Safety and Efficacy of 6% Hydroxyethyl Starch (HES) Solution Versus an Electrolyte Solution in Patients Undergoing Elective Abdominal Surgery (PHOENICS)

• ClinicalTrials.gov Identifier: NCT03278548
• Recruitment Status: Completed
• First Posted: September 11, 2017
• Last Update Posted: January 31, 2024
• Sponsor: Fresenius Kabi
• Collaborators: B. Braun Melsungen AG; European Society of Anaesthesiology and Intensive Care
• Information provided by (Responsible Party): Fresenius Kabi

Tracking Information

• First Submitted Date: September 8, 2017
• First Posted Date: September 11, 2017
• Last Update Posted Date: January 31, 2024
• Actual Study Start Date: September 28, 2017
• Actual Primary Completion Date: April 9, 2022 (Final data collection date for primary outcome measure)
• Current Primary Outcome Measures (submitted: September 8, 2017): 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 ]
• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: November 12, 2021)

• 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 ]

Original Secondary Outcome Measures (submitted: September 8, 2017)

• Renal function [ Time Frame: 1 year ]
• Calculated red blood cell (RBC) loss [ Time Frame: 1 day ]
• Estimated intra-operative blood loss [ Time Frame: 1 day ]
• Coagulation [ Time Frame: 1 day ]
• Inflammation [ Time Frame: 1 day ]
• Adverse events [ Time Frame: until post-operative day 90 ]
• Cystatin C [ Time Frame: until post-operative day 90 ]
• Major post-operative complications [ Time Frame: until post-operative day 90 ]
• Mortality [ Time Frame: 1 year ]

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Safety and Efficacy of 6% Hydroxyethyl Starch (HES) Solution Versus an Electrolyte Solution in Patients Undergoing Elective Abdominal Surgery
• 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
• Brief 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.
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 4
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor); Primary Purpose: Treatment
• Condition: Hypovolaemia Due to Acute Blood Loss

Intervention

• Drug: Volulyte 6%
  Solution for infusion
  Other Name: Hydroxyethyl starch 130/0.4
• Drug: Ionolyte
  Solution for infusion
  Other Name: Electrolyte solution

Study Arms

• Experimental: Volulyte 6%
  Volulyte 6% solution for infusion
  Intervention: Drug: Volulyte 6%
• Active Comparator: Ionolyte
  Ionolyte solution for infusion
  Intervention: Drug: Ionolyte

Publications *

• Buhre 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.
• 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.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: January 30, 2024): 2289
• Original Estimated Enrollment (submitted: September 8, 2017): 2280
• Actual Study Completion Date: July 6, 2022
• Actual Primary Completion Date: April 9, 2022 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion:

• 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

Exclusion:

• 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
• 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)

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 41 Years to 85 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Austria, Belgium, Croatia, Czechia, France, Germany, Netherlands, Poland, Romania, Spain

Administrative Information

• NCT Number: NCT03278548
• Other Study ID Numbers: HC-G-H-1504; HE06-024-CP4 ( Other Identifier: Fresenius Kabi )
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

• IPD Sharing Statement: Not Provided
• Current Responsible Party: Fresenius Kabi
• Original Responsible Party: B. Braun Melsungen AG
• Current Study Sponsor: Fresenius Kabi
• Original Study Sponsor: B. Braun Melsungen AG

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

• PRS Account: Fresenius Kabi
• Verification Date: January 2024