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Feasibility and Safety of Targeting Neutral vs Liberal Fluid Balance in Traumatic Brain Injured Patients- LIMIT-TBI Trial (LIMIT-TBI)

30. Mai 2026 aktualisiert von: Fabio Taccone, Erasme University Hospital

Feasibility and Safety of Targeting Neutral vs Liberal Fluid Balance in Traumatic Brain Injured Patients: a Phase II Randomized Controlled Trial - LIMIT-TBI Trial

The LIMIT-TBI trial is a multicenter, international, randomized, phase II clinical trial designed to evaluate the feasibility and safety of targeting a neutral fluid balance compared to standard care in critically ill adult patients with traumatic brain injury (TBI).

Fluid therapy is a cornerstone of TBI management, but optimal fluid balance remains uncertain, with both fluid overload and restriction potentially leading to adverse outcomes. This study aims to determine whether maintaining a daily fluid balance close to zero (±500 mL) during the first 5 days of ICU admission is achievable and safe.

Participants will be randomized within 48 hours of ICU admission to either a protocolized neutral fluid balance strategy or standard care. Outcomes include feasibility of achieving the target balance, organ complications, hemodynamic parameters, ICU resource utilization, and mortality and neurological outcomes up to 6 months.

Studienübersicht

Status

Rekrutierung

Bedingungen

Intervention / Behandlung

Detaillierte Beschreibung

Severe traumatic brain injury (TBI) is a major cause of mortality and long-term disability worldwide and frequently requires intensive care management. In these patients, preventing secondary brain injury is essential and involves optimizing cerebral perfusion pressure (CPP), systemic hemodynamics, and organ function. Fluid therapy plays a central role in achieving these goals.

However, the optimal fluid management strategy in TBI remains unclear. Excessive fluid administration may lead to complications such as pulmonary edema and worsening cerebral edema, while restrictive strategies may increase the risk of hypovolemia and impaired cerebral perfusion. Current guidelines provide limited or no specific recommendations due to the lack of high-quality randomized evidence. Observational data suggest that a more positive fluid balance is associated with worse outcomes, but causality has not been established.

The LIMIT-TBI trial is a pragmatic, international, multicenter, randomized, unblinded, parallel-group phase II study designed to address this evidence gap. Adult patients with TBI admitted to the ICU will be randomized within 48 hours in a 1:1 ratio to either:

A neutral fluid balance strategy, targeting a daily balance of 0 mL (±500 mL) and cumulative neutrality over the first 5 days, using a protocolized approach combining fluid restriction, vasopressors, and diuretics when needed; A standard of care strategy, in which fluid administration is guided by local practice and clinician judgment.

In the intervention group, all fluid inputs (intravenous fluids, medications, and enteral nutrition) and outputs are strictly monitored. Maintenance fluids are minimized, and adjustments are made daily to achieve neutrality while maintaining adequate mean arterial pressure and cerebral perfusion pressure targets.

The primary objective is to assess the feasibility and safety of achieving a neutral fluid balance, defined as maintaining a daily balance within ±500 mL. Secondary outcomes include systemic complications, hemodynamic parameters (including CPP), fluid administration metrics, vasopressor and diuretic use, organ support-free days, and ICU/hospital mortality. Long-term outcomes include 6-month mortality and neurological status assessed using the Glasgow Outcome Scale Extended (GOSE).

A total of 88 patients will be enrolled to provide adequate power to detect differences in fluid balance between groups. Statistical analyses will include linear mixed models for repeated measures and appropriate comparative tests for secondary outcomes, with multiple imputation for missing primary endpoint data.

This trial will provide important preliminary randomized evidence on fluid management in TBI and inform the design of future large-scale trials aimed at improving outcomes in this high-risk population.

Studientyp

Interventionell

Einschreibung (Geschätzt)

88

Phase

  • Phase 2

Kontakte und Standorte

Dieser Abschnitt enthält die Kontaktdaten derjenigen, die die Studie durchführen, und Informationen darüber, wo diese Studie durchgeführt wird.

Studienkontakt

Studienorte

  • Belgien
      • Brussels, Belgien, 1070
        • Rekrutierung
        • Erasme University Hospital
        • Kontakt:
  • Italien
      • Genova, Italien, 16132
        • Rekrutierung
        • IRCCS Ospedale Policlinico San Martino
        • Kontakt:
      • Roma, Italien, 00168
        • Rekrutierung
        • Fondazione Policlinico Universitario Agostino Gemelli IRCCS
        • Kontakt:

Teilnahmekriterien

Forscher suchen nach Personen, die einer bestimmten Beschreibung entsprechen, die als Auswahlkriterien bezeichnet werden. Einige Beispiele für diese Kriterien sind der allgemeine Gesundheitszustand einer Person oder frühere Behandlungen.

Zulassungskriterien

Studienberechtigtes Alter

  • Erwachsene
  • Älterer Erwachsener

Akzeptiert gesunde Freiwillige

Nein

Beschreibung

Inclusion Criteria:

  • Adult patients with traumatic brain injury (isolated or associated with extracranial injuries), with or without intracranial pressure monitoring
  • Admission to the intensive care unit
  • Age >18 years
  • Enrollment within 48 hours after ICU admission

Exclusion Criteria:

  • Enrollment in another clinical trial not approved for co-enrollment
  • Pregnancy or suspected pregnancy
  • Concomitant hemorrhagic shock expected to require surgical treatment within 24 hours from inclusion or requiring massive transfusion protocol
  • Hemodynamic instability at ICU admission, defined as heart rate >120 beats/min and systolic arterial pressure <100 mmHg despite at least 1 L of fluid resuscitation, or requirement for high-dose norepinephrine (>0.5 mcg/kg/min) or any inotropic support
  • Need for continuous venovenous hemodiafiltration (CVVHDF) at admission
  • Expected survival <48 hours

Studienplan

Dieser Abschnitt enthält Einzelheiten zum Studienplan, einschließlich des Studiendesigns und der Messung der Studieninhalte.

Wie ist die Studie aufgebaut?

Designdetails

  • Hauptzweck: Behandlung
  • Zuteilung: Zufällig
  • Interventionsmodell: Parallele Zuordnung
  • Maskierung: Keine (Offenes Etikett)

Waffen und Interventionen

Teilnehmergruppe / Arm
Intervention / Behandlung
Experimental: Neutral Fluid Balance Strategy

Participants randomized to the experimental arm will receive a protocolized fluid management strategy targeting a neutral fluid balance (0 ± 500 mL per day) during the first 5 days following ICU admission.

All fluid inputs (intravenous fluids, medications, enteral nutrition) and outputs (urine, drains, gastrointestinal losses, etc.) will be strictly monitored and included in the daily balance calculation.

Fluid administration will be minimized, and no routine maintenance fluids will be administered unless required to ensure a minimum daily intake of approximately 1 L (including medications and nutrition).

If the daily fluid balance exceeds ±500 mL, adjustments will be made in subsequent days by reducing fluid administration and/or introducing diuretics to achieve cumulative neutrality.

Hemodynamic targets (mean arterial pressure ≥70 mmHg, systolic arterial pressure ≥100 mmHg, and/or cerebral perfusion pressure ≥60 mmHg) will be maintained using vasopressors (e.g., norepinephrine)
Sonstiges: Neutral Fluid Balance Strategy
Protocolized strategy targeting a daily fluid balance of 0 ± 500 mL for 5 days using restricted fluids, diuretics, and vasopressors to maintain hemodynamic and cerebral perfusion targets.
Kein Eingriff: Standard of Care Fluid Management

Participants randomized to the control arm will receive standard fluid management according to local ICU practice and clinician judgment.

Intravenous fluids may be administered as maintenance therapy if part of local protocols, and to correct hypovolemia, dehydration, electrolyte imbalances, or ongoing losses.

Hemodynamic targets, including cerebral perfusion pressure, will be achieved using fluids and/or vasopressors at the discretion of the treating clinician, without a predefined protocol for fluid balance.

Fluid balance will be monitored but no specific target for neutrality will be enforced.

Was misst die Studie?

Primäre Ergebnismessungen

Ergebnis Maßnahme
Maßnahmenbeschreibung
Zeitfenster
Feasibility of achieving a neutral daily fluid balance
Zeitfenster: At 5 days after randomisation
Proportion of patients achieving a mean daily fluid balance within 0 ± 500 mL during the 5 days after ICU admission - mean daily fluid balance will be measured at day 5 as the mean of the fluid balances of the 5 previous days
At 5 days after randomisation

Sekundäre Ergebnismessungen

Ergebnis Maßnahme
Maßnahmenbeschreibung
Zeitfenster
Incidence of systemic organ complications
Zeitfenster: ICU discharge
Incidence of new organ dysfunction or complications during ICU stay.
ICU discharge
Cerebral perfusion pressure (CPP)
Zeitfenster: From randomisation to day 5 after randomisation
Mean and daily cerebral perfusion pressure during ICU stay.
From randomisation to day 5 after randomisation
Daily fluid balance and fluid input
Zeitfenster: From randomisation to day 5 after randomisation
Mean daily fluid balance and total fluid input during the first 5 days
From randomisation to day 5 after randomisation
Vasopressor and diuretic use
Zeitfenster: ICU discharge
Total and daily dose of vasopressors and diuretics during ICU stay.
ICU discharge
Vasopressor-free days
Zeitfenster: From randomisation to day 28 after randomisation
Number of days alive and free from vasopressor support.
From randomisation to day 28 after randomisation
Ventilator-free days
Zeitfenster: From randomisation to day 28 after randomisation
Number of days alive and free from invasive mechanical ventilation.
From randomisation to day 28 after randomisation
Therapy intensity level (TIL)
Zeitfenster: At day 5 after randomisation
Maximum therapy intensity level during the intervention period.
At day 5 after randomisation
ICU and hospital mortality
Zeitfenster: Hospital discharge
All-cause mortality during ICU and hospital stay.
Hospital discharge
Neurological outcome (GOSE)
Zeitfenster: Hospital discharge
Functional neurological outcome assessed by Glasgow Outcome Scale Extended.
Hospital discharge
Long-term mortality
Zeitfenster: 180 days after randomization
All-cause mortality at follow-up.
180 days after randomization
Long-term neurological outcome (GOSE)
Zeitfenster: 180 days after randomization
Functional neurological outcome assessed by Glasgow Outcome Scale Extended. Scale 1 to 8, 1= dead; 8=good recovery no social and mental deficits
180 days after randomization

Mitarbeiter und Ermittler

Hier finden Sie Personen und Organisationen, die an dieser Studie beteiligt sind.

Sponsor

Erasme University Hospital

Mitarbeiter

Fondazione Policlinico Universitario Agostino Gemelli IRCCS
Azienda Ospedaliero, Universitaria Pisana
IRCCS Azienda Ospedaliera Universitaria San Martino - IST Istituto Nazionale per la Ricerca sul Cancro, Genoa, Italy
Erasmus University Rotterdam
Hospital Clínico Universitario de Valencia
All India Institute of Medical Sciences

Publikationen und hilfreiche Links

Die Bereitstellung dieser Publikationen erfolgt freiwillig durch die für die Eingabe von Informationen über die Studie verantwortliche Person. Diese können sich auf alles beziehen, was mit dem Studium zu tun hat.

Allgemeine Veröffentlichungen

Studienaufzeichnungsdaten

Diese Daten verfolgen den Fortschritt der Übermittlung von Studienaufzeichnungen und zusammenfassenden Ergebnissen an ClinicalTrials.gov. Studienaufzeichnungen und gemeldete Ergebnisse werden von der National Library of Medicine (NLM) überprüft, um sicherzustellen, dass sie bestimmten Qualitätskontrollstandards entsprechen, bevor sie auf der öffentlichen Website veröffentlicht werden.

Haupttermine studieren

Studienbeginn (Tatsächlich)

1. Juli 2025

Primärer Abschluss (Geschätzt)

31. Dezember 2028

Studienabschluss (Geschätzt)

1. Februar 2029

Studienanmeldedaten

Zuerst eingereicht

22. April 2026

Zuerst eingereicht, das die QC-Kriterien erfüllt hat

30. Mai 2026

Zuerst gepostet (Tatsächlich)

4. Juni 2026

Studienaufzeichnungsaktualisierungen

Letztes Update gepostet (Tatsächlich)

4. Juni 2026

Letztes eingereichtes Update, das die QC-Kriterien erfüllt

30. Mai 2026

Zuletzt verifiziert

1. Mai 2026

Mehr Informationen

Begriffe im Zusammenhang mit dieser Studie

Schlüsselwörter

Zusätzliche relevante MeSH-Bedingungen

Andere Studien-ID-Nummern

  • SRB2023231

Plan für individuelle Teilnehmerdaten (IPD)

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UNENTSCHIEDEN

Arzneimittel- und Geräteinformationen, Studienunterlagen

Studiert ein von der US-amerikanischen FDA reguliertes Arzneimittelprodukt

Nein

Studiert ein von der US-amerikanischen FDA reguliertes Geräteprodukt

Nein

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