Plasma-Lyte 148® versUs Saline Study

Hypovolemia Clinical Trial

— PLUS  

Official title:

Comparison of Plasmalyte 148® and Saline for Fluid Resuscitation and Intravenous Fluid Therapy in Critically Ill Adults

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02721654
• Other study ID #: GI-CCT7587
• Secondary ID: U1111-1178-8334
• Status: Completed
• Phase: Phase 4
• Start date: September 1, 2017
• Est. completion date: June 30, 2021

Study information

• Verified date: August 2023
• Source: The George Institute
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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)

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 information / eligibility

• Status: Completed
• Enrollment: 5037
• Est. completion date: June 30, 2021
• Est. primary completion date: March 30, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Hypovolemia

Intervention

Drug:
• Plasma-Lyte 148®
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.
• 0.9% sodium chloride
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).

Locations

Country	Name	City	State
Australia	Royal Adelaide Hospital	Adelaide	South Australia
Australia	The Wesley Hospital	Auchenflower	Queensland
Australia	Ballarat Health Services	Ballarat	Victoria
Australia	Bendigo Hospital	Bendigo	Victoria
Australia	Blacktown Hospital	Blacktown	New South Wales
Australia	Box Hill Hospital	Box Hill	Victoria
Australia	Royal Prince Alfred Hospital	Camperdown	New South Wales
Australia	The Sutherland Hospital	Caringbah	New South Wales
Australia	Monash Medical Centre	Clayton	Victoria
Australia	Concord Repatriation General Hospital	Concord	New South Wales
Australia	Dandenong Hospital	Dandenong	Victoria
Australia	Footscray Hospital, Western Health	Footscray	Victoria
Australia	Frankston Hospital	Frankston	Victoria
Australia	Gosford Hospital	Gosford	New South Wales
Australia	Austin Hospital	Heidelberg	Victoria
Australia	Royal Brisbane and Women's Hospital	Herston	Queensland
Australia	Royal Hobart Hospital	Hobart	Tasmania
Australia	Hornsby Ku-ring-gai Hospital	Hornsby	New South Wales
Australia	St George Hospital	Kogarah	New South Wales
Australia	Launceston General Hospital	Launceston	Tasmania
Australia	Liverpool Hospital	Liverpool	New South Wales
Australia	Fiona Stanley Hospital	Murdoch	Western Australia
Australia	St John of God Murdoch Hospital	Murdoch	Western Australia
Australia	Royal Melbourne Hospital	Parkville	Victoria
Australia	Nepean	Penrith	New South Wales
Australia	Redcliffe Hospital	Redcliffe	Queensland
Australia	Maroondah Hospital	Ringwood East	Victoria
Australia	Robina Hospital	Robina	Queensland
Australia	Mater Misericordiae	South Brisbane	Queensland
Australia	Gold Coast University Hospital	Southport	Queensland
Australia	Sunshine Hospital, Western Health	St Albans	Victoria
Australia	Royal North Shore Hospital	St Leonards	New South Wales
Australia	Toowoomba Hospital	Toowoomba	Queensland
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	Westmead Hospital	Westmead	New South Wales
Australia	Wollongong Hospital	Wollongong	New South Wales
Australia	Princess Alexandra Hospital	Woolloongabba	Queensland
New Zealand	Auckland City Hospital (CVICU)	Auckland
New Zealand	Auckland City Hospital (DCCM)	Auckland
New Zealand	Middlemore Hospital	Auckland
New Zealand	Christchurch Hospital	Christchurch	Canterbury
New Zealand	Waikato Hospital	Hamilton
New Zealand	Hawkes Bay	Hastings	Camberley
New Zealand	Hutt Hospital	Lower Hutt	Wellington
New Zealand	Nelson Hospital	Nelson
New Zealand	Wellington Hospital	Newtown	Wellington
New Zealand	Rotorua Hospital	Rotorua	Bay Of Plenty
New Zealand	North Shore Hospital	Takapuna	Auckland
New Zealand	Tauranga Hospital	Tauranga

Sponsors (3)

Lead Sponsor	Collaborator
The George Institute	Australian and New Zealand Intensive Care Society Clinical Trials Group, Baxter Healthcare Corporation

Countries where clinical trial is conducted

Australia,  New Zealand, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Death from all causes		At 90 days after randomisation
Secondary	Mean and peak serum creatinine concentration		First seven days
Secondary	ICU, hospital and 28 day all-cause mortality		28 days and 6 months after randomisation
Secondary	Duration of ICU stay		28 days and 90 days after randomisation
Secondary	Duration of Hospital stay		28 days and 90 days after randomisation
Secondary	Proportion of patients newly treated with renal replacement therapy		up to 90 days after randomisation.
Secondary	Duration of mechanical ventilation in ICU		90 days after randomisation
Secondary	Proportion of patients treated with and duration of treatment with vasoactive drugs		90 days after randomisation
Secondary	Quality of life assessment using the EQ-5D-5L questionnaire		At 6 months after randomisation
Secondary	Maximum post-randomisation increase in serum creatinine in ICU during the index hospital admission.		90 days after randomisation
Secondary	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