None listed
Conditions
Brief summary
Aim The aim of the proposed RCT is to determine effectiveness of a strategy, where MAP 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 (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. This is an opportunity for the clinicians to support a clinical trial that aims to compare the effects of a simple intervention of individualized blood pressure targets over standard care for patients with shock in ICU.
Interventions
The intervention in this phase 3 RCT is identical to that of the linked pilot-phase protocol (ACTRN12618000571279). 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 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
The intervention in this phase 3 RCT is identical to that of the linked pilot-phase protocol (ACTRN12618000571279). 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 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. The range for MAP target is 55-95 mmHg. During the period of study treatment, a range of ±2 mmHg around the set target is acceptable. If the total additional vasopressor dose required to achieve these individualized MAP targets exceeds 0.75 microgram/kg/minute, or if in the opinion of the treating clinician the patient may be suffering possible adverse effects from high vasopressor dose, then the BP targets may be adjusted as deemed fit by the treating clinician. Protocol adherence for participants will be monitored during the screening rounds. Protocol deviation will be defined as failure to adjust dose of vasopressor agents while the MAP remained at least 6 mmHg above or below the set target for 4 consecutive hours, without a documented change of MAP target by 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.
Sponsors
Hunter New England Local Health District
Study design
Allocation
Randomised controlled trial
Intervention model
Parallel
Primary purpose
Prevention
Masking
Blinded (masking used) (Subject, Outcomes Assessor)
Eligibility
Sex/Gender
All
Age
40 Years to No maximum
Healthy volunteers
No
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: o Lactate level greater than or equal to 2 mmol/l or base deficit greater than or equal to 3 mmol/l, o Urine output less than or equal to 0.5 ml/kg/h or <40 ml/h for 2 or more consecutive hours o Respiratory rate >22 per minute o 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) o Cerebral perfusion pressure guided therapy e.g. intracranial hemorrhage or subarachnoid hemorrhage or traumatic brain injury o Abdominal perfusion pressure guided therapy o Aortic injury (e.g. dissection or post-operative) o Post cardiac surgery o Any other condition requiring higher or lower BP target specifically
Outcome results
None listed