Hemodynamic Phenotype-Based,Capillary Refill Time-Targeted Resuscitation In Early Septic Shock:ANDROMEDA-SHOCK-2

Not Applicable

Recruiting

• Conditions: Intensive Care Unit Acquired Weakness; Shock, Septic
• Interventions: Other: Usual care (UC)

• Registration Number: NCT06062303
• Lead Sponsor: Assistance Publique - Hôpitaux de Paris

Brief Summary

Over-resuscitation including fluid overload has been associated with increased morbidity (prolonged duration of organ failure) and mortality in septic shock. "One-size-fits-all" resuscitation strategies may increase septic shock mortality. However, clinical studies on individualized resuscitation are lacking. Hemodynamic phenotyping may allow to individualize septic shock resuscitation. The ANDROMEDA-SHOCK trial found that a simple clinical and bedside CRT-targeted resuscitation reduces organ dysfunction and 28-day mortality in septic shock. The current study will examine the hypothesis that a CRT-targeted resuscitation based on hemodynamic phenotyping considering within an decision tree usual bedside clinical parameters such as pulse pressure, diastolic blood pressure, fluid responsiveness and cardiac performance can further decrease mortality in septic shock as compared to usual care.

Detailed Description

Septic shock is associated with a high mortality risk related to progressive tissue hypoperfusion.However, despite extensive research on the best monitoring and resuscitation strategies, many uncertainties remain. Over-resuscitation, particularly when inducing fluid overload, might contribute to a worse outcome. Fluid overload more likely occurs when fluids are administered to fluid unresponsive patients, but also when inappropriate resuscitation goals are pursued, or a "one-size-fit all" strategy is followed. From a hemodynamic point of view, several pathogenic mechanisms determine a progressive circulatory dysfunction While loss of vascular tone and relative hypovolemia predominate in early phases, more complex mechanisms such as endothelial and microcirculatory dysfunction, progressive vasoplegia, and myocardial dysfunction may be involved later. In effect, from a clinical point of view, many patients despite been fluid loaded in pre-intensive care unit settings, are still evidently hypovolemic and benefit from further administration of fluid boluses. Others, however, present very low diastolic arterial pressures reflecting profound vasoplegia, and recent data suggest that these patients may benefit from early norepinephrine instead of fluids\[; on the contrary, administering fluids may fail to correct vascular tone and increase the risk of fluid overload\[2\]. In addition, a recent echocardiography-based study confirms that a relevant myocardial dysfunction is present in a significant number of patients, and that several cardiovascular phenotypes with a potentially different therapeutic approach may be recognized\[8\]. Unfortunately, despite the availability of most of the parameters at the bedside and research efforts, no universally applicable clinical phenotyping method for septic shock patients has been translated to usual practice. This is particularly problematic since chocardiography is not immediately available in the majority of centers worldwide, and therefore initial decisions on fluid resuscitation are usually based on clinical grounds and tend to follow the one-size-fits-all principle, leading to the risk of fluid overload.

Study Timeline

• Study First Submitted: 2023-09-25
• Study First Submitted QC: 2023-09-25
• Study First Posted: 2023-10-02
• Study Start: 2024-02-06
• Status Verified: 2024-11
• Last Update Submitted: 2024-12-03
• Last Update Posted: 2024-12-05
• Primary Completion: 2025-12-01
• Study Completion: 2026-05-30

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 180

Inclusion Criteria

• Consecutive adult patients (≥ 18 years)
• Patients with septic shock according to Sepsis-3 consensus conference. In short, septic shock is defined as suspected or confirmed infection, plus hyperlactatemia and NE requirements due to persistent hypotension, after a fluid load of at least 1000mL in 1h
• Patient and/or relative informed and having signed the information and consent form for participation in the study

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Exclusion Criteria

• More than 4 hours since septic shock diagnosis,
• Anticipated surgery or acute hemodialysis procedure to start during the 6h intervention period
• Active bleeding,
• Do not resuscitate status,
• Child B-C Cirrhosis
• Underlying disease process with a life expectancy < 90 days and/or the attending clinician deems aggressive resuscitation unsuitable
• Refractory shock (high risk of death within 24h)
• Pregnancy
• Concomitant severe acute respiratory distress syndrome
• Patients in whom CRT cannot be accurately assessed
• Non-affiliation to a social security scheme or to another social protection scheme
• Patient on AME (state medical aid) (unless exemption from affiliation
• Patient under legal protection (guardianship, curatorship)
• Participation in another interventional study involving human participants or being in the exclusion period at the end of a previous study involving human participants, if applicable
• Inability, according to the investigator, to understand the study (non-French-speaking patient, cognitive disorders)

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Capillary-refill time and phenotyping group	Usual care (UC)	Patients w/normal baseline CRT will be periodically monitored. Patients with abnormal CRT and septic shock will be categorized according to pulse pressure (PP). If \<40 mmHg, will go to fluid responsiveness (FR) assessment. FR (-) patients will undergo cardiac echo to rule out significant dysfunction. Fluid boluses will be administered in 30 min intervals and repeated as needed if CRT is still abnormal. Patients with PP ≥40 mmHg will proceed according to diastolic pressure (DAP). If ≥50 mmHg will move to FR assessment. If \<50 mmHg NE will be increased for MAP \>65 mmHg and DAP ≥50 mmHg w/CRT assessed 1 h after. NE will be increased in 0.1 mcg/k/m increments up to 0.5 mcg/k/m. If CRT is normal, patients will proceed to periodic monitoring. Patients with persistent abnormal CRT or that reached NE safety limit will proceed directly to echo. Patients that correct CRT with first tier interventions will not be subjected to obligatory echo but will just proceed to periodic monitoring.

Primary Outcome Measures

Name	Time	Method
A composite of all cause 28-days mortality plus time to cessation of vital support and length of hospital stay	28 days	A hierarchical composite of all cause mortality within 28 days, time to cessation of vital support (truncated at 28 days) and length of hospital stay (truncated at 28 days).

Secondary Outcome Measures

Name	Time	Method
All-cause mortality within 28 days	28 days	All-cause mortality within 28 days
Length of hospital stay	28 days	Number of days remaining hospitalized (from randomization up to hospital discharge), truncated at day 28.
Vital support free days	28 days	The number of calendar days between randomization and 28 days that the patient is alive and with no requirement of cardiovascular, respiratory and renal support. Patients who die within 28 days will have zero days counted for this variable, irrespective of vital support status.; Resolution of cardiovascular failure implies complete stopping of vasopressor support for at least 24 consecutive hours. Resolution of respiratory failure implies extubation / liberation from mechanical ventilation for at least 48 hours. Resolution of renal failure implies liberation of renal replacement therapy for at least 72 hours in those receiving continuous replacement modalities and at least 5 days for those receiving intermittent ones.

Trial Locations

Locations (1)

Hôpital Robert Debré, Université de Reims; 🇫🇷 Reims, France