Continuous Hyperosomolar Therapy for Traumatic Brain-injured Patients

NCT ID: NCT03143751

Last Updated: 2020-12-08

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE3

Total Enrollment

370 participants

Study Classification

INTERVENTIONAL

Study Start Date

2017-10-31

Study Completion Date

2020-03-05

Brief Summary

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Traumatic brain injury (TBI) is a major cause of death and severe prolonged disability. Intracranial hypertension (ICH) is a critical risk factor of bad outcomes after TBI. Continuous infusion of hyperosmolar therapy has been proposed for the prevention or the treatment of ICH. Whether an early administration of continuous hyperosmolar therapy improves long term outcomes is uncertain. The aim of the current study is to assess the efficiency and the safety of continuous hyperosmolar therapy in TBI patients.

The COBI trial is the first randomized controlled trial powered to investigate whether continuous hyperosmolar therapy in TBI patients improve long term recovery.

Hypothesis

Patients treated with early continuous hyperosmolar therapy have reduced morbidity and mortality rates compared to those receiving standard care alone after traumatic brain injury.

Research Questions

1. Does early continuous hyperosmolar therapy reduce morbidity and mortality rates at 3 and 6 months after TBI assessed by the GOSE questionnaire?
2. Does early continuous hyperosmolar therapy prevent intracranial hypertension?

Detailed Description

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Background Traumatic brain injury (TBI) is a major cause of death and severe prolonged disability. Intracranial hypertension (ICH) is a critical risk factor of bad outcomes after TBI.

Continuous infusion of hyperosmolar therapy has been proposed for the prevention or the treatment of ICH. Whether an early administration of continuous hyperosmolar therapy improves long term outcomes is uncertain. The aim of the current study is to assess the efficiency and the safety of continuous hyperosmolar therapy in TBI patients.

Methods The COBI (Continuous hyperosmolar therapy in traumatic brain-injured patients) trial is a multicenter, randomized, controlled, open-label, two-arms study with blinded adjudication of primary outcome. Three hundred and seventy patients hospitalized in Intensive Care Unit with a traumatic brain injury (Glasgow Coma Scale ≤ 12 and abnormal brain CT-scan) are randomized in the first 24 hours following trauma to standard care or continuous hyperosmolar therapy (NaCl 20%) plus standard care. Continuous hyperosmolar therapy is maintained for at least 48 hours in the treatment group and continued for as long as is necessary to prevent intracranial hypertension. The primary outcome is the score on the Extended Glasgow Outcome Scale (GOS-E) at 6 months. The treatment effect is estimated with ordinal logistic regression adjusted for pre-specified prognostic factors and expressed as a common odds ratio.

Discussion The COBI trial is the first randomized controlled trial powered to investigate whether continuous hyperosmolar therapy in TBI patients improve long term recovery.

Conditions

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Moderate to Severe Traumatic Brain Injury

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

SINGLE

Participants
Masking: Open label , Masked Roles: Subject and Outcomes assessor

Study Groups

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Continuous hyperosmolar therapy

Standard cares plus continuous hyperosmolar therapy (NaCl20%)

Group Type EXPERIMENTAL

NaCl20% (Continuous hyperosmolar therapy)

Intervention Type DRUG

Early intravenous administration (\<24 hours after traumatic brain injury) of NaCl20% for a minimal duration of 48 hours (continued for as long as is necessary to prevent intracranial hypertension)

1-hour bolus (15 g if Na+ \< 145 mmol/L; 7.5 g if 145 \< Na+ \< 150 mmol/L; or no bolus) followed by 1 g/hour as long as Na+\< 150 mmol/L, reduced to 0.5 g/L if 150 \< Na+ \< 155 mmol/L, Discontinuation when 155 mmol/L\<Na+

Control

Standard cares alone.

Group Type NO_INTERVENTION

No interventions assigned to this group

Interventions

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NaCl20% (Continuous hyperosmolar therapy)

Early intravenous administration (\<24 hours after traumatic brain injury) of NaCl20% for a minimal duration of 48 hours (continued for as long as is necessary to prevent intracranial hypertension)

1-hour bolus (15 g if Na+ \< 145 mmol/L; 7.5 g if 145 \< Na+ \< 150 mmol/L; or no bolus) followed by 1 g/hour as long as Na+\< 150 mmol/L, reduced to 0.5 g/L if 150 \< Na+ \< 155 mmol/L, Discontinuation when 155 mmol/L\<Na+

Intervention Type DRUG

Eligibility Criteria

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Inclusion Criteria

* 18-80 years old
* Moderate to severe traumatic brain injury defined as the association of a Coma Glasgow Scale ≤ 12 together with a traumatic abnormal brain CT-scan
* Time to inclusion inferior to 24 hours
* Informed consent (or emergency procedure)

Exclusion Criteria

* dependence for daily activity
* Coma Glasgow Scale of 3 and fixed dilated pupils
* associated cervical spine injury
* imminent death and do-not-resuscitate orders
* pregnancy.
* Major not legally responsible
* Oedemato-ascitic decompensation of hepatic cirrhosis
* State of hydro-sodium retention secondary to heart failure
Minimum Eligible Age

18 Years

Maximum Eligible Age

80 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Nantes University Hospital

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Olivier Huet, PU-PH

Role: PRINCIPAL_INVESTIGATOR

CHU de Brest

Lasocki Sigismond, PU-PH

Role: PRINCIPAL_INVESTIGATOR

University Hospital, Angers

Thomas Geerraerts, PU-PH

Role: PRINCIPAL_INVESTIGATOR

University Hospital, Toulouse

Francis Remerand, PU-PH

Role: PRINCIPAL_INVESTIGATOR

CHU de Tours

Philippe Seguin, PU-PH

Role: PRINCIPAL_INVESTIGATOR

Rennes University Hospital

Claire Dahyot, PU-PH

Role: PRINCIPAL_INVESTIGATOR

CHU Poitiers

Pierre François Perrigault, PU-PH

Role: PRINCIPAL_INVESTIGATOR

University Hospital, Montpellier

Jean Denis Moyer, PU-PH

Role: PRINCIPAL_INVESTIGATOR

AP-HP Beaujon

Tarek SHARSHAR, PU-PH

Role: PRINCIPAL_INVESTIGATOR

AP-HP Saint-Anne

Locations

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CHU Angers

Angers, , France

Site Status

CHU Brest Hopital La Cavale Blanche

Brest, , France

Site Status

AP-HP Beaujon

Clichy, , France

Site Status

CHU Montpellier

Montpellier, , France

Site Status

CHU de Nantes

Nantes, , France

Site Status

Centre Hospitalier Sainte-Anne

Paris, , France

Site Status

CHU Poitiers

Poitiers, , France

Site Status

CHU Rennes-Hopital Pontchaillou

Rennes, , France

Site Status

CHU Toulouse Hôpital Pierre-Paul Riquet

Toulouse, , France

Site Status

CHU Tours

Tours, , France

Site Status

Countries

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France

References

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Huet O, Chapalain X, Vermeersch V, Moyer JD, Lasocki S, Cohen B, Dahyot-Fizelier C, Chalard K, Seguin P, Hourmant Y, Asehnoune K, Roquilly A; Atlanrea Study Group and the Societe Francaise d'Anesthesie Reanimation (SFAR) Research Network. Impact of continuous hypertonic (NaCl 20%) saline solution on renal outcomes after traumatic brain injury (TBI): a post hoc analysis of the COBI trial. Crit Care. 2023 Jan 27;27(1):42. doi: 10.1186/s13054-023-04311-1.

Reference Type DERIVED
PMID: 36707841 (View on PubMed)

Roquilly A, Moyer JD, Huet O, Lasocki S, Cohen B, Dahyot-Fizelier C, Chalard K, Seguin P, Jeantrelle C, Vermeersch V, Gaillard T, Cinotti R, Demeure Dit Latte D, Mahe PJ, Vourc'h M, Martin FP, Chopin A, Lerebourg C, Flet L, Chiffoleau A, Feuillet F, Asehnoune K; Atlanrea Study Group and the Societe Francaise d'Anesthesie Reanimation (SFAR) Research Network. Effect of Continuous Infusion of Hypertonic Saline vs Standard Care on 6-Month Neurological Outcomes in Patients With Traumatic Brain Injury: The COBI Randomized Clinical Trial. JAMA. 2021 May 25;325(20):2056-2066. doi: 10.1001/jama.2021.5561.

Reference Type DERIVED
PMID: 34032829 (View on PubMed)

Roquilly A, Lasocki S, Moyer JD, Huet O, Perrigault PF, Dahyot-Fizelier C, Seguin P, Sharshar T, Geeraerts T, Remerand F, Feuillet F, Asehnoune K; COBI group. COBI (COntinuous hyperosmolar therapy for traumatic Brain-Injured patients) trial protocol: a multicentre randomised open-label trial with blinded adjudication of primary outcome. BMJ Open. 2017 Sep 24;7(9):e018035. doi: 10.1136/bmjopen-2017-018035.

Reference Type DERIVED
PMID: 28947465 (View on PubMed)

Other Identifiers

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RC16_0474

Identifier Type: -

Identifier Source: org_study_id