Hypovolaemia Due to Acute Blood LossPhase 4PHOENICSNCT03278548
Safety and Efficacy of 6% Hydroxyethyl Starch (HES) Solution Versus an Electrolyte Solution in Patients Undergoing Elective Abdominal Surgery
A Phase 4 study testing Volulyte 6% and Ionolyte in people with Hypovolaemia Due to Acute Blood Loss, run by Fresenius Kabi at 61 sites in 10 countries.
Trial summary
The aim of the study is to investigate the safety of a 6% HES (Hydroxyethyl Starch) solution (Volulyte 6%) versus an electrolyte solution (Ionolyte) in patients undergoing elective abdominal surgery. Read more about this study
- Who is it for?
- Ages 41 to 85 years
- Conditions the study is for
- Hypovolaemia Due to Acute Blood Loss
- What is being tested?
- Volulyte 6% and Ionolyte
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 2,289 participants
- Where
- 61 sitesin 10 countries
- Study dates
- 28 Sep 2017to 6 Jul 2022
- Phase
- Phase 4
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 41 to 85 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Male or female adult patients > 40 and ≤ 85 years of age. Women of child bearing potential must test negative on standard pregnancy test (urine or serum)
- Patients undergoing elective abdominal surgery with an expected blood loss of ≥ 500 ml
- ASA Physical Status II - III
- Signed written informed consent form
Who cannot join
- Hypersensitivity to the active substances or to any of the other excipients of the investigational medicinal products
- Body weight ≥ 140 kg
- Sepsis
- Burns
- Renal impairment (AKIN stage ≥ 1 or chronic) or acute and/or chronic renal replacement therapy
- Intracranial or cerebral haemorrhage
Show all 19Show fewer
- Critically ill patients (typically admitted to the intensive care unit)
- Hyperhydration
- Pulmonary oedema
- Dehydration
- Hyperkalaemia
- Severe hypernatraemia
- Severe hyperchloraemia
- 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)
Trial locations and contacts
61 sites in 10 countries.
61 sites in 10 countries
France11 sites
CHU Angers
Angers
Hospital Centre Pierre Oudot
Bourgoin
CHRU Lille
Lille
Hospital Centre Montauban
Montauban
Montpellier University Hospital
Montpellier
AP-HP Paris (Salpêtrière)
Paris
Hospital Saint-Antoine
Paris
Hôpital Européen Georges Pompidou
Paris
University Hospital of Strasbourg
Strasbourg
Hospital Foch Suresnes
Suresnes
Hospital Jean Bernard
Valenciennes
Spain11 sites
Barcelona Clinic Hospital
Barcelona
Hospital Santa Creu i Sant Pau
Barcelona
University Hospital General Del Elche
Elche
Hospital Universitario de Gran Canaria Dr. Negrín
Las Palmas de Gran Canaria
Hospital Gregorio Marañon
Madrid
Hospital Ramón y Cajal
Madrid
Hospital Universitario Fundacion Alcorcon
Madrid
Quironsalud
Málaga
Hospital Clinico Universitario Valencia
Valencia
Hospital Universitari i Politecnic la Fe
Valencia
Hospital Universitario Rio Hortega
Valladolid
Germany10 sites
Kliniken der Stadt Köln
Cologne
Carl-Thiem-Klinikum
Cottbus
Helios Amper-Klinikum
Dachau
Universitätsklinikum Carl Gustav Carus
Dresden
University Hospital Schleswig-Holstein Campus Kiel
Kiel
University Hospital Marburg
Marburg
University Hospital Munich
München
Universitätsklinikum Münster
Münster
Klinikum Oldenburg AÖR
Oldenburg
Regio Klinikum Pinneberg GmbH
Pinneberg
Poland9 sites
University Clinical Center Gdansk
Gdansk
Szpital Specjalistyczny im. Św. Łukasza
Gmina Końskie
Medical University of Silesia
Katowice
Wojewodzki Szpital Zespolony
Konin
Jagiollonian University Hospital Medical College
Krakow
Medical University of Lublin
Lublin
Karol Marcinkowski Medical University in Poznań
Poznan
University Hospital in Wroclaw
Wroclaw
Klinika Wiśniowa
Zielona Góra
Czechia4 sites
Kolín Hospital
Kolín
Central Military Hospital Prague
Prague
General University Hospital in Prague
Prague
University Hospital Motol
Prague
Netherlands4 sites
Amsterdam Medical Centre
Amsterdam
Martini General Hospital Groningen
Groningen
University Medical Center Groningen
Groningen
University Medical Center (UMC) Maastricht
Maastricht
Romania4 sites
Fundeni Clinical Institute 1
Bucharest
Fundeni Clinical Institute 2
Bucharest
University Hospital Elias Bucharest
Bucharest
Emergency county hospital Cluj
Cluj-Napoca
Belgium3 sites
Cliniques Universitaires Saint Luc
Brussels
AZ Maria Middelares
Ghent
Jessa Ziekenhuis
Hasselt
Croatia3 sites
Clinical Hospital Sveti Duh
Zagreb
University Hospital Sisters of Mercy
Zagreb
University Hospital Zagreb
Zagreb
Austria2 sites
General Hospital of Barmherzige Brüder
Sankt Veit
Social Medical Center East - Donauspital
Vienna
About this study
Official title: Prospective, Randomized, Controlled, Double-blind, Multi-centre, Multinational Study on the Safety and Efficacy of 6% Hydroxyethyl Starch (HES) Solution Versus an Electrolyte Solution in Patients Undergoing Elective Abdominal Surgery
The aim of the study is to investigate the safety of a 6% HES (Hydroxyethyl Starch) solution (Volulyte 6%) versus an electrolyte solution (Ionolyte) in patients undergoing elective abdominal surgery.
- Conditions
- Hypovolaemia Due to Acute Blood Loss
- Being tested
- Volulyte 6%, Ionolyte
- Keywords
- HES, HES 130, Hydroxyethyl starch
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Volulyte 6%Drug
Also called Hydroxyethyl starch 130/0.4
Solution for infusion
IonolyteDrug
Also called Electrolyte solution
Solution for infusion
| Study group | Role | What they receive |
|---|---|---|
| Volulyte 6% | Experimental | Volulyte 6% solution for infusion Receives: Drug: Volulyte 6% |
| Ionolyte | Active comparator | Ionolyte solution for infusion Receives: Drug: Ionolyte |
What is being measured
The primary outcome is the main question the study is designed to answer.
Difference in mean estimated glomerular filtration rate (eGFR) (calculated from highest cystatin-C levels measured during post-operative days 1-3 (POD 1-3)) between the two treatment groups
Measured: post-operative days 1-3
Secondary outcomes (34)
Renal function
Measured: until 1 year after surgery
Calculated red blood cell (RBC) loss
Measured: on post-operative day 3
Estimated intra-operative blood loss
Measured: end of surgery
Coagulation
Measured: until post-operative day 1
Inflammation
Measured: until post-operative day 1
Adverse events
Measured: until post-operative day 90
Major post-operative complications
Measured: until post-operative day 90
Mortality
Measured: 1 year
Composite of mortality and major post-operative complications (including renal)
Measured: until post-operative day 90
Total volume of administered investigational product
Measured: 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 intra-operative blood loss]
Measured: until post-operative day 3
Heart Rate
Measured: until post-operative day 3
Body temperature
Measured: until post-operative day 3
Mean arterial pressure
Measured: until post-operative day 3, if available
Systolic arterial blood pressure
Measured: until end of surgery
Diastolic arterial blood pressure
Measured: until end of surgery
Central venous pressure (if available)
Measured: until end of surgery
Haemodynamics readings as required to determine volume responsiveness [at least one parameter (stroke volume, stroke volume variation, stroke volume index, pulse pressure variation, mean arterial pressure) has to be used to guide volume administration]
Measured: until 24 hours after investigational product treatment start
Partial pressure of carbon dioxide
Measured: until end of surgery
Partial pressure of oxygen
Measured: until end of surgery
Bicarbonate
Measured: until end of surgery
Arterial oxygen saturation
Measured: until end of surgery
Haemoglobin
Measured: until post-operative day 3
Haematocrit
Measured: until post-operative day 3
pH
Measured: until end of surgery
Base Excess
Measured: until end of surgery
Lactate
Measured: until post-operative day 3
Central venous oxygen saturation (if available)
Measured: until post-operative day 1
Serum sodium
Measured: until post-operative day 1
Serum potassium
Measured: until post-operative day 1
Serum calcium
Measured: until post-operative day 1
Serum chloride
Measured: until post-operative day 1
Length of stay in the hospital/intensive care unit
Measured: until post-operative day 90
Hours on mechanical ventilation
Measured: until post-operative day 7
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 Sep 2017
- Study start28 Sep 2017
- Primary completion9 Apr 2022
- Study completion6 Jul 2022
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Hypovolaemia Due to Acute Blood LossStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 2,289 participants (actual)
Sponsor and investigators
- Lead sponsor
- Fresenius Kabi
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- B. Braun Melsungen AG, European Society of Anaesthesiology and Intensive Care
- Responsible party
- Sponsor
- Investigators
- Wolfgang F. Buhre, Prof. Dr. med., Study chair, Department of Anesthesiology and Pain Management, Maastricht University, The Netherlands
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03278548
- Sponsor's protocol ID
- HC-G-H-1504
- Other IDs
- HE06-024-CP4
- Acronym
- PHOENICS
- Status last verified
- Jan 2024
- First submitted
- 8 Sep 2017
- Last updated
- 31 Jan 2024
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
Publications
Buhre W, Diaz-Cambronero O, Schaefer S, Novacek M, Domingo MS, Stessel B, Rodriguez-Perez A, Richter T, Rohe G, Cholley B, Gruenewald M, Kuiper G, Jaber S, de Korte D, Belda J, de Abreu MG, Baronica R, Scheeren T, Ferrando-Ortola C, Szczeklik W, Tomescu D, Vyzamal T, Gavranovic Z, Argente-Navarro MP, Mazzinari G, Thaler S, Garcia-Gregorio N, Vandenbrande J, Zlotnik D, Wittenstein J, Schmier S, Rohn S, Glasmacher C, Holler M, Jungheinrich C, Niess U, Sessler DI, Westphal M; New Collective Author. Safety and efficacy of 6% hydroxyethyl starch in patients undergoing major surgery: The randomised controlled PHOENICS trial. Eur J Anaesthesiol. 2026 Jan 1;43(1):1-10. doi: 10.1097/EJA.0000000000002307. Epub 2025 Oct 24.
PubMed 41133731Buhre W, de Korte-de Boer D, de Abreu MG, Scheeren T, Gruenewald M, Hoeft A, Spahn DR, Zarbock A, Daamen S, Westphal M, Brauer U, Dehnhardt T, Schmier S, Baron JF, De Hert S, Gavranovic Z, Cholley B, Vymazal T, Szczeklik W, Bornemann-Cimenti H, Soro Domingo MB, Grintescu I, Jankovic R, Belda J. Prospective, randomized, controlled, double-blind, multi-center, multinational study on the safety and efficacy of 6% Hydroxyethyl starch (HES) sOlution versus an Electrolyte solutioN In patients undergoing eleCtive abdominal Surgery: study protocol for the PHOENICS study. Trials. 2022 Feb 22;23(1):168. doi: 10.1186/s13063-022-06058-6.
PubMed 35193648Chappell 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.
PubMed 30017128
Study at a glance
From the registry record, last updated by the sponsor on 31 Jan 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Prospective, Randomized, Controlled, Double-blind, Multi-centre, Multinational Study on the Safety and Efficacy of 6% Hydroxyethyl Starch (HES) Solution Versus an Electrolyte Solution in Patients Undergoing Elective Abdominal Surgery
- ClinicalTrials.gov ID
- NCT03278548
- Acronym / sponsor ID
- PHOENICS / HC-G-H-1504
- Conditions
- Hypovolaemia Due to Acute Blood Loss
- Keywords
- HES, HES 130, Hydroxyethyl starch
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 2,289 participants (actual)
- Lead sponsor
- Fresenius KabiIndustry (pharma, biotech, devices)
- Collaborators
- B. Braun Melsungen AG, European Society of Anaesthesiology and Intensive Care
- Study start
- 28 Sep 2017 (actual)
- Primary completion
- 9 Apr 2022 (actual)
- Study completion
- 6 Jul 2022 (actual)
- First posted
- 11 Sep 2017 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The aim of the study is to investigate the safety of a 6% HES (Hydroxyethyl Starch) solution (Volulyte 6%) versus an electrolyte solution (Ionolyte) in patients undergoing elective abdominal surgery.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Volulyte 6% | Experimental | Drug: Volulyte 6%Volulyte 6% solution for infusion |
| Ionolyte | Active comparator | Drug: IonolyteIonolyte solution for infusion |
Who may qualify
- Ages
- 41 to 85 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- Male or female adult patients > 40 and ≤ 85 years of age. Women of child bearing potential must test negative on standard pregnancy test (urine or serum)
- Patients undergoing elective abdominal surgery with an expected blood loss of ≥ 500 ml
- ASA Physical Status II - III
- Signed written informed consent form
Key exclusion criteria (19 listed)
- Hypersensitivity to the active substances or to any of the other excipients of the investigational medicinal products
- Body weight ≥ 140 kg
- Sepsis
- Burns
- Renal impairment (AKIN stage ≥ 1 or chronic) or acute and/or chronic renal replacement therapy
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Volulyte 6%Also: Hydroxyethyl starch 130/0.4Solution for infusion | Drug | Volulyte 6% |
| IonolyteAlso: Electrolyte solutionSolution for infusion | Drug | Ionolyte |
Primary outcome
Difference in mean estimated glomerular filtration rate (eGFR) (calculated from highest cystatin-C levels measured during post-operative days 1-3 (POD 1-3)) between the two treatment groups
Time frame: post-operative days 1-3
34 secondary outcomes
Renal function
Time frame: until 1 year after surgery
Calculated red blood cell (RBC) loss
Time frame: on post-operative day 3
Estimated intra-operative blood loss
Time frame: end of surgery
Coagulation
Time frame: until post-operative day 1
Inflammation
Time frame: until post-operative day 1
Adverse events
Time frame: until post-operative day 90
Major post-operative complications
Time frame: until post-operative day 90
Mortality
Time frame: 1 year
Composite of mortality and major post-operative complications (including renal)
Time frame: until post-operative day 90
Total volume of administered investigational product
Time frame: 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 intra-operative blood loss]
Time frame: until post-operative day 3
Heart Rate
Time frame: until post-operative day 3
Body temperature
Time frame: until post-operative day 3
Mean arterial pressure
Time frame: until post-operative day 3, if available
Systolic arterial blood pressure
Time frame: until end of surgery
Diastolic arterial blood pressure
Time frame: until end of surgery
Central venous pressure (if available)
Time frame: until end of surgery
Haemodynamics readings as required to determine volume responsiveness [at least one parameter (stroke volume, stroke volume variation, stroke volume index, pulse pressure variation, mean arterial pressure) has to be used to guide volume administration]
Time frame: until 24 hours after investigational product treatment start
Partial pressure of carbon dioxide
Time frame: until end of surgery
Partial pressure of oxygen
Time frame: until end of surgery
Bicarbonate
Time frame: until end of surgery
Arterial oxygen saturation
Time frame: until end of surgery
Haemoglobin
Time frame: until post-operative day 3
Haematocrit
Time frame: until post-operative day 3
pH
Time frame: until end of surgery
Base Excess
Time frame: until end of surgery
Lactate
Time frame: until post-operative day 3
Central venous oxygen saturation (if available)
Time frame: until post-operative day 1
Serum sodium
Time frame: until post-operative day 1
Serum potassium
Time frame: until post-operative day 1
Serum calcium
Time frame: until post-operative day 1
Serum chloride
Time frame: until post-operative day 1
Length of stay in the hospital/intensive care unit
Time frame: until post-operative day 90
Hours on mechanical ventilation
Time frame: until post-operative day 7
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 31 Jan 2024.
- Derived from this study: PubMed 41133731Buhre W, Diaz-Cambronero O, Schaefer S, Novacek M, Domingo MS, Stessel B, Rodriguez-Perez A, Richter T, Rohe G, Cholley B, Gruenewald M, Kuiper G, Jaber S, de Korte D, Belda J, de Abreu MG, Baronica R, Scheeren T, Ferrando-Ortola C, Szczeklik W, Tomescu D, Vyzamal T, Gavranovic Z, Argente-Navarro MP, Mazzinari G, Thaler S, Garcia-Gregorio N, Vandenbrande J, Zlotnik D, Wittenstein J, Schmier S, Rohn S, Glasmacher C, Holler M, Jungheinrich C, Niess U, Sessler DI, Westphal M; New Collective Author. Safety and efficacy of 6% hydroxyethyl starch in patients undergoing major surgery: The randomised controlled PHOENICS trial. Eur J Anaesthesiol. 2026 Jan 1;43(1):1-10. doi: 10.1097/EJA.0000000000002307. Epub 2025 Oct 24.
- Derived from this study: PubMed 35193648Buhre W, de Korte-de Boer D, de Abreu MG, Scheeren T, Gruenewald M, Hoeft A, Spahn DR, Zarbock A, Daamen S, Westphal M, Brauer U, Dehnhardt T, Schmier S, Baron JF, De Hert S, Gavranovic Z, Cholley B, Vymazal T, Szczeklik W, Bornemann-Cimenti H, Soro Domingo MB, Grintescu I, Jankovic R, Belda J. Prospective, randomized, controlled, double-blind, multi-center, multinational study on the safety and efficacy of 6% Hydroxyethyl starch (HES) sOlution versus an Electrolyte solutioN In patients undergoing eleCtive abdominal Surgery: study protocol for the PHOENICS study. Trials. 2022 Feb 22;23(1):168. doi: 10.1186/s13063-022-06058-6.
- Derived from this study: PubMed 30017128Chappell 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.
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Wolfgang F. Buhre, Prof. Dr. med. study chair
Department of Anesthesiology and Pain Management, Maastricht University, The Netherlands
61 sites in 10 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Volulyte 6% and Ionolyte in people with Hypovolaemia Due to Acute Blood Loss, run by Fresenius Kabi at 61 sites in 10 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 19 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 31 Jan 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 61 sites in France, Spain, Germany, Poland, Czechia and 5 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Difference in mean estimated glomerular filtration rate (eGFR) (calculated from highest cystatin-C levels measured during post-operative days 1-3 (POD 1-3)) between the two treatment groups (time frame: post-operative days 1-3). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03278548, which also lists 3 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 31 Jan 2024.