Septic ShockREPERFUSENCT06234592
The Effect of Vasopressor Therapy on Renal Perfusion in Septic Shock
A study testing Angiotensin II, Vasopressin and Norepinephrine in people with Septic Shock and Acute Kidney Injury, run by King's College Hospital NHS Trust at 1 site in United Kingdom.
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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Septic Shock, Acute Kidney Injury
- What is being tested?
- Angiotensin II, Vasopressin and Norepinephrine
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 45 participants
- Where
- 1 siteUnited Kingdom
- Study dates
- 5 Jan 2024to Jul 2026
- Phase
- Interventional
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
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- 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 locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
United Kingdom1 site, 1 recruiting
- Recruiting
King's College Hospital
London, SE5 9RS
Sam Hutchings, 02032994957, sam.hutchings@nhs.net
About this study
Official title: The Effect of Vasopressor Therapy on Renal Perfusion in Patients With Septic Shock - a Mechanistically Focussed Randomized Control Study
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
- Being tested
- Angiotensin II, Vasopressin, Norepinephrine
- Medical subject headings
- Shock, Septic, Acute Kidney Injury
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Angiotensin IIDrug
Angiotensin II infusion
VasopressinDrug
Vasopressin infusion
NorepinephrineDrug
Standard care vasopressor therapy, norepinephrine infusion
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: 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. Receives: 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. Receives: Drug: Norepinephrine |
What is being measured
The primary outcome is the main question the study is designed to answer.
Cortical mean transit time (mTT) measured in seconds
Contrast enhanced ultrasound measure of renal cortical tissue blood flow
Measured: Measured at +24 hours following study vasopressor infusion starting
Secondary outcomes (5)
Cortical mean transit time (mTT) measured in seconds
Contrast enhanced ultrasound measures of renal cortical tissue blood flow
Measured: Measured at +1 hour and +24 hours following study vasopressor infusion starting
Cortical perfusion index (PI) measured in arbitrary units
Contrast enhanced ultrasound measures of renal cortical tissue blood flow
Measured: Measured at +1 hour and +24 hours following study vasopressor infusion starting
Cortical wash in rate (WiR) measured in arbitrary units
Contrast enhanced ultrasound measures of renal cortical tissue blood flow
Measured: 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)
Mean urinary pO2
Measured: 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)
Biomarker analysis - regulatory proteins involved in initiating cell cycle arrest and associated with AKI
Measured: Measured at baseline and +24 hours following study vasopressor infusion starting
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted31 Jan 2024
- Study start5 Jan 2024
- Primary completionJan 2026 (estimated)
- Study completionJul 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Septic ShockStudies of the same condition, open and under way.
- More trials run by King's College Hospital NHS TrustThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Other
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind
- Who is masked
- Outcomes assessor
- Enrolment
- 45 participants (estimated)
Sponsor and investigators
- Lead sponsor
- King's College Hospital NHS Trust
- Sponsor type
- University, hospital or other
- Collaborators
- European Society of Intensive Care Medicine, Royal Centre for Defence Medicine
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06234592
- Sponsor's protocol ID
- 328797
- Acronym
- REPERFUSE
- Status last verified
- Mar 2025
- First submitted
- 3 Jan 2024
- Last updated
- 4 Apr 2025
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Publications
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.
PubMed 38870103
Study at a glance
From the registry record, last updated by the sponsor on 4 Apr 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Effect of Vasopressor Therapy on Renal Perfusion in Patients With Septic Shock - a Mechanistically Focussed Randomized Control Study
- ClinicalTrials.gov ID
- NCT06234592
- Acronym / sponsor ID
- REPERFUSE / 328797
- Conditions
- Septic Shock, Acute Kidney Injury
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 45 participants (estimated)
- Lead sponsor
- King's College Hospital NHS TrustUniversity, hospital or other
- Collaborators
- European Society of Intensive Care Medicine, Royal Centre for Defence Medicine
- Study start
- 5 Jan 2024 (actual)
- Primary completion
- Jan 2026 (estimated)
- Study completion
- Jul 2026 (estimated)
- First posted
- 31 Jan 2024 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Other
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (outcomes assessor)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Angiotensin II Infusion | Experimental | Drug: Angiotensin II, Drug: NorepinephrineAngiotensin 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: NorepinephrineVasopressin 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: NorepinephrineStandard care vasopressor therapy which recruited participants already receiving, titrated to achieve/maintain target mean arterial pressure (MAP) as directed by attending clinician. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- 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
Key exclusion criteria (9 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Angiotensin IIAngiotensin II infusion | Drug | Angiotensin II Infusion |
| VasopressinVasopressin infusion | Drug | Vasopressin Infusion |
| NorepinephrineStandard care vasopressor therapy, norepinephrine infusion | Drug | Angiotensin II Infusion, Norepinephrine Infusion, Vasopressin Infusion |
Primary outcome
Cortical mean transit time (mTT) measured in seconds
Time frame: Measured at +24 hours following study vasopressor infusion starting
Contrast enhanced ultrasound measure of renal cortical tissue blood flow
5 secondary outcomes
Cortical mean transit time (mTT) measured in seconds
Time frame: Measured at +1 hour and +24 hours following study vasopressor infusion starting
Cortical perfusion index (PI) measured in arbitrary units
Time frame: Measured at +1 hour and +24 hours following study vasopressor infusion starting
Cortical wash in rate (WiR) measured in arbitrary units
Time frame: 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)
Time frame: 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)
Time frame: Measured at baseline and +24 hours following study vasopressor infusion starting
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 4 Apr 2025.
- Derived from this study: PubMed 38870103McDonald 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Angiotensin II, Vasopressin and Norepinephrine in people with Septic Shock and Acute Kidney Injury, run by King's College Hospital NHS Trust at 1 site in United Kingdom.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 4 Apr 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Sam Hutchings (02032994957, sam.hutchings@nhs.net), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Cortical mean transit time (mTT) measured in seconds (time frame: Measured at +24 hours following study vasopressor infusion starting). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT06234592, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 4 Apr 2025.