Renin-guided Hemodynamic Management in Patients With Shock

Official title

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

Overview

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.

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.

Interventions

• 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.
• Procedure Usual care
  Standard of care

Primary outcome measures

• A composite of mortality or AKI progression at 30 days after randomization. [Time frame: 30 days]

Secondary outcome measures (9)

• All-cause mortality at intensive care unit discharge, hospital discharge, and 90 days after randomization. [Time frame: 90 days]
• The need for and duration of vasopressors at 30 days after randomization [Time frame: 30 days]
• Days alive and free from mechanical ventilation [Time frame: 30 days]
• Day alive and free from renal replacement therapy. [Time frame: 30 days]
• Days alive and outside the ICU. [Time frame: 30 days]
• Duration of hospital stay. [Time frame: 30 days]
• Major adverse kidney events at day 90. [Time frame: 90 days]
• Quality of life at day 90. [Time frame: 90 days]
• Adverse events during hospital stay. [Time frame: 30 days]

Eligibility criteria

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

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Single blind

Primary purpose

Treatment

Study locations

Italy · 2 centers

• Ospedale Mater Domini — Catanzaro
• IRCCS Ospedale San Raffaele — Milan

Croatia · 1 center

• University Hospital Dubrava — Dubrava

Publications

• Orban JC, Walrave Y, Mongardon N, Allaouchiche B, Argaud L, Aubrun F, Barjon G, Constantin JM, Dhonneur G, Durand-Gasselin J, Dupont H, Genestal M, Goguey C, Goutorbe P, Guidet B, Hyvernat H, Jaber S, Lefrant JY, Malledant Y, Morel J, Ouattara A, Pichon N, Guerin Robardey AM, Sirodot M, Theissen A, Wiramus S, Zieleskiewicz L, Leone M, Ichai C; AzuRea Network. Causes and Characteristics of Death in PMID 28296682
• Mayr VD, Dunser MW, Greil V, Jochberger S, Luckner G, Ulmer H, Friesenecker BE, Takala J, Hasibeder WR. Causes of death and determinants of outcome in critically ill patients. Crit Care. 2006;10(6):R154. doi: 10.1186/cc5086. PMID 17083735
• Marenzi G, Assanelli E, Campodonico J, De Metrio M, Lauri G, Marana I, Moltrasio M, Rubino M, Veglia F, Montorsi P, Bartorelli AL. Acute kidney injury in ST-segment elevation acute myocardial infarction complicated by cardiogenic shock at admission. Crit Care Med. 2010 Feb;38(2):438-44. doi: 10.1097/CCM.0b013e3181b9eb3b. PMID 19789449
• Bagshaw SM, Lapinsky S, Dial S, Arabi Y, Dodek P, Wood G, Ellis P, Guzman J, Marshall J, Parrillo JE, Skrobik Y, Kumar A; Cooperative Antimicrobial Therapy of Septic Shock (CATSS) Database Research Group. Acute kidney injury in septic shock: clinical outcomes and impact of duration of hypotension prior to initiation of antimicrobial therapy. Intensive Care Med. 2009 May;35(5):871-81. doi: 10.1007/ PMID 19066848
• Cecconi M, De Backer D, Antonelli M, Beale R, Bakker J, Hofer C, Jaeschke R, Mebazaa A, Pinsky MR, Teboul JL, Vincent JL, Rhodes A. Consensus on circulatory shock and hemodynamic monitoring. Task force of the European Society of Intensive Care Medicine. Intensive Care Med. 2014 Dec;40(12):1795-815. doi: 10.1007/s00134-014-3525-z. Epub 2014 Nov 13. PMID 25392034
• Hernandez G, Ospina-Tascon GA, Damiani LP, Estenssoro E, Dubin A, Hurtado J, Friedman G, Castro R, Alegria L, Teboul JL, Cecconi M, Ferri G, Jibaja M, Pairumani R, Fernandez P, Barahona D, Granda-Luna V, Cavalcanti AB, Bakker J; The ANDROMEDA SHOCK Investigators and the Latin America Intensive Care Network (LIVEN); Hernandez G, Ospina-Tascon G, Petri Damiani L, Estenssoro E, Dubin A, Hurtado J, Fr PMID 30772908
• Asfar P, Meziani F, Hamel JF, Grelon F, Megarbane B, Anguel N, Mira JP, Dequin PF, Gergaud S, Weiss N, Legay F, Le Tulzo Y, Conrad M, Robert R, Gonzalez F, Guitton C, Tamion F, Tonnelier JM, Guezennec P, Van Der Linden T, Vieillard-Baron A, Mariotte E, Pradel G, Lesieur O, Ricard JD, Herve F, du Cheyron D, Guerin C, Mercat A, Teboul JL, Radermacher P; SEPSISPAM Investigators. High versus low blood PMID 24635770
• Lamontagne F, Richards-Belle A, Thomas K, Harrison DA, Sadique MZ, Grieve RD, Camsooksai J, Darnell R, Gordon AC, Henry D, Hudson N, Mason AJ, Saull M, Whitman C, Young JD, Rowan KM, Mouncey PR; 65 trial investigators. Effect of Reduced Exposure to Vasopressors on 90-Day Mortality in Older Critically Ill Patients With Vasodilatory Hypotension: A Randomized Clinical Trial. JAMA. 2020 Mar 10;323(10) PMID 32049269

Identifiers

NCT: NCT05898126 · RENIN - 141/INT/2022 · GR-2021-12375069

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗