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CLINICAL REPORT
Statistical analysis plan for hemodynamic phenotype-based, capillary refill time-targeted resuscitation in early septic shock: the ANDROMEDA-SHOCK-2 randomized clinical trial
- Nicolas Orozco
, - Gustavo García-Gallardo ,
- Alexandre Biasi Cavalcanti ,
- Tiago Mendonça dos Santos ,
- Gustavo Ospina-Tascón , [ ... ],
- Eduardo Kattan
01-15-2025
Abstract
CLINICAL REPORTStatistical analysis plan for hemodynamic phenotype-based, capillary refill time-targeted resuscitation in early septic shock: the ANDROMEDA-SHOCK-2 randomized clinical trial
Critical Care Science. 2025;37:e20250140
01-15-2025DOI 10.62675/2965-2774.20250140
- Nicolas Orozco ,
- Gustavo García-Gallardo ,
- Alexandre Biasi Cavalcanti ,
- Tiago Mendonça dos Santos ,
- Gustavo Ospina-Tascón ,
- Jan Bakker ,
- Sebastián Morales ,
- Karla Ramos ,
- Leyla Alegria ,
- Jean Louis Teboul ,
- Daniel De Backer ,
- Antoine Vieillard-Baron ,
- Liliana Vallecilla Fernandez ,
- Lucas Martins de Lima ,
- Lucas Petri Damiani ,
- Erica Ribeiro Sady ,
- Eliana Vieira Santucci ,
- Glenn Hernandez ,
- Eduardo Kattan
Views155See moreABSTRACT
Background
ANDROMEDA-SHOCK 2 is an international, multicenter, randomized controlled trial comparing hemodynamic phenotype-based, capillary refill time-targeted resuscitation in early septic shock to standard care resuscitation to test the hypothesis that the former is associated with lower morbidity and mortality in terms of hierarchal analysis of outcomes.
Objective
To report the statistical plan for the ANDROMEDA--SHOCK 2 randomized clinical trial.
Methods
We briefly describe the trial design, patients, methods of randomization, interventions, outcomes, and sample size. We portray our planned statistical analysis for the hierarchical primary outcome using the stratified win ratio method, as well as the planned analysis for the secondary and tertiary outcomes. We also describe the subgroup and sensitivity analyses. Finally, we provide details for presenting our results, including mock tables, baseline characteristics, and the effects of treatments on outcomes.
Conclusion
According to best trial practices, we report our statistical analysis plan and data management plan prior to locking the database and initiating the analyses. We anticipate that this practice will prevent analysis bias and improve the utility of the study’s reported results.
Views155
Abstract
CLINICAL REPORTStatistical analysis plan for hemodynamic phenotype-based, capillary refill time-targeted resuscitation in early septic shock: the ANDROMEDA-SHOCK-2 randomized clinical trial
Critical Care Science. 2025;37:e20250140
01-15-2025DOI 10.62675/2965-2774.20250140
- Nicolas Orozco ,
- Gustavo García-Gallardo ,
- Alexandre Biasi Cavalcanti ,
- Tiago Mendonça dos Santos ,
- Gustavo Ospina-Tascón ,
- Jan Bakker ,
- Sebastián Morales ,
- Karla Ramos ,
- Leyla Alegria ,
- Jean Louis Teboul ,
- Daniel De Backer ,
- Antoine Vieillard-Baron ,
- Liliana Vallecilla Fernandez ,
- Lucas Martins de Lima ,
- Lucas Petri Damiani ,
- Erica Ribeiro Sady ,
- Eliana Vieira Santucci ,
- Glenn Hernandez ,
- Eduardo Kattan
Views155See moreABSTRACT
Background
ANDROMEDA-SHOCK 2 is an international, multicenter, randomized controlled trial comparing hemodynamic phenotype-based, capillary refill time-targeted resuscitation in early septic shock to standard care resuscitation to test the hypothesis that the former is associated with lower morbidity and mortality in terms of hierarchal analysis of outcomes.
Objective
To report the statistical plan for the ANDROMEDA--SHOCK 2 randomized clinical trial.
Methods
We briefly describe the trial design, patients, methods of randomization, interventions, outcomes, and sample size. We portray our planned statistical analysis for the hierarchical primary outcome using the stratified win ratio method, as well as the planned analysis for the secondary and tertiary outcomes. We also describe the subgroup and sensitivity analyses. Finally, we provide details for presenting our results, including mock tables, baseline characteristics, and the effects of treatments on outcomes.
Conclusion
According to best trial practices, we report our statistical analysis plan and data management plan prior to locking the database and initiating the analyses. We anticipate that this practice will prevent analysis bias and improve the utility of the study’s reported results.
- Nicolas Orozco
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ORIGINAL ARTICLE
Identification of distinct phenotypes and improving prognosis using metabolic biomarkers in COVID-19 patients
- Andressa Santana,
- Gabriele da Silveira Prestes ,
- Marinara Dagostin da Silva,
- Carolina Saibro Girardi ,
- Lucas dos Santos Silva , [ ... ],
- Cristiane Ritter
07-18-2024
Abstract
ORIGINAL ARTICLEIdentification of distinct phenotypes and improving prognosis using metabolic biomarkers in COVID-19 patients
Critical Care Science. 2024;36:e20240028en
07-18-2024DOI 10.62675/2965-2774.20240028-en
- Andressa Santana,
- Gabriele da Silveira Prestes ,
- Marinara Dagostin da Silva,
- Carolina Saibro Girardi ,
- Lucas dos Santos Silva ,
- José Cláudio Fonseca Moreira ,
- Daniel Pens Gelain ,
- Glauco Adrieno Westphal ,
- Emil Kupek ,
- Roger Walz ,
- Felipe Dal-Pizzol ,
- Cristiane Ritter
Views69See moreABSTRACT
Objective
To investigate the relationship between the levels of adipokines and other endocrine biomarkers and patient outcomes in hospitalized patients with COVID-19.
Methods
In a prospective study that included 213 subjects with COVID-19 admitted to the intensive care unit, we measured the levels of cortisol, C-peptide, glucagon-like peptide-1, insulin, peptide YY, ghrelin, leptin, and resistin.; their contributions to patient clustering, disease severity, and predicting in-hospital mortality were analyzed.
Results
Cortisol, resistin, leptin, insulin, and ghrelin levels significantly differed between severity groups, as defined by the World Health Organization severity scale. Additionally, lower ghrelin and higher cortisol levels were associated with mortality. Adding biomarkers to the clinical predictors of mortality significantly improved accuracy in determining prognosis. Phenotyping of subjects based on plasma biomarker levels yielded two different phenotypes that were associated with disease severity, but not mortality.
Conclusion
As a single biomarker, only cortisol was independently associated with mortality; however, metabolic biomarkers could improve mortality prediction when added to clinical parameters. Metabolic biomarker phenotypes were differentially distributed according to COVID-19 severity but were not associated with mortality.
Views69Abstract
ORIGINAL ARTICLEIdentification of distinct phenotypes and improving prognosis using metabolic biomarkers in COVID-19 patients
Critical Care Science. 2024;36:e20240028en
07-18-2024DOI 10.62675/2965-2774.20240028-en
- Andressa Santana,
- Gabriele da Silveira Prestes ,
- Marinara Dagostin da Silva,
- Carolina Saibro Girardi ,
- Lucas dos Santos Silva ,
- José Cláudio Fonseca Moreira ,
- Daniel Pens Gelain ,
- Glauco Adrieno Westphal ,
- Emil Kupek ,
- Roger Walz ,
- Felipe Dal-Pizzol ,
- Cristiane Ritter
Views69See moreABSTRACT
Objective
To investigate the relationship between the levels of adipokines and other endocrine biomarkers and patient outcomes in hospitalized patients with COVID-19.
Methods
In a prospective study that included 213 subjects with COVID-19 admitted to the intensive care unit, we measured the levels of cortisol, C-peptide, glucagon-like peptide-1, insulin, peptide YY, ghrelin, leptin, and resistin.; their contributions to patient clustering, disease severity, and predicting in-hospital mortality were analyzed.
Results
Cortisol, resistin, leptin, insulin, and ghrelin levels significantly differed between severity groups, as defined by the World Health Organization severity scale. Additionally, lower ghrelin and higher cortisol levels were associated with mortality. Adding biomarkers to the clinical predictors of mortality significantly improved accuracy in determining prognosis. Phenotyping of subjects based on plasma biomarker levels yielded two different phenotypes that were associated with disease severity, but not mortality.
Conclusion
As a single biomarker, only cortisol was independently associated with mortality; however, metabolic biomarkers could improve mortality prediction when added to clinical parameters. Metabolic biomarker phenotypes were differentially distributed according to COVID-19 severity but were not associated with mortality.
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Special Article
Hemodynamic phenotype-based, capillary refill time-targeted resuscitation in early septic shock: The ANDROMEDA-SHOCK-2 Randomized Clinical Trial study protocol
- Eduardo Kattan ,
- Jan Bakker ,
- Elisa Estenssoro ,
- Gustavo Adolfo Ospina-Tascón ,
- Alexandre Biasi Cavalcanti , [ ... ],
- Glenn Hernández
06-24-2022
Abstract
Special ArticleHemodynamic phenotype-based, capillary refill time-targeted resuscitation in early septic shock: The ANDROMEDA-SHOCK-2 Randomized Clinical Trial study protocol
Revista Brasileira de Terapia Intensiva. 2022;34(1):96-106
06-24-2022DOI 10.5935/0103-507X.20220004-en
- Eduardo Kattan ,
- Jan Bakker ,
- Elisa Estenssoro ,
- Gustavo Adolfo Ospina-Tascón ,
- Alexandre Biasi Cavalcanti ,
- Daniel De Backer ,
- Antoine Vieillard-Baron ,
- Jean-Louis Teboul ,
- Ricardo Castro ,
- Glenn Hernández
Views112ABSTRACT
Background:
Early reversion of sepsis-induced tissue hypoperfusion is essential for survival in septic shock. However, consensus regarding the best initial resuscitation strategy is lacking given that interventions designed for the entire population with septic shock might produce unnecessary fluid administration. This article reports the rationale, study design and analysis plan of the ANDROMEDA-2 study, which aims to determine whether a peripheral perfusion-guided strategy consisting of capillary refill time-targeted resuscitation based on clinical and hemodynamic phenotypes is associated with a decrease in a composite outcome of mortality, time to organ support cessation, and hospital length of stay compared to standard care in patients with early (< 4 hours of diagnosis) septic shock.
Methods:
The ANDROMEDA-2 study is a multicenter, multinational randomized controlled trial. In the intervention group, capillary refill time will be measured hourly for 6 hours. If abnormal, patients will enter an algorithm starting with pulse pressure assessment. Patients with pulse pressure less than 40mmHg will be tested for fluid responsiveness and receive fluids accordingly. In patients with pulse pressure > 40mmHg, norepinephrine will be titrated to maintain diastolic arterial pressure > 50mmHg. Patients who fail to normalize capillary refill time after the previous steps will be subjected to critical care echocardiography for cardiac dysfunction evaluation and subsequent management. Finally, vasopressor and inodilator tests will be performed to further optimize perfusion. A sample size of 1,500 patients will provide 88% power to demonstrate superiority of the capillary refill time-targeted strategy.
Conclusions:
If hemodynamic phenotype-based, capillary refill time-targeted resuscitation demonstrates to be a superior strategy, care processes in septic shock resuscitation can be optimized with bedside tools.
Keywords:AlgorithmCapillary refill timecritical careEchocardiographyLength of staynorepinephrinePerfusionPhenotypesepsisseptic shockSee moreViews112Abstract
Special ArticleHemodynamic phenotype-based, capillary refill time-targeted resuscitation in early septic shock: The ANDROMEDA-SHOCK-2 Randomized Clinical Trial study protocol
Revista Brasileira de Terapia Intensiva. 2022;34(1):96-106
06-24-2022DOI 10.5935/0103-507X.20220004-en
- Eduardo Kattan ,
- Jan Bakker ,
- Elisa Estenssoro ,
- Gustavo Adolfo Ospina-Tascón ,
- Alexandre Biasi Cavalcanti ,
- Daniel De Backer ,
- Antoine Vieillard-Baron ,
- Jean-Louis Teboul ,
- Ricardo Castro ,
- Glenn Hernández
Views112ABSTRACT
Background:
Early reversion of sepsis-induced tissue hypoperfusion is essential for survival in septic shock. However, consensus regarding the best initial resuscitation strategy is lacking given that interventions designed for the entire population with septic shock might produce unnecessary fluid administration. This article reports the rationale, study design and analysis plan of the ANDROMEDA-2 study, which aims to determine whether a peripheral perfusion-guided strategy consisting of capillary refill time-targeted resuscitation based on clinical and hemodynamic phenotypes is associated with a decrease in a composite outcome of mortality, time to organ support cessation, and hospital length of stay compared to standard care in patients with early (< 4 hours of diagnosis) septic shock.
Methods:
The ANDROMEDA-2 study is a multicenter, multinational randomized controlled trial. In the intervention group, capillary refill time will be measured hourly for 6 hours. If abnormal, patients will enter an algorithm starting with pulse pressure assessment. Patients with pulse pressure less than 40mmHg will be tested for fluid responsiveness and receive fluids accordingly. In patients with pulse pressure > 40mmHg, norepinephrine will be titrated to maintain diastolic arterial pressure > 50mmHg. Patients who fail to normalize capillary refill time after the previous steps will be subjected to critical care echocardiography for cardiac dysfunction evaluation and subsequent management. Finally, vasopressor and inodilator tests will be performed to further optimize perfusion. A sample size of 1,500 patients will provide 88% power to demonstrate superiority of the capillary refill time-targeted strategy.
Conclusions:
If hemodynamic phenotype-based, capillary refill time-targeted resuscitation demonstrates to be a superior strategy, care processes in septic shock resuscitation can be optimized with bedside tools.
Keywords:AlgorithmCapillary refill timecritical careEchocardiographyLength of staynorepinephrinePerfusionPhenotypesepsisseptic shockSee more
- Eduardo Kattan
Phenotype Archives - Critical Care Science (CCS)
