SUbstition of PERioperative Albumin Deficiency Disorders

Hypoalbuminemia Clinical Trial

— SUPERADD  

Official title:

Does Perioperative Substitution of Albumin Deficiency Reduce Postoperative Complications?

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03167645
• Other study ID #: SUPERADD
• Secondary ID: 2016-001313-24
• Status: Completed
• Phase: Phase 4
• Start date: June 19, 2017
• Est. completion date: April 21, 2021

Study information

• Verified date: April 2021
• Source: Technische Universität München
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

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).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 600
• Est. completion date: April 21, 2021
• Est. primary completion date: December 21, 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Hypoalbuminemia

Intervention

Drug:
• Human albumin
Substitution according to pre-specified dosage

Locations

Country	Name	City	State
Germany	Klinikum rechts der Isar Dept. of Anesthesiology	Munich

Sponsors (1)

Lead Sponsor	Collaborator
Technische Universität München

Country where clinical trial is conducted

Germany, 

References & Publications (2)

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. — View Citation

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. Epub 2007 May 7. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Length of hospital stay		until discharge from hospital, up to 6 month
Secondary	Length of stay in postoperative anaesthesia care unit		until discharge from postoperative anaesthesia care unit, up to 24 hours
Secondary	Length of stay in intensive care unit		until discharge from intensive care unit, up to 1 month
Secondary	Long term mortality (6 month)		6 month
Secondary	Short term mortality (hospital mortality)		until discharge from hospital, up to 6 month
Secondary	Acute kidney injury	Incidence according to AKIN score (at least AKIN 1)	until discharge from hospital, up to 6 month
Secondary	Quality of Recovery 9 Score	Assessed preoperatively and on day 1 and 3 an 6 month after surgery	6 month after surgery
Secondary	Amount of volume infused	Amount of infusion of ringer's acetate and gelafundin	until discharge from postoperative anaesthesia care unit, up to 24 hours
Secondary	Dosage of catecholamines	Intra- and postoperative dosage of catecholamines	until discharge from postoperative anaesthesia care unit, up to 24 hours
Secondary	Number of red packed cells transfused		until discharge from postoperative anaesthesia care unit, up to 24 hours
Secondary	Number of platelet concentrates transfused		until discharge from postoperative anaesthesia care unit, up to 24 hours
Secondary	Amount of coagulation factors infused	Amount of PPSB and fibrinogen	until discharge from postoperative anaesthesia care unit, up to 24 hours
Secondary	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
Secondary	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
Secondary	Therapy with diuretics	New onset or extension of diuretic treatment	until discharge from hospital, up to 6 month
Secondary	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