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Better Evidence for Selecting Transplant Fluids (BEST-Fluids)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03829488
Recruitment Status : Active, not recruiting
First Posted : February 4, 2019
Last Update Posted : August 13, 2020
Sponsor:
Collaborators:
Australian Government Department of Health
Health Research Council, New Zealand
Baxter Healthcare Corporation
Information provided by (Responsible Party):
The University of Queensland

Brief Summary:

End-stage kidney disease (ESKD) is a significant, expensive health problem. Kidney transplantation improves survival, quality of life, and is much cheaper than dialysis treatment for ESKD. However sometimes kidney transplants from a deceased donor function poorly after surgery, and a period of continued dialysis is needed, a condition known as delayed graft function (DGF). In addition to complicating recovery, DGF can adversely affect long-term kidney function and the health of the recipient.

Intravenous fluids given during and after transplantation (usually 0.9% sodium chloride or saline) are critical to preserve kidney transplant function, but there is evidence that 0.9% saline may not be the safest fluid to use due to its high chloride content.

BEST Fluids is a randomised controlled trial that aims to find out whether using a balanced low-chloride solution - Plasma-Lyte 148® - as an alternative to normal saline in deceased donor kidney transplantation, will improve kidney transplant function, reduce the impact of DGF, and improve long-term outcomes for patients.


Condition or disease Intervention/treatment Phase
End Stage Kidney Disease Delayed Graft Function Kidney Transplant; Complications Drug: Plasma-Lyte 148 (approx. pH 7.4) IV Infusion Drug: 0.9% SODIUM CHLORIDE 9g/L injection BP Phase 3

Detailed Description:

End-stage kidney disease is a significant public health problem worldwide, and its treatment imposes a high healthcare burden and cost. Kidney transplantation is considered the best treatment for ESKD, offering improved survival and quality of life at significantly lower cost that dialysis. However, many kidney transplants fail prematurely due in part due to injury sustained at the time of transplantation. Delayed graft function (DGF), i.e. the requirement for dialysis early after transplantation, affects approximately 30% of deceased donor kidney transplants, and increases the risk of graft failure and mortality.

Intravenous fluids are a critical, albeit inexpensive, aspect of care that impacts early transplant function with normal (0.9%) saline the current standard care at most centres. However, normal saline may in fact be harmful in the setting of kidney transplantation due to its high chloride content relative to plasma, causing metabolic acidosis, acute kidney injury and thus potentially increasing the risk of DGF. Utilising a balanced low-chloride crystalloid solution such as Plasma-Lyte 148® (Plasmalyte) as an alternative to 0.9% saline may therefore improve outcomes after kidney transplantation.

The BEST-Fluids study is an investigator-initiated, pragmatic, registry-based, multi-centre, double -blind randomised, controlled trial. The primary objective of the study is to evaluate the effect in deceased donor kidney transplant recipients of intravenous therapy with Plasmalyte versus 0.9% saline, commencing pre-operatively and continuing until intravenous fluids are no longer required or 48 hours post-transplant (whichever is earliest), on DGF, defined as the requirement for dialysis in the first seven days post-transplant.

Patients admitted for a deceased donor kidney transplant at participating centres will be invited to participate in the study prior to transplant surgery. Following informed consent, participants will be randomised to receive either blinded Plasmalyte or blinded 0.9% saline for all intravenous fluid therapy purposes until 48 hours post-transplant. The volume and rate of fluid therapy will be determined by treating clinicians; all other treatments will be as per local standard of care. Participants will be enrolled, randomised and followed up using ANZDATA, the Australia & New Zealand Dialysis & Transplant Registry.

The trial was prospectively registered with Australia New Zealand Clinical Trials Registry (ANZCTR) on 08/03/2017 (ACTRN12617000358347).

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 808 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: An Investigator-initiated, Pragmatic, Registry-based, Multi-centre, Double-blind, Randomised Controlled Trial Evaluating the Effect of Plasmalyte Versus 0.9% Saline on Early Kidney Transplant Function in Deceased Donor Kidney Transplantation
Actual Study Start Date : January 26, 2018
Estimated Primary Completion Date : August 17, 2020
Estimated Study Completion Date : August 31, 2021

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Plasma-Lyte 148 (approx. pH 7.4) IV Infusion
Plasma-Lyte 148 (approx. pH 7.4) IV Infusion intravenous fluid therapy will be used for all maintenance, replacement and resuscitation purposes from randomization onwards until 48 hours post-transplant, or until fluid therapy is no longer required, if earlier.
Drug: Plasma-Lyte 148 (approx. pH 7.4) IV Infusion
Plasma-Lyte 148 (approx. pH 7.4) IV Infusion is a sterile, clear, non-pyrogenic isotonic solution and when administered intravenously is a source of water, electrolytes and calories. Plasma-Lyte 148 intravenous infusion is indicated as a source of water & electrolytes or as an alkalinising agent.
Other Names:
  • Plasma-Lyte 148®
  • Plasmalyte
  • Balanced crystalloid solution

Active Comparator: 0.9% SODIUM CHLORIDE 9g/L injection BP
0.9% saline intravenous fluid therapy will be used for all maintenance, replacement and resuscitation purposes from randomization onwards until 48 hours post-transplant, or until fluid therapy is no longer required, if earlier.
Drug: 0.9% SODIUM CHLORIDE 9g/L injection BP
Sodium chloride (0.9% saline) infusion is a sterile, non-pyrogenic solution of sodium chloride in Water for Injections. The concentration of sodium chloride is 154mmol/L. Sodium chloride (0.9%) intravenous infusion is indicated for extra-cellular fluid replacement and in the management of metabolic alkalosis in the presence of fluid loss, and for restoring or maintaining the concentration of sodium and chloride ions.
Other Names:
  • 0.9% saline
  • Normal saline
  • Isotonic saline




Primary Outcome Measures :
  1. The proportion of participants with Delayed Graft Function [ Time Frame: 7 Days ]
    Delayed Graft Function defined as receiving treatment with any form of dialysis in the first seven days after transplant


Secondary Outcome Measures :
  1. Early Kidney Transplant Function [ Time Frame: a. Duration of Delayed Graft Function - 12 Weeks; b. Rate of recovery of kidney transplant graft function - 2 Days ]

    Early Kidney Transplant Function, a ranked composite of

    1. Duration of Delayed Graft Function Description: Participants who require dialysis within seven days post-transplant, the time from transplant to the final dialysis treatment in days (up to 84 days/12 weeks) will be ranked from best to worst (longer times are worse).
    2. Rate of recovery of kidney transplant graft function Description: for participants who do not require dialysis, graft function assessed using the creatinine reduction ratio on post-transplant day two (CRR2) will be ranked from best to worst (smaller reductions are worse).

  2. Number of dialysis sessions [ Time Frame: First 28 days post-transplant ]
    The number of dialysis sessions

  3. Total duration of dialysis [ Time Frame: 12 Weeks ]
    The total duration of dialysis in days

  4. Creatinine reduction ratio from day 1 to day 2 post-transplant [ Time Frame: Day 1 to Day 2 post-transplant ]
    Creatinine reduction ratio from day one to day two measured using serum assay, for those who do not require dialysis within the first 7 days

  5. Reduction in serum creatinine of greater than or equal to 10% [ Time Frame: First 7 days post-transplant ]
    The proportion of subjects with a reduction in serum creatinine of greater than or equal to 10% on three consecutive days in the first 7 days post-transplant

  6. Serum creatinine trends over 52 weeks [ Time Frame: 12 months ]
    Serum creatinine trends measured over 52 weeks

  7. Incidence of serum potassium greater than or equal to 5.5 mmol/L [ Time Frame: First 48 hours post-transplant ]
    Serum potassium greater than or equal to 5.5 mmol/L measured by serum assay

  8. Peak potassium level [ Time Frame: First 48 hours post-transplant ]
    Peak potassium level, measured by serum assay

  9. Treatment for hyperkalaemia [ Time Frame: First 48 hours post-transplant ]
    Treatment for hyperkalaemia with dialysis, Ca2+-gluconate, insulin, beta-agonists, sodium bicarbonate or ion exchange resins in the first 48 hours post-transplant

  10. Incidence of significant fluid overload [ Time Frame: Baseline to day 2 ]
    Incidence of significant fluid overload defined as >5% weight gain

  11. Aggregate urine output [ Time Frame: Until day 2 post-transplant ]
    Aggregate urine output until day 2 post-transplant

  12. Requirement for inotropic support (use of vasopressors or other drugs to maintain adequate blood pressure) [ Time Frame: Intra- and post-operatively to Day 2 ]
    Requirement for inotropic support both intra- and post-operatively to Day 2

  13. Number of acute rejection episodes [ Time Frame: 12 months ]
    Number of acute rejection episodes in the first 52 weeks as reported by ANZDATA routine data capture and as assessed by treating physicians

  14. Number of renal transplant biopsies [ Time Frame: First 28 days post-transplant ]
    Number of renal transplant biopsies performed in the first 28 days post-transplant

  15. Death from all causes [ Time Frame: Up to 52 weeks ]
    Death from all causes up to 52 weeks

  16. Graft survival [ Time Frame: 12 months ]
    Graft survival and death-censored graft survival as reported by ANZDATA and assessed by treating physician

  17. Graft function [ Time Frame: 4, 12, 26 and 52 weeks ]
    Graft function (estimated glomerular filtration rate; eGFR) at 4, 12, 26 and 52 weeks

  18. Health-related quality of life [ Time Frame: Baseline, day 7, day 28, week 12, week 26, and week 52 ]
    Health-related quality of life measured using EuroQol EQ-5D-5L for adults, and EQ-5D-Y in children under 18 years. EQ-5D has descriptive and visual analogue scale (VAS). Descriptive system consists of five dimensions mobility, self-care, usual activities, pain/discomfort and anxiety/depression. VAS records patient's self-rated health on vertical visual analogue scale with endpoints best to worst health with 0 being worst and 100 being best health.

  19. Length of hospital stay [ Time Frame: 12 months ]
    Length of hospital stay over 12 months using linked data state and country based health data

  20. Healthcare resource use [ Time Frame: 12 months ]
    Healthcare resource use over 12 months using linked data state and country based health data

  21. Cost-effectiveness [ Time Frame: 12 months ]
    Cost-effectiveness over 12 months using linked data state and country based health data



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   Child, Adult, Older Adult
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Adult or child with End-Stage Kidney Disease, of any cause, on maintenance dialysis, or who has pre-dialysis stage 5 chronic kidney disease with an estimated Glomerular Filtration Rate of <15 mL/min/1.73m2, AND
  2. Planned deceased donor kidney transplant from a brain-death (DBD) or circulatory-death (DCD) organ donor within 24 hours, AND
  3. Written informed consent, or consent given by their parent or guardian (if age <18), or other authorised person

Exclusion Criteria:

  1. Planned live donor kidney transplant (except where this is cancelled in favour or transplantation from a deceased donor)
  2. Planned multi-organ transplant (dual or en-bloc kidney transplants are not excluded)
  3. Children of weight <20 kg, or a child that the treating physician believes should not be included in a study of blinded fluids due to their small body size
  4. Known hypersensitivity to the trial fluid preparations or packaging

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): NCT03829488


Locations
Show Show 18 study locations
Sponsors and Collaborators
The University of Queensland
Australian Government Department of Health
Health Research Council, New Zealand
Baxter Healthcare Corporation
Investigators
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Study Chair: Michael Collins, MBChB,FRACP,PhD Auckland District Health Board & The University of Auckland
Principal Investigator: Steven Chadban, BMed(hons),FRACP,PhD Sydney Local Health District & The University of Sydney
Additional Information:
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: The University of Queensland
ClinicalTrials.gov Identifier: NCT03829488    
Other Study ID Numbers: 15.02
ACTRN12617000358347 ( Registry Identifier: Australian New Zealand Clinical Trials Registry )
First Posted: February 4, 2019    Key Record Dates
Last Update Posted: August 13, 2020
Last Verified: August 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: Yes Individual participant data that underlie the results reported in the primary publication, after de-identification (text, tables, figures and appendices) will be available for individual participant data meta-analysis.
Supporting Materials: Study Protocol
Statistical Analysis Plan (SAP)
Time Frame: Beginning 2 years and ending 5 years following main publication. Proposals may be submitted up to 5 years following article publication. After 5 years, the data will be available in our University's data warehouse but without investigator support other than deposited metadata.
Access Criteria: An independent review board will assess proposals based on the following criteria: sound science, benefit-risk balancing and research team expertise.

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Kidney Diseases
Kidney Failure, Chronic
Delayed Graft Function
Urologic Diseases
Pathologic Processes
Renal Insufficiency, Chronic
Renal Insufficiency
Plasma-lyte 148
Ophthalmic Solutions
Pharmaceutical Solutions