The Effect of Vasopressor Therapy on Renal Perfusion in Septic Shock

NCT06234592 — Not applicable, Recruiting, 45 participants, King's College Hospital NHS Trust

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The Effect of Vasopressor Therapy on Renal Perfusion in Patients With Septic Shock - a Mechanistically Focussed Randomized Control Study

Registry	NCT06234592, acronym REPERFUSE
Status	Recruiting
Phase	Not applicable
Study type	Interventional; randomized, parallel, masking: single, other
Enrollment	45 (Estimated)
Sponsor	King's College Hospital NHS Trust (Other); collaborators: European Society of Intensive Care Medicine, Royal Centre for Defence Medicine
Conditions	Septic Shock, Acute Kidney Injury
Interventions	Angiotensin II, Vasopressin, Norepinephrine (Drug)
Dates	start 2024-01-05, primary completion 2026-01-01 (estimated), completion 2026-07-01 (estimated), first posted 2024-01-31, last updated 2025-04-04
Locations	1 site in United Kingdom

-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.

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+Arms and interventions

Arm	Type	Interventions	Description
Angiotensin II Infusion	Experimental	Drug: Angiotensin II; Drug: Norepinephrine	Angiotensin II infusion commenced alongside standard care vasopressor therapy (norepinephrine). Angiotensin II up titrated in a protocolised manner to a target/maximum dose of 40 ng/kg/min whilst noradrenaline down titrated in order to achieve/maintain target mean arterial pressure (MAP) as directed by attending clinician.
Vasopressin Infusion	Experimental	Drug: Vasopressin; Drug: Norepinephrine	Vasopressin infusion commenced alongside standard care vasopressor therapy (norepinephrine). Vasopressin up titrated in a protocolised manner to a target/maximum dose of 0.04 IU/min whilst noradrenaline down titrated in order to achieve/maintain target mean arterial pressure (MAP) as directed by attending clinician.
Norepinephrine Infusion	Active comparator	Drug: Norepinephrine	Standard care vasopressor therapy which recruited participants already receiving, titrated to achieve/maintain target mean arterial pressure (MAP) as directed by attending clinician.

Angiotensin II (Drug): Angiotensin II infusion
Vasopressin (Drug): Vasopressin infusion
Norepinephrine (Drug): Standard care vasopressor therapy, norepinephrine infusion

+Outcome measures

Primary outcomes

Cortical mean transit time (mTT) measured in seconds [Measured at +24 hours following study vasopressor infusion starting]: Contrast enhanced ultrasound measure of renal cortical tissue blood flow

Secondary outcomes

Cortical mean transit time (mTT) measured in seconds [Measured at +1 hour and +24 hours following study vasopressor infusion starting]: Contrast enhanced ultrasound measures of renal cortical tissue blood flow
Cortical perfusion index (PI) measured in arbitrary units [Measured at +1 hour and +24 hours following study vasopressor infusion starting]: Contrast enhanced ultrasound measures of renal cortical tissue blood flow
Cortical wash in rate (WiR) measured in arbitrary units [Measured at +1 hour and +24 hours following study vasopressor infusion starting]: Contrast enhanced ultrasound measures of renal cortical tissue blood flow
Urinary oxygen tension (pO2) across 24 hours study period measured in millimetres of mercury (mmHg) [Across 24 hours study period]: Mean urinary pO2
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) [Measured at baseline and +24 hours following study vasopressor infusion starting]: Biomarker analysis - regulatory proteins involved in initiating cell cycle arrest and associated with AKI

Other outcomes

Perfused vessel density (PVD) measured in millimetres per square millimetre [Measured at +1 hour and +24 hours following study vasopressor infusion starting]: Incident dark field video microscopy measures of the systemic microcirculation
Microvascular flow index (MFI) (unitless score from 0 to 3 where 3 is the value see in health). [Measured at +1 hour and +24 hours following study vasopressor infusion starting]: Incident dark field video microscopy measures of the systemic microcirculation
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) [Measured at baseline and +24 hours following study vasopressor infusion starting]: Biomarker analysis - markers of inflammation and endothelial activation/function

+Eligibility

Sex: All, ages: 18 Years to any

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

+Locations (1)

Facility	City	Country	Status
King's College Hospital	London	United Kingdom	Recruiting

+Publications

Results publication: McDonald R, Watchorn J, Mehta R, Ostermann M, Hutchings S. The REPERFUSE study protocol: The effects of vasopressor therapy on renal perfusion in patients with septic shock-A mechanistically focused randomised control trial. PLoS One. 2024 Jun 13;19(6):e0304227. doi: 10.1371/journal.pone.0304227. eCollection 2024. PMID 38870103