The Effect of Vasopressor Therapy on Renal Perfusion in Septic Shock (REPERFUSE)

King's College Hospital NHS Trust

Status: Not yet enrolling

Conditions: Acute Kidney Injury; Septic Shock

Treatments: Drug: Vasopressin; Drug: Angiotensin II; Drug: Norepinephrine

Study type: Interventional

Funder types: Other

Identifiers

NCT06234592

328797

Details and patient eligibility

About

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.

Enrollment: 45 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Other

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Single Blind

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45 participants in 3 patient groups

Angiotensin II Infusion

Experimental group

Description:

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.

Treatment:

Drug: Norepinephrine

Drug: Angiotensin II

Vasopressin Infusion

Experimental group

Description:

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.

Treatment:

Drug: Norepinephrine

Drug: Vasopressin

Norepinephrine Infusion

Active Comparator group

Description:

Standard care vasopressor therapy which recruited participants already receiving, titrated to achieve/maintain target mean arterial pressure (MAP) as directed by attending clinician.

Treatment:

Drug: Norepinephrine