The Effect of Vasopressor Therapy on Renal Perfusion in Septic Shock

Acute Kidney Injury Clinical Trial

— REPERFUSE  

Official title:

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

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT06234592
• Other study ID #: 328797
• Status: Not yet recruiting
• Phase: N/A
• Start date: January 2024
• Est. completion date: July 2026

Study information

• Verified date: January 2024
• Source: King's College Hospital NHS Trust
• Contact: Sam Hutchings
• Phone: 02032994957
• Email: sam.hutchings[@]nhs.net
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 45
• Est. completion date: July 2026
• Est. primary completion date: January 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Acute Kidney Injury
• Septic Shock
• Shock
• Shock, Septic

Intervention

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

Locations

Country	Name	City	State
United Kingdom	King's College Hospital	London

Sponsors (3)

Lead Sponsor	Collaborator
King's College Hospital NHS Trust	European Society of Intensive Care Medicine, Royal Centre for Defence Medicine

Country where clinical trial is conducted

United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Perfused vessel density (PVD) measured in millimetres per square millimetre	Incident dark field video microscopy measures of the systemic microcirculation	Measured at +1 hour and +24 hours following study vasopressor infusion starting
Other	Microvascular flow index (MFI) (unitless score from 0 to 3 where 3 is the value see in health).	Incident dark field video microscopy measures of the systemic microcirculation	Measured at +1 hour and +24 hours following study vasopressor infusion starting
Other	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)	Biomarker analysis - markers of inflammation and endothelial activation/function	Measured at baseline and +24 hours following study vasopressor infusion starting
Primary	Cortical mean transit time (mTT) measured in seconds	Contrast enhanced ultrasound measure of renal cortical tissue blood flow	Measured at +24 hours following study vasopressor infusion starting
Secondary	Cortical mean transit time (mTT) measured in seconds	Contrast enhanced ultrasound measures of renal cortical tissue blood flow	Measured at +1 hour and +24 hours following study vasopressor infusion starting
Secondary	Cortical perfusion index (PI) measured in arbitrary units	Contrast enhanced ultrasound measures of renal cortical tissue blood flow	Measured at +1 hour and +24 hours following study vasopressor infusion starting
Secondary	Cortical wash in rate (WiR) measured in arbitrary units	Contrast enhanced ultrasound measures of renal cortical tissue blood flow	Measured at +1 hour and +24 hours following study vasopressor infusion starting
Secondary	Urinary oxygen tension (pO2) across 24 hours study period measured in millimetres of mercury (mmHg)	Mean urinary pO2	Across 24 hours study period
Secondary	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)	Biomarker analysis - regulatory proteins involved in initiating cell cycle arrest and associated with AKI	Measured at baseline and +24 hours following study vasopressor infusion starting