Active clinical trials for "Shock, Septic"

There is a knowledge gap regarding the optimal initial fluid to achieve effective resuscitation and improved outcomes in septic shock. The purpose of this study is to compare initial resuscitation with plasma to initial resuscitation with balanced crystalloids.

Despite recent medical advances, sepsis and septic shock remain a major cause of death. Sepsis is a syndrome with a wide array of physiologic, pathologic, and biochemical abnormalities. Several studies have shown vitamin C have decreased the circulating pro-inflammatory cytokines and oxidative stress.Thiamine had favorable effects on pro-inflammatory cytokines, oxidative stress and cellular hypoxia.The use of hydrocortisone in combination with vitamin C will increase the transport of vitamin C into the cells; since the pro inflammatory cytokines have shown to decrease the expression of the sodium-vitamin C transporter-2 (SVCT2) while glucocorticoids increase the SVCT2 expression. A recent small retrospective study , showed a significant decrease in mortality when patients with severe sepsis and septic shock are treated with a combination of Hydrocortisone, Vitamin C, and Thiamine. Conducting a similar study with a prospective randomized design will give clinicians all over the world more answers and will help clinicians to provide better care to millions of patients using highly safe therapeutic regimen. The objective of the current study is to explore the clinical benefits of using a combination of hydrocortisone, vitamin C, and thiamine (triple therapy) for the management of septic shock. To achieve this objective, we will compare two alternative treatment strategies, either triple therapy or usual care in patients with septic shock. First aim: To assess the effectiveness of the triple therapy for septic shock Second aim: To assess the safety of triple therapy

Septic shock is common in patients admitted to intensive care and hospital mortality occurs in close to 50% of these patients. In half of the cases, death occurs within the first 72 hours in a context of multiple organ failure that does not respond to conventional therapies, particularly circulatory therapies, despite increasing doses of catecholamines. Vasopressor resistance in septic patients defines refractory septic shock. In one study (Conrad et al. 2015), the increase in blood pressure observed with an infusion of increasing doses of phenylephrine (dose-response curve) made it possible to quickly and clearly identify patients resistant to vasopressors at a high risk of death by refractory shock (ROC AUC 0.92). This resistance is due in particular to a downregulation of α1 adrenergic receptors, linked to sympathetic hyper activation associated with septic shock. To date, there is no validated therapy in this situation. However, experimental data have shown that the administration of α2 agonists, usually used for their sedative (dexmedetomidine) or anti-hypertensive (clonidine) effect, normalizes sympathetic activity towards basal values. In animals, α2 agonists restore the sensitivity of alpha1 adrenergic receptors, resulting in improved vasopressor sensitivity and survival. In humans, a beneficial effect on mortality was suggested in the first trial testing dexmedetomidine in septic patients in 2017. This effect was observed especially in the most severe patients, suggesting a restoration of sensitivity to vasopressors. The hypothesis is that the administration of dexmedetomidine in patients in refractory septic shock may improve response to phenylephrine and decrease resistance to vasopressors. This pilot study could lay the foundation for a randomized controlled trial.

The proposed study will evaluate the potential benefit of a tapered course of hydrocortisone compared to abrupt cessation in patients initiated on hydrocortisone for septic shock. The study will include adult patients in the medical intensive care unit (MICU) who meet criteria for corticosteroid therapy for septic shock according to the current MICU protocol.All patients will receive 7 days of hydrocortisone (50mg/Q6hrs) as part of the routine management of septic shock, before being randomly assigned to receive hydrocortisone taper versus no taper. The primary study endpoint is the incidence of hypotension within 7 days after randomization. Secondary endpoints will include incidence of adrenal insufficiency, and changes in the inflammatory status (assessed by cytokine measurements) before, during, and after corticosteroid discontinuation. The cytokines to be measured include IL-1, IL-6, IL-9, IL-10, and TNF. Since there has not been a randomized clinical trial to investigate the potential benefit of weaning septic patients off low-dose hydrocortisone as opposed to stopping abruptly, this study has potential to change clinical practice by leading to a consistent approach of corticosteroid discontinuation and to a better understanding of their impact on the inflammatory modulation in septic shock.

This study is a pragmatic open-label international randomized trial comparing therapeutic dose intravenous unfractionated heparin (UFH) to standard care venous thromboprophylaxis in patients diagnosed with septic shock.

Efficacy and safety of octaplasLG® administration vs. crystalloids (standard) in patients with septic shock - a randomized, controlled, open-label investigator-initiated pilot trial.

Purpose/Objectives: Severe sepsis and septic shock are a common cause of new onset atrial fibrillation (NOAF) in the intensive care unit. Development of NOAF in this setting can prolong length of stay and increase mortality. Amiodarone is the most commonly used agent used in this setting to control rate and rhythm. However, limited data exist detailing appropriate dosing in this setting. The primary objective of this study is to evaluate two amiodarone dosing strategies, a full loading dose versus a partial loading dose, in patients with new-onset atrial fibrillation (AF) due to severe sepsis or septic shock to assess the mean heart rate every 6 hours after initiation of amiodarone infusion to day 7 or death. Research Design/Plan: Consecutive patients admitted to the medical or cardiac intensive care unit at University Hospital with NOAF in the setting of severe sepsis or septic shock will be screened for study inclusion. Data will be collected and stored using Microsoft Excel or Access and analyzed with JMP 12.0 and SPSS. Methods: Patients aged 18 years or older who develop new-onset atrial fibrillation in the setting of severe sepsis or septic shock and in whom the medical team deems appropriate to initiate amiodarone therapy in will be considered for study inclusion. Patients will receive intravenous (IV) and oral (PO) amiodarone, as per the standard of care. Patients will be randomized to a certain quantitative loading dose strategy; either a full loading dose (≥ 5g IV or ≥10g PO +/- 20%) or a partial loading dose (<4g IV or < 8g PO). Clinical Relevance: With intensive care unit length of stay (ICU LOS) and mortality being twice as high in NOAF with sepsis as compared to septic patients without NOAF, the investigators ultimately aim to identify a management strategy that may minimize this morbidity and mortality while also minimizing exposure to a drug that may cause serious adverse effects.

This Randomized, pragmatic, multicentric with blinding of patients and health professionals, intention-to-treat analysis has by primary endpoint to evaluate whether the aspirin use reduces the intensity of organic dysfunction measured by the variation of the SOFA score starting from the day of admission to the seventh day. Secundary endpoint: To evaluate if the aspirin use reduces the time of mechanical ventilation, length of stay in the ICU and in the hospital. In addition, to evaluate the safety of its administration regarding the occurrence of bleeding. The data will be collected directly from the chart of the patients admitted to the ICU. Data quality assurance will be made through periodic verification, aiming for complete and consistent data. The centers will receive periodic reports for adequacy of potentially inconsistent or incomplete data. The baseline SOFA of patients with sepsis is 8.8 with a standard deviation of 3. The expected reduction in the control group in the SOFA at day 7 is 2 points. Considering a power of 80% and a level of significance of 0.05, it is estimated that 109 patients will be needed in each group. A total of 218 patients will compose the sample. All analyzes will follow the intention-to-treat principle. We will evaluate the effect of aspirin compared to placebo on primary and binary outcomes by means of relative risks, 95% confidence intervals and chi-square tests. For continuous outcomes with normal distribution, we will present the mean difference, 95% confidence interval and P value calculated by t test. For continuous outcomes with asymmetric distribution, we will perform Wilcoxon test.

The main objectives of the study are 1)to examine the immediate (2 hours) and delayed (8 hours) effects of intravenous hydrocortison on macro and microvascular post-ischemic vasoreactivity, in septic shock adult patients; 2) to examine possible correlations between post-ischemic flow-mediated dilation (FMD) of the brachial artery (assessed by ultrasound imaging) and post-ischemic recovery slope of the thenar oxygen saturation (StO2) (assessed by near-infrared spectroscopy).

The investigators aim to perform a randomized, double-blind, placebo-controlled trial to investigate the efficacy of midodrine in decreasing time to IV vasopressor liberation in patients with septic shock.