The Effect of Vasopressor Therapy on Renal Perfusion in Septic Shock

NCT06234592 | Recruiting

• 1 other identifier: 328797
• Study Type: interventional
• Target: 45
• Locations: 1 country
• Sites: 1

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.

Conditions

Septic Shock; Acute Kidney Injury

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (5)

• Cortical mean transit time (mTT) measured in seconds

  Measured at +1 hour and +24 hours following study vasopressor infusion starting

• Cortical perfusion index (PI) measured in arbitrary units

  Measured at +1 hour and +24 hours following study vasopressor infusion starting

• Cortical wash in rate (WiR) measured in arbitrary units

  Measured at +1 hour and +24 hours following study vasopressor infusion starting

• Urinary oxygen tension (pO2) across 24 hours study period measured in millimetres of mercury (mmHg)

  Across 24 hours study period

• 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

Other Outcomes (3)

• Perfused vessel density (PVD) measured in millimetres per square millimetre

  Measured at +1 hour and +24 hours following study vasopressor infusion starting

• 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

• 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

Study Arms (3)

Angiotensin II Infusion

EXPERIMENTAL

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.

Drug: Angiotensin II; Drug: Norepinephrine

Vasopressin Infusion

EXPERIMENTAL

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.

Drug: Vasopressin; Drug: Norepinephrine

Norepinephrine Infusion

ACTIVE COMPARATOR

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

Drug: Norepinephrine

Interventions

Angiotensin II DRUG

Angiotensin II infusion

Angiotensin II Infusion

Vasopressin DRUG

Vasopressin infusion

Vasopressin Infusion

Norepinephrine DRUG

Standard care vasopressor therapy, norepinephrine infusion

Angiotensin II Infusion; Norepinephrine Infusion; Vasopressin Infusion

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• King's College Hospital NHS Trust: lead
• European Society of Intensive Care Medicine: collaborator
• Royal Centre for Defence Medicine: collaborator

Study Sites (1)

King's College Hospital

London, SE5 9RS, United Kingdom

RECRUITING

Related Publications (1)

• 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 DERIVED

MeSH Terms

Conditions

Shock, Septic; Acute Kidney Injury

Interventions

Angiotensin II; Vasopressins; Norepinephrine

Condition Hierarchy (Ancestors)

Sepsis; Infections; Systemic Inflammatory Response Syndrome; Inflammation; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Shock; Renal Insufficiency; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases

Intervention Hierarchy (Ancestors)

Angiotensins; Peptide Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Neuropeptides; Peptides; Amino Acids, Peptides, and Proteins; Oligopeptides; Nerve Tissue Proteins; Proteins; Autacoids; Inflammation Mediators; Biological Factors; Pituitary Hormones, Posterior; Pituitary Hormones; Ethanolamines; Amino Alcohols; Alcohols; Organic Chemicals; Amines; Biogenic Monoamines; Biogenic Amines; Catecholamines; Catechols; Phenols; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons

Central Study Contacts

Sam Hutchings

CONTACT

02032994957; sam.hutchings@nhs.net

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Purpose: OTHER
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 3, 2024
• First Posted: January 31, 2024
• Study Start: January 5, 2024
• Primary Completion: January 1, 2026
• Study Completion (Estimated): July 1, 2026
• Last Updated: April 4, 2025

Record last verified: 2025-03

Locations

GB (1)