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

NCT ID: NCT06663254

Last Updated: 2024-10-29

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

NOT_YET_RECRUITING

Clinical Phase

PHASE4

Total Enrollment

410 participants

Study Classification

INTERVENTIONAL

Study Start Date

2024-11-30

Study Completion Date

2026-08-30

Brief Summary

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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.

Detailed Description

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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.

The investigators will test the primary hypothesis that the maximum decrease in serum Cystatin-C-based estimated glomerular filtration rate (eGFR) from preoperatively through the initial 3 postoperative hospital days is non-inferior in patients who are randomized to a goal-directed combination of HES and crystalloid volume replacement versus goal-directed crystalloid alone.

Secondarily, the investigators will determine the long-term renal safety (cystatin C-based eGFR on postoperative 1 and 3 months) of HES and its effect on major adverse cardiovascular events and the length of hospitalization. Exploratory outcomes will include intraoperative hemodynamic indices, postoperative gastrointestinal indicators, the rate of unscheduled transferring to intensive care unit, the incidence of hospital re-admission within 30 days, the incidence of renal replacement therapy within 90 days after surgery, and the incidence of acute kidney injury based on serum creatine within 7 days.

Conditions

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Perioperative Volume Replacement Hydroxyethyl Starch

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

DOUBLE

Participants Outcome Assessors
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).

Study Groups

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6% hydroxyethyl starch 130/0.4

Group Type EXPERIMENTAL

Hydroxyethyl starch 130/0.4

Intervention Type 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.

Sodium acetate Ringer

Group Type OTHER

Sodium acetate Ringer

Intervention Type 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.

Interventions

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Hydroxyethyl starch 130/0.4

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.

Intervention Type DRUG

Sodium acetate Ringer

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.

Intervention Type DRUG

Other Intervention Names

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Volulyte 6% 6% Hydroxyethyl starch 130/0.4

Eligibility Criteria

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Inclusion Criteria

* 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:

1. Age ≥65 years;
2. History of peripheral arterial disease;
3. History of coronary artery disease;
4. History of stroke or transient ischemic attack;
5. Diabetes requiring medication;
6. Current smoking or 15-pack-year history of smoking tobacco;
7. Body mass index ≥30 kg/m2;
8. 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;
9. B-type natriuretic protein (BNP) ≥80 ng/L or N-terminal B-type natriuretic protein (NT-ProBNP) ≥200 ng/L within six months.

Exclusion Criteria

* 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;
* Have known hypersensitivity or contraindication to Volulyte 6% or any sodium acetate Ringer solution component.
Minimum Eligible Age

45 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Xiangya Hospital of Central South University

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Locations

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The First Affiliated Hospital of Zhengzhou University;

Zhengzhou, Henan, China

Site Status

Xiangya Hospital of Central South University

Changsha, Hunan, China

Site Status

The First Hospital of China Medical University

Shenyang, Liaoning, China

Site Status

Shandong Provincial Qianfoshan Hospital

Jinan, Shandong, China

Site Status

The First Affiliated Hospital of Xi'an Jiaotong University

Xi&#39;an, Shanxi, China

Site Status

Chaoyang Hospital of Capital Medical University

Beijing, , China

Site Status

Countries

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China

Central Contacts

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

Role: CONTACT

+8618874889950

Facility Contacts

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Director, Department of Anesthesiology

Role: primary

+86-0371-67966266

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

Role: primary

+86-0731-84327413

E Wang

Role: backup

Director, Department of Anesthesiology

Role: primary

+86-024-961200

Director, Department of Anesthesiology

Role: primary

+86-0531-89268763

Director, Department of Anesthesiology

Role: primary

+86-029-85323112

Director, Department of Anesthesiology

Role: primary

+86-010-85231777

References

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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.

Reference Type BACKGROUND
PMID: 32753064 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 24056586 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 31961418 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 30882476 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 29068831 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 34724045 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 29576114 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 31880630 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 34601955 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 33971968 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 34330414 (View on PubMed)

Other Identifiers

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2024060725

Identifier Type: OTHER

Identifier Source: secondary_id

XiangyaHMZKHES

Identifier Type: -

Identifier Source: org_study_id

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