Clinical trial NCT05850962: Individualised Blood Pressure Targets Versus Standard Care Among Critically Ill Patients With Shock
Official title: Individualised Blood Pressure Targets Versus Standard Care Among Critically Ill Patients With Shock - A Multicentre Randomised Controlled Trial
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Critical Illness
Shock
Keywords: Relative hypotension
Lead sponsor: University of Newcastle, Australia
Sponsor class: OTHER
First posted: 2023-05-09
Enrollment: 1260
Sex: ALL
Minimum age (years): 40
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: 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.


Eligibility criteria: 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

Primary outcomes:
measure: Mortality
timeFrame: 14 days
Secondary outcomes:
measure: Time to death through day 14
timeFrame: First 14 days of randomisation
measure: Major Adverse Kidney Events
timeFrame: 14 days from randomisation
measure: Renal replacement therapy free days until day 28
timeFrame: 28 days from randomisation
measure: Peak increase in serum creatinine levels
timeFrame: 28 days from randomisation
measure: Time to death through day 90
timeFrame: First 90 days of randomisation
measure: Mortality
timeFrame: 90 days
Other outcomes:
Locations:
city: Newcastle
country: Australia
facility: Hunter Medical Research Institute
state: New South Wales
Study officials:
References:
citation: Panwar R. Untreated Relative Hypotension Measured as Perfusion Pressure Deficit During Management of Shock and New-Onset Acute Kidney Injury-A Literature Review. Shock. 2018 May;49(5):497-507. doi: 10.1097/SHK.0000000000001033.
citation: Panwar R, Tarvade S, Lanyon N, Saxena M, Bush D, Hardie M, Attia J, Bellomo R, Van Haren F; REACT Shock Study Investigators and Research Coordinators. Relative Hypotension and Adverse Kidney-related Outcomes among Critically Ill Patients with Shock. A Multicenter, Prospective Cohort Study. Am J Respir Crit Care Med. 2020 Nov 15;202(10):1407-1418. doi: 10.1164/rccm.201912-2316OC.
citation: Panwar R, Van Haren F, Cazzola F, Nourse M, Brinkerhoff G, Quail A. Standard care versus individualized blood pressure targets among critically ill patients with shock: A multicenter feasibility and preliminary efficacy study. J Crit Care. 2022 Aug;70:154052. doi: 10.1016/j.jcrc.2022.154052. Epub 2022 May 5.
citation: Panwar R, Lanyon N, Davies AR, Bailey M, Pilcher D, Bellomo R. Mean perfusion pressure deficit during the initial management of shock--an observational cohort study. J Crit Care. 2013 Oct;28(5):816-24. doi: 10.1016/j.jcrc.2013.05.009. Epub 2013 Jul 10.
citation: Panwar R, Sullohern B, Shiel E, Alexis Brown C, Quail A. Validity of a protocol to estimate patients' pre-morbid basal blood pressure. Blood Press. 2018 Feb;27(1):10-18. doi: 10.1080/08037051.2017.1358055. Epub 2017 Jul 26.