Renin-guided Hemodynamic Management in Patients With Shock

NCT05898126 | Recruiting DMC

• 2 other identifiers: RENIN - 141/INT/2022GR-2021-12375069
• Study Type: interventional
• Target: 800
• Locations: 2 countries
• Sites: 3

Brief Summary

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.

Conditions

Shock

Keywords

Shock; Renin; Vasopressor; Lactate; Acute Kidney Injury; Intensive Care Unit; Mortality; Quality of life

Outcome Measures

Primary Outcomes (1)

• A composite of mortality or AKI progression at 30 days after randomization.

  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 Outcomes (9)

• All-cause mortality at intensive care unit discharge, hospital discharge, and 90 days after randomization.

  90 days

• The need for and duration of vasopressors at 30 days after randomization

  30 days

• Days alive and free from mechanical ventilation

  30 days

• Day alive and free from renal replacement therapy.

  30 days

• Days alive and outside the ICU.

  30 days

Study Arms (2)

Renin-guided hemodynamic management

EXPERIMENTAL

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

Usual care

SHAM COMPARATOR

Patients in the usual care group will be managed according to standard of practice at each participating center.

Procedure: Usual care

Interventions

Renin-guided hemodynamic management PROCEDURE

If normalization of renin levels is achieved (values within the normal laboratory range), we will continue with usual care according to local protocols.

Renin-guided hemodynamic management

Usual care PROCEDURE

Standard of care

Usual care

Eligibility Criteria

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

You may qualify if:

• ≥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.

You may not qualify if:

• 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

Sponsors & Collaborators

• Università Vita-Salute San Raffaele: lead

Study Sites (3)

University Hospital Dubrava

Dubrava, Croatia

RECRUITING

Ospedale Mater Domini

Catanzaro, Calabria, Italy

NOT YET RECRUITING

IRCCS Ospedale San Raffaele

Milan, 20132, Italy

RECRUITING

Related Publications (19)

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MeSH Terms

Conditions

Shock; Acute Kidney Injury

Condition Hierarchy (Ancestors)

Pathologic Processes; Pathological Conditions, Signs and Symptoms; Renal Insufficiency; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases

Central Study Contacts

Alessandro Belletti, MD

CONTACT

0039 0226436151; belletti.alessandro@hsr.it

Nicola Buzzatti, MD

CONTACT

0039 0226436151; buzzatti.nicola@hsr.it

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Masking Details: Single blind trial. Participants will be blinded to treatment allocation.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: MD, Full Professor

Model Details: Clinical trial in which patients affected by shock, randomly receive either renin-guided hemodynamic management or usual care.

Study Record Dates

• First Submitted: May 31, 2023
• First Posted: June 12, 2023
• Study Start: January 27, 2025
• Primary Completion (Estimated): April 28, 2027
• Study Completion (Estimated): July 28, 2027
• Last Updated: August 6, 2025

Record last verified: 2025-08

Locations

CR (1); IT (2)