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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT02721654




Registration number
NCT02721654
Ethics application status
Date submitted
15/03/2016
Date registered
29/03/2016
Date last updated
8/08/2023

Titles & IDs
Public title
Plasma-Lyte 148® versUs Saline Study
Scientific title
Comparison of Plasmalyte 148® and Saline for Fluid Resuscitation and Intravenous Fluid Therapy in Critically Ill Adults
Secondary ID [1] 0 0
U1111-1178-8334
Secondary ID [2] 0 0
GI-CCT7587
Universal Trial Number (UTN)
Trial acronym
PLUS
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Hypovolemia 0 0
Condition category
Condition code
Blood 0 0 0 0
Other blood disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Plasma-Lyte 148®
Treatment: Drugs - 0.9% sodium chloride

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).

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).


Treatment: Drugs: 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.

Treatment: Drugs: 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 code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Death from all causes
Timepoint [1] 0 0
At 90 days after randomisation
Secondary outcome [1] 0 0
Mean and peak serum creatinine concentration
Timepoint [1] 0 0
First seven days
Secondary outcome [2] 0 0
ICU, hospital and 28 day all-cause mortality
Timepoint [2] 0 0
28 days and 6 months after randomisation
Secondary outcome [3] 0 0
Duration of ICU stay
Timepoint [3] 0 0
28 days and 90 days after randomisation
Secondary outcome [4] 0 0
Duration of Hospital stay
Timepoint [4] 0 0
28 days and 90 days after randomisation
Secondary outcome [5] 0 0
Proportion of patients newly treated with renal replacement therapy
Timepoint [5] 0 0
up to 90 days after randomisation.
Secondary outcome [6] 0 0
Duration of mechanical ventilation in ICU
Timepoint [6] 0 0
90 days after randomisation
Secondary outcome [7] 0 0
Proportion of patients treated with and duration of treatment with vasoactive drugs
Timepoint [7] 0 0
90 days after randomisation
Secondary outcome [8] 0 0
Quality of life assessment using the EQ-5D-5L questionnaire
Timepoint [8] 0 0
At 6 months after randomisation
Secondary outcome [9] 0 0
Maximum post-randomisation increase in serum creatinine in ICU during the index hospital admission.
Timepoint [9] 0 0
90 days after randomisation
Secondary outcome [10] 0 0
Healthcare services usage during the six months after randomisation by healthcare record linkage using state and national data linkage units
Timepoint [10] 0 0
During the six months after randomisation

Eligibility
Key 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
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key 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

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 4
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
1/09/2017
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
30/06/2021
Sample size
Target
Accrual to date
Final
5037
Recruitment in Australia
Recruitment state(s)
NSW,QLD,SA,TAS,VIC,WA
Recruitment hospital [1] 0 0
Blacktown Hospital - Blacktown
Recruitment hospital [2] 0 0
Royal Prince Alfred Hospital - Camperdown
Recruitment hospital [3] 0 0
The Sutherland Hospital - Caringbah
Recruitment hospital [4] 0 0
Concord Repatriation General Hospital - Concord
Recruitment hospital [5] 0 0
Gosford Hospital - Gosford
Recruitment hospital [6] 0 0
Hornsby Ku-ring-gai Hospital - Hornsby
Recruitment hospital [7] 0 0
St George Hospital - Kogarah
Recruitment hospital [8] 0 0
Liverpool Hospital - Liverpool
Recruitment hospital [9] 0 0
Nepean - Penrith
Recruitment hospital [10] 0 0
Royal North Shore Hospital - St Leonards
Recruitment hospital [11] 0 0
Wagga Wagga Rural Referral Hospital - Wagga Wagga
Recruitment hospital [12] 0 0
The Sydney Adventist Hospital - Wahroonga
Recruitment hospital [13] 0 0
Calvary Mater Newcastle - Waratah
Recruitment hospital [14] 0 0
Westmead Hospital - Westmead
Recruitment hospital [15] 0 0
Wollongong Hospital - Wollongong
Recruitment hospital [16] 0 0
The Wesley Hospital - Auchenflower
Recruitment hospital [17] 0 0
Royal Brisbane and Women's Hospital - Herston
Recruitment hospital [18] 0 0
Redcliffe Hospital - Redcliffe
Recruitment hospital [19] 0 0
Robina Hospital - Robina
Recruitment hospital [20] 0 0
Mater Misericordiae - South Brisbane
Recruitment hospital [21] 0 0
Gold Coast University Hospital - Southport
Recruitment hospital [22] 0 0
Toowoomba Hospital - Toowoomba
Recruitment hospital [23] 0 0
Princess Alexandra Hospital - Woolloongabba
Recruitment hospital [24] 0 0
Royal Adelaide Hospital - Adelaide
Recruitment hospital [25] 0 0
Royal Hobart Hospital - Hobart
Recruitment hospital [26] 0 0
Launceston General Hospital - Launceston
Recruitment hospital [27] 0 0
Ballarat Health Services - Ballarat
Recruitment hospital [28] 0 0
Bendigo Hospital - Bendigo
Recruitment hospital [29] 0 0
Box Hill Hospital - Box Hill
Recruitment hospital [30] 0 0
Monash Medical Centre - Clayton
Recruitment hospital [31] 0 0
Dandenong Hospital - Dandenong
Recruitment hospital [32] 0 0
Footscray Hospital, Western Health - Footscray
Recruitment hospital [33] 0 0
Frankston Hospital - Frankston
Recruitment hospital [34] 0 0
Austin Hospital - Heidelberg
Recruitment hospital [35] 0 0
Royal Melbourne Hospital - Parkville
Recruitment hospital [36] 0 0
Maroondah Hospital - Ringwood East
Recruitment hospital [37] 0 0
Sunshine Hospital, Western Health - St Albans
Recruitment hospital [38] 0 0
St John of God Murdoch Hospital - Murdoch
Recruitment hospital [39] 0 0
Fiona Stanley Hospital - Murdoch
Recruitment postcode(s) [1] 0 0
2148 - Blacktown
Recruitment postcode(s) [2] 0 0
2050 - Camperdown
Recruitment postcode(s) [3] 0 0
2229 - Caringbah
Recruitment postcode(s) [4] 0 0
2139 - Concord
Recruitment postcode(s) [5] 0 0
2250 - Gosford
Recruitment postcode(s) [6] 0 0
2077 - Hornsby
Recruitment postcode(s) [7] 0 0
2217 - Kogarah
Recruitment postcode(s) [8] 0 0
2170 - Liverpool
Recruitment postcode(s) [9] 0 0
2751 - Penrith
Recruitment postcode(s) [10] 0 0
- St Leonards
Recruitment postcode(s) [11] 0 0
2650 - Wagga Wagga
Recruitment postcode(s) [12] 0 0
2076 - Wahroonga
Recruitment postcode(s) [13] 0 0
2298 - Waratah
Recruitment postcode(s) [14] 0 0
2145 - Westmead
Recruitment postcode(s) [15] 0 0
2500 - Wollongong
Recruitment postcode(s) [16] 0 0
4066 - Auchenflower
Recruitment postcode(s) [17] 0 0
4029 - Herston
Recruitment postcode(s) [18] 0 0
4020 - Redcliffe
Recruitment postcode(s) [19] 0 0
4226 - Robina
Recruitment postcode(s) [20] 0 0
4101 - South Brisbane
Recruitment postcode(s) [21] 0 0
4215 - Southport
Recruitment postcode(s) [22] 0 0
4350 - Toowoomba
Recruitment postcode(s) [23] 0 0
4102 - Woolloongabba
Recruitment postcode(s) [24] 0 0
5000 - Adelaide
Recruitment postcode(s) [25] 0 0
7000 - Hobart
Recruitment postcode(s) [26] 0 0
7250 - Launceston
Recruitment postcode(s) [27] 0 0
3350 - Ballarat
Recruitment postcode(s) [28] 0 0
3550 - Bendigo
Recruitment postcode(s) [29] 0 0
3128 - Box Hill
Recruitment postcode(s) [30] 0 0
3168 - Clayton
Recruitment postcode(s) [31] 0 0
3175 - Dandenong
Recruitment postcode(s) [32] 0 0
3011 - Footscray
Recruitment postcode(s) [33] 0 0
3199 - Frankston
Recruitment postcode(s) [34] 0 0
3084 - Heidelberg
Recruitment postcode(s) [35] 0 0
3050 - Parkville
Recruitment postcode(s) [36] 0 0
3135 - Ringwood East
Recruitment postcode(s) [37] 0 0
3021 - St Albans
Recruitment postcode(s) [38] 0 0
6150 - Murdoch
Recruitment postcode(s) [39] 0 0
6165 - Murdoch
Recruitment outside Australia
Country [1] 0 0
New Zealand
State/province [1] 0 0
Auckland
Country [2] 0 0
New Zealand
State/province [2] 0 0
Bay Of Plenty
Country [3] 0 0
New Zealand
State/province [3] 0 0
Camberley
Country [4] 0 0
New Zealand
State/province [4] 0 0
Canterbury
Country [5] 0 0
New Zealand
State/province [5] 0 0
Wellington
Country [6] 0 0
New Zealand
State/province [6] 0 0
Hamilton
Country [7] 0 0
New Zealand
State/province [7] 0 0
Nelson
Country [8] 0 0
New Zealand
State/province [8] 0 0
Tauranga

Funding & Sponsors
Primary sponsor type
Other
Name
The George Institute
Address
Country
Other collaborator category [1] 0 0
Other
Name [1] 0 0
Australian and New Zealand Intensive Care Society Clinical Trials Group
Address [1] 0 0
Country [1] 0 0
Other collaborator category [2] 0 0
Commercial sector/industry
Name [2] 0 0
Baxter Healthcare Corporation
Address [2] 0 0
Country [2] 0 0

Ethics approval
Ethics application status

Summary
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)
Trial website
https://clinicaltrials.gov/study/NCT02721654
Trial related presentations / publications
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.
Public notes

Contacts
Principal investigator
Name 0 0
Simon Finfer, Professor
Address 0 0
The George Institute
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/study/NCT02721654