Clinical Trial Results:
Influence of albumin on the development of acute renal dysfunction associated with cardiac surgery under extracorporeal circulation
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Summary
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EudraCT number |
2017-003027-30 |
Trial protocol |
ES |
Global end of trial date |
20 Dec 2019
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Results information
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Results version number |
v1(current) |
This version publication date |
06 Jun 2022
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First version publication date |
06 Jun 2022
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Other versions |
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Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
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Trial identification
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Sponsor protocol code |
IIBSP-ALB-2017-72
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
- | ||
WHO universal trial number (UTN) |
- | ||
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Sponsors
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Sponsor organisation name |
Institut de Recerca Hospital de la Santa Creu i Sant Pau
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Sponsor organisation address |
Carrer de Sant Quintí, 77, Barcelona, Spain, 08041
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Public contact |
UICEC Sant Pau, Institut de Recerca Hospital de la Santa Creu i Sant Pau, 34 935537636, uicec@santpau.cat
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Scientific contact |
UICEC Sant Pau, Institut de Recerca Hospital de la Santa Creu i Sant Pau, 34 935537636, uicec@santpau.cat
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Paediatric regulatory details
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Is trial part of an agreed paediatric investigation plan (PIP) |
No
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Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Results analysis stage
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Analysis stage |
Final
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Date of interim/final analysis |
29 Jun 2020
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Is this the analysis of the primary completion data? |
Yes
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Primary completion date |
20 Dec 2019
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Global end of trial reached? |
Yes
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Global end of trial date |
20 Dec 2019
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Was the trial ended prematurely? |
No
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General information about the trial
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Main objective of the trial |
To analyze the effect of the use of human albumin during ECC on the incidence of ARD-ACC in patients undergoing cardiac surgery with CPB diagnosed according to the KDIGO scale during the first 7 days after the intervention.
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Protection of trial subjects |
The study will be conducted in strict accordance with international ethical recommendations for research and clinical trials in humans. Likewise, the standards contained in the Declaration of Helsinki will be guaranteed and will be developed in accordance with the protocol and with the standard work procedures (SOPs) that ensure compliance with the standards of Good Clinical Practice (PCB).
The investigator should explain to the patient (when possible) or his authorized legal representative, the nature of the study, its purposes, procedures, estimated duration, the potential risks and benefits related to the participation in the study, as well as any inconvenience that this may cause. can suppose. Each of the participants should be warned that their participation in the study is voluntary and that they can leave the study at any time, without this affecting their subsequent treatment or their relationship with the professionals who treat them.
For this, an information / consent sheet has been designed for the patient or the authorized legal representative, which is attached.
Human albumin is currently used routinely in certain centers for priming the CEC circuit during cardiac surgery, its beneficial effect has been demonstrated in many respects, but its effect on renal function during the immediate postoperative period has not been evaluated. . The use of albumin in this context has shown benefits in terms of reducing postoperative bleeding, less need for fluid therapy, improved plasma oncotic pressure, as well as decreased formation of microthrombi, improved perfusion during circulation extracorporeal, decreased levels of nephrotoxic free radicals released during extracorporeal circulation and other effects that may be protective factors of kidney function during the period of extracorporeal circulation.
Monitoring, audits, CEIC reviews and regulatory inspections related to the test will be allowed, facilitating direct access to the original documents / data.
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Background therapy |
Albumin in cardiac surgery Albumin is a 66 kD protein synthesized in the liver, which is responsible for 75 to 80% of plasma oncotic pressure, with a half-life of around 20 days [19], being of high importance for proper function of the vascular barrier and the integrity of the glycocalix, bases of vascular permeability and homeostasis of the intracellular and interstitial spaces, in which albumin is a fundamental regulator of the passage of liquids between compartments according to the current model. As a drug it is obtained from human plasma and is used in solution at different concentrations for clinical use, being widely used in medicine and in the environment of the patient undergoing cardiac surgery as fluid therapy for its plasma-expanding properties with maintenance of oncotic pressure , antioxidant effect and as a transporter of molecules such as hormones, iron, bilirubin, free fatty acids, drugs and other elements, having a wide spectrum of indications. Unlike other colloids such as hydroxyethyl starch, its use has been associated with few negative effects. Its use for priming the circuit of extracorporeal circulation during cardiac surgery has been commonly used, first of all for the ability to form a layer on the surface of the circuit, protecting blood from direct contact with its surface. It can cause protein denaturation, activation of the complement cascade, release of inflammatory mediators, and platelet activation. Secondly, the use of albumin in circuit priming can attenuate the drop in oncotic pressure due to a dilutional effect during the ECC period, an effect that can cause edema in the different organs with consequent dysfunction. In a meta-analysis of the use of albumin in the priming of the CEC carried out in 2004, it was concluded that the priming with albumin preserved the platelet count better than the priming of the CEC with crystalloids, conserved the oncotic pressure better, favorably influenced fluid balance (less fluid requirement | ||
Evidence for comparator |
Given the growing evidence that the use of albumin can decrease the incidence of acute kidney injury in patients with hypoalbuminemia who underwent cardiac surgery without ECC, that the majority of patients present hypoalbuminemia after ECC, together with the fact that the high incidence of ARD during the immediate postoperative period and to the widely studied properties of albumin, our interest is to investigate the use of albumin for patients undergoing cardiac surgery with ECC, using it for purging the circuit, since this period supposes, as described above, a kidney injury perfectly delimited in time and clearly associated with a significant incidence of acute kidney injury, due to injury mechanisms that could be partially cushioned by the use of albumin, as a consequence of its properties. This study aims to obtain information about the effect that albumin can have in this population of patients with a high incidence of acute kidney dysfunction, and if this benefit exists, to know whether or not it is significant to justify its systematic use. Among the reasons that make this project potentially relevant from a scientific point of view, there is mainly the paucity of studies of this type that may allow establishing the recommendation for the use of albumin to reduce the incidence of ACC-DRA. Therefore, a great scientific impact of the results is expected. From the health point of view, the results can have a high socio-economic impact, since the costs associated with the management of ARD are high, so an improvement in the cost-effectiveness ratio through the use of albumin can produce significant savings in the SNS. We consider that this project will constitute a tool that will provide quality evidence, and its results could not only be the reason for publication in scientific journals, but also be included in clinical practice guidelines as a recommendation that allows optimizing the prognosis of patients who require undergoing cardiac surgery with ECC. | ||
Actual start date of recruitment |
02 Nov 2017
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Long term follow-up planned |
Yes
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Long term follow-up rationale |
Safety | ||
Long term follow-up duration |
1 Years | ||
Independent data monitoring committee (IDMC) involvement? |
No
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Population of trial subjects
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Number of subjects enrolled per country |
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Country: Number of subjects enrolled |
Spain: 248
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Worldwide total number of subjects |
248
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EEA total number of subjects |
248
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Number of subjects enrolled per age group |
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In utero |
0
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Preterm newborn - gestational age < 37 wk |
0
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Newborns (0-27 days) |
0
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Infants and toddlers (28 days-23 months) |
0
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Children (2-11 years) |
0
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Adolescents (12-17 years) |
0
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Adults (18-64 years) |
91
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From 65 to 84 years |
152
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85 years and over |
5
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Recruitment
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Recruitment details |
The population consists of patients who underwent cardiac surgery scheduled under ECC. Recruitment will take place at the pre-anesthetic visit. | |||||||||
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Pre-assignment
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Screening details |
Inclusion criteria: Adult patients (> 18 years) scheduled for cardiac surgery by ECC, who present GFR greater than or equal to 60 and left ventricular ejection fraction greater than or equal to 40%. Exclu | |||||||||
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Period 1
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Period 1 title |
Intervention (overall period)
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Is this the baseline period? |
Yes | |||||||||
Allocation method |
Randomised - controlled
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Blinding used |
Double blind | |||||||||
Roles blinded |
Subject, Investigator, Monitor, Data analyst, Assessor | |||||||||
Blinding implementation details |
Blinding will not be necessary since the primed preparation of the CEC circuit will be performed by the infusion nursing team, and the solution with the experimental drug (albumin) looks the same as the solution without it.
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Arms
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Are arms mutually exclusive |
Yes
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Arm title
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Plasmalyte | |||||||||
Arm description |
Control treatment: Plasmalyte serum used for priming the extracorporeal circulation circuit. | |||||||||
Arm type |
Active comparator | |||||||||
Investigational medicinal product name |
Plasmalyte
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Investigational medicinal product code |
B05BB01
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Other name |
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Pharmaceutical forms |
Concentrate for solution for infusion
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Routes of administration |
Extracorporeal use
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Dosage and administration details |
used during purged of CEC
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Arm title
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Albumin | |||||||||
Arm description |
Experimental treatment : Human Albumin for the priming of the CEC circuit , added to the usual solution (plasma serum ) in sufficient quantity to achieve a concentration of 4% of the total priming volume versus usual priming with serum . plasmalyte . Human albumin is already currently used for priming the CEC on certain occasions and in hospital centers. | |||||||||
Arm type |
Active comparator | |||||||||
Investigational medicinal product name |
Albumin
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Investigational medicinal product code |
B05A1
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Other name |
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Pharmaceutical forms |
Concentrate for solution for infusion
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Routes of administration |
Extracorporeal use
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Dosage and administration details |
Albumin 4% used during purged of CEC
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Baseline characteristics reporting groups
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Reporting group title |
Plasmalyte
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Reporting group description |
Control treatment: Plasmalyte serum used for priming the extracorporeal circulation circuit. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Albumin
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Reporting group description |
Experimental treatment : Human Albumin for the priming of the CEC circuit , added to the usual solution (plasma serum ) in sufficient quantity to achieve a concentration of 4% of the total priming volume versus usual priming with serum . plasmalyte . Human albumin is already currently used for priming the CEC on certain occasions and in hospital centers. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
Plasmalyte
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Reporting group description |
Control treatment: Plasmalyte serum used for priming the extracorporeal circulation circuit. | ||
Reporting group title |
Albumin
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Reporting group description |
Experimental treatment : Human Albumin for the priming of the CEC circuit , added to the usual solution (plasma serum ) in sufficient quantity to achieve a concentration of 4% of the total priming volume versus usual priming with serum . plasmalyte . Human albumin is already currently used for priming the CEC on certain occasions and in hospital centers. | ||
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End point title |
AKI | |||||||||||||||
End point description |
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End point type |
Primary
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End point timeframe |
5 days
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Statistical analysis title |
Comparation | |||||||||||||||
Comparison groups |
Plasmalyte v Albumin
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Number of subjects included in analysis |
248
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Analysis specification |
Pre-specified
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Analysis type |
equivalence | |||||||||||||||
P-value |
≥ 0.05 | |||||||||||||||
Method |
Chi-squared | |||||||||||||||
Parameter type |
Odds ratio (OR) | |||||||||||||||
Confidence interval |
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Variability estimate |
Standard deviation
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Adverse events information
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Timeframe for reporting adverse events |
1 year
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Adverse event reporting additional description |
All adverse events that occur will be collected and their causal relationship with the treatment received, severity and condition of unexpected will be evaluated.
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Assessment type |
Systematic | |||||||||||||||||||||||||||||||||||||||||||||
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Dictionary used for adverse event reporting
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Dictionary name |
MedDRA | |||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
23.0
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Reporting groups
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Reporting group title |
Plasmalyte
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Reporting group description |
Barcelona is not routinely applied to purge the CEC, it is carried out with crystalloid solution (plasmalyte serum), using albumin in CEC in certain exceptional circumstances (severe hypoproteinemia associated with anasarca, etc.) Control treatment: Plasmalyte serum used for priming the extracorporeal circulation circuit. | |||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Albumin
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Reporting group description |
Experimental treatment : Human Albumin for the priming of the CEC circuit , added to the usual solution (plasma serum ) in sufficient quantity to achieve a concentration of 4% of the total priming volume versus usual priming with serum . plasmalyte . Human albumin is already currently used for priming the CEC on certain occasions and in hospital centers. | |||||||||||||||||||||||||||||||||||||||||||||
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| Frequency threshold for reporting non-serious adverse events: 5% | ||||||||||||||||||||||||||||||||||||||||||||||
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Substantial protocol amendments (globally) |
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| Were there any global substantial amendments to the protocol? No | |||
Interruptions (globally) |
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| Were there any global interruptions to the trial? No | |||
Limitations and caveats |
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| Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data. | |||
| None reported | |||
