Noémi Zádori1, Noémi Gede2, Judit Antal3, Andrea Szentesi4, Hussain Alizadeh5, Áron Vincze6, Ferenc Izbéki7, Mária Papp8, László Czakó9, Márta Varga10, Enrique de-Madaria11, Ole H Petersen12, Vijay P Singh13, Julia Mayerle14, Nándor Faluhelyi15, Attila Miseta16, István Reiber17, Péter Hegyi18. 1. Institute for Translational Medicine, Szentágothai Research Centre, Medical School, University of Pécs, Pécs, Hungary. Electronic address: http://www.tm-centre.org. 2. Institute for Translational Medicine, Szentágothai Research Centre, Medical School, University of Pécs, Pécs, Hungary. Electronic address: gede.noemi@gmail.com. 3. Institute for Translational Medicine, Szentágothai Research Centre, Medical School, University of Pécs, Pécs, Hungary. Electronic address: juditantal2014@gmail.com. 4. Institute for Translational Medicine, Szentágothai Research Centre, Medical School, University of Pécs, Pécs, Hungary; Hungarian Academy of Sciences-University of Szeged, Translational Multidisciplinary Research Group, Szeged, Hungary. Electronic address: szentesiai@gmail.com. 5. Division of Hematology, First Department of Internal Medicine, University of Pécs Medical School, Pécs, Hungary. Electronic address: alizadeh.hussain@pte.hu. 6. Institute for Translational Medicine, Szentágothai Research Centre, Medical School, University of Pécs, Pécs, Hungary; Division of Gastroenterology, First Department of Internal Medicine, University of Pécs Medical School, Pécs, Hungary. Electronic address: vincze.aron@pte.hu. 7. Division of Gastroenterology, Fejér County Saint George Teaching Hospital of the University of Pécs, Székesfehérvár, Hungary. Electronic address: fizbeki@gmail.com. 8. Department of Internal Medicine, Division of Gastroenterology, Faculty of Medicine, University of Debrecen, Debrecen, Hungary. Electronic address: papp.maria@med.unideb.hu. 9. First Department of Internal Medicine, University of Szeged, Szeged, Hungary. Electronic address: czako.laszlo@med.u-szeged.hu. 10. Dr. Réthy Pál Hospital, Békéscsaba, Hungary. Electronic address: drvargamarta@gmail.com. 11. Department of Gastroenterology, Alicante University General Hospital, Alicante Institute for Health and Biomedical Research (ISABIAL), Alicante, Spain. Electronic address: madaria@hotmail.com. 12. School of Biosciences, Cardiff University, Wales, UK. Electronic address: PetersenOH@cardiff.ac.uk. 13. Department of Medicine, Mayo Clinic, Scottsdale, AZ, USA. Electronic address: Singh.Vijay@mayo.edu. 14. Medizinische Klinik und Poliklinik II, Klinikum der Universität München, München, Germany. Electronic address: Julia.Mayerle@med.uni-muenchen.de. 15. Department of Radiology, University of Pécs, Pécs, Hungary. Electronic address: nandor.faluhelyi@gmail.com. 16. Department of Laboratory Medicine, University of Pécs, Pécs, Hungary. Electronic address: rector@pte.hu. 17. Division of Gastroenterology, Fejér County Saint George Teaching Hospital of the University of Pécs, Székesfehérvár, Hungary. Electronic address: ireiber@mail.fmkorhaz.hu. 18. Institute for Translational Medicine, Szentágothai Research Centre, Medical School, University of Pécs, Pécs, Hungary; Hungarian Academy of Sciences-University of Szeged, Translational Multidisciplinary Research Group, Szeged, Hungary. Electronic address: http://www.tm-centre.org.
Abstract
INTRODUCTION: Acute pancreatitis (AP) is a life-threatening inflammatory disease, with no specific pharmacological treatment. However, concerning some etiologies, early specific intervention (such as ERCP in biliary AP) has proven to be remarkably beneficial. Hypertriglyceridemia (HTG) induces severe pancreatic damage by several direct (cellular damage) and indirect (deterioration of microcirculation) mechanisms. Published data suggest that early removal of triglycerides (TGs) and toxic free fatty acids (FFAs) may be advantageous; however, high-quality evidence is still missing in the literature. METHODS: Design: ELEFANT is a randomized controlled, multicenter, international trial testing the concept that early elimination of TGs and FFAs from the blood is beneficial in HTG-AP. The study will be performed with the adaptive "drop-the-loser" design, which supports the possibility of dropping the inferior treatment arm, based on the results of the interim analysis. Patients with HTG-AP defined by TG level over 11.3 mmol/l (1000 mg/dL) are randomized into three groups: (A) patients who undergo plasmapheresis and receive aggressive fluid resuscitation; (B) patients who receive insulin and heparin treatment with aggressive fluid resuscitation; and (C) patients with aggressive fluid resuscitation. Please note that all intervention must be started within 48 h from the onset of abdominal pain. Exclusion criteria are designed logically to decrease the possibility of any distorting effects of other diseases. The composite primary endpoint will include both severity and mortality. RESULTS: Our null hypothesis is that early elimination of HTG and FFAs reduces the risk of mortality and severity of AP. Sample size calculation suggests that 495 patients will need to be enrolled in order to confirm or reject the hypothesis with a 10% dropout, 80% power and 95% significance level. The general safety and quality checks required for high-quality evidence will be adhered to. The study will be organized between February 2020 and December 2025. CONCLUSION: Our study would provide the first direct evidence for or against early intervention in HTG-induced AP.
RCT Entities:
INTRODUCTION: Acute pancreatitis (AP) is a life-threatening inflammatory disease, with no specific pharmacological treatment. However, concerning some etiologies, early specific intervention (such as ERCP in biliary AP) has proven to be remarkably beneficial. Hypertriglyceridemia (HTG) induces severe pancreatic damage by several direct (cellular damage) and indirect (deterioration of microcirculation) mechanisms. Published data suggest that early removal of triglycerides (TGs) and toxic free fatty acids (FFAs) may be advantageous; however, high-quality evidence is still missing in the literature. METHODS: Design: ELEFANT is a randomized controlled, multicenter, international trial testing the concept that early elimination of TGs and FFAs from the blood is beneficial in HTG-AP. The study will be performed with the adaptive "drop-the-loser" design, which supports the possibility of dropping the inferior treatment arm, based on the results of the interim analysis. Patients with HTG-AP defined by TG level over 11.3 mmol/l (1000 mg/dL) are randomized into three groups: (A) patients who undergo plasmapheresis and receive aggressive fluid resuscitation; (B) patients who receive insulin and heparin treatment with aggressive fluid resuscitation; and (C) patients with aggressive fluid resuscitation. Please note that all intervention must be started within 48 h from the onset of abdominal pain. Exclusion criteria are designed logically to decrease the possibility of any distorting effects of other diseases. The composite primary endpoint will include both severity and mortality. RESULTS: Our null hypothesis is that early elimination of HTG and FFAs reduces the risk of mortality and severity of AP. Sample size calculation suggests that 495 patients will need to be enrolled in order to confirm or reject the hypothesis with a 10% dropout, 80% power and 95% significance level. The general safety and quality checks required for high-quality evidence will be adhered to. The study will be organized between February 2020 and December 2025. CONCLUSION: Our study would provide the first direct evidence for or against early intervention in HTG-induced AP.
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