Clinical trial NCT06062303: Hemodynamic Phenotype-Based,Capillary Refill Time-Targeted Resuscitation In Early Septic Shock:ANDROMEDA-SHOCK-2
Official title: Hemodynamic Phenotype-Based, Capillary Refill Time-Targeted Resuscitation In Early Septic Shock: The ANDROMEDA-SHOCK-2 Randomized Clinical Trial (A2)
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Intensive Care Unit Acquired Weakness
Shock, Septic
Lead sponsor: Assistance Publique - Hôpitaux de Paris
Sponsor class: OTHER
First posted: 2023-10-02
Enrollment: 180
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: comparative multicentre, open-label, investigator-led randomized controlled trial.
Primary purpose: SUPPORTIVE_CARE

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.

Eligibility criteria: 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

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)

Primary outcomes:
measure: A composite of all cause 28-days mortality plus time to cessation of vital support and length of hospital stay
timeFrame: 28 days
Secondary outcomes:
measure: All-cause mortality within 28 days
timeFrame: 28 days
measure: Vital support free days
timeFrame: 28 days
measure: Length of hospital stay
timeFrame: 28 days
Other outcomes:
measure: Length of ICU stay
timeFrame: 28 days
measure: Time to cessation of vasopressor support
timeFrame: 28 days
measure: Time to cessation of mechanical ventilation
timeFrame: 28 days
measure: Time to cessation of renal replacement therapy
timeFrame: 28 days
measure: Vasopressor support-free days
timeFrame: 28 days
measure: Mechanical ventilation-free days
timeFrame: 28 days
measure: Renal replacement therapy-free days
timeFrame: 28 days
measure: Variation in Sequential Organ Failure Assessment (SOFA) score
timeFrame: 7 days
measure: Variation of creatinine-based KDIGO stage
timeFrame: 7 days
measure: Volume of resuscitation fluids
timeFrame: 72 hours
measure: Net fluid balance
timeFrame: 72 hours
measure: Evolvement of capillary refill time (CRT)
timeFrame: 72 hours
measure: Evolvement of lactate levels
timeFrame: 72 hours
measure: Evolvement of central venous pressure
timeFrame: 72 hours
measure: Evolvement of central venous oxygen saturation
timeFrame: 72 hours
measure: Evolvement of central venous to arterial carbon dioxide difference
timeFrame: 72 hours
measure: All-cause mortality within 90 days
timeFrame: 90 days
measure: Length of hospital stay
timeFrame: 90 days
measure: Changes in CRT before and after fluid resuscitation or increase in norepinephrine
timeFrame: 72 hours
Locations:
city: Reims
country: France
facility: Hôpital Robert Debré, Université de Reims
Study officials:
References: