Browsing by Author "Ramos, Karla"

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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; 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.