Individualised Blood Pressure Targets Versus Standard Care Among Critically Ill Patients With Shock (REACT-SHOCK)

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

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.

Study Overview

• Status: Recruiting
• Conditions: Shock; Critical Illness
• Intervention / Treatment: Other: Individualised MAP target

• Study Type: Interventional
• Enrollment (Estimated): 1260
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Rakshit Panwar, PhD, MD, FCICM, MBBS; Phone Number: +61240420951; Email: rakshitpanwar@hotmail.com
• Study Contact Backup: Name: Flonda Probert; Email: REACTSHOCKRCT@newcastle.edu.au

Study Locations

• Australia
  • New South Wales
    • Newcastle, New South Wales, Australia
      • Recruiting
      • Hunter Medical Research Institute
      • Contact: Flonda Probert; Phone Number: 61240420951; Email: flonda.probert@hmri.org.au
      • Contact: Naomi Knoblauch; Phone Number: 61240420951; Email: naomi.knoblauch@hmri.org.au

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
No Intervention: Standard MAP target; 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; 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; 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.

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Rakshit Panwar

Publications and helpful links

General 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.
• 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.
• 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.
• 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.
• 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.

Study record dates

Study Major Dates

• Study Start (Actual): July 20, 2023
• Primary Completion (Estimated): January 30, 2028
• Study Completion (Estimated): October 30, 2028

Study Registration Dates

• First Submitted: April 29, 2023
• First Submitted That Met QC Criteria: April 29, 2023
• First Posted (Actual): May 9, 2023

Study Record Updates

• Last Update Posted (Actual): June 7, 2024
• Last Update Submitted That Met QC Criteria: June 6, 2024
• Last Verified: June 1, 2024

More Information

Terms related to this study

• Keywords: Relative hypotension
• Additional Relevant MeSH Terms: Pathologic Processes; Disease Attributes; Shock; Critical Illness
• Other Study ID Numbers: G2200761; ACTRN12623000044628 (Registry Identifier: Australian New Zealand Clinical Trials Registry)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No