Hemodynamic Phenotype and Capillary Refill Time-targeted Resuscitation Strategy

NCT05057611 | Recruiting DMC

• 1 other identifier: 2021_02
• Study Type: interventional
• Target: 1,500
• Locations: 1 country
• Sites: 1

Brief Summary

Septic shock is associated with a high mortality risk. Fluid overload occurs when fluids are administered to fluid unresponsive patients, but also when inappropriate resuscitation goals are pursued. Alongside, evidence confirms that abnormal peripheral perfusion after resuscitation is associated with increased morbidity and mortality. Targeted resuscitation associates with lower mortality, less organ dysfunction, and less intensity of treatment. Over-resuscitation may contribute to a worse outcome. Many patients remain hypovolemic after initial resuscitation. Others present very low diastolic arterial pressures (DAP) reflecting profound vasoplegia and may benefit from early norepinephrine (NE) instead of fluids. Administering fluids in this setting could increase the risk of fluid overload. In addition, relevant myocardial dysfunction is present in a significant number of patients. Pulse pressure (PP) and DAP evaluation may help clinicians to individualize initial management sparing unnecessary fluid loading. Objective: To test if a CRT-targeted resuscitation based on clinical hemodynamic phenotyping can improve a hierarchical clinical outcome - mortality, time to cessation of vital support, and length of hospital stay, all within 28 days - in septic shock patients as compared to usual care. A2 is a multicenter randomized controlled trial (RCT) comparing a CRT-targeted, hemodynamics-based resuscitation strategy with usual care in patients with early septic shock during a 6 h intervention period. A sample size of 1500 patients was calculated to detect a 6% absolute reduction in mortality in the CRT group, and the win-ratio method will be used to test the superiority in the hierarchical outcomes mentioned above. The combination of a CRT-targeted strategy with a clinical hemodynamic phenotyping may aid to personalize initial resuscitation with potential additional fluid-sparing effects. To categorize patients at baseline according to PP may conduct patients with low PP (\<40mmHg) to fluid responsiveness (FR) assessment and eventually fluid boluses, while patients with normal PP will be treated according to DAP, adjusting NE when to avoid further fluids loading in patients who normalize CRT. Fluid resuscitation will be focused on FR+ hypoperfused patients to prevent harmful fluid administration in FR- patients.

Conditions

Septic Shock

Outcome Measures

Primary Outcomes (1)

• A composite of all cause 28-days mortality plus time to cessation of vital support and length of hospital stay

  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).

  28 days

Secondary Outcomes (3)

• All-cause mortality within 28 days

  28 days

• Vital support free days

  28 days

• Length of hospital stay

  28 days

Other Outcomes (18)

• Length of ICU stay

  28 days

• Time to cessation of vasopressor support

  28 days

• Time to cessation of mechanical ventilation

  28 days

Study Arms (2)

Usual Care Group (UC)

ACTIVE COMPARATOR

\- 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.

Other: Usual care (UC)

Capillary-refill time and phenotyping group

EXPERIMENTAL

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.

Other: CRT-targeted strategy associated with a clinical hemodynamic phenotyping to personalize initial resuscitation in septic shock patients

Interventions

CRT-targeted strategy associated with a clinical hemodynamic phenotyping to personalize initial resuscitation in septic shock patients OTHER

A combination of combine a CRT-targeted strategy with a clinical hemodynamic phenotyping that may aid to personalize initial resuscitation with potential additional fluid-sparing effects.

Capillary-refill time and phenotyping group

Usual care (UC) 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.

Usual Care Group (UC)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Consecutive adult patients (≥ 18 years) with septic shock according to Sepsis-3 consensus conference (septic shock defined as suspected or confirmed infection, plus hyperlactatemia and NE requirements due to persistent hypotension, after a fluid load of at least 1000 mL in one hour)

You may not qualify if:

• 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.

Sponsors & Collaborators

• Pontificia Universidad Catolica de Chile: lead
• Fundacion Clinica Valle del Lili: collaborator
• Hospital do Coracao: collaborator
• Erasmus Medical Center: collaborator

Study Sites (1)

Pontificia Universidad Católica de Chile

Santiago, Santiago Metropolitan, 7500000, Chile

RECRUITING

Related Publications (3)

• ANDROMEDA-SHOCK-2 Investigators for the ANDROMEDA Research Network, Spanish Society of Anesthesiology, Reanimation and Pain Therapy (SEDAR), and Latin American Intensive Care Network (LIVEN); Hernandez G, Ospina-Tascon GA, Kattan E, Ibarra-Estrada M, Ramasco F, Orozco N, Ramos K, Aldana JL, Ferri G, Hamzaoui O, De Backer D, Teboul JL, Vieillard-Baron A, Petri Damiani L, Garcia-Gallardo GA, Morales S, Carmona Garcia P, Mendez R, Hernandez-Gilsoul T, Perez-Nieto OR, Olea Vielba C, Ramos S, Dominguez D, Bruna M, David S, Wendel-Garcia PD, Galiana-Ivars M, Myatra SN, Messina A, Cecconi M, Pozo M, Amthauer M, Higuera E, Al Duhalib Z, Rico-Feijoo J, Ferrer-Gomez C, Perez-Carbonell A, Martinez-Castro S, Redondo Calvo FJ, Vives M, Sanchez HF, Bilbao I, Fernandez P, Al-Fares A, Benitez-Cano A, Gonzalez C, Reyes LF, Rodriguez-Guillen JH, Cristino AV, Pendino JC, Ortiz G, Alonso-Gonzalez MC, Murias G, Aguirre-Avalos G, Hernandez L, Calderon Barajas ZA, Zarragoikoetxea I, Monnet X, Goury A, Mendonca Dos Santos T, Vallecilla L, Martins de Lima L, Sady E, Alegria L, Ostermann M, Bakker J, Biasi Cavalcanti A. Personalized Hemodynamic Resuscitation Targeting Capillary Refill Time in Early Septic Shock: The ANDROMEDA-SHOCK-2 Randomized Clinical Trial. JAMA. 2025 Dec 9;334(22):1988-1999. doi: 10.1001/jama.2025.20402.

  PMID: 41159835 DERIVED

• Prager R, Argaiz E, Pratte M, Rola P, Arntfield R, Beaubien-Souligny W, Denault AY, Haycock K, Miralles Aguiar F, Bakker J, Ospina-Tascon G, Orozco N, Rochwerg B, Lewis K, Quazi I, Kattan E, Hernandez G, Basmaji J. Doppler identified venous congestion in septic shock: protocol for an international, multi-centre prospective cohort study (Andromeda-VEXUS). BMJ Open. 2023 Jul 24;13(7):e074843. doi: 10.1136/bmjopen-2023-074843.

  PMID: 37487682 DERIVED

• Kattan E, Bakker J, Estenssoro E, Ospina-Tascon GA, Cavalcanti AB, Backer D, Vieillard-Baron A, Teboul JL, Castro R, Hernandez G. Hemodynamic phenotype-based, capillary refill time-targeted resuscitation in early septic shock: The ANDROMEDA-SHOCK-2 Randomized Clinical Trial study protocol. Rev Bras Ter Intensiva. 2022 Jan-Mar;34(1):96-106. doi: 10.5935/0103-507X.20220004-pt.

  PMID: 35766659 DERIVED

MeSH Terms

Conditions

Shock, Septic

Condition Hierarchy (Ancestors)

Sepsis; Infections; Systemic Inflammatory Response Syndrome; Inflammation; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Shock

Study Officials

• Glenn Hernandez, MD, PhD

  Pontificia Universidad Catolica de Chile

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Glenn Hernandez, MD, PhD

CONTACT

56940209609; glennguru@gmail.com

Eduardo Kattan, MD, PhD

CONTACT

56994793024; e.kattan@gmail.com

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 6, 2021
• First Posted: September 27, 2021
• Study Start: March 18, 2022
• Primary Completion: March 30, 2025
• Study Completion: June 30, 2025
• Last Updated: July 22, 2024

Record last verified: 2024-07

Data Sharing

• IPD Sharing: Will not share

Locations

CL (1)