Browsing by Author "Ramos, Karla"

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    Personalized Hemodynamic Resuscitation Targeting Capillary Refill Time in Early Septic Shock
    (2025) Hernández Poblete, Glenn Wilson; Ospina-Tascón, Gustavo A.; Kattan Tala, Eduardo José; Ibarra-Estrada, Miguel; Ramasco, Fernando; Orozco, Nicolás; Ramos, Karla; Luis Aldana, José; Ferri, Giorgio; Hamzaoui, Olfa; De Backer, Daniel; Teboul, Jean-Louis; Vieillard-Baron, Antoine; Petri Damiani, Lucas; García-Gallardo, Gustavo A.; Morales Zapata, Sebastián Andrés; Carmona García, Paula; Amthauer Rojas, Macarena Paz; Alegria Vargas, Leyla; Bakker, Jan
    Importance: The optimal strategy for hemodynamic resuscitation in early septic shock remains uncertain.Objective: To determine the effect of a personalized hemodynamic resuscitation protocol targeting capillary refill time (CRT-PHR) on a hierarchical composite outcome of mortality, duration of vital support, and length of hospital stay.Design, setting, and participants: This randomized clinical trial was conducted in 86 centers in 19 countries. Patients within the first 4 hours of septic shock were included between March 2022 and April 2025, with last follow-up in July 2025.Interventions: Patients were randomized to undergo CRT-PHR (n = 720), including assessment of pulse pressure, diastolic arterial pressure, fluid responsiveness, and bedside echocardiography, to tailor fluids, vasopressors, and inotropes, vs usual care (n = 747).Main outcomes and measures: The primary outcome was a hierarchical composite of mortality, duration of vital support (vasoactives, mechanical ventilation, and kidney replacement therapy), and length of hospital stay assessed at 28 days. A win ratio was calculated for the primary outcome by comparing all possible patient pairs, starting with the first event in the hierarchy and stratified by median APACHE (Acute Physiology and Chronic Health Evaluation) II score at admission. Secondary outcomes were mortality, vital support-free days, and length of hospital stay at 28 days.Results: From 1501 randomized patients, 1467 were included in the primary analysis (mean age, 66 [17] years; 43.3% female). There were 131 131 wins (48.9%) in the CRT-PHR group vs 112 787 (42.1%) in the usual care group for the hierarchical composite primary outcome, with a win ratio of 1.16 (95% CI, 1.02-1.33; P = .04). Individual wins for death were 19.1% vs 17.8%; duration of vital support, 26.4% vs 21.1%; and length of hospital stay, 3.4% vs 3.2% in the intervention vs usual care groups, respectively.Conclusions and relevance: Among patients with early septic shock, a personalized hemodynamic resuscitation protocol targeting capillary refill time was superior to usual care for the primary composite outcome, primarily due to a lower duration of vital support.
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    Safety and Pharmacokinetics of a Combined Antioxidant Therapy against Myocardial Reperfusion Injury: A Phase I Randomized Clinical Trial in Healthy Humans
    (2024) Gajardo Cortez, Abraham I. J.; Lillo-Moya, Jose; San-Martin-Martinez, Daniel; Pozo-Martinez, Josue; Morales, Pablo; Prieto, Juan C.; Aguayo, Ruben; Puentes, Angel; Ramos, Cristobal; Silva, Solange; Catalan, Mabel; Ramos, Karla; Olea-Azar, Claudio; Rodrigo, Ramon
    Myocardial reperfusion injury (MRI) accounts for up to 50% of the final size in acute myocardial infarction and other conditions associated with ischemia-reperfusion. Currently, there is still no therapy to prevent MRI, but it is well known that oxidative stress has a key role in its mechanism. We previously reduced MRI in rats through a combined antioxidant therapy (CAT) of ascorbic acid, N-acetylcysteine, and deferoxamine. This study determines the safety and pharmacokinetics of CAT in a Phase I clinical trial. Healthy subjects (n = 18) were randomized 2:1 to CAT or placebo (NaCl 0.9% i.v.). Two different doses/infusion rates of CATs were tested in a single 90-minute intravenous infusion. Blood samples were collected at specific times for 180 minutes to measure plasma drug concentrations (ascorbic acid, N-acetylcysteine, and deferoxamine) and oxidative stress biomarkers. Adverse events were registered during infusion and followed for 30 days. Both CAT1 and CAT2 significantly increased the CAT drug concentrations compared to placebo (P < .05). Most of the pharmacokinetic parameters were similar between CAT1 and CAT2. In total, 6 adverse events were reported, all nonserious and observed in CAT1. The ferric-reducing ability of plasma (an antioxidant biomarker) increased in both CAT groups compared to placebo (P < .001). The CAT is safe in humans and a potential treatment for patients with acute myocardial infarction undergoing reperfusion therapy.
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    Statistical analysis plan for hemodynamic phenotype-based, capillary refill time-targeted resuscitation in early septic shock: the ANDROMEDA-SHOCK-2 randomized clinical trial
    (Associacao de Medicina Intensiva Brasileira - AMIB, 2025) Orozco, Nicolás; Garcia-Gallardo, Gustavo; Cavalcanti, Alexandre Biasi; Dos Santos, Tiago Mendonça; Ospina Tascón, Gustavo A.; Bakker, Jan; Morales Ahumada, Sebastián Alonso; Ramos, Karla; Alegría Vargas, Leyla; Teboul, Jean Louis; De Backer, Daniel; Vieillard-Baron, Antoine; Hernández, Liliana Vallecilla; De Lima, Lucas Martins; Damiani, Lucas Petri; Sady, Erica Ribeiro; Santucci, Eliana Vieira; Hernández P., Glenn; Kattan Tala, Eduardo José
    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.