SUbstition of PERioperative Albumin Deficiency Disorders (SUPERADD)

Does Perioperative Substitution of Albumin Deficiency Reduce Postoperative Complications?

Aim of this study is to reduce postoperative complications (assessed by POMS-Score and graded by Clavien-Dindo-Score) by substitution of perioperative hypoalbuminaemia in high-risk patients or patients undergoing high risk surgery.

Study Overview

• Status: Completed
• Conditions: Hypoalbuminemia
• Intervention / Treatment: Drug: Human albumin

Detailed Description

Perioperative hypoalbuminaemia is a common condition in high risk surgery and in high risk patients. It is associated with increased morbidity and mortality. Although many studies investigated albumin substitution in critically ill patients there is still no clear recommendation for its use over any other colloid. Except for some smaller studies especially in the setting of cardiac surgery the effect of perioperative albumin substitution has not been studied yet.

This study is designed to investigate the effect of perioperative albumin substitution in high risk patients or patients undergoing high risk surgery on postoperative complications assessed by the POMS-Score and graded according to severity by the Clavien-Dindo-Score.

Patients eligible for the study are informed in detail during the pre-medication visit and written informed consent will be obtained. Additionally the Quality of Recovery 9 Score (QoR-9) will be determined. During induction of anesthesia blood is taken from every patient and the serum albumin level is determined. In case albumin is greater than 30 g/l albumin levels are controlled every 3 hours and one last time on admission to the postoperative anaesthesia care unit (PACU). Should the albumin level do not fall below 30 g/l over the whole period the patient is not randomized.

Patients with albumin ≤30g/l will be randomized using a web-based computer-generated randomization list into one of two groups:

Group human albumin (HA):

In this group hypoalbuminaemia is treated with infusion of human albumin until serum albumin is greater than 30g/l. To verify success of the therapy, serum albumin levels are controlled every 3 hours during surgery, on admission to the PACU and if necessary again in the PACU.

Group control:

In this group patients are treated according to standard clinical care. To compare the effect of albumin substitution serum albumin is measured every 3 hours from beginning of anesthesia until discharge from the PACU.

In both groups patients will be discharged from the PACU when the patient is rated fit for discharge by the attending anesthetist and albumin level is >30g/l in the HA group.

A blinded investigator assesses the patients postoperative complications. He visits the patient on day 3, 5, 8 and 15 after surgery and determines the POMS-score (see reference: Grocott MP). If a complication is detected the assessor grades the complication according to its severity with the Clavien-Dindo-Score (see reference: Clavien PA). Additionally serum albumin and creatinine levels will be determined in routine blood tests. The patients QoR-9, the Charlson Comorbidity Score, the Preoperative Score to Predict Postoperative Mortality (POSPOM) and other secondary outcome (see Outcome Measures section) parameters will be obtained.

6 Month after surgery the patient or next of kin will be contacted in order to determine 6-month mortality and the QoR-9 score.

Postulating an incidence of complications (graded Clavien-Dindo-Score 2 or higher) of 52% in group control and a reduced incidence of 38% in group HA results in a total number of 400 patients (chi-square-test, α = 0,048, power 80%). As the actual incidence is unknown but has a significant impact on the number needed per group, an interims analysis will be performed after 100 included patients. Is the difference of the incidence of postoperative complications between the two groups significant with an α < 0,002 the study will be finished. Otherwise, the sample size needed per group will be corrected assuming a relative risk reduction of 25% (52% vs. 38%), an α = 0,048, a two-tailed test and a power of 80%.

The blinded and independent interims analysis after 100 patients revealed a corrected sample size of 300 patients per group (total 600 patients).

• Study Type: Interventional
• Enrollment (Actual): 600
• Phase: Phase 4

Contacts and Locations

Study Locations

• Germany
  • Munich, Germany, 81675
    • Klinikum rechts der Isar Dept. of Anesthesiology

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• age: 18 years or older
• written informed consent
• ASA state 3 and 4 OR
• elective high risk surgery (open aortic surgery, open leg revascularization, thrombectomy, oesophagectomy, pancreatic surgery, cystectomy, liver surgery, change of knee- or hip-prothesis, amputation)

Exclusion Criteria:

• emergency surgery
• severe liver cirrhosis (child pugh C)
• need for dialysis
• patients already included in SUPERADD
• patients with a legal representative
• contraindications for human albumin: hypersensitivity for human albumin or any substance included in the preparation
• pregnancy
• breastfeeding women
• ASA state 5
• BMI > 35 kg/m2

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Human albumin; Substitution of human albumin until serum albumin >30g/l; dosage: (30 g/l - serum albumin [g/l] ) x 0,04 l/kg x body weight [kg] x 2	Drug: Human albumin; Substitution according to pre-specified dosage; Other Names: Human-Albumin 20 % Behring, salzarm
No Intervention: Control; Standard clinical care

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Postoperative complications assessed with POMS- and graded with Clavien-Dindo-Score	Postoperative complications will be detected using the POMS score. The severity of the complications will be graded with the Clavien-Dindo-Score. A complication will be regarded as clinical relevant when it is graded Clavien-Dindo-Score 2 or higher on at least one of the four days examined.	15 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Length of hospital stay		until discharge from hospital, up to 6 month
Length of stay in postoperative anaesthesia care unit		until discharge from postoperative anaesthesia care unit, up to 24 hours
Length of stay in intensive care unit		until discharge from intensive care unit, up to 1 month
Long term mortality (6 month)		6 month
Short term mortality (hospital mortality)		until discharge from hospital, up to 6 month
Acute kidney injury	Incidence according to AKIN score (at least AKIN 1)	until discharge from hospital, up to 6 month
Quality of Recovery 9 Score	Assessed preoperatively and on day 1 and 3 an 6 month after surgery	6 month after surgery
Amount of volume infused	Amount of infusion of ringer's acetate and gelafundin	until discharge from postoperative anaesthesia care unit, up to 24 hours
Dosage of catecholamines	Intra- and postoperative dosage of catecholamines	until discharge from postoperative anaesthesia care unit, up to 24 hours
Number of red packed cells transfused		until discharge from postoperative anaesthesia care unit, up to 24 hours
Number of platelet concentrates transfused		until discharge from postoperative anaesthesia care unit, up to 24 hours
Amount of coagulation factors infused	Amount of PPSB and fibrinogen	until discharge from postoperative anaesthesia care unit, up to 24 hours
Intra- and postoperative Hypotension	Decrease of more than 30% compared to value before induction	until discharge from postoperative anaesthesia care unit, up to 24 hours
Incidence of pulmonal venous congestion	Incidence of pulmonal venous congestion assessed using chest x-ray	until discharge from postoperative anaesthesia care unit, up to 24 hours
Therapy with diuretics	New onset or extension of diuretic treatment	until discharge from hospital, up to 6 month
Efficacy of albumin treatment	Efficacy of albumin treatment in order to increase serum albumin and colloid osmotic pressure	until discharge from hospital, up to 6 month

Collaborators and Investigators

• Sponsor: Technical University of Munich
• Investigators: Principal Investigator: Manfred Blobner, MD, Klinikum rechts der Isar, Technical University Munich, Dept. of Anesthesiology

Publications and helpful links

General Publications

• Grocott MP, Browne JP, Van der Meulen J, Matejowsky C, Mutch M, Hamilton MA, Levett DZ, Emberton M, Haddad FS, Mythen MG. The Postoperative Morbidity Survey was validated and used to describe morbidity after major surgery. J Clin Epidemiol. 2007 Sep;60(9):919-28. doi: 10.1016/j.jclinepi.2006.12.003. Epub 2007 May 7.
• Clavien PA, Sanabria JR, Strasberg SM. Proposed classification of complications of surgery with examples of utility in cholecystectomy. Surgery. 1992 May;111(5):518-26.
• Schaller SJ, Fuest K, Ulm B, Schmid S, Bubb C, von Eisenhart-Rothe R, Friess H, Kirchhoff C, Stadlbauer T, Luppa P, Blobner M, Jungwirth B. Substitution of perioperative albumin deficiency disorders (SuperAdd) in adults undergoing vascular, abdominal, trauma, or orthopedic surgery: protocol for a randomized controlled trial. Trials. 2020 Aug 18;21(1):726. doi: 10.1186/s13063-020-04626-2.

Study record dates

Study Major Dates

• Study Start (Actual): June 19, 2017
• Primary Completion (Actual): December 21, 2019
• Study Completion (Actual): April 21, 2021

Study Registration Dates

• First Submitted: October 18, 2016
• First Submitted That Met QC Criteria: May 23, 2017
• First Posted (Actual): May 30, 2017

Study Record Updates

• Last Update Posted (Actual): April 23, 2021
• Last Update Submitted That Met QC Criteria: April 22, 2021
• Last Verified: April 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Hematologic Diseases; Blood Protein Disorders; Hypoproteinemia; Hypoalbuminemia
• Other Study ID Numbers: SUPERADD; 2016-001313-24 (EudraCT Number)

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