Active clinical trials for "Shock"

Long-term follow-up of IDE patients for publication

The beneficial effect of statins to prevent cardiovascular events in patients at risk is well established. Recent trials demonstrated that statins can exert a number of vascular actions independent of lipid lowering. Short-term simvastatin therapy recently has been reported to reduce mortality in 2 different animal models of sepsis. Pleiner and coworkers could demonstrate potent vasoprotective properties of simvastatin during Escherichia coli endotoxin induced endotoxemia in healthy volunteers. In a population-based cohort analysis it was demonstrated that administration of statins was associated with a reduced risk of subsequent sepsis. Thus, simvastatin treatment may offer a new therapeutic strategy for clinical conditions associated with inflammation like severe sepsis and septic shock. The aim of the present study is to test the hypothesis that short term treatment with simvastatin may mitigate the detrimental vascular effects of acute inflammation in patients admitted to the intensive care unit requiring treatment for septic shock.

Fluid resuscitation is the most effective treatment of shock. Isotonic crystalloid solution is the current recommended initial fluid resuscitation. However, this kind of fluid has high volume of distribution and may require large volume administration before achieve therapeutic goal of shock reversal. There are rising concern about the delay in shock reversal and adverse consequences of large amount volume of fluid therapy. Colloid fluid have been used as the alternate fluid resuscitation, aiming to limit the volume of fluid resuscitation and promote shock reversal. Whether colloid infusion can improve shock reversal rate and decrease complication associated with fluid resuscitation, had inconclusive information.

The study objective is to clarify whether the application of high doses CPFA (Coupled Plasma-Filtration Adsorption) in addition to the current clinical practice is able to reduce hospital mortality in septic shock patients in intensive care unit (ICU).

OBJECTIVES. To establish the therapeutic efficiency of melatonin in adult patients with severe sepsis and septic shock. Specifically: To evaluate the survival to 28 days of mechanical assisted ventilation, days with vasoactive drugs, need of hemodialysis-hemofiltration, superinfection and evolution towards the failure of other organs. To evaluate, waiting for reduction under the influence of the treatment with melatonin, : clinical - analytical parameters of sepsis; levels of cytokines; oxidative and nitrosative stress; acute-phase proteins (APP), specially of the ITIH4; immune response; endocrine response. METHODOLOGY. Patients will be randomized in two groups, n = 55 in each group: 1) treatment with melatonin 30mg/12 hours 28 days; 2) placebo. Determinations: a) clinical - analytical parameters relative to the sepsis; b) melatonin plasmatic levels; c) quantification of malonyldialdehyde and 4-hydroxynonenal, protein carbonyl content, nitrites, erythrocyte membrane fluidity, and superoxide dismutase, catalase, glutathione reductase and glutathione peroxidase activity; d) Interleukins-1,2,4,5, 6, 7,8,10,12,13, IFN-γ; TNF-α and GM-CSF; e) acute-phase proteins: PCR, haptoglobin, Apo A-I, α1-GPA and ITIH4; f) lymphocytes T, B, NK, T CD4, and T CD8, and immunoglobulins; g) cortisol, aldosterone, ACTH, ADH, insulin, glucagon and 25-hydroxyvitamin D3. Data will be analyzed following a prospectively define plan and by intention-to-treat (ITT) analysis.

Chronic pelvic pain (CPP) can affect both sexes and lasts at least for 3 months. CPP in women could be due to endometrioses, ovarian cyst, colitis, etc, making the correct diagnosis important (1-3). The most prevalent reason for CPP in men is non-bacterial chronic prostatitis and in many cases they are considered equivalent to each other (4). Chronic non-bacterial prostatitis is associated with pain in pelvic region and could be associated with other symptoms such as dysuria, myalgia, arthralgia, chronic fatigue, burning sensation in the urethra, abdominal, urine frequency, and pain after ejaculation (4-6). Chronic prostatitis / chronic pelvic pain syndrome (CP/CPPS) is devided into two groups: III A Type (inflammatory) and III B (Non-inflammatory). The difference between the two groups is the presence of leukocytes in prostatic secretions after prostate massage, urine and semen (7,8). In general population, the prevalence of chronic pelvic pain syndrome is about 0.5 percent because many patients do not consider their symptoms as disease, while 6.3% of people may show symptoms (9-11). One of the most important challenges in the treatment of chronic prostatitis / chronic pelvic pain syndrome, is that its etiology is obscure and it is known as a multi-factorial syndrome. The proposed explanations are infection, psychological reasons, autoimmunity and neuro-myospasm. Hypotheses about endothelial cells defect and cardio vascular disease have also been proposed, upon which the new therapies have been based. In duplex mapping study of prostatic vessels in two groups of healthy and chronic non-bacterial prostatitis people, it was shown that there was a significant reduction in systolic flow in prostatic arteries in people who had chronic non-bacterial prostatitis, and there was a direct association between pain and blood flow intensity, suggesting chronic ischemia as a possible cause for pain (13). Pain in prostate without significant infection is the hallmark of chronic prostatitis / chronic pelvic pain syndrome (5). In physical exam, prostate or pelvic tenderness may be observed in half of the patients. The diagnosis of chronic prostatitis / chronic pelvic pain syndrome is challenging. No specific lab test exists for its detection. Prostate specific antigen (PSA) level, which is typically increased in acute infection, is usually normal in this condition. The diagnostic approach in these patients is based on ruling out other curable causes such as benign prostatic hyperplasia or bladder cancer (14-20). NIH Chronic Prostatitis Symptom Index (NIH-CPSI) is used to evaluate symptom severity and response to treatment in these patients. A reduction of 4-6 points in the score is considered significant response to the treatment (21). There is no first line treatment for patients of chronic pelvic pain syndrome. The use of anti-bacterial, alpha-blockers or anti-inflammatory drug is logical. However, if the patient does not respond, further administration is not helpful. In non-responders, combination of drugs or other non-medical methods should be considered (23-26). As discussed earlier, blood flow reduction, ischemia and disorders in endothelium of vessels may cause pain in these patients and methods to improve blow flow may help(13,27). One of these methods is extracorporeal shockwave therapy (ESWT) which is typically used for tendonitis, acceleration in bone reunion and wound healing, improvement in muscle movements through a reduction in passive muscular tonus, increasing muscular range of motion after cerebrovascular accident (CVA), treatment of Peyronie's disease and erectile dysfunction (28-30). Shoskes et al compared 24 chronic prostatitis patients with 11 controls in terms of vascular stiffness, indexes of increased blood flow, vasodilation and reactive vascular hyperemia, using Endo-PAT ® 2000-Machine. They showed that endothelial disorder and stiffness along with the risk of cardiovascular disorders are increased in CP/CPPS (31). The use of ESWT for the treatment of CP/CPPS has been evaluated in a few studies. In a double-blind randomized control trial, Zimmermann et al placed 60 patients with chronic pelvic pain syndrome from chronic non-bacterial prostatitis into two groups and treated one of them in 4 sessions with a frequency of 3000 per session. The treatment group showed superior results in terms of symptom improvement(32). In another study, Zimmermann et al followed 34 patients with chronic pelvic pain syndrome, after one, four and twelve weeks post ESWT in terms of quality of life and pain reduction. They showed that this method is useful and without any complications (33). Considering the promising results of the cited articles along with the paucity of data in this regard we decided to perform a double-blind sham-controlled study to evaluate the effectiveness of ESWT in CP/CPPS.

HW6 can prolong animal's survival time and increase the survival rate. HW6 enhances cardiac function, improves microcirculation, and increases blood pressure and pulse pressure, and improves blood perfusion of important organs; HW6's anti-shock activity comes from a combined multiple target pharmacological effects. Based on a completed phase II trial conducted in China, HW6 can effectively treatment shock patient. This is a phase II clinical study to further evaluate the efficacy and safety of Polydatin Injectable 100mg/5mL/via (HW6) in the treatment of shock in the United States. Patients with traumatic/hemorrhagic shock or septic shock admitted to the emergency room or ICU with systolic blood pressure < 90mmHg, or is on vasopressor(s) for systolic blood pressure stabilization, regardless the types of completed, on-going, or projected Standard of Care or surgery will be recruited to participant in the trial. A total of 120 patients with traumatic/hemorrhagic shock and 120 patients with septic shock will be enrolled. For each type of shock, sixty patients each will be in test group and control group. Both adult males and females aged 18-80 years are eligible. The primary clinical endpoint is the time length (TL) between the start of HW6 administration to the onset of the first treatment success, that is: the systolic blood pressure is stabilized at ≥90mmHg and MAP≥65mmHg for 1 hour without the use of vasopressors. Several secondary endpoints and biomarkers will be measured. Efficacy data will be compared using group t-test or Wilcoxon log-rank test between treatment groups and placebo groups. Safety data will also be reported accordingly.

After initial hemodynamic stabilization, 36 septic shock patients with heart rate > of 90 bpm and requiring norepinephrine to maintain mean arterial pressure (MAP) more than 65 mmHg will be randomised into two groups, esmolol group and control group. Patients allocated to esmolol group will receive a continuous esmolol infusion to maintain a lowering of heart rate of 10%. Norepinephrine will be titrated to achieve a MAP more than 65 mmHg. To investigate myocardial performance, the investigators will assess Tissue Doppler imaging by echocardiography and hemodynamic measures. Data will be obtained at baseline ,after esmolol infusion once achieved the predefined heart rate threshold and 72hours after esmolol infusion.

The purpose of this multicentric, randomized controlled trial is to assess whether the timing of renal replacement therapy initiation (early vs delayed) has an impact on mortality at 90 days in patients with severe acute kidney injury at the failure stage (according to RIFLE criteria) during the initial phase of septic shock.

Vasoplegic syndrome after cardiac surgery is a common complication after cardiac surgery, with negative impact on patient outcomes and hospital costs. Pathogenesis of vasodilatory phenomenon after cardiac surgery remains a matter of controversy. Loss of vascular tone can be partly explained by the depletion of neurohypophyseal arginine vasopressin stores. The investigators hypothesized that the use of arginine vasopressin would be more effective on treatment of shock after cardiac surgery than norepinephrine, decreasing the composite end point of mortality and severe morbidity.