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Plasma-Lyte 148® versUs Saline Study (PLUS)

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ClinicalTrials.gov Identifier: NCT02721654
Recruitment Status : Recruiting
First Posted : March 29, 2016
Last Update Posted : April 18, 2018
Sponsor:
Collaborators:
Australian and New Zealand Intensive Care Society Clinical Trials Group
Baxter Healthcare Corporation
Information provided by (Responsible Party):
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)

Condition or disease Intervention/treatment Phase
Hypovolemia Drug: Plasma-Lyte 148® Drug: 0.9% sodium chloride Phase 4

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.


Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 8800 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Comparison of Plasmalyte 148® and Saline for Fluid Resuscitation and Intravenous Fluid Therapy in Critically Ill Adults
Actual Study Start Date : September 1, 2017
Estimated Primary Completion Date : December 2020
Estimated Study Completion Date : March 2021

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: 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).
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.
Other Name: Balanced crystalloid solution

Active Comparator: 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).
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 bioavailablity (absorption) of the active components is complete (100 per cent).
Other Name: Saline




Primary Outcome Measures :
  1. Death from all causes [ Time Frame: At 90 days after randomisation ]

Secondary Outcome Measures :
  1. Mean and peak serum creatinine concentration [ Time Frame: First seven days ]
  2. ICU, hospital and 28 day all-cause mortality [ Time Frame: 28 days and 6 months after randomisation ]
  3. Duration of ICU stay [ Time Frame: 28 days and 90 days after randomisation ]
  4. Duration of Hospital stay [ Time Frame: 28 days and 90 days after randomisation ]
  5. Proportion of patients newly treated with renal replacement therapy [ Time Frame: up to 90 days after randomisation. ]
  6. Duration of mechanical ventilation in ICU [ Time Frame: 90 days after randomisation ]
  7. Proportion of patients treated with and duration of treatment with vasoactive drugs [ Time Frame: 90 days after randomisation ]
  8. Quality of life assessment using the EQ-5D-5L questionnaire [ Time Frame: At 6 months after randomisation ]
  9. Maximum post-randomisation increase in serum creatinine in ICU during the index hospital admission. [ Time Frame: 90 days after randomisation ]
  10. 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 ]


Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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 previously received fluid resuscitation (as defined above) prescribed in the ICU during this current ICU admission
  • Patients transferred directly from another ICU who have received 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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02721654


Contacts
Contact: Simon Finfer, Professor +61 2 8052 4381 sfinfer@georgeinstitute.org.au
Contact: Sharon Micallef +61 2 8052 4324 smicallef@georgeinstitute.org.au

  Show 43 Study Locations
Sponsors and Collaborators
The George Institute
Australian and New Zealand Intensive Care Society Clinical Trials Group
Baxter Healthcare Corporation
Investigators
Study Chair: Simon Finfer, Professor The George Institute

Responsible Party: The George Institute
ClinicalTrials.gov Identifier: NCT02721654     History of Changes
Other Study ID Numbers: GI-CCT7587
U1111-1178-8334 ( Other Identifier: World Health Organisation (WHO) Universal Trial Number (UTN) )
First Posted: March 29, 2016    Key Record Dates
Last Update Posted: April 18, 2018
Last Verified: September 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes

Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by The George Institute:
Plasma-Lyte
Sodium chloride
Saline
Fluid resuscitation
Intravenous fluid therapy
Critically ill
Critical care

Additional relevant MeSH terms:
Hypovolemia
Pathologic Processes
Plasma-lyte 148
Pharmaceutical Solutions
Ophthalmic Solutions