Active clinical trials for "Shock"

This study has been approved as a nested substudy of a multicenter trial (CORVICTES, Clinicaltrials.gov Identifier: NCT03592693). The current, randomized, placebo-controlled study will compare steroids/vitamin C versus placebo/placebo in septic shock, with respect to cerebral autoregulation, biomarkers, and functional outcome. The following hypotheses will be tested: The steroids/vitamin C/thiamine intervention may result in attenuation of the septic shock-associated impairment in cerebral autoregulation; and 2) The increased frequency of intact cerebral autoregulation in the intervention group may result in more neurologic failure free days and ventilator free days during a 60-day follow-up; improved survival to hospital discharge with good functional outcome; and better patient-reported health-related outcomes at 90-day follow-up.

Prior data has shown that both corticosteroids and vitamin C reduce the activation of nuclear factor ƘB (NFƘB), thereby ultimately attenuating the systemic inflammatory response to sepsis/septic shock and augmenting the responsiveness to vasopressors. Therefore, the current investigators hypothesized that the combined use of vitamin C and stress-dose hydrocortisone may improve the outcomes of patients with septic shock. The investigators intend to perform a randomized, multicenter, parallel group, double-blind, placebo-controlled trial of vitamin C plus stress-dose hydrocortisone or placebo plus placebo for a total of four days after randomization of patients fulfilling the current consensus criteria for septic shock. The primary outcome will be hospital mortality, whereas the scondary outcomes will include 60-day, 28-day mortality, time to vasopressor cessation, procalcitonin clearance and change in the Sequential Organ Failure Assessment score over the first 4 days after randomization, neurologic failure-free days, and length of stay in the intensive care unit (ICU) and the hospital. Target enrollment will be 400 patients.

Immunonutrition in intensive care has not yet demonstrated a beneficial effect on organ failure, the acquisition of nosocomial infections, or mortality. It did not correct for acquired immunosuppression in intensive care patients. Despite numerous methodological problems (use of several pharmaconutrients, very heterogeneous set of patients) and the absence of clinical data, deleterious effects have been attributed to immunonutrition in intensive care, in particular in septic patients and patients in intensive care . Arginine (ARG) is a semi-essential amino acid involved in many immunological mechanisms. It is synthesized in sufficient quantity under normal conditions but quickly becomes insufficient under catabolic conditions such as in severe sepsis. Arginine is not only the precursor of nitrogen monoxide (NO) but also an essential substrate for numerous enzymatic reactions which participate in the maintenance of immune homeostasis, in particular T lymphocyte function. Depletion of the cellular medium in arginine will induce an abnormality in the metabolism of immune cells responsible for a dysfunction of these cells (lymphopenia linked to early apoptosis) and thus expose patients to organ failure and nosocomial infections. It has been found that hypoargininemia in intensive care patients is associated with the persistence of organ dysfunction (SOFA score), the occurrence of nosocomial infections and mortality. Also, it has been demonstrated that in these patients, enteral administration of ARG was not deleterious and increased ornithine synthesis, suggesting a preferential use of ARG via the arginases route, without significant increase in argininaemia or effect on immune functions. L-citrulline (CIT), an endogenous precursor of ARG, constitutes an interesting alternative for increasing the availability of ARG. Sponsor recent data demonstrate that the administration of CIT in intensive care is not deleterious and that it very significantly reduces mortality in an animal model of sepsis, corrects hypoargininemia, with convincing data on immunological parameters such as lymphopenia, which is associated with mortality, organ dysfunction and the occurrence of nosocomial infections. The availability of ARG directly impacts the mitochondrial metabolism of T lymphocytes and their function. Our hypothesis is therefore that CIT supplementation is more effective than administration of ARG in correcting hypoargininemia, reducing lymphocyte dysfunction, correcting immunosuppression and organ dysfunction in septic patients admitted to intensive care.

To demonstrate that external drainage of thoracic duct lymph during sepsis results in a reduction in circulating pro-inflammatory cytokines. To demonstrate safety and feasibility of early thoracic duct cannulation and external lymph drainage for up to 7 days in adult surgical intensive care patients. To explore other biochemical and physiological endpoints that can be used for the design of future randomized controlled trials and estimate effect size of external drainage.

The purpose of this protocol is to perform a prospective, randomized, double-blinded, pacebo-controlled clinical trial to determine the influence of a non-invasive positive pressure ventilation device on exercise capacity and symptoms in adult patients with ECAC. Primary outcome will include the total distance traversed by the study subject during a standard 6-minute walk test, and secondary outcomes will include peak flow measurement and symptom reporting before and after the exercise testing. The study will focus on the use of continuous positive airway pressure (CPAP) device. CPAP is FDA-approved for the treatment of various medical conditions, including obstructive sleep apnea and heart failure, but is not FDA-approved for the treatment of ECAC. The study will enroll 32 ambulatory study subjects with confirmed ECAC at the BIDMC, and each study subject will be monitored for up to 3 months.

In the last decade, venoarterial extracorporeal membrane oxygenation (VA-ECMO) has become the first-line therapy in patients with refractory cardiogenic shock. VA-ECMO provides both respiratory and cardiac support, is easy to insert, even at the bedside, provides stable flow rates, and is associated with less organ failure after implantation compared to large biventricular assist-devices that require open-heart surgery. In patients with potentially reversible cardiac failure (e.g. myocarditis, myocardial stunning post-myocardial infarction, post-cardiotomy or post-cardiac arrest), VA-ECMO might be weaned after a few days of support and used as a bridge to recovery. Although considered as the ultimate life-saving technology for refractory cardiac failure, veno-arterial ECMO is still associated with severe complications. Specifically, excessive LV afterload and lack of LV unloading under VA-ECMO might induce LV stasis with thrombus formation, pulmonary edema, myocardial ischemia caused by ventricular distension and ultimately increase mortality. ECMO support also exposes to many complications such as infections, hemorrhage or peripheral vascular embolism. These complications are more frequent with prolonged support and are responsible for significant morbidity and mortality, prolonged ICU and hospital stays and higher costs. Levosimendan, which acts to sensitize myocardial contractile proteins to calcium, improves cardiac contractility without increasing the intracellular calcium concentration. Unlike traditional inotropes such as dobutamine, levosimendan neither increases myocardial oxygen consumption nor impairs diastolic function or possess proarrhythmic effects. It also influences the opening of ATP-dependent potassium channels, including those in vascular smooth muscle cells, leading to coronary, pulmonary, and peripheral vasodilation and antiinflammatory, antioxidative, antiapoptotic, anti-stunning and cardioprotective effects. Additionally, Levosimendan which has a long lasting action (up to 7-9 d), resulting from the formation of active metabolite, may be used as a single 24h perfusion. In recent preliminary studies, the drug was associated with accelerated weaning from VA-ECMO and even improved survival. Therefore, a multicenter randomized trial with sufficient statistical power is needed in refractory cardiogenic shock patients supported by VA-ECMO to test if the early administration of Levosimendan can facilitate and accelerate VA-ECMO weaning, and ultimately translate in significantly less morbidity, reduced ICU and hospital length of stays and associated costs.

Diarrhea is one of the leading causes of under-five childhood mortality and accounts for 8% of 5.4 million global under-5 deaths. The coexistence of sepsis and hypovolemic shock in children with severe acute malnutrition (SAM) having diarrhea is common. At Dhaka hospital of icddr,b, the death rate is as high as 40% and 69% in children with severe sepsis and septic shock respectively with co-morbidities such as severe malnutrition. The conventional management of SAM children with features of severe sepsis recommended by WHO includes administration of boluses of isotonic saline followed by blood transfusion in unresponsive cases with septic shock; whereas the Surviving Sepsis Campaign (SSC) guideline recommends vasoactive support. To date, no study has evaluated systematically the effects of inotrope(s) and vasopressor or blood transfusion in children with dehydrating diarrhea (for example, in cholera) and SAM having shock and unresponsive to WHO standard fluid therapy. This randomized trial will generate evidence whether inotrope and vasopressor or blood transfusion should be selected for severely malnourished children having hypotensive shock and who failed to respond to WHO standard fluid bolus.

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.

This prospective randomized single center study investigates to what extent the removal of elevated cytokine levels by hemoadsorption has a positive effect on the treatment of patients in septic shock by stabilizing the circulatory situation.

This trial will be a randomized controlled single-center pilot trial comparing the use of angiotensin II versus standard-of-care (SOC) vasopressor therapy in adult patients with persistent vasodilatory shock despite moderate-dose norepinephrine, with a primary outcome of the ability of novel biomarkers (renin and DPP3) to predict blood pressure response to angiotensin II. Given our angiotensin II will be compared to SOC, this will be an unblinded study.