Safety and Efficacy of Perioperative Volume Replacement with Volulyte 6% in Moderate-to-high Cardiovascular Risk Patients Having Major Abdominal Surgery

NCT06663254 | Not Yet Recruiting Phase 4 DMC

• 2 other identifiers: XiangyaHMZKHES2024060725
• Study Type: interventional
• Target: 410
• Locations: 1 country
• Sites: 6

Brief Summary

The investigators propose a multicenter randomized trial to test the renal safety of 6% hydroxyethyl starch (HES) 130/0.4 combined with sodium acetate Ringer's crystalloid solution in moderate-to-high cardiovascular risk patients having major abdominal surgery. The reference group will only be given sodium acetate Ringer's crystalloid.

Conditions

Perioperative Volume Replacement; Hydroxyethyl Starch

Outcome Measures

Primary Outcomes (1)

• Maximum change in serum Cystatin-C based estimated glomerular filtration rate (eGFR) from baseline through initial 3 postoperative hospital days

  The decrease in cystatin-C-based eGFR from preoperatively to the minimum value recorded during the initial three postoperative hospital days. Increases in postoperative eGFR will be considered a reduction of 0 for analysis purposes.

  Baseline and postoperative 1/2/3 day

Secondary Outcomes (4)

• Cystatin-C based eGFR on postoperative 1 month

  Postoperative 1 month

• Cystatin-C based eGFR on postoperative 3 months

  Postoperative 3 months

• Postoperative major adverse cardiovascular events composite

  Postoperative 30 days

• The length of hospitalization

  Postoperative 3 month

Other Outcomes (11)

• Average cardiac index

  Perioperative

• Responses to boluses of each fluid

  Perioperative

• Total fluid volume

  Perioperative and the subsequent first 24 postoperative hours

Study Arms (2)

6% hydroxyethyl starch 130/0.4

EXPERIMENTAL

Drug: Hydroxyethyl starch 130/0.4

Sodium acetate Ringer

OTHER

Drug: Sodium acetate Ringer

Interventions

Hydroxyethyl starch 130/0.4 DRUG

Individualized goal-directed administration of 6% Hydroxyethyl starch (HES) 130/0.4: After the induction of anesthesia, 200 ml trial fluid will be infused over 20 min. If stroke volume (SV) increases \>10%, another 200 ml fluid will be given. After that, the use of trial fluid will be determined by the patients' Stroke Volume Variation (SVV). If the SVV exceeds 12%, 200 ml trial fluid will be given over 20 min; this will be repeated until SVV \<12%. If the use of HES exceeds 30 ml/kg, sodium acetate Ringer will be replaced. In addition, patients will have a background infusion of sodium acetate Ringer's solution at 4 ml/kg/h to satisfy the maintenance fluid requirements during surgery.

Also known as: Volulyte 6%, 6% Hydroxyethyl starch 130/0.4

6% hydroxyethyl starch 130/0.4

Sodium acetate Ringer DRUG

Individualized goal-directed administration of crystalloid alone: After the induction of anesthesia, 200 ml trial fluid will be infused over 20 min. If stroke volume (SV) increases \>10%, another 200 ml fluid will be given. After that, the use of trial fluid will be determined by the patients' Stroke Volume Variation (SVV). If the SVV exceeds 12%, 200 ml trial fluid will be given over 20 min; this will be repeated until SVV \<12%. In addition, patients will have a background infusion of sodium acetate, the maintenance fluid requirement during surgery.

Sodium acetate Ringer

Eligibility Criteria

• Age: 45 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Are at least 45 years old;
• Scheduled for elective open or laparoscopic gastrointestinal surgery expected to last ≥2 hours;
• Having general anesthesia;
• Expected to require at least overnight hospitalization;
• Subject to at least one of the following risk factors:
• Age ≥65 years;
• History of peripheral arterial disease;
• History of coronary artery disease;
• History of stroke or transient ischemic attack;
• Diabetes requiring medication;
• Current smoking or 15-pack-year history of smoking tobacco;
• Body mass index ≥30 kg/m2;
• Preoperative high-sensitivity troponin T ≥14 ng/L or troponin I equivalent, defined as ≥15 ng/L (Abbott assay), 19 ng/L (Siemens assay), or 25% of the 99% percentile for other assays - all within 6 months;
• B-type natriuretic protein (BNP) ≥80 ng/L or N-terminal B-type natriuretic protein (NT-ProBNP) ≥200 ng/L within six months.

You may not qualify if:

• Participate in conflicting studies;
• Are designated American Society of Anesthesiologists physical status 4;
• Are pregnant and/or breastfeeding;
• Have hypoproteinemia (serum albumin \<30 g/L) or were given preoperative intravenous colloids, including albumin;
• Have recent intracranial or cerebral hemorrhage;
• Have preoperative acute kidney injury or chronic renal insufficiency (Serum Creatine ≥140 µmol/L for men, Serum Creatine≥120 µmol/L for women and/or oliguria/anuria) or renal replacement therapy;
• Have severe hepatic impairment (Alanine Transaminase (ALT) and/or Aspartate Aminotransferase (AST) more than two times the upper limit of normal);
• Are in congestive heart failure or have pulmonary edema;
• Are critically ill or septic;
• Have electrolyte disorders such as hypernatremia, hyperchloremia, hyperkalemia, or severe alkalosis;
• Are fluid overloaded or dehydrated;
• Have clinically meaningful coagulation or bleeding disorders;
• Had a solid organ transplant;
• Have a current serious burn injury;
• Have a mental illness that precludes adequate consent or cooperation with the proposed trial;

Sponsors & Collaborators

• Xiangya Hospital of Central South University: lead

Study Sites (6)

The First Affiliated Hospital of Zhengzhou University;

Zhengzhou, Henan, China

Location

Xiangya Hospital of Central South University

Changsha, Hunan, 410008, China

Location

The First Hospital of China Medical University

Shenyang, Liaoning, China

Location

Shandong Provincial Qianfoshan Hospital

Jinan, Shandong, China

Location

The First Affiliated Hospital of Xi'an Jiaotong University

Xi&#39;an, Shanxi, China

Location

Chaoyang Hospital of Capital Medical University

Beijing, China

Location

Related Publications (11)

• Reiterer C, Kabon B, Taschner A, Zotti O, Kurz A, Fleischmann E. A comparison of intraoperative goal-directed intravenous administration of crystalloid versus colloid solutions on the postoperative maximum N-terminal pro brain natriuretic peptide in patients undergoing moderate- to high-risk noncardiac surgery. BMC Anesthesiol. 2020 Aug 4;20(1):192. doi: 10.1186/s12871-020-01104-9.

  PMID: 32753064 BACKGROUND

• Yates DR, Davies SJ, Milner HE, Wilson RJ. Crystalloid or colloid for goal-directed fluid therapy in colorectal surgery. Br J Anaesth. 2014 Feb;112(2):281-9. doi: 10.1093/bja/aet307. Epub 2013 Sep 20.

  PMID: 24056586 BACKGROUND

• Futier E, Garot M, Godet T, Biais M, Verzilli D, Ouattara A, Huet O, Lescot T, Lebuffe G, Dewitte A, Cadic A, Restoux A, Asehnoune K, Paugam-Burtz C, Cuvillon P, Faucher M, Vaisse C, El Amine Y, Beloeil H, Leone M, Noll E, Piriou V, Lasocki S, Bazin JE, Pereira B, Jaber S; FLASH Trial Group; Lasocki S, Huet O, Cadic A, Jacob C, Paugam-Burtz C, Restoux A, Ouattara A, Feitita I, Deloge E, Defaye M, Joannes-Boyau O, Carles P, Napolitano G, Monziols S, Futier E, Vignaud M, Paul S, Gahbiche K, Fayon J, Laroche E, Bazin JE, Brandely A, Le Moal C, Lebuffe G, Garot M, Piriou V, Jaber S, Chanques G, Verzilli D, De Jong A, Millot A, Castagnoli A, Leone M, Pastene B, Castelli C, Medam S, Velly L, Vaisse C, Faucher M, Asehnoune K, Samba E, Roquilly A, Le Penndu M, Cuvillon P, Yves Lefrant J, Wira O, Dubout E, Mfam WS, Lescot T, Begneu E, Burey J, Cirilovic T, Beloeil H, Allo G, Pottecher J, Lebas B, Venot C, Rameau JP, Dimache F, Leger PS, El Amine Y. Effect of Hydroxyethyl Starch vs Saline for Volume Replacement Therapy on Death or Postoperative Complications Among High-Risk Patients Undergoing Major Abdominal Surgery: The FLASH Randomized Clinical Trial. JAMA. 2020 Jan 21;323(3):225-236. doi: 10.1001/jama.2019.20833.

  PMID: 31961418 BACKGROUND

• Kabon B, Sessler DI, Kurz A; Crystalloid-Colloid Study Team. Effect of Intraoperative Goal-directed Balanced Crystalloid versus Colloid Administration on Major Postoperative Morbidity: A Randomized Trial. Anesthesiology. 2019 May;130(5):728-744. doi: 10.1097/ALN.0000000000002601.

  PMID: 30882476 BACKGROUND

• Joosten A, Delaporte A, Ickx B, Touihri K, Stany I, Barvais L, Van Obbergh L, Loi P, Rinehart J, Cannesson M, Van der Linden P. Crystalloid versus Colloid for Intraoperative Goal-directed Fluid Therapy Using a Closed-loop System: A Randomized, Double-blinded, Controlled Trial in Major Abdominal Surgery. Anesthesiology. 2018 Jan;128(1):55-66. doi: 10.1097/ALN.0000000000001936.

  PMID: 29068831 BACKGROUND

• Reiterer C, Kabon B, Halvorson S, Sessler DI, Mascha EJ, Kurz A; Crystalloid-Colloid Research Group. Hemodynamic Responses to Crystalloid and Colloid Fluid Boluses during Noncardiac Surgery. Anesthesiology. 2022 Jan 1;136(1):127-137. doi: 10.1097/ALN.0000000000004040.

  PMID: 34724045 BACKGROUND

• Calvo-Vecino JM, Ripolles-Melchor J, Mythen MG, Casans-Frances R, Balik A, Artacho JP, Martinez-Hurtado E, Serrano Romero A, Fernandez Perez C, Asuero de Lis S; FEDORA Trial Investigators Group. Effect of goal-directed haemodynamic therapy on postoperative complications in low-moderate risk surgical patients: a multicentre randomised controlled trial (FEDORA trial). Br J Anaesth. 2018 Apr;120(4):734-744. doi: 10.1016/j.bja.2017.12.018. Epub 2018 Feb 3.

  PMID: 29576114 BACKGROUND

• Ruetzler K, Khanna AK, Sessler DI. Myocardial Injury After Noncardiac Surgery: Preoperative, Intraoperative, and Postoperative Aspects, Implications, and Directions. Anesth Analg. 2020 Jul;131(1):173-186. doi: 10.1213/ANE.0000000000004567.

  PMID: 31880630 BACKGROUND

• Ruetzler K, Smilowitz NR, Berger JS, Devereaux PJ, Maron BA, Newby LK, de Jesus Perez V, Sessler DI, Wijeysundera DN. Diagnosis and Management of Patients With Myocardial Injury After Noncardiac Surgery: A Scientific Statement From the American Heart Association. Circulation. 2021 Nov 9;144(19):e287-e305. doi: 10.1161/CIR.0000000000001024. Epub 2021 Oct 4.

  PMID: 34601955 BACKGROUND

• Xu Y, Wang S, He L, Yu H, Yu H. Hydroxyethyl starch 130/0.4 for volume replacement therapy in surgical patients: a systematic review and meta-analysis of randomized controlled trials. Perioper Med (Lond). 2021 May 11;10(1):16. doi: 10.1186/s13741-021-00182-8.

  PMID: 33971968 BACKGROUND

• Chappell D, van der Linden P, Ripolles-Melchor J, James MFM. Safety and efficacy of tetrastarches in surgery and trauma: a systematic review and meta-analysis of randomised controlled trials. Br J Anaesth. 2021 Oct;127(4):556-568. doi: 10.1016/j.bja.2021.06.040. Epub 2021 Jul 28.

  PMID: 34330414 BACKGROUND

MeSH Terms

Interventions

Hydroxyethyl Starch Derivatives

Intervention Hierarchy (Ancestors)

Starch; Dietary Carbohydrates; Carbohydrates; Glucans; Polysaccharides

Central Study Contacts

E Wang, M.D., Ph.D.

CONTACT

+8618874889950; ewang324@csu.edu.cn

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, OUTCOMES ASSESSOR
• Masking Details: Specifically, everyone except anesthesia clinicians will be blinded to treatment. Anesthesia clinicians who are not blinded will conduct treatment and record intraoperative conditions. Outcome assessors responsible for postoperative follow-up are blinded to patient randomization; Statistical analysis performed independently by the designated blinded statistician. Emergency unblinding will only be done by an investigator and/or dedicated authorized personnel (e.g., the Pharmacovigilance Department of the Sponsor).
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 5, 2024
• First Posted: October 29, 2024
• Study Start: November 30, 2024
• Primary Completion: March 30, 2026
• Study Completion (Estimated): August 30, 2026
• Last Updated: October 29, 2024

Record last verified: 2024-09

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL
• Time Frame: Beginning 9 months and ending 36 months following article publication.
• Access Criteria: Investigators whose proposed use of the data has been approved by an independent review committee ("learned intermediary") identified for individual participant data meta-analysis.

Locations

CN (6)