Moderate to Severe Traumatic Brain InjuryPhase 3COBINCT03143751
Continuous Hyperosomolar Therapy for Traumatic Brain-injured Patients
A Phase 3 study testing NaCl20% (Continuous hyperosmolar therapy) in people with Moderate to Severe Traumatic Brain Injury, run by Nantes University Hospital at 10 sites in France.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 18 to 80 years
- Conditions the study is for
- Moderate to Severe Traumatic Brain Injury
- What is being tested?
- NaCl20% (Continuous hyperosmolar therapy)
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 370 participants
- Where
- 10 sitesFrance
- Study dates
- 31 Oct 2017to 5 Mar 2020
- Phase
- Phase 3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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)
Who cannot join
- 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
Trial locations and contacts
10 sites in 1 country.
10 sites in 1 country
France10 sites
CHU Angers
Angers
CHU Brest Hopital La Cavale Blanche
Brest, 29600
AP-HP Beaujon
Clichy, 92118
CHU Montpellier
Montpellier
CHU de Nantes
Nantes, 44093
Centre Hospitalier Sainte-Anne
Paris, 75014
CHU Poitiers
Poitiers, 86000
CHU Rennes-Hopital Pontchaillou
Rennes
CHU Toulouse Hôpital Pierre-Paul Riquet
Toulouse, 31059
CHU Tours
Tours, 37044
About this study
Official title: Continuous Hyperosomolar Therapy for Traumatic Brain-injured Patients Study Protocol for a Multicenter Randomized Open-label Trial With Blinded Adjudication of Primary Outcome
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.
Read more
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
- Does early continuous hyperosmolar therapy reduce morbidity and mortality rates at 3 and 6 months after TBI assessed by the GOSE questionnaire?
- Does early continuous hyperosmolar therapy prevent intracranial hypertension?
Read the detailed description
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.
- Being tested
- NaCl20% (Continuous hyperosmolar therapy)
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
NaCl20% (Continuous hyperosmolar therapy)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+
| Study group | Role | What they receive |
|---|---|---|
| Continuous hyperosmolar therapy | Experimental | Standard cares plus continuous hyperosmolar therapy (NaCl20%) Receives: Drug: NaCl20% (Continuous hyperosmolar therapy) |
| Control | No intervention | Standard cares alone. |
What is being measured
The primary outcome is the main question the study is designed to answer.
Score on the Extended Glasgow Outcome Scale (GOS-E) at 6 months
The GOS-E is a scale measuring the neurological recovery after traumatic brain injuries
Measured: 6 months
Secondary outcomes (23)
Mortality rate in ICU
Measured: 3 months
Mortality rate in ICU
Measured: 6 months
GOS-E
The GOS-E is a scale measuring the neurological recovery after traumatic brain injuries
Measured: 3 months
functional independence measure : ADL (Activities of Daily Living) of Katz
Scale measuring the autonomy of patient
Measured: 3 months
functional independence measure : ADL (Activities of Daily Living) of Katz
Scale measuring the autonomy of patient
Measured: 6 months
Short Form 36
Scale measuring the quality of life
Measured: 3 months
Short Form 36
Scale measuring the quality of life
Measured: 6 months
Rate of patients with anterograde amnesia
Measured: 3 months
Rate of patients with anterograde amnesia
Measured: 6 months
Intracranial pressure control
Measured: 7 Days
Blood level of sodium
Measured: 7 Days
blood osmolality
Measured: 7 Days
Rate of thrombo-embolic events
Measured: 28 days
Rate of acute kidney injury
KDIGO 3
Measured: 28 days
Rate of centropontine myelinolysis
Diagnosis on MRI realized in case of clinical suspicion
Measured: 28 days
Blood level of chlore
Measured: 7 Days
Blood level of potassium
Measured: 5 Days
Blood level of pH (Hydrogen Potention)
Measured: 5 Days
brain oxygenation (PtiO2)
Measured: 5 Days
blood level of creatinine
Measured: 5 Days
Diuresis
Measured: 5 Days
weight
Measured: 5 Days
Ancillary study: questionnaire HADS (Hospital Anxiety and Depression Scale) in patient's relative
Scale measuring the quality of life
Measured: 6 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted8 May 2017
- Study start31 Oct 2017
- Primary completion5 Mar 2020
- Study completion5 Mar 2020
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Moderate to Severe Traumatic Brain InjuryStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind
- Who is masked
- Participant
- Enrolment
- 370 participants (actual)
Sponsor and investigators
- Lead sponsor
- Nantes University Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Olivier Huet, PU-PH, Principal investigator, CHU de BrestLasocki Sigismond, PU-PH, Principal investigator, University Hospital, AngersThomas Geerraerts, PU-PH, Principal investigator, University Hospital, ToulouseFrancis Remerand, PU-PH, Principal investigator, CHU de ToursPhilippe Seguin, PU-PH, Principal investigator, Rennes University HospitalClaire Dahyot, PU-PH, Principal investigator, CHU PoitiersPierre François Perrigault, PU-PH, Principal investigator, University Hospital, MontpellierJean Denis Moyer, PU-PH, Principal investigator, AP-HP Beaujon
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03143751
- Sponsor's protocol ID
- RC16_0474
- Acronym
- COBI
- Status last verified
- Dec 2020
- First submitted
- 28 Apr 2017
- Last updated
- 8 Dec 2020
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
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.
PubMed 36707841Roquilly 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.
PubMed 34032829Roquilly 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.
PubMed 28947465
Study at a glance
From the registry record, last updated by the sponsor on 8 Dec 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Continuous Hyperosomolar Therapy for Traumatic Brain-injured Patients Study Protocol for a Multicenter Randomized Open-label Trial With Blinded Adjudication of Primary Outcome
- ClinicalTrials.gov ID
- NCT03143751
- Acronym / sponsor ID
- COBI / RC16_0474
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 370 participants (actual)
- Lead sponsor
- Nantes University HospitalUniversity, hospital or other
- Study start
- 31 Oct 2017 (actual)
- Primary completion
- 5 Mar 2020 (actual)
- Study completion
- 5 Mar 2020 (actual)
- First posted
- 8 May 2017 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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
- Does early continuous hyperosmolar therapy reduce morbidity and mortality rates at 3 and 6 months after TBI assessed by the GOSE questionnaire?
- Does early continuous hyperosmolar therapy prevent intracranial hypertension?
Detailed description
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (participant)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Continuous hyperosmolar therapy | Experimental | Drug: NaCl20% (Continuous hyperosmolar therapy)Standard cares plus continuous hyperosmolar therapy (NaCl20%) |
| Control | No intervention | –Standard cares alone. |
Who may qualify
- Ages
- 18 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- 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)
Key exclusion criteria (8 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| 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+ | Drug | Continuous hyperosmolar therapy |
Primary outcome
Score on the Extended Glasgow Outcome Scale (GOS-E) at 6 months
Time frame: 6 months
The GOS-E is a scale measuring the neurological recovery after traumatic brain injuries
23 secondary outcomes
Mortality rate in ICU
Time frame: 3 months
Mortality rate in ICU
Time frame: 6 months
GOS-E
Time frame: 3 months
functional independence measure : ADL (Activities of Daily Living) of Katz
Time frame: 3 months
functional independence measure : ADL (Activities of Daily Living) of Katz
Time frame: 6 months
Short Form 36
Time frame: 3 months
Short Form 36
Time frame: 6 months
Rate of patients with anterograde amnesia
Time frame: 3 months
Rate of patients with anterograde amnesia
Time frame: 6 months
Intracranial pressure control
Time frame: 7 Days
Blood level of sodium
Time frame: 7 Days
blood osmolality
Time frame: 7 Days
Rate of thrombo-embolic events
Time frame: 28 days
Rate of acute kidney injury
Time frame: 28 days
Rate of centropontine myelinolysis
Time frame: 28 days
Blood level of chlore
Time frame: 7 Days
Blood level of potassium
Time frame: 5 Days
Blood level of pH (Hydrogen Potention)
Time frame: 5 Days
brain oxygenation (PtiO2)
Time frame: 5 Days
blood level of creatinine
Time frame: 5 Days
Diuresis
Time frame: 5 Days
weight
Time frame: 5 Days
Ancillary study: questionnaire HADS (Hospital Anxiety and Depression Scale) in patient's relative
Time frame: 6 months
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 8 Dec 2020.
- Derived from this study: PubMed 36707841Huet 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.
- Derived from this study: PubMed 34032829Roquilly 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.
- Derived from this study: PubMed 28947465Roquilly 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.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Olivier Huet, PU-PH principal investigator
CHU de Brest
Lasocki Sigismond, PU-PH principal investigator
University Hospital, Angers
Thomas Geerraerts, PU-PH principal investigator
University Hospital, Toulouse
10 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing NaCl20% (Continuous hyperosmolar therapy) in people with Moderate to Severe Traumatic Brain Injury, run by Nantes University Hospital at 10 sites in France.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 8 Dec 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 10 sites in France. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Score on the Extended Glasgow Outcome Scale (GOS-E) at 6 months (time frame: 6 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03143751, which also lists 3 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 8 Dec 2020.