BACKGROUND: Hydroxyethyl starch (HES) solutions are used for volume therapy to treat hypovolemia due to acute blood loss and to maintain hemodynamic stability. This study was requested by the European Medicines Agency (EMA) to provide more evidence on the long-term safety and efficacy of HES solutions in the perioperative setting. METHODS: PHOENICS is a randomized, controlled, double-blind, multi-center, multinational phase IV (IIIb) study with two parallel groups to investigate non-inferiority regarding the safety of a 6% HES 130 solution (Volulyte 6%, Fresenius Kabi, Germany) compared with a crystalloid solution (Ionolyte, Fresenius Kabi, Germany) for infusion in patients with acute blood loss during elective abdominal surgery. A total of 2280 eligible patients (male and female patients willing to participate, with expected blood loss ≥ 500 ml, aged > 40 and ≤ 85 years, and ASA Physical status II-III) are randomly assigned to receive either HES or crystalloid solution for the treatment of hypovolemia due to surgery-induced acute blood loss in hospitals in up to 11 European countries. The dosing of investigational products (IP) is individualized to patients' volume needs and guided by a volume algorithm. Patients are treated with IP for maximally 24 h or until the maximum daily dose of 30 ml/kg body weight is reached. The primary endpoint is the treatment group mean difference in the change from the pre-operative baseline value in cystatin-C-based estimated glomerular filtration rate (eGFR), to the eGFR value calculated from the highest cystatin-C level measured during post-operative days 1-3. Further safety and efficacy parameters include, e.g., combined mortality/major post-operative complications until day 90, renal function, coagulation, inflammation, hemodynamic variables, hospital length of stay, major post-operative complications, and 28-day, 90-day, and 1-year mortality. DISCUSSION: The study will provide important information on the long-term safety and efficacy of HES 130/0.4 when administered according to the approved European product information. The results will be relevant for volume therapy of surgical patients. TRIAL REGISTRATION: EudraCT 2016-002162-30 . ClinicalTrials.gov NCT03278548.

Anesthesiology Intensive Care Medicine and OR Facilities University and University Hospital of Zürich Zürich Switzerland

Clinic for Anesthesiology and Intensive Therapy University Clinical Center Nis School of Medicine University of Nis Nis Serbia

Clinic of Anaesthesia and Intensive Care Medicine Clinical Emergency Hospital of Bucharest Bucharest Romania

Department of Anaesthesia and Intensive Care Medicine Faculty of Medicine 'Carol Davila' University of Medicine and Pharmacy Bucharest Romania

Department of Anaesthesiology and Intensive Therapy 5th Military Clinical Hosptial Krakow Poland

Department of Anesthesia Reanimation and Pain Therapy Clinic University Hospital Valencia Spain

Department of Anesthesiology and Intensive Care Medicine Medical University of Graz Graz Austria

Department of Anesthesiology and Intensive Care Medicine Pulmonary Engineering Group University Hospital Carl Gustav Carus Technische Universität Dresden Dresden Germany

Department of Anesthesiology and Intensive Care Medicine University Hospital Schleswig Holstein Kiel Germany

Department of Anesthesiology and Intensive Care University Hospital Center Sestre Milosrdnice Zagreb Croatia

Department of Anesthesiology and Intensive Medicine University Hospital Motol Prague Czech Republic

Department of Anesthesiology and Operative Intensive Care Medicine University Hospital Bonn Bonn Germany

Department of Anesthesiology and Pain Medicine Maastricht University Medical Centre Maastricht The Netherlands

Department of Anesthesiology Intensive Care and Pain Medicine University Hospital Muenster Muenster Germany

Department of Anesthesiology University Medical Center Groningen Groningen The Netherlands

Department of Anesthesioloy and Perioperative Medicine Gent University Hospital Gent University Ghent Belgium

Department of Intensive Care and Resuscitation Anesthesiology Institute Cleveland Clinic Cleveland OH USA

Department of Medical Scientific Affairs Hospital Care Division B Braun Melsungen AG Melsungen Germany

Department of Outcomes Research Anesthesiology Institute Cleveland Clinic Cleveland OH USA

Department of Surgery Clinic University Hospital Valencia Spain

Division of Acute and Critical Medicine Maastricht University Medical Centre Maastricht The Netherlands

European Society of Anaesthesiology and Intensive Care Brussels Belgium

Fresenius Kabi Deutschland GmbH Bad Homburg Germany

Institute of Anesthesiology University and University Hospital of Zürich Zürich Switzerland

Service d'Anesthésie Réanimation Hôpital Européen Georges Pompidou Paris France

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ClinicalTrials.gov
NCT03278548