Individualised Blood Pressure Targets Versus Standard Care Among Critically Ill Patients With Shock

Study Overview
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Brief Summary
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Aim The aim of the proposed RCT is to determine effectiveness of a strategy, where MAP (mean arterial blood pressure) targets during vasopressor therapy for shock in ICU are individualized based on patients' own pre-illness MAP that would be derived as an average of up to five most recent pre-illness blood pressure readings. Hypothesis We hypothesize that targeting a patient's pre-illness MAP during management of shock can minimize the degree of MAP-deficit (a measure of relative hypotension), which may help reduce the risk of 14-day mortality and major adverse kidney events by day 14 in ICU. Endpoints The primary endpoint will be the all-cause mortality rate at day 14. Secondary endpoints will be the time to death through day 14 and day 90, major adverse kidney events (MAKE-14), renal replacement therapy (RRT) free days until day 28, and 90-day all-cause mortality. Significance To date no major RCT has tested this strategy among ICU patients with shock. This pivotal trial will provide evidence to fulfil a crucial knowledge gap regarding a common and a fundamental intervention in critical care.

Official Title
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Individualised Blood Pressure Targets Versus Standard Care Among Critically Ill Patients With Shock - A Multicentre Randomised Controlled Trial

Conditions
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Critical Illness, Shock

Intervention / Treatment
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* Other: Individualised MAP target


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: ICU patients aged greater than or equal to 40 years The patient is deemed to be in shock, defined as clinician-initiated vasopressor/inotropic therapy AND supported by any of the following within the last 24 hours: Lactate level greater than or equal to 2 mmol/l or base deficit greater than or equal to 3 mmol/l, Urine output less than or equal to 0.5 ml/kg/h or <40 ml/h for 2 or more consecutive hours Respiratory rate >22 per minute Altered mentation (Glasgow Coma Score <14) Exclusion Criteria: Patients who are moribund, or have documented not-for-resuscitation orders At least 24 hours have lapsed from the time of initiation of vasopressor or inotropic support Patients who are either receiving or are deemed to imminently need renal replacement therapy. Patients who already have an increase in serum creatinine of >350 µmol/l from baseline. End stage renal disease Patients where trauma is the main reason for the current ICU admission. Previously enrolled in the REACT Shock RCT Pregnancy, if known Active bleeding (clinical suspicion or >2 packed red blood cells within last 24 hours) Insufficient (less than two) pre-illness BP readings are available. Patients on extracorporeal support (such as extracorporeal membrane oxygenation, intra-aortic balloon pump, or ventricular assist device). Potential contraindications to either higher or lower BP targets (including but not limited to) Cerebral perfusion pressure guided therapy e.g. intracranial hemorrhage or subarachnoid hemorrhage or traumatic brain injury Abdominal perfusion pressure guided therapy Aortic injury (e.g. dissection or post-operative) Post cardiac surgery Any other condition requiring higher or lower BP target specifically

Ages Eligible for Study
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Minimum Age: 40 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| No Intervention: Standard MAP target<br>The comparator or the control group will be comprised of patients assigned to standard care, where vasopressor support will be titrated to maintain a default MAP of 65 mmHg, unless the treating clinician considers a different MAP target as more appropriate. | |
| Active Comparator: Individualised MAP target<br>In the intervention arm, a patient's own pre-illness mean arterial pressure (MAP) would be targeted (range: 55-95 mmHg) during vasopressor support in ICU. The pre-illness MAP will be estimated from most recent pre-illness BP readings following a standardized method (Panwar et al,. Blood Press. 2017:1-9) and will be targeted for the duration of vasopressor therapy for up to a maximum of five days. The treating clinician can tailor these BP targets as deemed suitable for current clinical state. The type of vasopressor that will be used is at the discretion of the treating clinician. Study intervention will cease if a patient is considered well enough by the treating clinician for discharge out of ICU. If a patient is transported out of ICU for procedural intervention, then standard (non-study) treatment should be provided. | Other: Individualised MAP target<br>* The project will test an intervention that initially targets a patient's own pre-illness mean arterial pressure (MAP) during vasopressor support in ICU. The pre-illness MAP will be estimated from the most recent pre-illness BP readings recorded in medical records.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mortality | All deaths from randomisation to 14 days | 14 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to death through day 14 |  | First 14 days of randomisation | 
| Major Adverse Kidney Events | Defined as a composite of death, new renal replacement therapy, or final serum creatinine level >= 200% of the latest preillness creatinine level, as assessed from patient medical records. | 14 days from randomisation | 
| Renal replacement therapy free days until day 28 |  | 28 days from randomisation | 
| Peak increase in serum creatinine levels |  | 28 days from randomisation | 
| Time to death through day 90 |  | First 90 days of randomisation | 
| Mortality | All deaths from randomisation to 90 days | 90 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Relative hypotension