TY  - JOUR
A1  - Palma, Clementina Duran
A1  - Mamba, Musawenkosi
A1  - Geldenhuys, Johan
A1  - Fadahun, Oluwafolajimi
A1  - Rossaint, Rolf
A1  - Zacharowski, Kai
A1  - Brand, Martin
A1  - Díaz-Cambronero, Óscar
A1  - Belda, Javier
A1  - Westphal, Martin
A1  - Brauer, Ute
A1  - Dormann, Dirk
A1  - Dehnhardt, Tamara
A1  - Hernandez-Gonzalez, Martin
A1  - Schmier, Sonja
A1  - Korte, Dianne de
A1  - Plani, Frank
A1  - Buhre, Wolfgang Friedrich
T1  - PragmaTic, prospEctive, randomized, controlled, double-blind, mulTi-centre, multinational study on the safety and efficacy of a 6% HydroxYethyl Starch (HES) solution versus an electrolyte solution in trauma patients: study protocol for the TETHYS study
T2  - Trials
N2  - Background: Trauma may be associated with significant to life-threatening blood loss, which in turn may increase the risk of complications and death, particularly in the absence of adequate treatment. Hydroxyethyl starch (HES) solutions are used for volume therapy to treat hypovolemia due to acute blood loss to maintain or re-establish hemodynamic stability with the ultimate goal to avoid organ hypoperfusion and cardiovascular collapse. The current study compares a 6% HES 130 solution (Volulyte 6%) versus an electrolyte solution (Ionolyte) for volume replacement therapy in adult patients with traumatic injuries, as requested by the European Medicines Agency to gain more insights into the safety and efficacy of HES in the setting of trauma care.
Methods: TETHYS is a pragmatic, prospective, randomized, controlled, double-blind, multicenter, multinational trial performed in two parallel groups. Eligible consenting adults ≥ 18 years, with an estimated blood loss of ≥ 500 ml, and in whom initial surgery is deemed necessary within 24 h after blunt or penetrating trauma, will be randomized to receive intravenous treatment at an individualized dose with either a 6% HES 130, or an electrolyte solution, for a maximum of 24 h or until reaching the maximum daily dose of 30 ml/kg body weight, whatever occurs first. Sample size is estimated as 175 patients per group, 350 patients total (α = 0.025 one-tailed, power 1–β = 0.8). Composite primary endpoint evaluated in an exploratory manner will be 90-day mortality and 90-day renal failure, defined as AKIN stage ≥ 2, RIFLE injury/failure stage, or use of renal replacement therapy (RRT) during the first 3 months. Secondary efficacy and safety endpoints are fluid administration and balance, changes in vital signs and hemodynamic status, changes in laboratory parameters including renal function, coagulation, and inflammation biomarkers, incidence of adverse events during treatment period, hospital, and intensive care unit (ICU) length of stay, fitness for ICU or hospital discharge, and duration of mechanical ventilation and/or RRT.
Discussion: This pragmatic study will increase the evidence on safety and efficacy of 6% HES 130 for treatment of hypovolemia secondary to acute blood loss in trauma patients.
Trial registration:Registered in EudraCT, No.: 2016-002176-27 (21 April 2017) and ClinicalTrials.gov, ID: NCT03338218 (09 November 2017).
KW  - Volume therapy
KW  - Colloids
KW  - Hydroxyethyl starch
KW  - HES
KW  - Trauma
KW  - Blood loss
KW  - Acute kidney injury
Y1  - 2022
UR  - http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/62891
UR  - https://nbn-resolving.org/urn:nbn:de:hebis:30:3-628914
SN  - 1745-6215
SN  - 1468-6694
N1  - This clinical study is financed by Fresenius Kabi Deutschland GmbH (Else-Kröner-Straße 1, 61352 Bad Homburg, Germany). Investigational test and reference products are produced and delivered by Fresenius Kabi to all participating sites.
VL  - 23
IS  - 456
SP  - 1
EP  - 12, art. 456
PB  - BioMed Central
CY  - London
ER  -