Safety and Efficacy of a 6% Hydroxyethyl Starch (HES) Solution Versus an Electrolyte Solution in Trauma Patients (TETHYS)

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

The aim of the study is to investigate the safety of a 6% hydroxyethyl starch (HES) solution (Volulyte 6%) versus an electrolyte solution (Ionolyte) in trauma patients.

Study Overview

• Status: Completed
• Conditions: Hypovolemia Due to Acute Blood Loss
• Intervention / Treatment: Drug: Volulyte 6%; Drug: Ionolyte

• Study Type: Interventional
• Enrollment (Actual): 238
• Phase: Phase 4

Contacts and Locations

Study Locations

• Belgium
  • Genk, Belgium
    • Ziekenhuis Oost-Limburg-ZOL
• Czechia
  • Brno, Czechia
    • Fakultni nemocnice Brno
  • Prague, Czechia
    • Military University Hospital
• France
  • Nancy, France
    • CHRU Nancy - Hôpital central
  • Strasbourg, France
    • Hopital de Hautepierre
• Germany
  • Aachen, Germany
    • Universitätsklinikum Aachen
  • Dresden, Germany
    • Universitätsklinikum Carl Gustav Carus Dresden
  • Frankfurt, Germany
    • Universitätsklinikum Frankfurt
  • Kiel, Germany
    • University Hospital Schleswig-Holstein Campus Kiel
• Netherlands
  • Amsterdam, Netherlands
    • Academic Medical Center (AMC) Anesthesiology
  • Maastricht, Netherlands
    • University Medical Center (UMC) Maastricht
• South Africa
  • Cape Town, South Africa
    • Groote Schuur Hospital
  • Germiston, South Africa
    • Gama Research Centre Emergency Department, Leratong Hospital
  • Germiston, South Africa
    • Gama Research Centre
  • Johannesburg, South Africa
    • Chris Hani Baragwanath Hospital
  • Kimberley, South Africa
    • Trident Clinical, Homestead Medical Centre
  • Pretoria, South Africa
    • Steve Biko Academic Hospital
  • Vereeniging, South Africa
    • FCRN Clinical Trials Centre
  • Worcester, South Africa
    • Clinical Projects Research SA
• Spain
  • Madrid, Spain
    • Hospital Universitario Gregorio Marañón
  • Valencia, Spain
    • Hospital Clinico Universitario
  • Valencia, Spain
    • Hospital Universitari i Politecnic La Fe

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion:

• Male or female adult patients ≥18 years of age. Women of child bearing potential must test negative on standard pregnancy test (urine or serum) (as soon as possible during emergency care)
• Patients with blunt or penetrating trauma suffering from estimated blood loss of ≥ 500 ml
• Initial surgery deemed necessary within 24 hrs after trauma
• Deferred signed written informed consent form or as locally required
• No signs of intracranial or cerebral hemorrhage
• Administration of less than 15 ml/kg body weight colloid between trauma injury and hospital admission.

Exclusion:

• Hypersensitivity to the active substances or to any of the other excipients of the Investigational Products
• Body weight ≥ 140 kg
• Patients expected to die within 24h after traumatic injury
• Sepsis
• Burns
• Renal impairment (AKIN stage ≥ 1 or chronic) or acute and/or chronic Renal Replacement Therapy
• Critically ill patients (typically admitted to the intensive care unit)
• Hyperhydration
• Pulmonary edema
• Dehydration
• Hyperkalemia
• Severe hypernatremia
• Severe hyperchloremia
• Severely impaired hepatic function
• Congestive heart failure
• Severe coagulopathy
• Organ transplant patients
• Metabolic alkalosis
• Simultaneous participation in another interventional clinical trial (drugs or medical devices studies)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Volulyte 6%; Volulyte 6% solution for infusion	Drug: Volulyte 6%; Solution for infusion; Other Names: Hydroxyethyl starch 130
Active Comparator: Ionolyte; Ionolyte solution for infusion	Drug: Ionolyte; Solution for infusion; Other Names: Ionolyte Electrolyte Solution

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Composite endpoint of 90 day mortality and 90 day renal failure defined as biomarker increase as defined by AKIN stage 2 or RIFLE injury stage or need for RRT at any time during the first 3 months.	90 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mortality		90 days after randomization
Serum creatinine		7 days post-trauma
Serum creatinine-based estimated glomerular filtration rate		7 days post-trauma
Cystatin-C		3 days post-trauma
Cystatin-C-based mean estimated glomerular filtration rate		3 days post-trauma
AKIN stages		7 days post-trauma
Highest AKIN stage reached on each day during the first week		7 days post-trauma
RIFLE stages		7 days post-trauma
Urine output (if available)		7 days post-trauma
Days on Renal Replacement Therapy		90 days after randomization
Patients on Renal Replacement Therapy		90 days after randomization
Platelet count		3 days post-trauma
International normalized ratio		3 days post-trauma
Activated partial thromboplastin time		3 days post-trauma
Adverse Events		90 days after randomization
Length of Stay in ICU/hospital		90 days after randomization
C-reactive protein		3 days post-trauma
Hours on mechanical ventilation		7 days post-trauma
Total volume of administered investigational products		until 24 hours after investigational product treatment start
Fluid balance	Sum of volume of all intravenous medication (including investigational product and blood products) minus sum of volume of urine output (if available), drainage and estimated due to surgeries and trauma	7 days post-trauma
Heart rate		7 days post-trauma
Temperature		7 days post-trauma
Mean arterial pressure		7 days post-trauma
Systolic arterial blood pressure		7 days post-trauma
Diastolic arterial blood pressure		7 days post-trauma
Central venous pressure (if available)		7 days post-trauma
Partial pressure of carbon dioxide		3 days post-trauma
Partial pressure of oxygen		3 days post-trauma
Bicarbonate		3 days post-trauma
Arterial oxygen saturation		3 days post-trauma
Hemoglobin		3 days post-trauma
Hematocrit		3 days post-trauma
pH		3 days post-trauma
Base excess		3 days post-trauma
Lactate		3 days post-trauma
Central venous oxygen saturation (if available)		3 days post-trauma
Serum sodium		3 days post-trauma
Serum potassium		3 days post-trauma
Serum calcium		3 days post-trauma
Serum chloride		3 days post-trauma

Collaborators and Investigators

• Sponsor: Fresenius Kabi
• Collaborators: B. Braun Melsungen AG; European Society of Anaesthesiology and Intensive Care
• Investigators: Study Chair: Wolfgang F. Buhre, Prof. Dr. med., Department of Anesthesiology and Pain Management, Maastricht University, The Netherlands

Publications and helpful links

General Publications

• Palma CD, Mamba M, Geldenhuys J, Fadahun O, Rossaint R, Zacharowski K, Brand M, Diaz-Cambronero O, Belda J, Westphal M, Brauer U, Dormann D, Dehnhardt T, Hernandez-Gonzalez M, Schmier S, de Korte D, Plani F, Buhre W. 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. Trials. 2022 Jun 2;23(1):456. doi: 10.1186/s13063-022-06390-x.
• Chappell D, Jacob M. Should hydroxyethyl starch be banned? Lancet. 2018 Jul 14;392(10142):118. doi: 10.1016/S0140-6736(18)31174-7. No abstract available.

Study record dates

Study Major Dates

• Study Start (Actual): February 23, 2019
• Primary Completion (Actual): June 25, 2022
• Study Completion (Actual): June 25, 2022

Study Registration Dates

• First Submitted: November 1, 2017
• First Submitted That Met QC Criteria: November 7, 2017
• First Posted (Actual): November 9, 2017

Study Record Updates

• Last Update Posted (Actual): August 5, 2022
• Last Update Submitted That Met QC Criteria: August 4, 2022
• Last Verified: August 1, 2022

More Information

Terms related to this study

• Keywords: HES; Hydroxyethyl starch; HES 130
• Additional Relevant MeSH Terms: Pathologic Processes; Hypovolemia
• Other Study ID Numbers: HC-G-H-1505; HE06-021-CP4 (Other Identifier: Fresenius Kabi)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No