Clinical trial NCT02721654: Plasma-Lyte 148® versUs Saline Study
Official title: Comparison of Plasmalyte 148® and Saline for Fluid Resuscitation and Intravenous Fluid Therapy in Critically Ill Adults
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Hypovolemia
Keywords: Plasma-Lyte
Sodium chloride
Saline
Fluid resuscitation
Intravenous fluid therapy
Critically ill
Critical care
Lead sponsor: The George Institute
Sponsor class: OTHER
Collaborators: name: Australian and New Zealand Intensive Care Society Clinical Trials Group
name: Baxter Healthcare Corporation
First posted: 2016-03-29
Enrollment: 5037
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Death from all causes
timeFrame: At 90 days after randomisation
Secondary outcomes:
measure: Mean and peak serum creatinine concentration
timeFrame: First seven days
measure: ICU, hospital and 28 day all-cause mortality
timeFrame: 28 days and 6 months after randomisation
measure: Duration of ICU stay
timeFrame: 28 days and 90 days after randomisation
measure: Duration of Hospital stay
timeFrame: 28 days and 90 days after randomisation
measure: Proportion of patients newly treated with renal replacement therapy
timeFrame: up to 90 days after randomisation.
measure: Duration of mechanical ventilation in ICU
timeFrame: 90 days after randomisation
measure: Proportion of patients treated with and duration of treatment with vasoactive drugs
timeFrame: 90 days after randomisation
measure: Quality of life assessment using the EQ-5D-5L questionnaire
timeFrame: At 6 months after randomisation
measure: Maximum post-randomisation increase in serum creatinine in ICU during the index hospital admission.
timeFrame: 90 days after randomisation
measure: Healthcare services usage during the six months after randomisation by healthcare record linkage using state and national data linkage units
timeFrame: During the six months after randomisation
Other outcomes:
Locations:
city: Blacktown
country: Australia
facility: Blacktown Hospital
state: New South Wales
city: Camperdown
country: Australia
facility: Royal Prince Alfred Hospital
state: New South Wales
city: Caringbah
country: Australia
facility: The Sutherland Hospital
state: New South Wales
city: Concord
country: Australia
facility: Concord Repatriation General Hospital
state: New South Wales
city: Gosford
country: Australia
facility: Gosford Hospital
state: New South Wales
city: Hornsby
country: Australia
facility: Hornsby Ku-ring-gai Hospital
state: New South Wales
city: Kogarah
country: Australia
facility: St George Hospital
state: New South Wales
city: Liverpool
country: Australia
facility: Liverpool Hospital
state: New South Wales
city: Penrith
country: Australia
facility: Nepean
state: New South Wales
city: St Leonards
country: Australia
facility: Royal North Shore Hospital
state: New South Wales
city: Wagga Wagga
country: Australia
facility: Wagga Wagga Rural Referral Hospital
state: New South Wales
city: Wahroonga
country: Australia
facility: The Sydney Adventist Hospital
state: New South Wales
city: Waratah
country: Australia
facility: Calvary Mater Newcastle
state: New South Wales
city: Westmead
country: Australia
facility: Westmead Hospital
state: New South Wales
city: Wollongong
country: Australia
facility: Wollongong Hospital
state: New South Wales
city: Auchenflower
country: Australia
facility: The Wesley Hospital
state: Queensland
city: Herston
country: Australia
facility: Royal Brisbane and Women's Hospital
state: Queensland
city: Redcliffe
country: Australia
facility: Redcliffe Hospital
state: Queensland
city: Robina
country: Australia
facility: Robina Hospital
state: Queensland
city: South Brisbane
country: Australia
facility: Mater Misericordiae
state: Queensland
city: Southport
country: Australia
facility: Gold Coast University Hospital
state: Queensland
city: Toowoomba
country: Australia
facility: Toowoomba Hospital
state: Queensland
city: Woolloongabba
country: Australia
facility: Princess Alexandra Hospital
state: Queensland
city: Adelaide
country: Australia
facility: Royal Adelaide Hospital
state: South Australia
city: Hobart
country: Australia
facility: Royal Hobart Hospital
state: Tasmania
city: Launceston
country: Australia
facility: Launceston General Hospital
state: Tasmania
city: Ballarat
country: Australia
facility: Ballarat Health Services
state: Victoria
city: Bendigo
country: Australia
facility: Bendigo Hospital
state: Victoria
city: Box Hill
country: Australia
facility: Box Hill Hospital
state: Victoria
city: Clayton
country: Australia
facility: Monash Medical Centre
state: Victoria
city: Dandenong
country: Australia
facility: Dandenong Hospital
state: Victoria
city: Footscray
country: Australia
facility: Footscray Hospital, Western Health
state: Victoria
city: Frankston
country: Australia
facility: Frankston Hospital
state: Victoria
city: Heidelberg
country: Australia
facility: Austin Hospital
state: Victoria
city: Parkville
country: Australia
facility: Royal Melbourne Hospital
state: Victoria
city: Ringwood East
country: Australia
facility: Maroondah Hospital
state: Victoria
city: St Albans
country: Australia
facility: Sunshine Hospital, Western Health
state: Victoria
city: Murdoch
country: Australia
facility: St John of God Murdoch Hospital
state: Western Australia
city: Murdoch
country: Australia
facility: Fiona Stanley Hospital
state: Western Australia
city: Takapuna
country: New Zealand
facility: North Shore Hospital
state: Auckland
city: Rotorua
country: New Zealand
facility: Rotorua Hospital
state: Bay Of Plenty
city: Hastings
country: New Zealand
facility: Hawkes Bay
state: Camberley
city: Christchurch
country: New Zealand
facility: Christchurch Hospital
state: Canterbury
city: Lower Hutt
country: New Zealand
facility: Hutt Hospital
state: Wellington
city: Newtown
country: New Zealand
facility: Wellington Hospital
state: Wellington
city: Auckland
country: New Zealand
facility: Auckland City Hospital (CVICU)
city: Auckland
country: New Zealand
facility: Auckland City Hospital (DCCM)
city: Auckland
country: New Zealand
facility: Middlemore Hospital
city: Hamilton
country: New Zealand
facility: Waikato Hospital
city: Nelson
country: New Zealand
facility: Nelson Hospital
city: Tauranga
country: New Zealand
facility: Tauranga Hospital
Study officials:
affiliation: The George Institute
name: Simon Finfer, Professor
role: STUDY_CHAIR
References:
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.