Plasmalyte Versus Saline in Trauma Patients (ASTRAU)

January 29, 2024 updated by: Assistance Publique - Hôpitaux de Paris

Renal Effects of Fluid Resuscitation With Plasmalyte Viaflo Versus Saline in Trauma Patients (the ASTRAU Study)

Fluid resuscitation remains the cornerstone for the care of severe trauma patients to compensate for blood loss, to compensate for capillary leak induced by systemic inflammation but also to prevent the detrimental consequences of traumatic rhabdomyolysis. Isotonic saline (NaCl 0.9%), called "physiological serum" is the standard fluid for the resuscitation of severely injured patients. However, the formulation of NaCl 0.9% is not really physiological since its chloride concentration is 1.5 higher than the one of human plasma. This excessive chloride concentration leads to hyperchloremic acidosis and to a drop in renal perfusion after isotonic saline infusion. For this reason, we wonder whether fluid resuscitation with Plasmalyte would be beneficial for renal function of trauma patients in comparison with NaCl 0.9%. Our research question is:

In a population of trauma patients at high risk of acute kidney injury, does a fluid resuscitation with Plasmalyte Viaflo lower the incidence of severe acute kidney injury (stage 2 or 3 according to the KDIGO classification) compared with a resuscitation with isotonic saline (NaCl 0.9%)?

Study Overview

Status

Terminated

Conditions

Intervention / Treatment

Detailed Description

Fluid resuscitation remains the cornerstone for the care of severe trauma patients to compensate for blood loss, to compensate for capillary leak induced by systemic inflammation but also to prevent the detrimental consequences of traumatic rhabdomyolysis. Isotonic saline (NaCl 0.9%), called "physiological serum" is the standard fluid for the resuscitation of severely injured patients. However, the formulation of NaCl 0.9% is not really physiological since its chloride concentration is 1.5 higher than plasma. This excessive chloride concentration leads to hyperchloremic acidosis and to a drop in renal perfusion after isotonic saline infusion. A retrospective study conducted in the perioperative setting (abdominal surgery) reported a significant decrease in mortality and acute kidney injury in 926 patients receiving balanced crystalloid solution compared to a propensity-matched population of 2778 patients receiving isotonic saline. Yunos et al. conducted a prospective sequential period study including 760 patients receiving chloride-rich solution during the first 6-month period and 773 patients receiving chloride-poor solution during the next 6-month period. They reported a decrease in severe acute kidney injury (I or F in the RIFLE classification) in the group receiving chloride-poor solution. Large retrospective studies in intensive care confirmed a beneficial effect of the use of chloride-poor solutions on survival compared to chloride-rich solutions. A recent meta-analysis including 5 small size randomized controlled trials, 1 controlled trial and two retrospective studies, reported also a decrease in acute kidney injury. A recent multicenter study randomized 2778 patients to receive either Plasmalyte 148 or NaCl 0.9% during their ICU stay. No AKI or mortality differences were reported. However, this study included patients with low ICU severity score (mean APACHE II = 14) and at low risk of severe AKI (severe AKI incidence = 9%). Moreover, they received a median amount of fluid of 2000 mL during their ICU stay. This small fluid volume may not be enough to show any difference between rich-chloride and poor-chloride solutions on AKI in this population with low ICU severity scores.

Trauma patients are particularly at risk of AKI during the acute phase of trauma because of hypovolemia (bleeding), rhabdomyolysis and systemic inflammation (traumatic tissue injuries and emergency surgeries). AKI is reported in 18 to 26 % of trauma patients. In our database (TraumaBase®, traumabase.eu) that included at the time of the study the 6 trauma centers of the Paris area (France), we reported a 24% incidence of severe AKI (stage I or F of the RIFLE classification) in the subpopulation of patients needing at least one red blood cell unit transfusion in the 6 first hours of care. Moreover, this subpopulation receives an average amount of 6000 mL of fluid during the first 24 hours of care. We postulate that trauma patients at high risk of AKI receiving high volume of fluid can be the best population target to demonstrate a beneficial effect of Plasmalyte vs isotonic saline on severe AKI occurrence in a prospective, blinded, randomized manner.

Thus, we formulate the following hypothesis:

In a population of trauma patients, at high risk of AKI, a fluid resuscitation with Plasmalyte Viaflo during the 5 first days of care will lower decrease the incidence of severe acute kidney injury (stage 2 or 3 according to the KDIGO classification) compared with a resuscitation with isotonic saline (NaCl 0.9%)

Study Type

Interventional

Enrollment (Actual)

365

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • France
      • Le Kremlin-Bicêtre, France, 94270
        • Département d'Anesthésie Réanimation - Kremlin Bicêtre

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • Severe trauma defined by at least one Vittel criteria
  • Prescription for at least one red blood cell unit transfusion within 6 hours after trauma
  • Delay between trauma and study randomization ≤ 6 hours
  • Patient able to give consent or included in emergency situation
  • Patient affiliated to Health security system

Exclusion Criteria:

  • Age < 18 years
  • Chronic kidney disease needing requiring renal replacement therapy
  • Participation to another interventional trial interacting with renal function or which requires the use of a fluid resuscitation
  • Fluid resuscitation > 4000 mL before inclusion

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Double

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Plasmalyte Viaflo
Intervention type: drug (Plasmalyte Viaflo) Intervention name: plasmalyte Intervention description: fluid resuscitation using exclusively Plasmalyte up to 20L during the first 5 days
Drug: Plasmalyte Viaflo
Intervention description: fluid resuscitation using exclusively Plasmalyte up to 20L during the first 5 days
Active Comparator: NaCl 0.9%
Intervention type: drug (NaCl 0.9%) Intervention name: NaCl 0.9% Intervention description: fluid resuscitation using exclusively NaCl 0.9% up to 20L during the first 5 days
Drug: NaCl 0.9%
Intervention name: NaCl 0.9% Intervention description: fluid resuscitation using exclusively NaCl 0.9% up to 20L during the first 5 days

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Proportion of Acute Kidney Injury (stage 2 or 3 according to KDIGO classification) over the 5 first days after trauma
Time Frame: over the 5 first days after trauma
over the 5 first days after trauma

Secondary Outcome Measures

Outcome Measure
Time Frame
Mortality
Time Frame: at 28 days
at 28 days
Proportion of patients requiring renal replacement therapy (during 28 days)
Time Frame: during 28 days
during 28 days
Amount of transfused blood product units (during the first 5 days)
Time Frame: during the first 5 days
during the first 5 days
Number of days alive without free of mechanical ventilation (during 28 days)
Time Frame: during 28 days
during 28 days
Days spent alive outside the ICU (during 28 days)
Time Frame: during 28 days
during 28 days
Difference between the serum creatinine peak in the 5 first days of ICU stay and the baseline creatinine
Time Frame: during the 5 first days
during the 5 first days

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Assistance Publique - Hôpitaux de Paris

Investigators

  • Principal Investigator: Anatole HARROIS, Assistance Publique - Hôpitaux de Paris

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

June 24, 2019

Primary Completion (Actual)

August 18, 2023

Study Completion (Actual)

August 18, 2023

Study Registration Dates

First Submitted

August 10, 2018

First Submitted That Met QC Criteria

August 10, 2018

First Posted (Actual)

August 14, 2018

Study Record Updates

Last Update Posted (Actual)

January 31, 2024

Last Update Submitted That Met QC Criteria

January 29, 2024

Last Verified

January 1, 2024

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • P160919J
  • 2017-004206-17 (Other Identifier: IDRCB)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

UNDECIDED

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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