View clinical trials related to Azotemia.
Filter by:Hemolytic Uremic Syndrome (HUS) is a foodborne disease which mainly affects children. It is caused by Escherichia coli bacteria, which release a toxin called Shiga toxin within the body. This infectious form of HUS, defined as STEC-HUS, can cause sporadic cases or outbreaks, as observed in different countries. Argentina has the highest incidence of STEC-HUS worldwide. The disease is endemic, representing approximately 95% of all HUS cases nationwide. STEC-HUS generally begins with diarrhea (with or without blood), and can also cause fever, abdominal pain, and cramps. Then the child may have pallor, altered consciousness, decreased urine output, seizures, and other symptoms. Although death is uncommon (it occurs in 2-4% of cases), it is a very serious disease that mainly affects the kidneys, and also other organs such as the brain. About half of children need to undergo a risky procedure such as dialysis (due to malfunctioning kidneys); and most of them also receive blood transfusions. Around 30% of the patients are left with lifelong consequences that can range from permanent kidney damage to the need for a transplant. So far there is no drug, antibiotic or vaccine to prevent or treat HUS. Current treatment protocols include hospitalization for all patients with HUS, and supportive therapy such as hydration and salt intake. Support therapy is not a specific treatment, but rather helps the body better defend itself against the disease. The purpose of this study is to establish whether it is safe and effective to treat patients who are diagnosed with STEC-HUS, with INM004 (study drug). INM004 is an investigational product "Fraction F(ab')2 of Equine Shiga Antitoxin Immunoglobulin". It is a concentrated and sterile serum obtained from healthy horses immunized against Shiga toxin that contains antibodies capable of neutralizing it. The initial hypothesis is that INM004 would neutralize the entry of Shiga toxin into the body's cells thus preventing the consequent toxic damage. With the proposed treatment, INM004 would eliminate the Shiga toxin, preventing the progression of HUS symptoms and its serious complications (such as the need for and duration of dialysis, duration of hospital stays, as well as neurological, cardiovascular, intestinal complications, among others) which are associated with high morbidity and mortality. This treatment could then have an impact in health costs of STEC-HUS as well as the social costs.
It is a multicenter observational non-comparative study of the efficacy and safety of long-term pathogenetic Elizaria® therapy in patients with atypical Hemolytic Uremic Syndrome
This study will evaluate the impact of early administration of erythropoietin in the number of red blood cell transfusions in children with Shiga toxin-producing Escherichia coli hemolytic uremic syndrome (STEC-HUS).
Hematopoietic stem cell transplantation (HCT)-associated thrombotic microangiopathy (TMA) is an understudied complication of HCT that significantly affects transplant related morbidity and mortality. The investigators hypothesize that early intervention with complement blocker eculizumab will double survival in HCT recipients with high risk TMA, as compared to historical untreated controls. An optimal eculizumab dosing schedule can be determined for this population through eculizumab pharmacokinetic/pharmacodynamic (PK/PD) testing.
The purpose of the study is to assess the efficacy of ravulizumab to control disease activity in children and adolescents with aHUS who have not previously used a complement inhibitor (complement inhibitor treatment-naïve), as well as in complement inhibitor-experienced (eculizumab-experienced) adolescent participants.
The purpose of the study is to assess the safety and efficacy of ravulizumab to control disease activity in adolescent and adult participants with aHUS who had not previously used a complement inhibitor.
Atypical hemolytic syndrome (aHUS) is a severe renal disease affecting children and adults. It is characterized by the occlusion of intrarenal vessels due to the presence of platelet/fibrin thrombi, and leads to end-stage renal disease in up to 2/3 of patients. The discovery of complement alternative pathway as a major risk factor for aHUS has led to the design of a disease-specific treatment, the anti-C5 monoclonal antibody, eculizumab. Complement inhibition using eculizumab has clearly improved the renal outcome of aHUS patients with a dramatic decrease in the risk of end-stage renal disease. However, the optimal duration of eculizumab therapy is still debated. The present study aims to assess the feasibility and safety of the discontinuation of eculizumab treatment in children and adults with aHUS.
Post diarrheal hemolytic and uremic syndrome (D+HUS) is the first etiology of acute renal failure in children less than 5 years old in France. Previous works highlighted a mortality rate of 2 % and a prevalence of renal sequelae at one year after D+HUS onset in 25 % of patients D+HUS is a consequence of a gastrointestinal infection with shiga toxin (Stx) producing E.coli (STEC). The most frequent straight is E.coli O157H7. The sequence of STEC induced HUS is now well known. Typically, digestive symptoms appear five days following STEC ingestion. STEC colonize the intestinal mucosa, adhere to the enterocyte and cause a typical attaching/effacing lesion and inflammation. Then, diarrhea and vomiting occurred. D+HUS occurs in about 10% of patients and is a consequence of Stx systemic absorption. Indeed, Stx are released in the gastrointestinal tract, then after transferred to the systemic circulation. At the cellular level, Stx binds the globotriosylceramide (Gb3Cer) localized at the surface of the endothelial and epithelial cells of target organs. Following binding to Gb3Cer, the A subunits of Stx are internalized and trigger the activation of the apoptotic program leading to cell death. In addition, Stx are also able to enhance the production and the release of pro inflammatory factor (IL-1, TNFα, IL-6). Cytokines locally produced by Stx-stimulated cells can amplify the inflammatory processes and the prothrombotic state leading to the constitution of the microangiopathic lesions of HUS. To this day, management of D+HUS involves supportive care mainly based on fluid management, dialysis and red blood cells transfusions. Specific therapies used in D+HUS (plasma infusion, antithrombotic and anti inflammatory agents) failed to improve the course of D+HUS. The use of antibiotics remains not recommended while meta-analysis clearly showed that the use of bactericidal antibiotics could worse the course of D+HUS. In vitro experimentations highlighted that some classes of antibiotics like fluoroquinolones dramatically increase the production and the release of Stx before bacterial lysis and worsen the outcome of D+HUS in animal models. By contrast, azythromycin, a bacteriostatic antibiotic of the macrolides family blocking the protein synthesis in bacteria, has a strong inhibitory effect on Stx production and release by STEC as well as it inhibits the in vitro growth of STEC strains. In addition, azithromycin is able to inhibit the Stx-induced production of inflammatory cytokines which are considered to be essential for the development of D+HUS. Consistently the use of azithromycin in animal models of D+HUS dramatically improved the survival rate. Preliminary data on humans with D+HUS treated with azithromycin highlighted a lower prevalence of severe gastrointestinal involvement than in control patients. All these data supported the hypothesis that azithromycin should have a beneficial effect on D+HUS and should improve the short and long term outcome and deserves to be formally demonstrated in human with D+HUS.
The investigators aim to perform the first controlled randomized prospective study using ECZ in pediatric STEC-HUS. This is of great interest as there is still no efficient specific therapy in that potentially devastating disease. Furthermore, published data concerning the use of ECZ in STEC-HUS are controversial, reflecting statistical bias in retrospective or uncontrolled studies, thus emphasizing the need for prospective studies.
The objective of this retrospective trial is to assess safety and efficacy of eculizumab in aHUS patients treated outside of an Alexion-sponsored controlled clinical trial.