Use of 6% Hydroxyethylstarch (130/0.4) in Cardiac Surgical Patients (SHARP)

A Randomized Controlled Investigation of the Effects of 6% Hydroxyethylstarch 130/0.4 (Voluven) on Renal Function in Patients Having Aortic Valve Replacement With or Without Coronary Artery Bypass Grafting

The purpose of this study is to evaluate the safety of a standard volume replacement called HES 130/0.4 (Voluven) during surgery on recovery. HES 130/0.4 (Voluven) may offer an alternative to pure fluid replacement solutions that are associated with problems after surgery including fluid overload and respiratory difficulties. The safety of HES 130/0.4 (Voluven) will be evaluated by examining its effects on kidney function, and coagulation parameters and platelet (part of the blood that help it clot) function.

Participants will be randomized (like flipping a coin) to receive one of two possible volume replacements during surgery, if fluid volume decreases enough to need replacement with one of the fluids. The two possible volume replacements are Voluven (a starch-containing fluid) or human albumin 5% (a protein-containing solution).

To examine kidney function, urine will be-sampled when the participant is put under general anesthesia, before surgical incision, within one hour of arrival to the ICU and 24 hours after completion of surgery. Two tubes (2 teaspoons) of blood (from an already established line) will be taken the morning of the surgery, within one hour of arrival to the ICU, 24 hours after surgery and every morning during the participants postoperative ICU stay.

Additionally, health and recovery information will be recorded from the participant's medical record. We will phone participants around 90 days and one year after surgery to ask a few questions about one's health and recovery. We will also record blood sample analysis results from follow up appointments within the first year after surgery. If this analysis is not conducted at the Cleveland Clinic, with permission, we will obtain the results from a treating physician.

Study Overview

• Status: Completed
• Conditions: Postoperative Kidney Injury
• Intervention / Treatment: Drug: HES 130/0.4 (Voluven); Drug: human albumin 5%

• Study Type: Interventional
• Enrollment (Actual): 149
• Phase: Phase 3

Contacts and Locations

Study Locations

• United States
  • Ohio
    • Cleveland, Ohio, United States, 44195
      • Cleveland Clinic Foundation

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 40 years to 85 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Age 50 - 85 years old
• Scheduled for elective aortic valve replacement with or without coronary artery bypass grafting with or without additional minor surgical procedure.
• Written, informed consent for participation in this investigation.

Exclusion Criteria:

• Patients with renal failure with oliguria or anuria not related to hypovolemia.
• Patients receiving dialysis.
• Patients with preoperative renal insufficiency (Creatinine > 1.6 mg/dL)
• Anticipated deep hypothermic circulatory arrest
• Known hypersensitivity or allergy to hydroxyethyl starch or the excipients of hydroxyethyl starch
• Clinical conditions with volume overload (e.g., patients in pulmonary edema or congestive heart failure)
• Patients with severe hypernatremia or severe hyperchloremia
• Patients with intracranial bleeding
• Pregnant or breast feeding women
• Critically ill adult patients, including patients with sepsis, due to increased risk of mortality and renal replacement therapy, (e.g. patients who are hospitalized in the intensive care unit prior to surgery)
• Severe liver disease
• Pre-existing coagulation or bleeding disorders
• Any contraindications to proposed interventions.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: TRIPLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: HES 130/0.4 (Voluven); 6% HES 130/0.4 during surgery	Drug: HES 130/0.4 (Voluven)
ACTIVE_COMPARATOR: human albumin 5%; human albumin 5% during surgery	Drug: human albumin 5%

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Urine Neutrophil Gelatinase-associated Lipocalin (NGAL) [Time Frame: 24 Hours After Surgery] [Designated as Safety Issue: Yes]	To assess the safety of HES 130/0.4 (Voluven) versus albumin 5% on renal function we will measure urinary concentrations of neutrophil gelatinase-associated lipocalin (NGAL), an important marker of renal function, measured at baseline (following anesthetic induction and prior to surgical incision), at one hour of arrival to intensive care unit (ICU), at 24 hours following completion of surgery.	3 measurements in total from baseline to 24 hours after surgery: the first one is at baseline; the second one is at one hour of arrive to ICU and last one is at 24 hours after surgery

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Kidney Function	Postoperative kidney dysfunction using RIFLE diagnostic criteria was also assessed. Patients were assessed for risk for kidney dysfunction (RIFLE-R), injury to the kidney (RIFLE-I), failure of kidney function (RIFLE-F) using criteria based on only peak serum creatinine concentrations within the first seven postoperative days. Due to too few events, this outcome was redefined to risk (or worse) vs. no risk for this analysis. RIFLE classification criteria is listed below: Risk (RIFLE-R) Increase in serum creatinine x 1.5 from baseline Injury (RIFLE-I) Increase in serum creatinine x 2 from baseline Failure (RIFLE-F) Increase in serum creatinine x 3 from baseline Loss (RIFLE-L) Complete loss of kidney function > 4 weeks End stage (RIFLE-E) End-stage kidney failure > 3 months	within first 7 postoperative days
Postop Urine IL-18	Postop Urine IL-18 (interleukin-18) measured at 1 h of arrival to ICU	postoperative 1 hour
Postop Urine IL-18	Postoperative urine IL-18 (interleukin-18) measured at 24 hours after surgery	24 hours after surgery

Collaborators and Investigators

• Sponsor: The Cleveland Clinic
• Collaborators: Fresenius Kabi
• Investigators: Principal Investigator: Andra Duncan, M.D., The Cleveland Clinic

Publications and helpful links

General Publications

• Lee MJ, Tannenbaum C, Mao G, Jia Y, Leung S, Yilmaz HO, Ince I, Soltesz E, Duncan AE. Effect of 6% Hydroxyethyl Starch 130/0.4 on Inflammatory Response and Pulmonary Function in Patients Having Cardiac Surgery: A Randomized Clinical Trial. Anesth Analg. 2021 Oct 1;133(4):906-914. doi: 10.1213/ANE.0000000000005664.
• Katabi LJ, Pu X, Yilmaz HO, Jia Y, Leung S, Duncan AE. Prognostic Utility of KDIGO Urine Output Criteria After Cardiac Surgery. J Cardiothorac Vasc Anesth. 2021 Oct;35(10):2991-3000. doi: 10.1053/j.jvca.2021.02.027. Epub 2021 Feb 13.
• Duncan AE, Jia Y, Soltesz E, Leung S, Yilmaz HO, Mao G, Timur AA, Kottke-Marchant K, Rogers HJ, Ma C, Ince I, Karimi N, Yagar S, Trombetta C, Sessler DI. Effect of 6% hydroxyethyl starch 130/0.4 on kidney and haemostatic function in cardiac surgical patients: a randomised controlled trial. Anaesthesia. 2020 Sep;75(9):1180-1190. doi: 10.1111/anae.14994. Epub 2020 Feb 18.

Study record dates

Study Major Dates

• Study Start (ACTUAL): March 1, 2015
• Primary Completion (ACTUAL): February 1, 2018
• Study Completion (ACTUAL): February 1, 2020

Study Registration Dates

• First Submitted: July 15, 2014
• First Submitted That Met QC Criteria: July 15, 2014
• First Posted (ESTIMATE): July 16, 2014

Study Record Updates

• Last Update Posted (ESTIMATE): February 14, 2023
• Last Update Submitted That Met QC Criteria: February 9, 2023
• Last Verified: February 1, 2023

More Information

Terms related to this study

• Other Study ID Numbers: 012-973