Plasma-Lyte 148® versUs Saline Study
- Registration Number
- NCT02721654
- Lead Sponsor
- The George Institute
- 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.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 5037
- 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
- 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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Plasma-Lyte 148® Plasma-Lyte 148® 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). 0.9% sodium chloride 0.9% sodium chloride 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).
- Primary Outcome Measures
Name Time Method Death from all causes At 90 days after randomisation
- Secondary Outcome Measures
Name Time Method Duration of ICU stay 28 days and 90 days after randomisation Proportion of patients treated with and duration of treatment with vasoactive drugs 90 days after randomisation Mean and peak serum creatinine concentration First seven days Quality of life assessment using the EQ-5D-5L questionnaire At 6 months after randomisation Maximum post-randomisation increase in serum creatinine in ICU during the index hospital admission. 90 days after randomisation Duration of mechanical ventilation in ICU 90 days after randomisation Healthcare services usage during the six months after randomisation by healthcare record linkage using state and national data linkage units During the six months after randomisation ICU, hospital and 28 day all-cause mortality 28 days and 6 months after randomisation Proportion of patients newly treated with renal replacement therapy up to 90 days after randomisation. Duration of Hospital stay 28 days and 90 days after randomisation
Trial Locations
- Locations (51)
Fiona Stanley Hospital
🇦🇺Murdoch, Western Australia, Australia
Royal Prince Alfred Hospital
🇦🇺Camperdown, New South Wales, Australia
Blacktown Hospital
🇦🇺Blacktown, New South Wales, Australia
Liverpool Hospital
🇦🇺Liverpool, New South Wales, Australia
Concord Repatriation General Hospital
🇦🇺Concord, New South Wales, Australia
Wagga Wagga Rural Referral Hospital
🇦🇺Wagga Wagga, New South Wales, Australia
The Sydney Adventist Hospital
🇦🇺Wahroonga, New South Wales, Australia
Calvary Mater Newcastle
🇦🇺Waratah, New South Wales, Australia
Wollongong Hospital
🇦🇺Wollongong, New South Wales, Australia
The Wesley Hospital
🇦🇺Auchenflower, Queensland, Australia
Redcliffe Hospital
🇦🇺Redcliffe, Queensland, Australia
Launceston General Hospital
🇦🇺Launceston, Tasmania, Australia
Monash Medical Centre
🇦🇺Clayton, Victoria, Australia
North Shore Hospital
🇳🇿Takapuna, Auckland, New Zealand
Auckland City Hospital (DCCM)
🇳🇿Auckland, New Zealand
Nelson Hospital
🇳🇿Nelson, New Zealand
Tauranga Hospital
🇳🇿Tauranga, New Zealand
Royal North Shore Hospital
🇦🇺St Leonards, New South Wales, Australia
Nepean
🇦🇺Penrith, New South Wales, Australia
The Sutherland Hospital
🇦🇺Caringbah, New South Wales, Australia
Gosford Hospital
🇦🇺Gosford, New South Wales, Australia
Hornsby Ku-ring-gai Hospital
🇦🇺Hornsby, New South Wales, Australia
St George Hospital
🇦🇺Kogarah, New South Wales, Australia
Westmead Hospital
🇦🇺Westmead, New South Wales, Australia
Royal Brisbane and Women's Hospital
🇦🇺Herston, Queensland, Australia
Mater Misericordiae
🇦🇺South Brisbane, Queensland, Australia
Royal Adelaide Hospital
🇦🇺Adelaide, South Australia, Australia
Robina Hospital
🇦🇺Robina, Queensland, Australia
Toowoomba Hospital
🇦🇺Toowoomba, Queensland, Australia
Royal Hobart Hospital
🇦🇺Hobart, Tasmania, Australia
Bendigo Hospital
🇦🇺Bendigo, Victoria, Australia
Box Hill Hospital
🇦🇺Box Hill, Victoria, Australia
Royal Melbourne Hospital
🇦🇺Parkville, Victoria, Australia
St John of God Murdoch Hospital
🇦🇺Murdoch, Western Australia, Australia
Sunshine Hospital, Western Health
🇦🇺St Albans, Victoria, Australia
Christchurch Hospital
🇳🇿Christchurch, Canterbury, New Zealand
Wellington Hospital
🇳🇿Newtown, Wellington, New Zealand
Hutt Hospital
🇳🇿Lower Hutt, Wellington, New Zealand
Rotorua Hospital
🇳🇿Rotorua, Bay Of Plenty, New Zealand
Auckland City Hospital (CVICU)
🇳🇿Auckland, New Zealand
Hawkes Bay
🇳🇿Hastings, Camberley, New Zealand
Waikato Hospital
🇳🇿Hamilton, New Zealand
Middlemore Hospital
🇳🇿Auckland, New Zealand
Frankston Hospital
🇦🇺Frankston, Victoria, Australia
Gold Coast University Hospital
🇦🇺Southport, Queensland, Australia
Princess Alexandra Hospital
🇦🇺Woolloongabba, Queensland, Australia
Ballarat Health Services
🇦🇺Ballarat, Victoria, Australia
Dandenong Hospital
🇦🇺Dandenong, Victoria, Australia
Footscray Hospital, Western Health
🇦🇺Footscray, Victoria, Australia
Austin Hospital
🇦🇺Heidelberg, Victoria, Australia
Maroondah Hospital
🇦🇺Ringwood East, Victoria, Australia