COGiTATE (TBI patients)

CPPOpt Guided Therapy: Assessment of Target Effectiveness (COGITATE)

Autoregulation guided treatment is a plausible management strategy for traumatic brain injury (TBI). It aims to minimise harm from global or regional either hypo- and hyperperfusion by targeting a point where pressure autoregulation is best preserved or “optimal”. Observational data suggests that management of patients above or below CPPopt is associated with worse outcomes and mortality respectively. However, there is no prospective evidence to support its use and observational data is insufficient to draw firm conclusions as to how to operationalize the use of autoregulation measurements as part of treatment. Despite this, the concept of CPPopt is already being used clinically; either ad hoc or even as part of a formal protocol in some centres.

It is not yet possible to design a clinical outcome study at this time because;

➤ There is still much we do not know about targeting CPPopt. In particular;

    • Should CPPopt be targeted outright or be a guide given other parameters (and if so, how)?
    • Is CPPopt the most appropriate target or some other associated parameter (such as the lower limit of
    • Should we target CPPopt even if autoregulation at CPPopt is still absent?
    • Is CPPopt guided therapy beneficial in all TBI patients?
    • Is CPPopt guided therapy equally beneficial in contusional, pericontusional and ‘normal’ TBI

➤ Clinical outcome studies in intensive care are typically underpowered and a physiological end-point is probably more realistic.

➤  Most importantly: The physiological effect of targeting CPPopt has not been prospectively established. Optimal autoregulation often occurs at CPPs somewhat higher than the (recent adjusted) recommended range of 60-70mmHg given by the brain trauma foundation (BFT), although these are based on weak evidence. It is unknown whether augmenting CPP to benefit cerebral perfusion may instead drive further oedema or contusion expansion over the next days or lead to excess respiratory, renal or myocardial injury.

The bottom line is that the physiological effect of targeting CPPopt must first be established as a prerequisite for any future clinical outcome study. At the same time, a feasibility study employing randomisation would also have the benefit of providing information on the down-stream physiological effects of targeting CPPopt and the feasibility of doing this.

We will assess whether the new intervention protocol provides a greater percentage of time during which CPP is within 5 mmHg of CPPopt. This window has been chosen based on past studies which show significant impacts on outcome with greater variation from CPPopt, and on an initial feasibility study across participating centres. Therefore, the major endpoint of this study is to evaluate whether a CPPopt monitor, along with a CPP targeting protocol, is effective in reducing the difference between patient’s CPP and target ‘Optimal’ CPPopt (mainly by changing the patient’s blood pressure).

Worsening of ICP is likely to be a poor primary endpoint for a safety study, as neuro-intensive care will attempt to control this and keep it constant with escalating levels of (potentially harmful) therapeutically intense interventions. Thus one of the secondary endpoints for this proposed study will be a change in daily TBI Therapeutic Intensity Level (TIL) score. The TIL score is a global summary measure of therapy intensity for control of intracranial pressure .We know that increasing TIL score involves therapies with increasing risk of harm. We will assess if targeting CPPopt in TBI patients causes a significant increase in daily TIL score.


The primary objective is to demonstrate that CPPopt targeting is feasible in severe TBI patients.

Participating institutions (2017):

Cambridge University Hospitals NHS (local coordinator Dr. Ari Ercole, Dr. Peter Smielewski)

University Hospitals Leuven (local coordinator Dr. Geert Meyfroidt, Dr. Bart Depreitere)

Maastricht University Medical Center (project coordinator Dr. Marcel Aries)


Update COGiTATE!

COGITATE an update aug 2017


For more information about this study please contact:
Dr. Marcel Aries, neuro-intensivist, Medical University Centre Maastricht, Maastricht, The Netherlands.


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