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

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ClinicalTrials.gov Identifier: NCT03654001
Recruitment Status : Recruiting
First Posted : August 31, 2018
Last Update Posted : December 1, 2020
Sponsor:
Collaborator:
Istituto Di Ricerche Farmacologiche Mario Negri
Information provided by (Responsible Party):
Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico

Tracking Information
First Submitted Date  ICMJE August 3, 2018
First Posted Date  ICMJE August 31, 2018
Last Update Posted Date December 1, 2020
Actual Study Start Date  ICMJE May 7, 2019
Estimated Primary Completion Date December 31, 2020   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: August 29, 2018)
  • All-cause 90-day mortality [ Time Frame: Up to 90 days ]
    All-cause death from randomization to 90 days
  • Combined co-primary endpoint [ Time Frame: Up to 90 days ]
    The composite of all-cause death from randomization to 90 days and new occurrence of acute kidney injury (AKI).
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: August 29, 2018)
  • ICU mortality [ Time Frame: Up to ICU discharge, a median of 9 days ]
    All-cause death occurring in Intensive Care Unit (ICU)
  • In-hospital mortality [ Time Frame: Up to hospital discharge, a median of 20 days ]
    All-cause death occurring during hospital stay
  • 1-year mortality [ Time Frame: Up to 1 year ]
    All-cause death from randomization to 1 year
  • SOFA score [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: Up to ICU discharge, a median of 9 days ]
    Duration expressed as number of days spent in ICU
  • Duration of stay in hospital [ Time Frame: Up to hospital discharge, a median of 20 days ]
    Duration expressed as number of days spent in hospital
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures
 (submitted: August 29, 2018)
  • Severe metabolic acidosis [ Time Frame: Up to 90 days or ICU discharge - a median of 9 days - whichever comes first ]
    Incidence of severe metabolic acidosis
  • Severe hyperkalemia [ Time Frame: Up to 90 days or ICU discharge - a median of 9 days - whichever comes first ]
    Incidence of severe hyperkalemia
Original Other Pre-specified Outcome Measures Same as current
 
Descriptive Information
Brief Title  ICMJE ALBumin Italian Outcome Septic Shock-BALANCED Trial (ALBIOSS-BALANCED)
Official Title  ICMJE 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
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).

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Factorial Assignment
Intervention Model Description:
2-by-2 factorial design, open-label, multicenter, randomized, controlled trial, 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 groups (Albumin + BAL, Albumin + NS, BAL, NS).
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Septic Shock
Intervention  ICMJE
  • 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).
    Other Name: Ringer Lactate, Ringer Acetate, Crystalsol
Study Arms  ICMJE
  • Experimental: Albumin + 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
    Interventions:
    • Biological: Albumin
    • Other: Balanced
  • Experimental: Albumin + Saline

    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).

    Intervention: Biological: Albumin
  • Experimental: Balanced
    Balanced crystalloid solutions (Ringer Lactate, Ringer Acetate, Crystalsol)
    Intervention: Other: Balanced
  • No Intervention: Saline
    Normal Saline Na+ 154 mEq/L, Cl- 154 mEq/L (0.9% NaCl).
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: August 29, 2018)
1252
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE February 28, 2022
Estimated Primary Completion Date December 31, 2020   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 100 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Antonio Pesenti, MD +390255033231 antonio.pesenti@unimi.it
Contact: Pietro Caironi, MD +393316171966 pietro.caironi@unito.it
Listed Location Countries  ICMJE Italy
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03654001
Other Study ID Numbers  ICMJE RF-2016-02361583
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico
Study Sponsor  ICMJE Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico
Collaborators  ICMJE Istituto Di Ricerche Farmacologiche Mario Negri
Investigators  ICMJE
Principal Investigator: Pietro Caironi, MD AOU S. Luigi Gonzaga, Orbassano
PRS Account Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico
Verification Date December 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP