Renin-guided Hemodynamic Management in Patients With Shock (RENIN)

August 5, 2025 updated by: Giovanni Landoni, Università Vita-Salute San Raffaele

Effect of Personalized Hemodynamic Management Based on Serum Renin Concentration on Acute Kidney Injury Progression in Patients With Shock: a Randomized Controlled Trial.

Shock is a major risk factor for mortality among patients admitted to intensive care units (ICUs). Since various hemodynamic strategies uniformly delivered to patients with shock have failed to improve clinically relevant outcomes, individualized approaches for shock supported by robust evidence are required. This study will be a prospective, multicenter, parallel-group, single-blind, randomized controlled trial. The investigators will randomly assign 800 critically ill patients requiring norepinephrine infusion to the renin-guided or usual care groups. The investigators hypothesize that renin-guided hemodynamic management, compared to usual care, can reduce a composite of mortality and acute kidney injury (AKI) progression in patients requiring vasopressor support.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

Shock is a common cause of death among patients admitted to intensive care units. Acute kidney injury (AKI) frequently occurs in patients with shock (3, 4). Maintaining adequate perfusion pressure and oxygen delivery is crucial in the hemodynamic management of shock (5). Several randomized controlled trials have evaluated the effect of various hemodynamic protocols treating shock patients with a "one size fits all" approach. However, such protocols did not reduce mortality (6-8). The task force of the surviving sepsis campaign identified the personalization of sepsis resuscitation as a research priority (9). Moreover, a large RCT showed that personalizing blood pressure targets reduced the risk of postoperative organ dysfunction in patients undergoing major surgery (10). These findings suggest that applying individualized hemodynamic strategy may optimize shock treatment and potentially improve outcomes (11).

Recent studies have investigated renin as a novel marker of tissue hypoperfusion in critically ill patients. While serum lactate level has been the most common and validated marker for tissue hypoperfusion (12), several studies are now suggesting that renin may predict mortality better than lactate in critically ill patients (13, 14). Notably, relative renin increase is associated with adverse clinical outcomes and shock reversal has been shown to decrease renin concentration (15).

The investigators aim to perform the Randomized Evaluation of persoNalized hemodynamIc maNagement based on serum renin concentration (RENIN) trial to test the hypothesis that renin-guided hemodynamic management can reduce a composite of mortality and acute kidney injury (AKI) progression during the hospital stay in patients requiring vasopressors compared with usual care.

Study Type

Interventional

Enrollment (Estimated)

800

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

  • Croatia
      • Dubrava, Croatia
        • Recruiting
        • University Hospital Dubrava
        • Contact:
          • Nikola Bradic, MD
  • Italy
      • Milan, Italy, 20132
        • Recruiting
        • IRCCS Ospedale San Raffaele
        • Contact:
    • Calabria
      • Catanzaro, Calabria, Italy
        • Not yet recruiting
        • Ospedale Mater Domini
        • Contact:
          • Andrea Bruni, MD

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • ≥18 years old
  • Admitted to an intensive care unit (ICU)
  • Requiring norepinephrine infusion at any dose to maintain a mean arterial pressure (MAP) of ≥65 mmHg after initial fluid resuscitation
  • Expected to stay in the ICU for at least 24 hours
  • Written informed consent from the patient him-/herself or the patient's next of kin as requested by the ethics committee.

Exclusion Criteria:

  • Pregnancy
  • Refused informed consent
  • Current enrollment into another randomized controlled trial that does not allow concomitant enrollment
  • Requiring vasopressors for >12 hours before the enrollment
  • Renal failure with an imminent need for renal replacement therapy (RRT)
  • Intention to use RRT by clinical judgment despite lack of urgent clinical indication
  • AKI stage 2 and 3 at enrollment according to the KDIGO criteria
  • Prior enrollment in this study
  • Severe liver disease (Child-Pugh score >7 points)
  • Chronic kidney disease (CKD) equal to or worse than CKD stage IV (eGFR <30 mL/min/1.73 m2)
  • History of kidney transplant
  • Any condition explicitly requiring a higher or lower blood pressure target according to clinical judgment

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Single

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Renin-guided hemodynamic management
We will measure serum renin values every six hours. If the measured renin concentration increases by more that 20% compared with the last value, the target mean arterial pressure (MAP) will be elevated to 75-80 mmHg. If the subsequent renin level is still rising, the target MAP will be further raised to 85-90 mmHg and the addition of inotropes will be considered. If the first subsequent renin level decreases or increases by ≤20%, the target MAP will be kept at 75-80 mmHg. If the renin level at the subsequent measurement after reaching the highest step of management protocol is still increasing, a failure of the intervention will be declared, the target MAP will return to 65-70 mmHg. If renin level further decreases or increases ≤20% for two consecutive measurements, we will downgrade the target MAP to the previous step.
Procedure: Renin-guided hemodynamic management
If normalization of renin levels is achieved (values within the normal laboratory range), we will continue with usual care according to local protocols.
Sham Comparator: Usual care
Patients in the usual care group will be managed according to standard of practice at each participating center.
Procedure: Usual care
Standard of care

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
A composite of mortality or AKI progression at 30 days after randomization.
Time Frame: 30 days
The primary outcome will be a composite of mortality or AKI progression at 30 days after randomization. We will define AKI progression as increasing at least two AKI stages compared to the AKI stage at study enrollment. We will define and stage AKI according to the current international criteria, the KDIGO guidelines (16). We will use both creatinine and urine output criteria.
30 days

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
All-cause mortality at intensive care unit discharge, hospital discharge, and 90 days after randomization.
Time Frame: 90 days
90 days
The need for and duration of vasopressors at 30 days after randomization
Time Frame: 30 days
Deaths within the initial 30 days were assigned 30 days of duration of vasopressors at day 30.
30 days
Days alive and free from mechanical ventilation
Time Frame: 30 days
Deaths within the initial 30 days were assigned zero days alive and free from mechanical ventilation at day 30.
30 days
Day alive and free from renal replacement therapy.
Time Frame: 30 days
Deaths within the initial 30 days were assigned zero days alive and free from renal replacement therapy at day 30.
30 days
Days alive and outside the ICU.
Time Frame: 30 days
Deaths within the initial 30 days were assigned zero days alive and outside the ICU at day 30.
30 days
Duration of hospital stay.
Time Frame: 30 days
Deaths within the initial 30 days were assigned 30 days of hospital stay.
30 days
Major adverse kidney events at day 90.
Time Frame: 90 days
Major adverse kidney events are defined as a composite of death, the dependence of renal replacement therapy, and persistent renal dysfunction (defined as a 25% or greater decline in estimated glomerular filtration rate (eGFR) from the baseline) (17).
90 days
Quality of life at day 90.
Time Frame: 90 days
EQ-5D-5L is the most widely used measure of health-related quality of life.
90 days
Adverse events during hospital stay.
Time Frame: 30 days
Adverse events will include atrial fibrillation, acute myocardial infarction, ventricular fibrillation or tachycardia, digital ischemia, mesenteric ischemia, bleeding, reintubation, need for non-invasive ventilation, delirium, and stroke.
30 days

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Università Vita-Salute San Raffaele

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

January 27, 2025

Primary Completion (Estimated)

April 28, 2027

Study Completion (Estimated)

July 28, 2027

Study Registration Dates

First Submitted

May 31, 2023

First Submitted That Met QC Criteria

May 31, 2023

First Posted (Actual)

June 12, 2023

Study Record Updates

Last Update Posted (Actual)

August 6, 2025

Last Update Submitted That Met QC Criteria

August 5, 2025

Last Verified

August 1, 2025

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • RENIN - 141/INT/2022
  • GR-2021-12375069 (Other Grant/Funding Number: Italian Ministry of Health)

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on Shock

Clinical Trials on Renin-guided hemodynamic management

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

CROs by country

CROs in Ecuador

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

Subscribe