Brain Injuries, TraumaticCOGITATENCT02982122
CPPopt Guided Therapy: Assessment of Target Effectiveness
A study of Brain Injuries, Traumatic and Cerebrovascular Circulation, run by Maastricht University Medical Center at 2 sites in 2 countries.
Trial summary
Despite improvements in management, mortality in severe traumatic brain injury (TBI) remains 25% and only 40% of patients survive without major handicap. Medical/surgical interventions aim to maintain adequate brain perfusion, which is critically dependent on cerebral perfusion pressure (CPP); calculated as the… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Brain Injuries, Traumatic, Cerebrovascular Circulation, Homeostasis
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 60 participants
- Where
- 2 sitesin 2 countries
- Study dates
- 1 Mar 2018to 27 Feb 2020
- Phase
- Interventional
- 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 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Any adult severe TBI patient requiring multimodality monitoring and ICP-directed therapy for at least 24 hrs on the assessment of the recruiting team.
- Start randomization within 24 hrs after ICU admission.
- Deferred informed consent or deferred proxy assent from relatives/legal representative (consultee).
- Exception for enrolling a patient past the 24 hour window: A patient who is admitted to the hospital and later experiences neuro-worsening that is not due to a systemic insult, (e.g. myocardial infarction, arrhythmia, pulmonary embolus, systemic hemorrhage) but due to a presumptive intracranial cause, and subsequently requires an ICP monitor, may be screened for enrolment. Consent, randomization, and monitor placement must be done within 48 hours from injury in order for the patient to qualify.
Who cannot join
- Patients < 18 years old.
- Known pregnancy.
- Moribund at presentation (e.g. bilaterally absent pupillary responses)
- Patients with primary decompressive craniectomy.
- Patients already enrolled in > 1 other research studies.
Trial locations and contacts
2 sites in 2 countries.
2 sites in 2 countries
About this study
Official title: A Randomized Clinical Trial Assessing the Effect of "Optimal" Cerebral Perfusion Pressure Monitoring in the Management of Severe Traumatic Brain Injury
Despite improvements in management, mortality in severe traumatic brain injury (TBI) remains 25% and only 40% of patients survive without major handicap. Medical/surgical interventions aim to maintain adequate brain perfusion, which is critically dependent on cerebral perfusion pressure (CPP); calculated as the difference between mean arterial pressure (MAP) and intracranial pressure (ICP). Current guidelines aim for a CPP above 50 mmHg, based on population means. However, this 'one size fits all' approach is flawed, because the relation between CPP and brain perfusion varies between individuals. Further, this approach takes no account of autoregulation, a key protective mechanism that maintains cerebral perfusion despite CPP fluctuations.
Autoregulation is variably preserved following TBI, and there are large between patient variances in the 'optimal' CPP (CPPopt) at which autoregulation operates best. Individual CPPopt can be retrieved automatically by plotting autoregulation data against the CPP over a certain time window. The investigators have shown that maintenance of CPP close to CPPopt is associated with improved outcomes. These data pose the hypothesis that optimisation of management in individuals may be achieved by using the zone of optimal autoregulation as a basis for defining individualised CPP targets.
Read more
The investigators propose, together with collaborators in the CPPopt study group (Maastricht, Cambridge, Leuven and Aachen) to set up a pilot (multicenter) feasibility study to develop a protocol for a definitive outcome randomized controlled trial (RCT). This study aims to develop protocols for CPPopt guided critical care, and show that they maintain patients closer to their optimum perfusion levels than standard protocols which keep above a population CPP threshold of 60 mmHg.
Hence, the main objective is to offer clinicians monitoring and therapy algorithms that achieve individualized optimal CPPopt targets and potentially improve TBI outcome.
- Being tested
- For both groups, CPP targets will be achieved first by ICP control if this is raised and then by ABP support by titration (up or down) of vasopressors and fluids according to local protocols.
- Medical subject headings
- Brain Injuries, Traumatic
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
For both groups, CPP targets will be achieved first by ICP control if this is raised and then by ABP support by titration (up or down) of vasopressors and fluids according to local protocols.Other
For both groups, CPP targets will be achieved first by ICP control if this is raised and then by ABP support by titration (up or down) of vasopressors and fluids according to local protocols.
| Study group | Role | What they receive |
|---|---|---|
| CPPopt intervention group | Experimental | Patients are managed according to Brain Trauma Foundation guidelines, except for CPP where the CPPopt is targeted. Receives: Other: For both groups, CPP targets will be achieved first by ICP control if this is raised and then by ABP support by titration (up or down) of vasopressors and fluids according to local protocols. |
| CPP control group | Active comparator | Patients are managed according to Brain Trauma Foundation guidelines with CPP between 60 and 70 mmHg.
CPPopt information is recorded but hidden for the treating clinicians. Receives: Other: For both groups, CPP targets will be achieved first by ICP control if this is raised and then by ABP support by titration (up or down) of vasopressors and fluids according to local protocols. |
What is being measured
The primary outcome is the main question the study is designed to answer.
Percentage of monitoring time with measured CPP within 5 mmHg of calculated CPPopt
Main feasible endpoint: In pilot studies, we showed that, on average, patients spent a mean (+SD) of 30% ( 8%) of their monitored time with measured CPP within 5 mmHg of CPPopt. The study will be powered to target an increase in this metric to 50% of monitored time.
Measured: First 5 days during intensive care unit admission
Secondary outcomes (1)
Treatment Intensity Level (TIL) score
Main safety secondary endpoint: A change in daily TIL score of > 3 is representative of a clinical significant escalation of TBI treatment from basic ICP management to second tier therapies known to carry risk of harm and therefore is expected to represent a clinically significant potentially harmful effect of CPPopt guided management.
Measured: First 5 days during intensive care unit admission
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted5 Dec 2016 (estimated)
- Study start1 Mar 2018
- Primary completion27 Feb 2020
- Study completion27 Feb 2020
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (6)Papers the sponsor has linked to this study.
- Other trials for Brain Injuries, TraumaticStudies 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 N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 60 participants (actual)
Sponsor and investigators
- Lead sponsor
- Maastricht University Medical Center
- Sponsor type
- University, hospital or other
- Collaborators
- European Society of Intensive Care Medicine
- Responsible party
- Sponsor
- Investigators
- Paul Roekaerts, professor, Study chair, Maastricht University Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02982122
- Sponsor's protocol ID
- COGITATE
- Acronym
- COGITATE
- Status last verified
- Sep 2020
- First submitted
- 23 Nov 2016
- Last updated
- 30 Sep 2020
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
Publications
Aries MJ, Wesselink R, Elting JW, Donnelly J, Czosnyka M, Ercole A, Maurits NM, Smielewski P. Enhanced Visualization of Optimal Cerebral Perfusion Pressure Over Time to Support Clinical Decision Making. Crit Care Med. 2016 Oct;44(10):e996-9. doi: 10.1097/CCM.0000000000001816.
PubMed 27270178Zuercher P, Groen JL, Aries MJ, Steyerberg EW, Maas AI, Ercole A, Menon DK. Reliability and Validity of the Therapy Intensity Level Scale: Analysis of Clinimetric Properties of a Novel Approach to Assess Management of Intracranial Pressure in Traumatic Brain Injury. J Neurotrauma. 2016 Oct 1;33(19):1768-1774. doi: 10.1089/neu.2015.4266. Epub 2016 Feb 11.
PubMed 26866876Donnelly J, Aries MJ, Czosnyka M. Further understanding of cerebral autoregulation at the bedside: possible implications for future therapy. Expert Rev Neurother. 2015 Feb;15(2):169-85. doi: 10.1586/14737175.2015.996552.
PubMed 25614952Aries MJ, Czosnyka M, Budohoski KP, Steiner LA, Lavinio A, Kolias AG, Hutchinson PJ, Brady KM, Menon DK, Pickard JD, Smielewski P. Continuous determination of optimal cerebral perfusion pressure in traumatic brain injury. Crit Care Med. 2012 Aug;40(8):2456-63. doi: 10.1097/CCM.0b013e3182514eb6.
PubMed 22622398Beqiri E, Tas J, Czosnyka M, van Kaam RCR, Donnelly J, Haeren RH, van der Horst ICC, Hutchinson PJ, van Kuijk SMJ, Liberti AL, Menon DK, Hoedemaekers CWE, Depreitere B, Meyfroidt G, Ercole A, Aries MJH, Smielewski P. Does Targeting CPP at CPPopt Actually Improve Cerebrovascular Reactivity? A Secondary Analysis of the COGiTATE Randomized Controlled Trial. Neurocrit Care. 2025 Jun;42(3):937-944. doi: 10.1007/s12028-024-02168-y. Epub 2024 Dec 2.
PubMed 39623160Beqiri E, Smielewski P, Robba C, Czosnyka M, Cabeleira MT, Tas J, Donnelly J, Outtrim JG, Hutchinson P, Menon D, Meyfroidt G, Depreitere B, Aries MJ, Ercole A. Feasibility of individualised severe traumatic brain injury management using an automated assessment of optimal cerebral perfusion pressure: the COGiTATE phase II study protocol. BMJ Open. 2019 Sep 20;9(9):e030727. doi: 10.1136/bmjopen-2019-030727.
PubMed 31542757
Study at a glance
From the registry record, last updated by the sponsor on 30 Sep 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Randomized Clinical Trial Assessing the Effect of "Optimal" Cerebral Perfusion Pressure Monitoring in the Management of Severe Traumatic Brain Injury
- ClinicalTrials.gov ID
- NCT02982122
- Acronym / sponsor ID
- COGITATE / COGITATE
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 60 participants (actual)
- Lead sponsor
- Maastricht University Medical CenterUniversity, hospital or other
- Collaborators
- European Society of Intensive Care Medicine
- Study start
- 1 Mar 2018 (actual)
- Primary completion
- 27 Feb 2020 (actual)
- Study completion
- 27 Feb 2020 (actual)
- First posted
- 5 Dec 2016 (estimated)
- 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.
Despite improvements in management, mortality in severe traumatic brain injury (TBI) remains 25% and only 40% of patients survive without major handicap. Medical/surgical interventions aim to maintain adequate brain perfusion, which is critically dependent on cerebral perfusion pressure (CPP); calculated as the difference between mean arterial pressure (MAP) and intracranial pressure (ICP). Current guidelines aim for a CPP above 50 mmHg, based on population means. However, this 'one size fits all' approach is flawed, because the relation between CPP and brain perfusion varies between individuals. Further, this approach takes no account of autoregulation, a key protective mechanism that maintains cerebral perfusion despite CPP fluctuations.
Autoregulation is variably preserved following TBI, and there are large between patient variances in the 'optimal' CPP (CPPopt) at which autoregulation operates best. Individual CPPopt can be retrieved automatically by plotting autoregulation data against the CPP over a certain time window. The investigators have shown that maintenance of CPP close to CPPopt is associated with improved outcomes. These data pose the hypothesis that optimisation of management in individuals may be achieved by using the zone of optimal autoregulation as a basis for defining individualised CPP targets.
The investigators propose, together with collaborators in the CPPopt study group (Maastricht, Cambridge, Leuven and Aachen) to set up a pilot (multicenter) feasibility study to develop a protocol for a definitive outcome randomized controlled trial (RCT). This study aims to develop protocols for CPPopt guided critical care, and show that they maintain patients closer to their optimum perfusion levels than standard protocols which keep above a population CPP threshold of 60 mmHg.
Hence, the main objective is to offer clinicians monitoring and therapy algorithms that achieve individualized optimal CPPopt targets and potentially improve TBI outcome.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| CPPopt intervention group | Experimental | Other: For both groups, CPP targets will be achieved first by ICP control if this is raised and then by ABP support by titration (up or down) of vasopressors and fluids according to local protocols.Patients are managed according to Brain Trauma Foundation guidelines, except for CPP where the CPPopt is targeted. |
| CPP control group | Active comparator | Other: For both groups, CPP targets will be achieved first by ICP control if this is raised and then by ABP support by titration (up or down) of vasopressors and fluids according to local protocols.Patients are managed according to Brain Trauma Foundation guidelines with CPP between 60 and 70 mmHg. CPPopt information is recorded but hidden for the treating clinicians. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- Any adult severe TBI patient requiring multimodality monitoring and ICP-directed therapy for at least 24 hrs on the assessment of the recruiting team.
- Start randomization within 24 hrs after ICU admission.
- Deferred informed consent or deferred proxy assent from relatives/legal representative (consultee).
- Exception for enrolling a patient past the 24 hour window: A patient who is admitted to the hospital and later experiences neuro-worsening that is not due to a systemic insult, (e.g. myocardial infarction, arrhythmia, pulmonary embolus, systemic hemorrhage) but due to a presumptive intracranial cause, and subsequently requires an ICP monitor, may be screened for enrolment. Consent, randomization, and monitor placement must be done within 48 hours from injury in order for the patient to qualify.
Key exclusion criteria (5 listed)
- Patients < 18 years old.
- Known pregnancy.
- Moribund at presentation (e.g. bilaterally absent pupillary responses)
- Patients with primary decompressive craniectomy.
- Patients already enrolled in > 1 other research studies.
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 |
|---|---|---|
| For both groups, CPP targets will be achieved first by ICP control if this is raised and then by ABP support by titration (up or down) of vasopressors and fluids according to local protocols.For both groups, CPP targets will be achieved first by ICP control if this is raised and then by ABP support by titration (up or down) of vasopressors and fluids according to local protocols. | Other | CPP control group, CPPopt intervention group |
Primary outcome
Percentage of monitoring time with measured CPP within 5 mmHg of calculated CPPopt
Time frame: First 5 days during intensive care unit admission
Main feasible endpoint: In pilot studies, we showed that, on average, patients spent a mean (+SD) of 30% ( 8%) of their monitored time with measured CPP within 5 mmHg of CPPopt. The study will be powered to target an increase in this metric to 50% of monitored time.
1 secondary outcome
Treatment Intensity Level (TIL) score
Time frame: First 5 days during intensive care unit admission
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 30 Sep 2020.
- Results publication: PubMed 27270178Aries MJ, Wesselink R, Elting JW, Donnelly J, Czosnyka M, Ercole A, Maurits NM, Smielewski P. Enhanced Visualization of Optimal Cerebral Perfusion Pressure Over Time to Support Clinical Decision Making. Crit Care Med. 2016 Oct;44(10):e996-9. doi: 10.1097/CCM.0000000000001816.
- Results publication: PubMed 26866876Zuercher P, Groen JL, Aries MJ, Steyerberg EW, Maas AI, Ercole A, Menon DK. Reliability and Validity of the Therapy Intensity Level Scale: Analysis of Clinimetric Properties of a Novel Approach to Assess Management of Intracranial Pressure in Traumatic Brain Injury. J Neurotrauma. 2016 Oct 1;33(19):1768-1774. doi: 10.1089/neu.2015.4266. Epub 2016 Feb 11.
- Results publication: PubMed 25614952Donnelly J, Aries MJ, Czosnyka M. Further understanding of cerebral autoregulation at the bedside: possible implications for future therapy. Expert Rev Neurother. 2015 Feb;15(2):169-85. doi: 10.1586/14737175.2015.996552.
- Results publication: PubMed 22622398Aries MJ, Czosnyka M, Budohoski KP, Steiner LA, Lavinio A, Kolias AG, Hutchinson PJ, Brady KM, Menon DK, Pickard JD, Smielewski P. Continuous determination of optimal cerebral perfusion pressure in traumatic brain injury. Crit Care Med. 2012 Aug;40(8):2456-63. doi: 10.1097/CCM.0b013e3182514eb6.
- Derived from this study: PubMed 39623160Beqiri E, Tas J, Czosnyka M, van Kaam RCR, Donnelly J, Haeren RH, van der Horst ICC, Hutchinson PJ, van Kuijk SMJ, Liberti AL, Menon DK, Hoedemaekers CWE, Depreitere B, Meyfroidt G, Ercole A, Aries MJH, Smielewski P. Does Targeting CPP at CPPopt Actually Improve Cerebrovascular Reactivity? A Secondary Analysis of the COGiTATE Randomized Controlled Trial. Neurocrit Care. 2025 Jun;42(3):937-944. doi: 10.1007/s12028-024-02168-y. Epub 2024 Dec 2.
- Derived from this study: PubMed 31542757Beqiri E, Smielewski P, Robba C, Czosnyka M, Cabeleira MT, Tas J, Donnelly J, Outtrim JG, Hutchinson P, Menon D, Meyfroidt G, Depreitere B, Aries MJ, Ercole A. Feasibility of individualised severe traumatic brain injury management using an automated assessment of optimal cerebral perfusion pressure: the COGiTATE phase II study protocol. BMJ Open. 2019 Sep 20;9(9):e030727. doi: 10.1136/bmjopen-2019-030727.
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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.
Paul Roekaerts, professor study chair
Maastricht University Medical Center
2 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study of Brain Injuries, Traumatic and Cerebrovascular Circulation, run by Maastricht University Medical Center at 2 sites in 2 countries.
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 5 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 30 Sep 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in Belgium, United Kingdom. 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.
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?
Percentage of monitoring time with measured CPP within 5 mmHg of calculated CPPopt (time frame: First 5 days during intensive care unit admission). 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 NCT02982122, which also lists 6 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 30 Sep 2020.