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

NCT07625995 | Recruiting Phase 2

• 1 other identifier: SRB2023231
• Study Type: interventional
• Target: 88
• Locations: 2 countries
• Sites: 3

Brief Summary

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.

Conditions

Severe Traumatic Brain Injury; Acute Brain Injury; Traumatic Brain Injury; Neurocritical Care

Keywords

Fluid Balance; Fluid Therapy; Hemodynamic Management; Feasibility Study; Intracranial Pressure

Outcome Measures

Primary Outcomes (1)

• Feasibility of achieving a neutral daily fluid balance

  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

Secondary Outcomes (11)

• Incidence of systemic organ complications

  ICU discharge

• Cerebral perfusion pressure (CPP)

  From randomisation to day 5 after randomisation

• Daily fluid balance and fluid input

  From randomisation to day 5 after randomisation

• Vasopressor and diuretic use

  ICU discharge

• Vasopressor-free days

  From randomisation to day 28 after randomisation

Study Arms (2)

Neutral Fluid Balance Strategy

EXPERIMENTAL

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)

Other: Neutral Fluid Balance Strategy

Standard of Care Fluid Management

NO INTERVENTION

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.

Interventions

Neutral Fluid Balance Strategy OTHER

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.

Neutral Fluid Balance Strategy

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• Enrollment in another clinical trial not approved for co-enrollment
• Pregnancy or suspected pregnancy
• 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

Sponsors & Collaborators

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

Study Sites (3)

Erasme University Hospital

Brussels, 1070, Belgium

RECRUITING

IRCCS Ospedale Policlinico San Martino

Genova, 16132, Italy

RECRUITING

Fondazione Policlinico Universitario Agostino Gemelli IRCCS

Roma, 00168, Italy

RECRUITING

Related Publications (6)

• Wiegers EJA, Lingsma HF, Huijben JA, Cooper DJ, Citerio G, Frisvold S, Helbok R, Maas AIR, Menon DK, Moore EM, Stocchetti N, Dippel DW, Steyerberg EW, van der Jagt M; CENTER-TBI; OzENTER-TBI Collaboration Groups. Fluid balance and outcome in critically ill patients with traumatic brain injury (CENTER-TBI and OzENTER-TBI): a prospective, multicentre, comparative effectiveness study. Lancet Neurol. 2021 Aug;20(8):627-638. doi: 10.1016/S1474-4422(21)00162-9.

  PMID: 34302787 BACKGROUND

• Oddo M, Poole D, Helbok R, Meyfroidt G, Stocchetti N, Bouzat P, Cecconi M, Geeraerts T, Martin-Loeches I, Quintard H, Taccone FS, Geocadin RG, Hemphill C, Ichai C, Menon D, Payen JF, Perner A, Smith M, Suarez J, Videtta W, Zanier ER, Citerio G. Fluid therapy in neurointensive care patients: ESICM consensus and clinical practice recommendations. Intensive Care Med. 2018 Apr;44(4):449-463. doi: 10.1007/s00134-018-5086-z. Epub 2018 Mar 2.

  PMID: 29500701 BACKGROUND

• Carney N, Totten AM, O'Reilly C, Ullman JS, Hawryluk GW, Bell MJ, Bratton SL, Chesnut R, Harris OA, Kissoon N, Rubiano AM, Shutter L, Tasker RC, Vavilala MS, Wilberger J, Wright DW, Ghajar J. Guidelines for the Management of Severe Traumatic Brain Injury, Fourth Edition. Neurosurgery. 2017 Jan 1;80(1):6-15. doi: 10.1227/NEU.0000000000001432.

  PMID: 27654000 BACKGROUND

• Messina A, Bakker J, Chew M, De Backer D, Hamzaoui O, Hernandez G, Myatra SN, Monnet X, Ostermann M, Pinsky M, Teboul JL, Cecconi M. Pathophysiology of fluid administration in critically ill patients. Intensive Care Med Exp. 2022 Nov 4;10(1):46. doi: 10.1186/s40635-022-00473-4.

  PMID: 36329266 BACKGROUND

• Clifton GL, Miller ER, Choi SC, Levin HS. Fluid thresholds and outcome from severe brain injury. Crit Care Med. 2002 Apr;30(4):739-45. doi: 10.1097/00003246-200204000-00003.

  PMID: 11940738 BACKGROUND

• Majdan M, Plancikova D, Brazinova A, Rusnak M, Nieboer D, Feigin V, Maas A. Epidemiology of traumatic brain injuries in Europe: a cross-sectional analysis. Lancet Public Health. 2016 Dec;1(2):e76-e83. doi: 10.1016/S2468-2667(16)30017-2. Epub 2016 Nov 29.

  PMID: 29253420 RESULT

MeSH Terms

Conditions

Brain Injuries, Traumatic; Brain Injuries

Condition Hierarchy (Ancestors)

Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Craniocerebral Trauma; Trauma, Nervous System; Wounds and Injuries

Central Study Contacts

Fabio Silvio Taccone, MD, PhD

CONTACT

+32 2 555 33 95; fabio.taccone@hubruxelles.be

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Head of department of Intensive care, Clinical Professor, Principal investigator

Model Details: Restrictive Fluid Management Strategy (INTERVENTION) vs. Routine Fluid Management Strategy (CONTROL)

Study Record Dates

• First Submitted: April 22, 2026
• First Posted: June 4, 2026
• Study Start: July 1, 2025
• Primary Completion (Estimated): December 31, 2028
• Study Completion (Estimated): February 1, 2029
• Last Updated: June 4, 2026

Record last verified: 2026-05

Locations

IT (2); BE (1)