Personalisation of Mean Arterial Pressure in Adult Patients With Cardiogenic Shock

Official title

Prospective, Randomized, Multicenter, Controlled Trial Assessing the Personalization of Mean Arterial Pressure in Adult Patients With Cardiogenic Shock

Overview

Cardiogenic shock is a life-threatening condition characterized by inadequate cardiac output, leading to organ hypoperfusion and high mortality. Maintaining mean arterial pressure (MAP) is crucial, but standard targets may be insufficient due to venous congestion. Central venous pressure (CVP) can help assess effective perfusion pressure. This study investigates whether a personalized MAP target adjusted by CVP improves organ function and survival compared to standard MAP management.

Detailed description

Cardiogenic shock is a severe and life-threatening condition. Its prognosis remains very poor with a high mortality rate (up to 50% in clinical series) despite recent therapeutic advances. Current recommendations suggest the use of inotropes and vasopressors to maintain tissue perfusion and prevent organ failure.

During cardiogenic shock, the mean arterial pressure (MAP) level is associated with survival. A post hoc analysis of a recent randomized trial found increased mortality among patients in cardiogenic shock whose average MAP was \<70 mmHg during the first 36 hours after randomization, compared to patients with MAP ≥70 mmHg (58% vs. 29%, p\<0.01). Another observational study found higher mortality among patients with a mean MAP \<65 mmHg during the first 24 hours of shock compared to those with MAP ≥65 mmHg (57% vs. 28%, p\<0.001). In this study, the incidence of renal failure was also inversely associated with MAP level. The optimal MAP target remains unknown during cardiogenic shock.

Due to the characteristic venous congestion, the effective perfusion pressure may be very low during cardiogenic shock despite MAP being within the usual target (65 mmHg). Furthermore, increased central venous pressure (CVP) is associated with higher mortality during cardiogenic shock. Considering venous congestion by measuring or estimating CVP is necessary to assess the effective perfusion pressure (MAP minus CVP) in order to protect against organ dysfunction. In this perspective, the MAP target should be increased by the value of the CVP.

The investigators hypothesize that personalizing the MAP target (to achieve an effective perfusion pressure of 65 mmHg) improves organ perfusion and survival during cardiogenic shock compared to the usual MAP target of 65 mmHg.

Interventions

• Other Personalized MAP
  Patients receive blood pressure management targeting a personalized MAP ranging from 65 mmHg + CVP to 75 mmHg + CVP, without exceeding 90 mmHg.CVP is measured via a central venous catheter positioned in the superior vena cava. After 48 hours, if tissue perfusion is restored, the MAP target may be reduced to 65-70 mmHg.
• Other Standard MAP
  Patients receive blood pressure management aiming for a standard MAP target of 65-70 mmHg, according to international guidelines for cardiogenic shock management.

Primary outcome measures

• The primary endpoint will be a composite of mortality, use of cardiac mechanical circulatory support, and severe renal failure. [Time frame: 7 days and 28 days after randomization]

Secondary outcome measures (12)

• Mortality in the intensive care unit (ICU), and in hospital [Time frame: 28 days and 90 days after randomization]
• Length of stay in the ICU and in the hospital [Time frame: 28 days and 90 days after randomization]
• Proportion of patients requiring cardiac mechanical circulatory support [Time frame: 28 days after randomization]
• Proportion of patients requiring renal replacement therapy [Time frame: 28 days after randomization]
• Proportion of patients with severe acute kidney injury (stage 2 and stage 3 according to KDIGO AKI classification) [Time frame: 7 days after randomization]
• Duration of inotrope and vasopressor support [Time frame: 28 days after randomization]
• Use of mechanical ventilation [Time frame: 28 days after randomization]
• Number of ventilator-free days [Time frame: 28 days after randomization]
• Evolution of the vasoactive inotropic score (VIS) [Time frame: 5 days after randomization]
• Evolution of lactate levels [Time frame: 5 days after randomization]
• Evaluation of mottling score [Time frame: 5 days after randomisation]
• Evaluation of capillary refill time [Time frame: 5 days after randomization]

Eligibility criteria

Inclusion criteria

• Aged ≥18 years
• Cardiogenic shock state, according to the consensus definition,
• SCAI (Society for Cardiovascular Angiography and Interventions) classification ≥ C
• Consent from the patient or close relative / trusted person or emergency inclusion procedure
• Benefiting fromciary of a social security scheme

Exclusion criteria

• Catecholamine infusion for more than 24 consecutive hours;
• CVP < 5 mm Hg at inclusion;
• MAP > 70 mmHg at inclusion;
• Chronic kidney disease stage G4 (defined by an eGFR between 15-29 ml/min/1.73 m²) or G5 (defined by an eGFR less than 15 ml/min/1.73 m²) according to the KDIGO CKD classification at inclusion;
• Chronic dialysis or presence of renal replacement therapy criteria at inclusion ;
• Recovered cardiopulmonary arrest within 7 days prior to inclusion;
• Patient already on mechanical circulatory support at inclusion before enrollment (patients who receive support after inclusion will not be excluded);
• Primary diagnosis of tamponade, pulmonary embolism, or septic shock;
• Hypersensitivity to norepinephrine tartrate or to any of the following excipients: sodium chloride, hydrochloric acid or sodium hydroxide water for injectable preparations;
• Absence of central venous access;
• Known pregnancy or current breastfeeding;
• Under legal guardianship, curatorship, or judicial protection.

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

Open label

Primary purpose

Other

Study locations

France · 11 centers

• CHU d'Amiens-Picardie — Amiens
• Hôpital Henri Mondor — Créteil
• Hôpital Privé Jacques Cartier — Massy
• CMC Ambroise Paré - Hartmann — Neuilly-sur-Seine
• CHU d'Orléans — Orléans
• Hôpital Lariboisière — Paris
• Hôpital Cochin — Paris
• Clinique NCT + /Saint-Gatien — Saint-Cyr-sur-Loire
• … and 3 more centers

Identifiers

NCT: NCT07345559 · 2024/01 · 2024-A00253-44

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗