ALBumin Italian Outcome Septic Shock-BALANCED Trial (ALBIOSS-BALANCED)
- Registration Number
- NCT03654001
- Brief 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.
- Detailed 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 & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 1319
Patients with septic shock if they meet the two following criteria:
-
Presence of an infection (known or suspected) in at least one site:
- Lung
- Abdomen
- Urinary tract
- Others (blood, skin and soft tissues, central nervous system, bones and joints, cardiac system, reproductive organs).
-
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.
- Age < 18 years
- Moribund state
- Known or suspected adverse reaction to albumin administration
- Septic shock in patients with traumatic brain injury or a clinically active cerebral lesion (known or suspected)
- Severe congestive heart failure (NYHA III and IV classes)
- 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)
- More than 24 hours after the onset of septic shock
- Religious objection to the administration of human blood products
- Presence of chronic end-stage renal disease
- Severe hyperkalemia (> 6 mmol/L)
- Known or suspected pregnancy based on patient information
- Enrollment in other experimental interventional studies
- Laboratory confirmation for SARS-CoV-2 infection
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- FACTORIAL
- Arm && Interventions
Group Intervention Description Balanced Balanced Balanced crystalloid solutions (Ringer Lactate, Ringer Acetate, Crystalsol) Albumin + Balanced 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. Balanced crystalloid solutions According to the preference and the standard use of the participating center: * Ringer Lactate * Ringer Acetate * Crystalsol Albumin + Balanced Balanced 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. Balanced crystalloid solutions According to the preference and the standard use of the participating center: * Ringer Lactate * Ringer Acetate * Crystalsol Albumin + Saline 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. Normal Saline Na+ 154 mEq/L, Cl- 154 mEq/L (0.9% NaCl).
- Primary Outcome Measures
Name Time Method All-cause 90-day mortality Up to 90 days All-cause death from randomization to 90 days
Combined co-primary endpoint Up to 90 days The composite of all-cause death from randomization to 90 days and new occurrence of acute kidney injury (AKI).
- Secondary Outcome Measures
Name Time Method ICU mortality Up to ICU discharge, a median of 9 days All-cause death occurring in Intensive Care Unit (ICU)
In-hospital mortality Up to hospital discharge, a median of 20 days All-cause death occurring during hospital stay
1-year mortality Up to 1 year All-cause death from randomization to 1 year
SOFA score Up to 90 days or ICU discharge - a median of 9 days - whichever comes first 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.
Incidence of AKI during ICU stay Up to 90 days or ICU discharge - a median of 9 days - whichever comes first 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.
RRT Up to 90 days or ICU discharge - a median of 9 days - whichever comes first First use of Renal Replacement Therapy (RRT) during ICU stay
Need for vasopressors Up to 90 days or ICU discharge - a median of 9 days - whichever comes first Duration of the need for vasopressors during ICU stay
Mechanical ventilation Up to 90 days or ICU discharge - a median of 9 days - whichever comes first Duration of mechanical ventilation during ICU stay
Secondary infections in ICU Up to 90 days or ICU discharge - a median of 9 days - whichever comes first Incidence of secondary-acquired infections during ICU stay
Duration of stay in ICU Up to ICU discharge, a median of 9 days Duration expressed as number of days spent in ICU
Duration of stay in hospital Up to hospital discharge, a median of 20 days Duration expressed as number of days spent in hospital
1-year functional and physical disability Up to 1 year Evaluation by specific psyco-functional tests
Trial Locations
- Locations (37)
Ospedali Riuniti di Ancona
🇮🇹Ancona, AN, Italy
AOU Policlinico di Bari
🇮🇹Bari, BA, Italy
ASST Papa Giovanni XXIII
🇮🇹Bergamo, BG, Italy
ASST Grande Ospedale Metropolitano Niguarda
🇮🇹Milano, MI, Italy
ASST BG Est - Ospedale Bolognini
🇮🇹Seriate, BG, Italy
AST BG Ovest - PO Treviglio
🇮🇹Treviglio, BG, Italy
Policlinico Sant'Orsola-Malpighi
🇮🇹Bologna, BO, Italy
Azienda Ospedaliero - Universitaria di Ferrara - Arcispedale Sant'Anna
🇮🇹Cona, FE, Italy
Ospedale del Mugello
🇮🇹Borgo San Lorenzo, FI, Italy
Ospedale San Giuseppe
🇮🇹Empoli, FI, Italy
IRCCS Policlinico San Donato
🇮🇹San Donato Milanese, MI, Italy
AOU Careggi
🇮🇹Firenze, FI, Italy
Ospedale Colline dell'Albegna
🇮🇹Orbetello, GR, Italy
Presidio Ospedaliero di Desio
🇮🇹Desio, MB, Italy
Fondazione IRCCS San Gerardo dei Tintori
🇮🇹Monza, MB, Italy
Azienda Ospedaliero-Universitaria di Modena, Policlinico di Modena
🇮🇹Modena, MO, Italy
ASST Nord Milano - Ospedale Bassini
🇮🇹Cinisello Balsamo, MI, Italy
ASST Ovest Milano
🇮🇹Legnano, MI, Italy
Fondazione IRCCS Ca' Granda - Ospedale Maggiore Policlinico
🇮🇹Milano, MI, Italy
ASST Fatebenefratelli - Sacco P.O. Sacco
🇮🇹Milano, MI, Italy
AOU Policlinico Paolo Giaccone
🇮🇹Palermo, PA, Italy
ISMETT
🇮🇹Palermo, PA, Italy
AOU Pisana
🇮🇹Pisa, PI, Italy
As FO Azienda sanitaria Friuli Occidentale
🇮🇹Pordenone, PN, Italy
Fondazione IRCCS Policlinico San Matteo
🇮🇹Pavia, PV, Italy
IRCCS ASMN Reggio Emilia
🇮🇹Reggio Emilia, RE, Italy
Fondazione Policlinico Universitario A. Gemelli, Università Cattolica del Sacro Cuore
🇮🇹Roma, RM, Italy
Ospedale Santa Chiara
🇮🇹Trento, TN, Italy
Ospedale Santa Croce
🇮🇹Moncalieri, TO, Italy
Azienda Ospedaliero - Universitaria S. Luigi Gonzaga
🇮🇹Orbassano, TO, Italy
AOU Città della Salute e della Scienza di Torino
🇮🇹Torino, TO, 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, Italy
Ospedale SS. Antonio e Biagio e Cesare Arrigo
🇮🇹Alessandria, Italy
Ospedale Infermi di Rimini
🇮🇹Rimini, Italy