Plasma-Lyte 148® versUs Saline Study

NCT ID: NCT02721654

Last Updated: 2023-08-08

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE4
• Total Enrollment: 5037 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2017-09-01
• Study Completion Date: 2021-06-30

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.

Conditions

Hypovolemia

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

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).

Group Type: EXPERIMENTAL

Plasma-Lyte 148®

Intervention Type: DRUG

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

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).

Group Type: ACTIVE_COMPARATOR

0.9% sodium chloride

Intervention Type: DRUG

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).

Interventions

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.

Intervention Type: DRUG

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).

Intervention Type: DRUG

Other Intervention Names

Balanced crystalloid solution; Saline

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Australian and New Zealand Intensive Care Society Clinical Trials Group

NETWORK

Sponsor Role: collaborator

Baxter Healthcare Corporation

INDUSTRY

Sponsor Role: collaborator

The George Institute

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Simon Finfer, Professor

Role: STUDY_CHAIR

The George Institute

Locations

Blacktown Hospital

Blacktown, New South Wales, Australia

Royal Prince Alfred Hospital

Camperdown, New South Wales, Australia

The Sutherland Hospital

Caringbah, New South Wales, Australia

Concord Repatriation General Hospital

Concord, 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

Liverpool Hospital

Liverpool, New South Wales, Australia

Nepean

Penrith, New South Wales, Australia

Royal North Shore Hospital

St Leonards, 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

Westmead Hospital

Westmead, New South Wales, Australia

Wollongong Hospital

Wollongong, New South Wales, Australia

The Wesley Hospital

Auchenflower, Queensland, Australia

Royal Brisbane and Women's Hospital

Herston, Queensland, Australia

Redcliffe Hospital

Redcliffe, Queensland, Australia

Robina Hospital

Robina, Queensland, Australia

Mater Misericordiae

South Brisbane, Queensland, Australia

Gold Coast University Hospital

Southport, Queensland, Australia

Toowoomba Hospital

Toowoomba, Queensland, Australia

Princess Alexandra Hospital

Woolloongabba, Queensland, Australia

Royal Adelaide Hospital

Adelaide, South Australia, Australia

Royal Hobart Hospital

Hobart, Tasmania, Australia

Launceston General Hospital

Launceston, Tasmania, Australia

Ballarat Health Services

Ballarat, Victoria, Australia

Bendigo Hospital

Bendigo, Victoria, Australia

Box Hill Hospital

Box Hill, Victoria, Australia

Monash Medical Centre

Clayton, Victoria, Australia

Dandenong Hospital

Dandenong, Victoria, Australia

Footscray Hospital, Western Health

Footscray, Victoria, Australia

Frankston Hospital

Frankston, Victoria, Australia

Austin Hospital

Heidelberg, Victoria, Australia

Royal Melbourne Hospital

Parkville, Victoria, Australia

Maroondah Hospital

Ringwood East, Victoria, Australia

Sunshine Hospital, Western Health

St Albans, Victoria, Australia

St John of God Murdoch Hospital

Murdoch, Western Australia, Australia

Fiona Stanley Hospital

Murdoch, Western Australia, Australia

North Shore Hospital

Takapuna, Auckland, New Zealand

Rotorua Hospital

Rotorua, Bay of Plenty, New Zealand

Hawkes Bay

Hastings, Camberley, New Zealand

Christchurch Hospital

Christchurch, Canterbury, New Zealand

Hutt Hospital

Lower Hutt, Wellington Region, New Zealand

Wellington Hospital

Newtown, Wellington Region, New Zealand

Auckland City Hospital (CVICU)

Auckland, , New Zealand

Auckland City Hospital (DCCM)

Auckland, , New Zealand

Middlemore Hospital

Auckland, , New Zealand

Waikato Hospital

Hamilton, , New Zealand

Nelson Hospital

Nelson, , New Zealand

Tauranga Hospital

Tauranga, , New Zealand

Countries

Australia; New Zealand

References

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.

Reference Type: DERIVED

PMID: 35041780 (View on PubMed)

Other Identifiers

U1111-1178-8334

Identifier Type: OTHER

Identifier Source: secondary_id

GI-CCT7587

Identifier Type: -

Identifier Source: org_study_id