytic. Onalytica analyzed tweets over the last 6 months mentioning the keywords M2M OR “Machine to Machine.” They then identified the top 100 most influential brands and individuals leading the discussion on Twitter.
Apr. 30, 2017 07:15 PM EDT Reads: 1,620
In his keynote at 19th Cloud Expo, Sheng Liang, co-founder and CEO of Rancher Labs, discussed the technological advances and new business opportunities created by the rapid adoption of containers. With the success of Amazon Web Services (AWS) and various open source technologies used to build private clouds, cloud computing has become an essential component of IT strategy. However, users continue to face challenges in implementing clouds, as older technologies evolve and newer ones like Docker c...
Apr. 30, 2017 07:00 PM EDT Reads: 1,431
Developers want to create better apps faster. Static clouds are giving way to scalable systems, with dynamic resource allocation and application monitoring. You won't hear that chant from users on any picket line, but helping developers to create better apps faster is the mission of Lee Atchison, principal cloud architect and advocate at New Relic Inc., based in San Francisco. His singular job is to understand and drive the industry in the areas of cloud architecture, microservices, scalability ...
Apr. 30, 2017 07:00 PM EDT Reads: 3,761
Five years ago development was seen as a dead-end career, now it’s anything but – with an explosion in mobile and IoT initiatives increasing the demand for skilled engineers. But apart from having a ready supply of great coders, what constitutes true ‘DevOps Royalty’? It’ll be the ability to craft resilient architectures, supportability, security everywhere across the software lifecycle. In his keynote at @DevOpsSummit at 20th Cloud Expo, Jeffrey Scheaffer, GM and SVP, Continuous Delivery Busine...
Apr. 30, 2017 07:00 PM EDT Reads: 1,492
Most technology leaders, contemporary and from the hardware era, are reshaping their businesses to do software in the hope of capturing value in IoT. Although IoT is relatively new in the market, it has already gone through many promotional terms such as IoE, IoX, SDX, Edge/Fog, Mist Compute, etc. Ultimately, irrespective of the name, it is about deriving value from independent software assets participating in an ecosystem as one comprehensive solution.
Apr. 30, 2017 06:45 PM EDT Reads: 779
SYS-CON Events announced today that T-Mobile will exhibit at SYS-CON's 20th International Cloud Expo®, which will take place on June 6-8, 2017, at the Javits Center in New York City, NY. As America's Un-carrier, T-Mobile US, Inc., is redefining the way consumers and businesses buy wireless services through leading product and service innovation. The Company's advanced nationwide 4G LTE network delivers outstanding wireless experiences to 67.4 million customers who are unwilling to compromise on ...
Apr. 30, 2017 06:15 PM EDT Reads: 1,664
The 20th International Cloud Expo has announced that its Call for Papers is open. Cloud Expo, to be held June 6-8, 2017, at the Javits Center in New York City, brings together Cloud Computing, Big Data, Internet of Things, DevOps, Containers, Microservices and WebRTC to one location. With cloud computing driving a higher percentage of enterprise IT budgets every year, it becomes increasingly important to plant your flag in this fast-expanding business opportunity. Submit your speaking proposal ...
Apr. 30, 2017 05:30 PM EDT Reads: 1,830
SYS-CON Events announced today that CollabNet, a global leader in enterprise software development, release automation and DevOps solutions, will be a Bronze Sponsor of SYS-CON's 20th International Cloud Expo®, taking place from June 6-8, 2017, at the Javits Center in New York City, NY. CollabNet offers a broad range of solutions with the mission of helping modern organizations deliver quality software at speed. The company’s latest innovation, the DevOps Lifecycle Manager (DLM), supports Value S...
Apr. 30, 2017 05:15 PM EDT Reads: 1,531
Cybersecurity is a critical component of software development in many industries including medical devices. However, code is not always written to be robust or secure from the unknown or the unexpected. This gap can make medical devices susceptible to cybersecurity attacks ranging from compromised personal health information to life-sustaining treatment. In his session at @ThingsExpo, Clark Fortney, Software Engineer at Battelle, will discuss how programming oversight using key methods can incre...
Apr. 30, 2017 05:15 PM EDT Reads: 4,234