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

Overview

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.

Interventions

• Other Individualised MAP target
  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.

Primary outcome measures

• Mortality [Time frame: 14 days]

Secondary outcome measures (6)

• Time to death through day 14 [Time frame: First 14 days of randomisation]
• Major Adverse Kidney Events [Time frame: 14 days from randomisation]
• Renal replacement therapy free days until day 28 [Time frame: 28 days from randomisation]
• Peak increase in serum creatinine levels [Time frame: 28 days from randomisation]
• Time to death through day 90 [Time frame: First 90 days of randomisation]
• Mortality [Time frame: 90 days]

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

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Open label

Primary purpose

Prevention

Study locations

Australia · 1 center

• Hunter Medical Research Institute — Newcastle

Publications

• 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. PMID 29040214
• 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. PMID 32614244
• 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. PMID 35525132
• 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. PMID 23849541
• 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. PMID 28745077
• Panwar R, Gibberd A, Oldmeadow C, Tiruvoipati R, Aneman A, Kansal A; REACT SHOCK investigators. REACT SHOCK trial protocol and analysis plan-a multicenter randomised controlled trial comparing individualised blood pressure target versus standard blood pressure target among critically ill patients with shock. Trials. 2025 Oct 14;26(1):409. doi: 10.1186/s13063-025-09142-9. PMID 41088147

Identifiers

NCT: NCT05850962 · G2200761 · ACTRN12623000044628

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗