ALBumin Italian Outcome Septic Shock-BALANCED Trial (ALBIOSS-BALANCED)

Septic Shock Clinical Trial

— ALBIOSS-BAL  

Official title:

Efficacy of Albumin Replacement and Balanced Solution in Patients With Septic Shock (the ALBIOSS-BALANCED Trial): a 2-by-2 Factorial, Investigator-initiated, Open- Label, Multicenter, Randomized, Controlled Trial

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03654001
• Other study ID #: RF-2016-02361583
• Status: Recruiting
• Phase: Phase 3
• Start date: May 7, 2019
• Est. completion date: February 28, 2022

Study information

• Verified date: April 2021
• Source: Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico
• Contact: Antonio Pesenti, MD
• Phone: +390255033231
• Email: antonio.pesenti[@]unimi.it
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Septic shock is a devastating condition often observed in ICU. It is characterized by pro-inflammatory and immune responses, organ failures, high incidence of AKI and lethality. Fluid resuscitation is pivotal as supportive therapy. At present, there are no effective therapies to improve survival of such clinical condition, often characterized by a mortality as high as 40% during the first 90 days from diagnosis.

This project proposes a large 2-by-2 factorial randomized clinical trial testing the efficacy of albumin and the low- chloride balanced crystalloid solutions (either Ringer Lactate, Ringer Acetate, or Crystalsol - BAL) in septic shock.

The investigators have recently concluded a multicenter, randomized trial, the ALBIOS trial, in which, in a post-hoc analysis, albumin, in addition to crystalloids, reduced 90-day mortality in patients with septic shock, as compared to crystalloids alone (Caironi P et al, 2014). Crystalloids with supra-physiological chloride content may deteriorate renal perfusion, increasing the risk of acute kidney injury (AKI) and mortality.

Description:

The project will consist of a 2-by-2 factorial, investigator-initiated, open-label, multicenter, randomized, controlled trial, with PROBE design (Prospective Randomized Open Trial with Blinded Evaluation of Outcomes), in patients with septic shock, as defined according to clinical criteria.

Patients will be randomized in a 1:1:1:1 ratio to one of the 4 study groups (Albumin + BAL, Albumin + NS, BAL, NS).

Both the primary endpoints will include events evaluated objectively: 90-day mortality and incidence of AKI, as assessed by KDIGO criteria (KDIGO Acute Kidney Injury Work Group, 2012).

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 1252
• Est. completion date: February 28, 2022
• Est. primary completion date: December 31, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 100 Years

Eligibility

Inclusion Criteria:

Patients with septic shock if they meet the two following criteria:

1. Presence of an infection (known or suspected) in at least one site:

1. Lung

2. Abdomen

3. Urinary tract

4. Others (blood, skin and soft tissues, central nervous system, bones and joints, cardiac system, reproductive organs).

2. Presence of a severe and acute, sepsis-related cardiovascular failure (as assessed by the SOFA score - see Annex 1), requiring vasopressor to maintain mean arterial pressure >=65 mmHg, despite adequate volume resuscitation a) Cardiovascular SOFA score > 2 (3 or 4) If the patient is unable to provide informed consent, she/he can be included in the trial provided that the requirements of ongoing laws are fulfilled; details on this approach are provided in the protocol, par 11.1 and related Annex 3. The patient will be informed about having been included in a clinical trial, as soon as she/he will regain consciousness.

Exclusion Criteria:

1. Age < 18 years

2. Moribund state

3. Known or suspected adverse reaction to albumin administration

4. Septic shock in patients with traumatic brain injury or a clinically active cerebral lesion (known or suspected)

5. Severe congestive heart failure (NYHA III and IV classes)

6. Clinical situations in which the use of albumin is known or supposed to be clinically beneficial (hepatic cirrhosis with ascites, malabsorption syndrome or protein-losing enteropathy, nephrotic syndrome, burns)

7. More than 24 hours after the onset of septic shock

8. Religious objection to the administration of human blood products

9. Presence of chronic end-stage renal disease

10. Severe hyperkalemia

11. Enrollment in other experimental interventional studies

Related Conditions & MeSH terms

• Septic Shock
• Shock
• Shock, Septic

Intervention

Biological:
• Albumin
Human Albumin In parallel with fluid administration for volume resuscitation, patients will receive 400 ml of 20% albumin solution both at randomization (D0) and at day 1 (D1). Subsequently, from day 2 (D2) until day 90 (D90) or ICU discharge (whichever comes first), 20% albumin will be administered on a daily basis, to maintain serum albumin concentration equal to or greater than 30 g/L, based upon serum albumin determination.

Other:
• Balanced
Balanced crystalloid solutions are traditionally crystalloid solutions containing a relatively low concentration of chloride as compared to 0.9% NaCl containing solutions (Normal Saline).

Locations

Country	Name	City	State
Italy	Ospedale SS. Antonio e Biagio e Cesare Arrigo	Alessandria
Italy	Ospedali Riuniti di Ancona	Ancona	AN
Italy	Ospedale Regionale Umberto Parini	Aosta	AO
Italy	AOU Policlinico di Bari	Bari	BA
Italy	ASST Papa Giovanni XXIII	Bergamo	BG
Italy	Policlinico Sant'Orsola-Malpighi	Bologna	BO
Italy	Ospedale del Mugello	Borgo San Lorenzo	FI
Italy	AOU Mater Domini Catanzaro	Catanzaro	CZ
Italy	ASST Nord Milano - Ospedale Bassini	Cinisello Balsamo	MI
Italy	Azienda Ospedaliero - Universitaria di Ferrara - Arcispedale Sant'Anna	Cona	FE
Italy	Presidio Ospedaliero di Desio	Desio	MB
Italy	Ospedale San Giuseppe	Empoli	FI
Italy	AOU Careggi	Firenze	FI
Italy	Ospedali Riuniti di Foggia	Foggia	FG
Italy	Ente Ospedaliero Ospedali Galliera	Genova	GE
Italy	Ospedale Policlinico San Martino	Genova	GE
Italy	Ospedale Vito Fazzi	Lecce	LE
Italy	ASST Lecco AO Manzoni	Lecco	LC
Italy	ASST Ovest Milano	Legnano	MI
Italy	ASST Fatebenefratelli - Sacco P.O. Sacco	Milano	MI
Italy	ASST Grande Ospedale Metropolitano Niguarda	Milano	MI
Italy	ASST Santi Paolo e Carlo, Ospedale San Paolo	Milano	MI
Italy	Fondazione IRCCS Ca' Granda - Ospedale Maggiore Policlinico	Milano	MI
Italy	Ospedale San Carlo Borromeo	Milano
Italy	Azienda Ospedaliero-Universitaria di Modena, Policlinico di Modena	Modena	MO
Italy	Ospedale Santa Croce	Moncalieri	TO
Italy	Azienda Ospedaliera S. Gerardo	Monza	MB
Italy	Azienda Ospedaliero - Universitaria S. Luigi Gonzaga	Orbassano	TO
Italy	Ospedale Colline dell'Albegna	Orbetello	GR
Italy	AOU Policlinico Paolo Giaccone	Palermo	PA
Italy	ISMETT	Palermo	PA
Italy	Azienda Ospedaliero - Universitaria di Parma	Parma	PR
Italy	Fondazione IRCCS Policlinico San Matteo	Pavia	PV
Italy	AOU Pisana	Pisa	PI
Italy	As FO Azienda sanitaria Friuli Occidentale	Pordenone	PN
Italy	IRCCS ASMN Reggio Emilia	Reggio Emilia	RE
Italy	Azienda Ospedaliero-Universitaria Sant'Andrea	Roma
Italy	Fondazione Policlinico Universitario A. Gemelli, Università Cattolica del Sacro Cuore	Roma	RM
Italy	IRCCS Policlinico San Donato	San Donato Milanese	MI
Italy	Azienda Ospedaliera Universitaria Sassari	Sassari	SS
Italy	ASST BG Est - Ospedale Bolognini	Seriate	BG
Italy	AOU Città della Salute e della Scienza di Torino	Torino	TO
Italy	Ospedale Galmarini Tradate	Tradate	VA
Italy	Ospedale Santa Chiara	Trento	TN
Italy	AST BG Ovest - PO Treviglio	Treviglio	BG
Italy	ASU Giuliano Isontina	Trieste	TS
Italy	Azienda Sanitaria Universitaria Integrata di Udine	Udine	UD
Italy	Ospedale di Circolo e Fondazione Macchi	Varese	VA
Italy	Azienda Ospedaliera Universitaria Integrata di Verona	Verona	VR

Sponsors (2)

Lead Sponsor	Collaborator
Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico	Istituto Di Ricerche Farmacologiche Mario Negri

Country where clinical trial is conducted

Italy, 

References & Publications (5)

Angus DC, van der Poll T. Severe sepsis and septic shock. N Engl J Med. 2013 Aug 29;369(9):840-51. doi: 10.1056/NEJMra1208623. Review. Erratum in: N Engl J Med. 2013 Nov 21;369(21):2069. — View Citation

Caironi P, Tognoni G, Masson S, Fumagalli R, Pesenti A, Romero M, Fanizza C, Caspani L, Faenza S, Grasselli G, Iapichino G, Antonelli M, Parrini V, Fiore G, Latini R, Gattinoni L; ALBIOS Study Investigators. Albumin replacement in patients with severe sep — View Citation

Patel A, Laffan MA, Waheed U, Brett SJ. Randomised trials of human albumin for adults with sepsis: systematic review and meta-analysis with trial sequential analysis of all-cause mortality. BMJ. 2014 Jul 22;349:g4561. doi: 10.1136/bmj.g4561. Review. Errat — View Citation

SAFE Study Investigators, Finfer S, McEvoy S, Bellomo R, McArthur C, Myburgh J, Norton R. Impact of albumin compared to saline on organ function and mortality of patients with severe sepsis. Intensive Care Med. 2011 Jan;37(1):86-96. doi: 10.1007/s00134-01 — View Citation

Semler MW, Self WH, Rice TW. Balanced Crystalloids versus Saline in Critically Ill Adults. N Engl J Med. 2018 May 17;378(20):1951. doi: 10.1056/NEJMc1804294. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Severe metabolic acidosis	Incidence of severe metabolic acidosis	Up to 90 days or ICU discharge - a median of 9 days - whichever comes first
Other	Severe hyperkalemia	Incidence of severe hyperkalemia	Up to 90 days or ICU discharge - a median of 9 days - whichever comes first
Primary	All-cause 90-day mortality	All-cause death from randomization to 90 days	Up to 90 days
Primary	Combined co-primary endpoint	The composite of all-cause death from randomization to 90 days and new occurrence of acute kidney injury (AKI).	Up to 90 days
Secondary	ICU mortality	All-cause death occurring in Intensive Care Unit (ICU)	Up to ICU discharge, a median of 9 days
Secondary	In-hospital mortality	All-cause death occurring during hospital stay	Up to hospital discharge, a median of 20 days
Secondary	1-year mortality	All-cause death from randomization to 1 year	Up to 1 year
Secondary	SOFA score	Severity and incidence of organ failures, as assessed by the Sequential Organ Failure Assessment (SOFA) score. SOFA score is used to determine the extent of organ function in a patient while in the intensive care unit. The score is based on 6 different scores, one each for the respiratory, cardiovascular, hepatic, coagulation, renal and neurological systems. The scale of each score ranges from 0 (no dysfunction) to 4 (maximal dysfunction). The 6 scores are then added up to provide a global score: the highest the value, the worst the condition of the patient.	Up to 90 days or ICU discharge - a median of 9 days - whichever comes first
Secondary	Incidence of AKI	Assessed by the Kidney Disease Improving Global Outcome (KDIGO) criteria as any of the following: (1) increase in serum creatinine >=0.3 mg/dl (26.5 mmol/l) within 48 hours; or (2) increase in SCr to >=1.5 times baseline, which is known or presumed to have occurred within the prior 7 days; or (3) urine volume <0.5 ml/kg/h for 6 hours.	Up to 90 days or ICU discharge - a median of 9 days - whichever comes first
Secondary	RRT	First use of Renal Replacement Therapy (RRT) during ICU stay	Up to 90 days or ICU discharge - a median of 9 days - whichever comes first
Secondary	Need for vasopressors	Duration of the need for vasopressors during ICU stay	Up to 90 days or ICU discharge - a median of 9 days - whichever comes first
Secondary	Mechanical ventilation	Duration of mechanical ventilation during ICU stay	Up to 90 days or ICU discharge - a median of 9 days - whichever comes first
Secondary	Secondary infections in ICU	Incidence of secondary-acquired infections during ICU stay	Up to 90 days or ICU discharge - a median of 9 days - whichever comes first
Secondary	Duration of stay in ICU	Duration expressed as number of days spent in ICU	Up to ICU discharge, a median of 9 days
Secondary	Duration of stay in hospital	Duration expressed as number of days spent in hospital	Up to hospital discharge, a median of 20 days