Clinical trial NCT06234592: The Effect of Vasopressor Therapy on Renal Perfusion in Septic Shock
Official title: The Effect of Vasopressor Therapy on Renal Perfusion in Patients With Septic Shock - a Mechanistically Focussed Randomized Control Study
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Septic Shock
Acute Kidney Injury
Lead sponsor: King's College Hospital NHS Trust
Sponsor class: OTHER
Collaborators: name: European Society of Intensive Care Medicine
name: Royal Centre for Defence Medicine
First posted: 2024-01-31
Enrollment: 45
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: OTHER

Brief summary: Acute kidney injury (AKI) is a common complication of septic shock and together these conditions carry a high mortality risk. In septic patients who develop severe AKI renal cortical perfusion is deficient despite normal macrovascular organ blood flow. This intra-renal perfusion abnormality may be amenable to pharmacological manipulation, which may offer mechanistic insight into the pathophysiology of septic AKI. The aim of the current study is to investigate the effects of vasopressin and angiotensin II on renal microcirculatory perfusion in a cohort of patients with septic shock.


Eligibility criteria: Inclusion Criteria:

* Within 48 hours of intensive care admission
* Evidence of suspected or confirmed infection
* Sequential Organ Failure (SOFA) score increase of 2 or more (assuming a baseline of 0 if no previous measures)
* Requirement for norepinephrine infusion as the sole vasopressor agent in a dose of \>0.1mcg/kg/min
* Lactate \>2mmol/L at any stage prior to randomisation

Exclusion Criteria:

* Known intolerance to Sonovue™ contrast medium, vasopressin or angiotensin II
* Patients receiving other vasoactive drugs in addition to norepinephrine
* Patients with known chronic kidney disease (CKD) stage 4 or 5 (baseline glomerular filtration rate (GFR) \<30mls/min)
* Patients receiving extra corporal membrane oxygenation (ECMO)
* Patients with acute occlusive coronary syndromes requiring intervention
* Patients with mesenteric ischaemia
* Patients with a history or presence of aortic dissection or abdominal aortic aneurysm
* Patients with Raynaud's syndrome or acute vaso-occlusive conditions
* Pregnancy

Primary outcomes:
measure: Cortical mean transit time (mTT) measured in seconds
timeFrame: Measured at +24 hours following study vasopressor infusion starting
Secondary outcomes:
measure: Cortical mean transit time (mTT) measured in seconds
timeFrame: Measured at +1 hour and +24 hours following study vasopressor infusion starting
measure: Cortical perfusion index (PI) measured in arbitrary units
timeFrame: Measured at +1 hour and +24 hours following study vasopressor infusion starting
measure: Cortical wash in rate (WiR) measured in arbitrary units
timeFrame: Measured at +1 hour and +24 hours following study vasopressor infusion starting
measure: Urinary oxygen tension (pO2) across 24 hours study period measured in millimetres of mercury (mmHg)
timeFrame: Across 24 hours study period
measure: Tissue inhibitor of metalloproteinases-2 (TIMP-2) and insulin-like growth factor binding protein-7 (IGFBP-7). Both measured in nanograms per millilitre (ng/ml)
timeFrame: Measured at baseline and +24 hours following study vasopressor infusion starting
Other outcomes:
measure: Perfused vessel density (PVD) measured in millimetres per square millimetre
timeFrame: Measured at +1 hour and +24 hours following study vasopressor infusion starting
measure: Microvascular flow index (MFI) (unitless score from 0 to 3 where 3 is the value see in health).
timeFrame: Measured at +1 hour and +24 hours following study vasopressor infusion starting
measure: Syndecan 1, angiopoietin 1 & 2, Interleukin 6 & 8 (IL-6, IL-8) and tissue necrosis factor (TNF). All measured in nanograms per millilitre (ng/ml)
timeFrame: Measured at baseline and +24 hours following study vasopressor infusion starting
Locations:
city: London
country: United Kingdom
facility: King's College Hospital
Study officials:
References: