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

Primary Purpose

Hypovolemia Due to Acute Blood Loss

Status
Completed
Phase
Phase 4
Locations
International
Study Type
Interventional
Intervention
Volulyte 6%
Ionolyte
Sponsored by
Fresenius Kabi
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Hypovolemia Due to Acute Blood Loss focused on measuring Hydroxyethyl starch, HES, HES 130

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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)

Sites / Locations

  • Ziekenhuis Oost-Limburg-ZOL
  • Fakultni nemocnice Brno
  • Military University Hospital
  • CHRU Nancy - Hôpital Central
  • Hôpital de Hautepierre
  • Universitätsklinikum Aachen
  • Universitätsklinikum Carl Gustav Carus Dresden
  • Universitätsklinikum Frankfurt
  • University Hospital Schleswig-Holstein Campus Kiel
  • Academic Medical Center (AMC) Anesthesiology
  • University Medical Center (UMC) Maastricht
  • Groote Schuur Hospital
  • Gama Research Centre Emergency Department, Leratong Hospital
  • Gama Research Centre
  • Chris Hani Baragwanath Hospital
  • Trident Clinical, Homestead Medical Centre
  • Steve Biko Academic Hospital
  • FCRN Clinical Trials Centre
  • Clinical Projects Research SA
  • Hospital Universitario Gregorio Marañón
  • Hospital Clinico Universitario
  • Hospital Universitari i Politecnic la Fe

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Active Comparator

Arm Label

Volulyte 6%

Ionolyte

Arm Description

Volulyte 6% solution for infusion

Ionolyte solution for infusion

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

Serum creatinine
Serum creatinine-based estimated glomerular filtration rate
Cystatin-C
Cystatin-C-based mean estimated glomerular filtration rate
AKIN stages
Highest AKIN stage reached on each day during the first week
RIFLE stages
Urine output (if available)
Days on Renal Replacement Therapy
Patients on Renal Replacement Therapy
Platelet count
International normalized ratio
Activated partial thromboplastin time
Adverse Events
Mortality
Length of Stay in ICU/hospital
C-reactive protein
Hours on mechanical ventilation
Total volume of administered investigational products
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
Heart rate
Temperature
Mean arterial pressure
Systolic arterial blood pressure
Diastolic arterial blood pressure
Central venous pressure (if available)
Partial pressure of carbon dioxide
Partial pressure of oxygen
Bicarbonate
Arterial oxygen saturation
Hemoglobin
Hematocrit
pH
Base excess
Lactate
Central venous oxygen saturation (if available)
Serum sodium
Serum potassium
Serum calcium
Serum chloride

Full Information

First Posted
November 1, 2017
Last Updated
August 4, 2022
Sponsor
Fresenius Kabi
Collaborators
B. Braun Melsungen AG, European Society of Anaesthesiology and Intensive Care
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1. Study Identification

Unique Protocol Identification Number
NCT03338218
Brief Title
Safety and Efficacy of a 6% Hydroxyethyl Starch (HES) Solution Versus an Electrolyte Solution in Trauma Patients
Acronym
TETHYS
Official Title
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 Type
Interventional

2. Study Status

Record Verification Date
August 2022
Overall Recruitment Status
Completed
Study Start Date
February 23, 2019 (Actual)
Primary Completion Date
June 25, 2022 (Actual)
Study Completion Date
June 25, 2022 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Fresenius Kabi
Collaborators
B. Braun Melsungen AG, European Society of Anaesthesiology and Intensive Care

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

Brief Summary
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Hypovolemia Due to Acute Blood Loss
Keywords
Hydroxyethyl starch, HES, HES 130

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 4
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
238 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Volulyte 6%
Arm Type
Experimental
Arm Description
Volulyte 6% solution for infusion
Arm Title
Ionolyte
Arm Type
Active Comparator
Arm Description
Ionolyte solution for infusion
Intervention Type
Drug
Intervention Name(s)
Volulyte 6%
Other Intervention Name(s)
Hydroxyethyl starch 130
Intervention Description
Solution for infusion
Intervention Type
Drug
Intervention Name(s)
Ionolyte
Other Intervention Name(s)
Ionolyte Electrolyte Solution
Intervention Description
Solution for infusion
Primary Outcome Measure Information:
Title
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.
Time Frame
90 days
Secondary Outcome Measure Information:
Title
Serum creatinine
Time Frame
7 days post-trauma
Title
Serum creatinine-based estimated glomerular filtration rate
Time Frame
7 days post-trauma
Title
Cystatin-C
Time Frame
3 days post-trauma
Title
Cystatin-C-based mean estimated glomerular filtration rate
Time Frame
3 days post-trauma
Title
AKIN stages
Time Frame
7 days post-trauma
Title
Highest AKIN stage reached on each day during the first week
Time Frame
7 days post-trauma
Title
RIFLE stages
Time Frame
7 days post-trauma
Title
Urine output (if available)
Time Frame
7 days post-trauma
Title
Days on Renal Replacement Therapy
Time Frame
90 days after randomization
Title
Patients on Renal Replacement Therapy
Time Frame
90 days after randomization
Title
Platelet count
Time Frame
3 days post-trauma
Title
International normalized ratio
Time Frame
3 days post-trauma
Title
Activated partial thromboplastin time
Time Frame
3 days post-trauma
Title
Adverse Events
Time Frame
90 days after randomization
Title
Mortality
Time Frame
90 days after randomization
Title
Length of Stay in ICU/hospital
Time Frame
90 days after randomization
Title
C-reactive protein
Time Frame
3 days post-trauma
Title
Hours on mechanical ventilation
Time Frame
7 days post-trauma
Title
Total volume of administered investigational products
Time Frame
until 24 hours after investigational product treatment start
Title
Fluid balance
Description
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
Time Frame
7 days post-trauma
Title
Heart rate
Time Frame
7 days post-trauma
Title
Temperature
Time Frame
7 days post-trauma
Title
Mean arterial pressure
Time Frame
7 days post-trauma
Title
Systolic arterial blood pressure
Time Frame
7 days post-trauma
Title
Diastolic arterial blood pressure
Time Frame
7 days post-trauma
Title
Central venous pressure (if available)
Time Frame
7 days post-trauma
Title
Partial pressure of carbon dioxide
Time Frame
3 days post-trauma
Title
Partial pressure of oxygen
Time Frame
3 days post-trauma
Title
Bicarbonate
Time Frame
3 days post-trauma
Title
Arterial oxygen saturation
Time Frame
3 days post-trauma
Title
Hemoglobin
Time Frame
3 days post-trauma
Title
Hematocrit
Time Frame
3 days post-trauma
Title
pH
Time Frame
3 days post-trauma
Title
Base excess
Time Frame
3 days post-trauma
Title
Lactate
Time Frame
3 days post-trauma
Title
Central venous oxygen saturation (if available)
Time Frame
3 days post-trauma
Title
Serum sodium
Time Frame
3 days post-trauma
Title
Serum potassium
Time Frame
3 days post-trauma
Title
Serum calcium
Time Frame
3 days post-trauma
Title
Serum chloride
Time Frame
3 days post-trauma

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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)
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Wolfgang F. Buhre, Prof. Dr. med.
Organizational Affiliation
Department of Anesthesiology and Pain Management, Maastricht University, The Netherlands
Official's Role
Study Chair
Facility Information:
Facility Name
Ziekenhuis Oost-Limburg-ZOL
City
Genk
Country
Belgium
Facility Name
Fakultni nemocnice Brno
City
Brno
Country
Czechia
Facility Name
Military University Hospital
City
Prague
Country
Czechia
Facility Name
CHRU Nancy - Hôpital Central
City
Nancy
Country
France
Facility Name
Hôpital de Hautepierre
City
Strasbourg
Country
France
Facility Name
Universitätsklinikum Aachen
City
Aachen
Country
Germany
Facility Name
Universitätsklinikum Carl Gustav Carus Dresden
City
Dresden
Country
Germany
Facility Name
Universitätsklinikum Frankfurt
City
Frankfurt
Country
Germany
Facility Name
University Hospital Schleswig-Holstein Campus Kiel
City
Kiel
Country
Germany
Facility Name
Academic Medical Center (AMC) Anesthesiology
City
Amsterdam
Country
Netherlands
Facility Name
University Medical Center (UMC) Maastricht
City
Maastricht
Country
Netherlands
Facility Name
Groote Schuur Hospital
City
Cape Town
Country
South Africa
Facility Name
Gama Research Centre Emergency Department, Leratong Hospital
City
Germiston
Country
South Africa
Facility Name
Gama Research Centre
City
Germiston
Country
South Africa
Facility Name
Chris Hani Baragwanath Hospital
City
Johannesburg
Country
South Africa
Facility Name
Trident Clinical, Homestead Medical Centre
City
Kimberley
Country
South Africa
Facility Name
Steve Biko Academic Hospital
City
Pretoria
Country
South Africa
Facility Name
FCRN Clinical Trials Centre
City
Vereeniging
Country
South Africa
Facility Name
Clinical Projects Research SA
City
Worcester
Country
South Africa
Facility Name
Hospital Universitario Gregorio Marañón
City
Madrid
Country
Spain
Facility Name
Hospital Clinico Universitario
City
Valencia
Country
Spain
Facility Name
Hospital Universitari i Politecnic la Fe
City
Valencia
Country
Spain

12. IPD Sharing Statement

Citations:
PubMed Identifier
35655234
Citation
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.
Results Reference
derived
PubMed Identifier
30017128
Citation
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.
Results Reference
derived

Learn more about this trial

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

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