Comparison Between Hyperoncotic and Isooncotic Albumin to Support Blood Loss Replacement (VASCALB)

Randomized Trial of Intraoperative Intravascular Effect of Hyper-oncotic 20% Albumin, Iso-oncotic 5% Albumin and Ringer Lactate During Haemorrhage in Cystectomy. A Prospective Randomized Active-controlled Single Centre Trial

Fluid intravascular replacement is usually performed with either balanced crystalloids or iso-oncotic colloids, (synthetic colloids, plasma and 5% albumin). Doubts have been raised about synthetic colloids, and albumin solutions have been used more extensively. Albumin is the main protein responsible for plasma oncotic pressure and its volume expansion effect. The mobilization of extravascular fluid by infusing a hyper-oncotic solution like 20% albumin solution has been shown, causing endogenous fluid recruitment and blood volume expansion.

The primary objective of this study is to compare the effect on plasma volume expansion and fluid recruitment of 3 different types of fluids (Albumin 5% and Albumin 20% and Ringer-lactate) during the hemorrhagic phase of the cystectomy procedure.

Secondary objectives are the assessment of the hemodynamic parameters during surgery and the follow-up of pro-ANP and pro-BNP peptides. Glycocalyx proteins will be followed to evaluate endothelial wall shedding and microcirculation damages.

Study Overview

• Status: Completed
• Conditions: Blood Loss, Surgical; Fluid Retention
• Intervention / Treatment: Drug: Hyperoncotic Albumin 20%; Drug: Isooncotic Albumin 5%; Drug: Ringer's Lactate Crystalloid Solutions (control group)

Detailed Description

Bladder cancer occurs mainly in old comorbid patients. The standard treatment of localized muscle invasive bladder cancer is pelvic lymph node dissection and radical cystectomy with urinary diversion. Optimal perioperative fluid management for this surgery is challenging and still controversial in terms of how much to perfuse, choice of fluids to restore hydrated state and volemia.

Fluid treatment is usually performed with either balanced crystalloids fluids or iso-oncotic synthetic colloids, or albumin 5%. Because crystalloids quickly equilibrate between the intravascular and interstitial volumes, they are mainly used to treat dehydration and temporary volume deficits. Doubts have been raised about synthetic colloids and the natural albumin has been used more extensively. Albumin is the main protein responsible for plasma oncotic pressure and its volume expansion effect.

Iso-oncotic colloids (Albumine 5%) remain intravascular for a prolonged period, but they play a neutral role in terms of endogenous fluid recruitment, as the oncotic pressure is equilibrated between the intra- and extra- vascular territories.

An alternative therapeutic option is the mobilization of tissue fluid by infusing a small amount of hyper-oncotic fluid like the albumin 20% solution, which has showed the advantage in its blood volume expansion capacities over crystalloids (endogenous fluid recruitment).

The effects of the Albumin 20% solution have until now never been compared in a same perioperative setting to the Albumin 5% nor to Ringer-lactate solution.

The investigators will evaluate the physiological effects and their outcomes between these fluid therapies in the frame of blood loss replacement during the hemorrhagic part of cystectomy procedures. The investigators will as well assess the variation of hemodynamic parameters (pro-ANP, pro-BNP) and the resulting microcirculation damages (endothelial wall shedding).

• Study Type: Interventional
• Enrollment (Actual): 42
• Phase: Phase 4

Contacts and Locations

Study Locations

• Switzerland
  • BE
    • Bern, BE, Switzerland, 3010
      • Patrick Wuethrich, Department of Anaesthesiology and Pain Therapy, University Hospital Bern Inselspital Bern

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Non emergent radical cystectomy with urinary diversion
• Adult: older than 18 years
• Written informed consent

Exclusion Criteria:

• Contraindications to the class of drugs under study (i.e: known hypersensitivity/ allergy to class of drugs or to the investigational product).
• Renal insufficiency: GFR: <60ml/min/1.73m2 (KDIGO Clinical Practice Guideline for Acute Kidney Injury, stage 3 and over).
• History of heart failure.
• Use of diuretic treatment.
• Women who are pregnant or breast feeding (exclusion of surgery per se).
• Inability to follow the procedures of the study, e.g. due to language problems, psychological disorders, dementia, etc. of the participant.
• Enrolment of the investigator, his/her family members, employees and other dependent persons.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Albumin 20%; 3mL/kg (ideal body weight) completed by a Ringer-lactate crystalloid ratio 1:1 to total amount of blood loss during removal of the bladder (i.e. the bleeding part) of cystectomy procedures.	Drug: Hyperoncotic Albumin 20%; Intravenous administration during removal of the bladder (i.e. the bleeding part) of cystectomy procedures.; Other Names: Albumin 20%
Experimental: Albumin 5%; 12ml/kg (ideal body weight) completed by a Ringer-lactate crystalloid ratio 1:1 to total amount of blood loss during removal of the bladder (i.e. the bleeding part) of cystectomy procedures.	Drug: Isooncotic Albumin 5%; Intravenous administration of Albumin 5% 12ml/kg (ideal body weight) completed by a Ringer-lactate crystalloid ratio 1:1 to total amount of blood loss during removal of the bladder (i.e. the bleeding part) of cystectomy procedures.; Other Names: Albumin 5%
Active Comparator: Ringer-lactate; Ratio 3:1 of total of blood loss during removal of the bladder (i.e. the bleeding part) of cystectomy procedures.	Drug: Ringer's Lactate Crystalloid Solutions (control group); Intravenous administration of Ringer-lactate ratio 3:1 of total of blood loss during removal of the bladder (i.e. the bleeding part) of cystectomy procedures.; Other Names: Ringer Lactate

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Plasma volume expansion	Difference in plasma volume expansion of albumin 20%, albumin 5% and Ringer lactate calculated by volume kinetics	5 hours

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Biological markers (pro-ANP and pro-BNP)	Variation and comparison of kinetics hemodynamics biological markers such as pro-ANP and pro-BNP	24 hours
Cardiac output (CO)	Evolution of cardiac output (CO) at the start of surgery, begin of infusion, stop of infusion and end of surgery.	5 hours
Endothelial damage	Assessment of microcirculation damage due to peroperative stress and fluid therapy through Glycocalyx proteins (CD-138/syndecan 1, heparan sulfate and hyaluronic acid).	24 hours
Stroke volume (SV)	Evolution of stroke volume at the start of surgery, begin of infusion, stop of infusion and end of surgery.	5 hours
Pleth variability index (PVI)	Evolution of pleth variability index (PVI) at the start of surgery, begin of infusion, stop of infusion and end of surgery.	5 hours

Collaborators and Investigators

• Sponsor: University Hospital Inselspital, Berne
• Investigators: Principal Investigator: Patrick Y Wuethrich, MD, University Hospital Inselspital, Bern

Study record dates

Study Major Dates

• Study Start (Actual): May 25, 2022
• Primary Completion (Actual): March 30, 2023
• Study Completion (Actual): April 10, 2023

Study Registration Dates

• First Submitted: May 17, 2022
• First Submitted That Met QC Criteria: May 25, 2022
• First Posted (Actual): May 26, 2022

Study Record Updates

• Last Update Posted (Actual): April 13, 2023
• Last Update Submitted That Met QC Criteria: April 12, 2023
• Last Verified: May 1, 2022

More Information

Terms related to this study

• Keywords: blood loss; hemorrhage; hyaluronic acid; volume expansion; cystectomy; hyperoncotic; isooncotic; albumin 20%; albumin 5%; ringer lactate; fluid replacement; intravascular effect; pro-ANP; pro-BNP; glycocalyx proteins; microcirculation damages; endothelial shedding; CD138/syndecan 1; heparan sulfate
• Additional Relevant MeSH Terms: Pathologic Processes; Intraoperative Complications; Hemorrhage; Blood Loss, Surgical
• Other Study ID Numbers: VASCALB

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No