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Plasma-Lyte 148® versUs Saline Study (PLUS)

Primary Purpose

Hypovolemia

Status
Completed
Phase
Phase 4
Locations
International
Study Type
Interventional
Intervention
Plasma-Lyte 148®
0.9% sodium chloride
Sponsored by
The George Institute
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Hypovolemia focused on measuring Plasma-Lyte, Sodium chloride, Saline, Fluid resuscitation, Intravenous fluid therapy, Critically ill, Critical care

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • The patient will receive fluid resuscitation defined as a bolus of fluid, prescribed to be administered over one hour or less to increase or maintain intravascular volume that is in addition to maintenance fluids, or specific fluids used to replace non-physiological fluid losses
  • The patient is expected to be in the ICU the day after tomorrow
  • The patient is not expected to be well enough to be eating tomorrow
  • An arterial or central venous catheter is in situ, or placement is imminent as part of routine management
  • Both Plasma-Lyte 148® and 0.9% saline are considered equally appropriate for the patient
  • The requirement for fluid resuscitation is supported by at least one of seven pre-specified clinical signs: heart rate > 90 beats per minute; systolic blood pressure < 100 mmHg or mean arterial pressure < 75 mmHg; central venous pressure < 10 mmHg; pulmonary artery wedge pressure < 12 mmHg; capillary refill time > 1 second; OR urine output < 0.5 ml/kg for at least one hour

Exclusion Criteria:

  • Age less than 18 years
  • Patients who have received more than 500mls of fluid resuscitation (as defined above) prescribed in the ICU during this current ICU admission
  • Patients transferred directly from another ICU who have received more than 500mls of fluid resuscitation (as defined above) during that ICU admission
  • Contraindication to either study fluid e.g. previous allergic reaction to Plasma-Lyte 148®
  • Patients admitted to the ICU with specific fluid requirements: the treatment of burns; following liver transplantation surgery; for correction of specific electrolyte abnormalities
  • Patients with traumatic brain injury or those considered at risk of developing cerebral oedema
  • Patients in whom death is deemed imminent and inevitable
  • Patients with an underlying disease process with a life expectancy of <90 days
  • Patients in whom it is unlikely the primary outcome can be ascertained
  • Patients who have previously been enrolled in PLUS
  • Known or suspected pregnancy

Sites / Locations

  • Blacktown Hospital
  • Royal Prince Alfred Hospital
  • The Sutherland Hospital
  • Concord Repatriation General Hospital
  • Gosford Hospital
  • Hornsby Ku-ring-gai Hospital
  • St George Hospital
  • Liverpool Hospital
  • Nepean
  • Royal North Shore Hospital
  • Wagga Wagga Rural Referral Hospital
  • The Sydney Adventist Hospital
  • Calvary Mater Newcastle
  • Westmead Hospital
  • Wollongong Hospital
  • The Wesley Hospital
  • Royal Brisbane and Women's Hospital
  • Redcliffe Hospital
  • Robina Hospital
  • Mater Misericordiae
  • Gold Coast University Hospital
  • Toowoomba Hospital
  • Princess Alexandra Hospital
  • Royal Adelaide Hospital
  • Royal Hobart Hospital
  • Launceston General Hospital
  • Ballarat Health Services
  • Bendigo Hospital
  • Box Hill Hospital
  • Monash Medical Centre
  • Dandenong Hospital
  • Footscray Hospital, Western Health
  • Frankston Hospital
  • Austin Hospital
  • Royal Melbourne Hospital
  • Maroondah Hospital
  • Sunshine Hospital, Western Health
  • St John of God Murdoch Hospital
  • Fiona Stanley Hospital
  • North Shore Hospital
  • Rotorua Hospital
  • Hawkes Bay
  • Christchurch Hospital
  • Hutt Hospital
  • Wellington Hospital
  • Auckland City Hospital (CVICU)
  • Auckland City Hospital (DCCM)
  • Middlemore Hospital
  • Waikato Hospital
  • Nelson Hospital
  • Tauranga Hospital

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Active Comparator

Arm Label

Plasma-Lyte 148®

0.9% sodium chloride

Arm Description

Following randomisation, each study participant will receive either Plasma-Lyte 148® or 0.9% saline alone for all resuscitation episodes and for all compatible intravenous crystalloid therapy while in ICU (for up to 90 days).

Following randomisation, each study participant will receive either Plasma-Lyte 148® or 0.9% saline alone for all resuscitation episodes and for all compatible intravenous crystalloid therapy while in ICU (for up to 90 days).

Outcomes

Primary Outcome Measures

Death from all causes

Secondary Outcome Measures

Mean and peak serum creatinine concentration
ICU, hospital and 28 day all-cause mortality
Duration of ICU stay
Duration of Hospital stay
Proportion of patients newly treated with renal replacement therapy
Duration of mechanical ventilation in ICU
Proportion of patients treated with and duration of treatment with vasoactive drugs
Quality of life assessment using the EQ-5D-5L questionnaire
Maximum post-randomisation increase in serum creatinine in ICU during the index hospital admission.
Healthcare services usage during the six months after randomisation by healthcare record linkage using state and national data linkage units

Full Information

First Posted
March 15, 2016
Last Updated
August 6, 2023
Sponsor
The George Institute
Collaborators
Australian and New Zealand Intensive Care Society Clinical Trials Group, Baxter Healthcare Corporation
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1. Study Identification

Unique Protocol Identification Number
NCT02721654
Brief Title
Plasma-Lyte 148® versUs Saline Study
Acronym
PLUS
Official Title
Comparison of Plasmalyte 148® and Saline for Fluid Resuscitation and Intravenous Fluid Therapy in Critically Ill Adults
Study Type
Interventional

2. Study Status

Record Verification Date
August 2023
Overall Recruitment Status
Completed
Study Start Date
September 1, 2017 (Actual)
Primary Completion Date
March 30, 2021 (Actual)
Study Completion Date
June 30, 2021 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
The George Institute
Collaborators
Australian and New Zealand Intensive Care Society Clinical Trials Group, Baxter Healthcare Corporation

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

Brief Summary
The aim of PLUS is to conduct a multi-centre, blinded, randomised, controlled trial (RCT) to determine whether fluid resuscitation and therapy with a "balanced" crystalloid solution (Plasma-Lyte 148®) decreases 90-day mortality in critically ill patients requiring fluid resuscitation when compared with the same treatment using 0.9% sodium chloride (saline)
Detailed Description
Fluid resuscitation is a fundamental component of the management of acutely and critically ill patients and the choice of fluid is a longstanding issue of debate. Worldwide, 0.9% saline has traditionally been the most widely used resuscitation fluid, however its use is increasingly challenged by emerging evidence that suggests its high chloride content may have clinically important adverse effects and that resuscitation with so-called "balanced" or "buffered" crystalloids (such as Plasma-Lyte 148®) offer patients better outcomes. Given the limitations of current evidence, there is now a scientific, ethical and health economic imperative to provide an accurate and reliable estimate of the comparative risks versus benefit of Plasma-Lyte 148® versus 0.9% saline. The PLUS study is a prospective, multi-centre, parallel group, concealed, blinded, randomised, controlled trial. The study will test the hypothesis that in a heterogeneous population of critically ill adults, random assignment to Plasma-Lyte 148® for intravascular volume resuscitation and crystalloid fluid therapy in the Intensive Care Unit (ICU) results in different 90-day all-cause mortality when compared with random assignment to 0.9% sodium chloride (saline) for the same treatment. Each patient who meets all inclusion criteria and no exclusion criteria will be randomised to receive either Plasma-Lyte 148® or 0.9% saline for all resuscitation episodes and for all compatible crystalloid therapy while in ICU for up to 90 days after randomisation. Other crystalloid fluids may be used as carrier fluids for the infusion of any drug for which either Plasma-Lyte 148® or 0.9% saline is considered incompatible.The study treatments will be supplied in identical 1000 ml bags and treatment assignment will be concealed. The volume of study fluid being administered will be titrated against clinical endpoints determined by the treating clinicians and reviewed as clinically appropriate during the period of resuscitation and ICU treatment.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Hypovolemia
Keywords
Plasma-Lyte, Sodium chloride, Saline, Fluid resuscitation, Intravenous fluid therapy, Critically ill, Critical care

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 4
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
5037 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Plasma-Lyte 148®
Arm Type
Experimental
Arm Description
Following randomisation, each study participant will receive either Plasma-Lyte 148® or 0.9% saline alone for all resuscitation episodes and for all compatible intravenous crystalloid therapy while in ICU (for up to 90 days).
Arm Title
0.9% sodium chloride
Arm Type
Active Comparator
Arm Description
Following randomisation, each study participant will receive either Plasma-Lyte 148® or 0.9% saline alone for all resuscitation episodes and for all compatible intravenous crystalloid therapy while in ICU (for up to 90 days).
Intervention Type
Drug
Intervention Name(s)
Plasma-Lyte 148®
Other Intervention Name(s)
Balanced crystalloid solution
Intervention Description
Plasma-Lyte 148 (approx pH 7.4) IV infusion is a sterile, clear nonpyrogenic isotonic solution & when administered intravenously it is a source of water, electrolytes & calories. Plasma-Lyte 148 intravenous infusion is indicated as a source of water & electrolytes or as an alkalinising agent.
Intervention Type
Drug
Intervention Name(s)
0.9% sodium chloride
Other Intervention Name(s)
Saline
Intervention Description
The active ingredient is sodium chloride formulated in Water for Injections. The chemical name is sodium chloride with molecular formula NaCl. Sodium Chloride (0.9%) intravenous infusion preparation is a sterile & non-pyrogenic solution & is indicated for extracellular fluid replacement & in the management of metabolic alkalosis in the presence of fluid loss, & for restoring or maintaining the concentration of sodium & chloride ions. As sodium chloride intravenous infusion is administered to the systemic circulation by intravenous infusion, the bioavailability (absorption) of the active components is complete (100 per cent).
Primary Outcome Measure Information:
Title
Death from all causes
Time Frame
At 90 days after randomisation
Secondary Outcome Measure Information:
Title
Mean and peak serum creatinine concentration
Time Frame
First seven days
Title
ICU, hospital and 28 day all-cause mortality
Time Frame
28 days and 6 months after randomisation
Title
Duration of ICU stay
Time Frame
28 days and 90 days after randomisation
Title
Duration of Hospital stay
Time Frame
28 days and 90 days after randomisation
Title
Proportion of patients newly treated with renal replacement therapy
Time Frame
up to 90 days after randomisation.
Title
Duration of mechanical ventilation in ICU
Time Frame
90 days after randomisation
Title
Proportion of patients treated with and duration of treatment with vasoactive drugs
Time Frame
90 days after randomisation
Title
Quality of life assessment using the EQ-5D-5L questionnaire
Time Frame
At 6 months after randomisation
Title
Maximum post-randomisation increase in serum creatinine in ICU during the index hospital admission.
Time Frame
90 days after randomisation
Title
Healthcare services usage during the six months after randomisation by healthcare record linkage using state and national data linkage units
Time Frame
During the six months after randomisation

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: The patient will receive fluid resuscitation defined as a bolus of fluid, prescribed to be administered over one hour or less to increase or maintain intravascular volume that is in addition to maintenance fluids, or specific fluids used to replace non-physiological fluid losses The patient is expected to be in the ICU the day after tomorrow The patient is not expected to be well enough to be eating tomorrow An arterial or central venous catheter is in situ, or placement is imminent as part of routine management Both Plasma-Lyte 148® and 0.9% saline are considered equally appropriate for the patient The requirement for fluid resuscitation is supported by at least one of seven pre-specified clinical signs: heart rate > 90 beats per minute; systolic blood pressure < 100 mmHg or mean arterial pressure < 75 mmHg; central venous pressure < 10 mmHg; pulmonary artery wedge pressure < 12 mmHg; capillary refill time > 1 second; OR urine output < 0.5 ml/kg for at least one hour Exclusion Criteria: Age less than 18 years Patients who have received more than 500mls of fluid resuscitation (as defined above) prescribed in the ICU during this current ICU admission Patients transferred directly from another ICU who have received more than 500mls of fluid resuscitation (as defined above) during that ICU admission Contraindication to either study fluid e.g. previous allergic reaction to Plasma-Lyte 148® Patients admitted to the ICU with specific fluid requirements: the treatment of burns; following liver transplantation surgery; for correction of specific electrolyte abnormalities Patients with traumatic brain injury or those considered at risk of developing cerebral oedema Patients in whom death is deemed imminent and inevitable Patients with an underlying disease process with a life expectancy of <90 days Patients in whom it is unlikely the primary outcome can be ascertained Patients who have previously been enrolled in PLUS Known or suspected pregnancy
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Simon Finfer, Professor
Organizational Affiliation
The George Institute
Official's Role
Study Chair
Facility Information:
Facility Name
Blacktown Hospital
City
Blacktown
State/Province
New South Wales
ZIP/Postal Code
2148
Country
Australia
Facility Name
Royal Prince Alfred Hospital
City
Camperdown
State/Province
New South Wales
ZIP/Postal Code
2050
Country
Australia
Facility Name
The Sutherland Hospital
City
Caringbah
State/Province
New South Wales
ZIP/Postal Code
2229
Country
Australia
Facility Name
Concord Repatriation General Hospital
City
Concord
State/Province
New South Wales
ZIP/Postal Code
2139
Country
Australia
Facility Name
Gosford Hospital
City
Gosford
State/Province
New South Wales
ZIP/Postal Code
2250
Country
Australia
Facility Name
Hornsby Ku-ring-gai Hospital
City
Hornsby
State/Province
New South Wales
ZIP/Postal Code
2077
Country
Australia
Facility Name
St George Hospital
City
Kogarah
State/Province
New South Wales
ZIP/Postal Code
2217
Country
Australia
Facility Name
Liverpool Hospital
City
Liverpool
State/Province
New South Wales
ZIP/Postal Code
2170
Country
Australia
Facility Name
Nepean
City
Penrith
State/Province
New South Wales
ZIP/Postal Code
2751
Country
Australia
Facility Name
Royal North Shore Hospital
City
St Leonards
State/Province
New South Wales
Country
Australia
Facility Name
Wagga Wagga Rural Referral Hospital
City
Wagga Wagga
State/Province
New South Wales
ZIP/Postal Code
2650
Country
Australia
Facility Name
The Sydney Adventist Hospital
City
Wahroonga
State/Province
New South Wales
ZIP/Postal Code
2076
Country
Australia
Facility Name
Calvary Mater Newcastle
City
Waratah
State/Province
New South Wales
ZIP/Postal Code
2298
Country
Australia
Facility Name
Westmead Hospital
City
Westmead
State/Province
New South Wales
ZIP/Postal Code
2145
Country
Australia
Facility Name
Wollongong Hospital
City
Wollongong
State/Province
New South Wales
ZIP/Postal Code
2500
Country
Australia
Facility Name
The Wesley Hospital
City
Auchenflower
State/Province
Queensland
ZIP/Postal Code
4066
Country
Australia
Facility Name
Royal Brisbane and Women's Hospital
City
Herston
State/Province
Queensland
ZIP/Postal Code
4029
Country
Australia
Facility Name
Redcliffe Hospital
City
Redcliffe
State/Province
Queensland
ZIP/Postal Code
4020
Country
Australia
Facility Name
Robina Hospital
City
Robina
State/Province
Queensland
ZIP/Postal Code
4226
Country
Australia
Facility Name
Mater Misericordiae
City
South Brisbane
State/Province
Queensland
ZIP/Postal Code
4101
Country
Australia
Facility Name
Gold Coast University Hospital
City
Southport
State/Province
Queensland
ZIP/Postal Code
4215
Country
Australia
Facility Name
Toowoomba Hospital
City
Toowoomba
State/Province
Queensland
ZIP/Postal Code
4350
Country
Australia
Facility Name
Princess Alexandra Hospital
City
Woolloongabba
State/Province
Queensland
ZIP/Postal Code
4102
Country
Australia
Facility Name
Royal Adelaide Hospital
City
Adelaide
State/Province
South Australia
ZIP/Postal Code
5000
Country
Australia
Facility Name
Royal Hobart Hospital
City
Hobart
State/Province
Tasmania
ZIP/Postal Code
7000
Country
Australia
Facility Name
Launceston General Hospital
City
Launceston
State/Province
Tasmania
ZIP/Postal Code
7250
Country
Australia
Facility Name
Ballarat Health Services
City
Ballarat
State/Province
Victoria
ZIP/Postal Code
3350
Country
Australia
Facility Name
Bendigo Hospital
City
Bendigo
State/Province
Victoria
ZIP/Postal Code
3550
Country
Australia
Facility Name
Box Hill Hospital
City
Box Hill
State/Province
Victoria
ZIP/Postal Code
3128
Country
Australia
Facility Name
Monash Medical Centre
City
Clayton
State/Province
Victoria
ZIP/Postal Code
3168
Country
Australia
Facility Name
Dandenong Hospital
City
Dandenong
State/Province
Victoria
ZIP/Postal Code
3175
Country
Australia
Facility Name
Footscray Hospital, Western Health
City
Footscray
State/Province
Victoria
ZIP/Postal Code
3011
Country
Australia
Facility Name
Frankston Hospital
City
Frankston
State/Province
Victoria
ZIP/Postal Code
3199
Country
Australia
Facility Name
Austin Hospital
City
Heidelberg
State/Province
Victoria
ZIP/Postal Code
3084
Country
Australia
Facility Name
Royal Melbourne Hospital
City
Parkville
State/Province
Victoria
ZIP/Postal Code
3050
Country
Australia
Facility Name
Maroondah Hospital
City
Ringwood East
State/Province
Victoria
ZIP/Postal Code
3135
Country
Australia
Facility Name
Sunshine Hospital, Western Health
City
St Albans
State/Province
Victoria
ZIP/Postal Code
3021
Country
Australia
Facility Name
St John of God Murdoch Hospital
City
Murdoch
State/Province
Western Australia
ZIP/Postal Code
6150
Country
Australia
Facility Name
Fiona Stanley Hospital
City
Murdoch
State/Province
Western Australia
ZIP/Postal Code
6165
Country
Australia
Facility Name
North Shore Hospital
City
Takapuna
State/Province
Auckland
ZIP/Postal Code
740
Country
New Zealand
Facility Name
Rotorua Hospital
City
Rotorua
State/Province
Bay Of Plenty
ZIP/Postal Code
3010
Country
New Zealand
Facility Name
Hawkes Bay
City
Hastings
State/Province
Camberley
ZIP/Postal Code
4120
Country
New Zealand
Facility Name
Christchurch Hospital
City
Christchurch
State/Province
Canterbury
ZIP/Postal Code
8140
Country
New Zealand
Facility Name
Hutt Hospital
City
Lower Hutt
State/Province
Wellington
ZIP/Postal Code
5014
Country
New Zealand
Facility Name
Wellington Hospital
City
Newtown
State/Province
Wellington
ZIP/Postal Code
6021
Country
New Zealand
Facility Name
Auckland City Hospital (CVICU)
City
Auckland
ZIP/Postal Code
1023
Country
New Zealand
Facility Name
Auckland City Hospital (DCCM)
City
Auckland
ZIP/Postal Code
1142
Country
New Zealand
Facility Name
Middlemore Hospital
City
Auckland
ZIP/Postal Code
1640
Country
New Zealand
Facility Name
Waikato Hospital
City
Hamilton
ZIP/Postal Code
3240
Country
New Zealand
Facility Name
Nelson Hospital
City
Nelson
ZIP/Postal Code
7010
Country
New Zealand
Facility Name
Tauranga Hospital
City
Tauranga
ZIP/Postal Code
3110
Country
New Zealand

12. IPD Sharing Statement

Plan to Share IPD
Yes
Citations:
PubMed Identifier
35041780
Citation
Finfer S, Micallef S, Hammond N, Navarra L, Bellomo R, Billot L, Delaney A, Gallagher M, Gattas D, Li Q, Mackle D, Mysore J, Saxena M, Taylor C, Young P, Myburgh J; PLUS Study Investigators and the Australian New Zealand Intensive Care Society Clinical Trials Group. Balanced Multielectrolyte Solution versus Saline in Critically Ill Adults. N Engl J Med. 2022 Mar 3;386(9):815-826. doi: 10.1056/NEJMoa2114464. Epub 2022 Jan 18.
Results Reference
derived

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Plasma-Lyte 148® versUs Saline Study

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