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

NCT ID: NCT06062303

Last Updated: 2024-12-05

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: NA
• Total Enrollment: 180 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2024-02-06
• Study Completion Date: 2026-05-30

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.

Conditions

Intensive Care Unit Acquired Weakness; Shock, Septic

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: SUPPORTIVE_CARE
• Blinding Strategy: NONE

Study Groups

Compartor arm

\- Patients allocated to the usual care group will be managed by the clinical staff according to usual practice at their sites including decisions about hemodynamic and perfusion monitoring, and all treatments, but should follow general recommendations of the Surviving Sepsis Campaign to avoid extremes of clinical practice. This includes basic hemodynamic targets such as a MAP \>65 mmHg, HR (heart rate) \<120 beats per minute (BPM), arterial oxygen saturation (SaO2) \>94%, Hb \> 7 gr/dl, and the use of NE as the first vasopressor and crystalloids as the fluid of choice.

Group Type: NO_INTERVENTION

No interventions assigned to this group

Capillary-refill time and phenotyping group

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.

Group Type: ACTIVE_COMPARATOR

Usual care (UC)

Intervention Type: OTHER

\- Patients allocated to the UC group will be managed by the clinical staff according to usual practice at their sites including decisions about hemodynamic and perfusion monitoring, and all treatments, but should follow general recommendations of the Surviving Sepsis Campaign to avoid extremes of clinical practice. This includes basic hemodynamic targets such as a MAP \>65 mmHg, heart rate (HR) \<120 beats per minute (BPM), arterial oxygen saturation (SaO2) \>94%, Hb \> 7 gr/dl, and the use of NE as the first vasopressor and crystalloids as the fluid of choice.

Interventions

Usual care (UC)

\- Patients allocated to the UC group will be managed by the clinical staff according to usual practice at their sites including decisions about hemodynamic and perfusion monitoring, and all treatments, but should follow general recommendations of the Surviving Sepsis Campaign to avoid extremes of clinical practice. This includes basic hemodynamic targets such as a MAP \>65 mmHg, heart rate (HR) \<120 beats per minute (BPM), arterial oxygen saturation (SaO2) \>94%, Hb \> 7 gr/dl, and the use of NE as the first vasopressor and crystalloids as the fluid of choice.

Intervention Type: OTHER

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)

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Assistance Publique - Hôpitaux de Paris

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

Hôpital Robert Debré, Université de Reims

Reims, , France

Site Status: RECRUITING

Countries

France

Central Contacts

Olfa MD Hamzaoui, PhD

Role: CONTACT

Phone: 0033310736973

Email: ohamzaoui@chu-reims.fr

Facility Contacts

Hamzaoui MD Olfa, PhD

Role: primary

Other Identifiers

APHP220794

Identifier Type: -

Identifier Source: org_study_id