53 Clinical Trials for Various Conditions
At the University of Iowa, the investigators led a multicenter randomized clinical trial comparing standard prophylactic dose to intermediate dose enoxaparin in hospitalized patients with COVID-19 (NCT04360824). As part of an exploratory biomarker component of this trial, blood samples were collected from hospitalized COVID-19 patients at enrollment and weekly for up to 30 days of hospitalization. The pilot results, as well as reports from other groups, demonstrate increased potential for thrombin generation in the plasma of COVID-19 patients. In particular, in the COVID-19 patient cohort enhanced thrombin generation potential persisted for at least 30 days of hospitalization. The investigators now propose to explore the mechanistic roles of activation of blood cells (such as platelets and neutrophils) and products of cellular activation as mediators of enhanced thrombin generation in patients with COVID-19. The study design will be a longitudinal cohort study, which will allow for the determination of the time course of enhanced thrombin generation potential in relation to clinical outcomes and changes in markers of cellular activation in serial samples obtained from COVID-19 patients for up to 3 years after infection with SARS-CoV-2. This study may provide clues to why a subset of COVID-19 patients present with late thrombotic complications even after apparent recovery from SARS-CoV-2 infection. An ongoing question in the field relates to the comparative prothrombotic effects of acute COVID-19 versus incidental SARS-CoV-2 infection versus acute infection with influenza viruses. Therefore, we will include three categories of hospitalized patients in this study: (1) acute COVID-19, (2) incidental COVID-19, and (3) acute influenza A or B. This project has a strong scientific rationale with direct clinical implications, especially given the emergence of SARS-CoV-2 variants such as delta and omicron that may prolong the pandemic and/or cause surges of COVID-19 in the coming months.
Phase 2a study to assess the safety and efficacy of IV infused spray-dried solvent/detergent -treated plasma (Resusix) when compared with an equal volume of plasma frozen within 24 hours after phlebotomy (FP24) in patients with liver disease who are actively bleeding or who require prophylaxis for surgical bleeding
While a number of factors are known to be associated with the development of trauma induced coagulopathy (TIC), inflammation, and multi-organ failure, we currently cannot predict which patients are at risk for developing these life threatening conditions with any certainty. In this prospective observational study, we will investigate the many factors that contribute to the development of trauma induced coagulopathy, post injury inflammation and the development of organ dysfunction in order to develop a multi scale computational algorithm of clinical prediction. Using a convenience sample technique, demographic data, physiologic data, blood samples and clinical variables will be collected over 5 days following traumatic injury. A computational model will be used to predict the development of TIC and multi-organ failure.
The purpose of this study is to determine the effect of antioxidant vitamins (vitamins C and E) on the development of coagulation derangements and nosocomial pneumonia after severe trauma in patients.
The purpose of the study is to evaluate if ART-123 given to patients who have severe sepsis can decrease mortality.
The purpose of this study is to evaluate the clinical utility of thrombelastography (TEG) to predict and identify trauma patients at increased risk of receiving blood transfusion, develop multiple organ failure and mortality. TEG has been proposed as a superior tool to rapidly diagnose and help guide resuscitation with blood products and preclinical data suggest that TEG is both more sensitive and specific than PT or PTT for coagulation abnormalities. Based on the preclinical work led by Dr. Holcomb, our hypothesis is that the Rapid TEG will help to identify these coagulopathic patients earlier, allow for rapid MT protocol activation, and assist in developing data driven blood product transfusion guidelines.
The purpose of this study is to evaluate efficacy, safety and tolerance of Beriplex® P/N (Kcentra) compared with plasma in regard to rapid reversal of coagulopathy induced by vitamin K antagonists in subjects who require immediate correction of international normalized ratio (INR) because of emergency surgery.
Excessive prolongation of the international normalized ratio (INR) occurs frequently in patients taking warfarin; in fact, about one in six INR values is above the desired range. Excessive prolongation of the INR is clinically important because the risk of bleeding approximately doubles for each one point increase in the INR beyond the usual therapeutic range. Thus, treatment strategies which rapidly and reliably lower an excessively prolonged INR into the desired range have the potential to reduce bleeding. When taken by patients with INR values between 4.5 and 10, a small dose of oral vitamin K (1 mg to 2.5mg) reduces the INR into the desired INR range in about 75% of cases within 24 hours of its administration. If warfarin is simply withheld, and no vitamin K is given, about 25% of patients will have an INR in the desired range at 24 hours. However, vitamin K is rarely given to such patients. In a recent survey carried out by our group, less than 20% of such patients would have been given low dose oral vitamin K by a group of physicians who regularly supervise warfarin therapy. The most common treatment for excessive prolongation of the INR is to simply withhold warfarin and allow the INR to fall into the therapeutic range. Although this strategy is effective its safety has never been adequately examined. In fact, recent evidence suggests that patients with INR values of more than 6.0 who are treated with simple warfarin withdrawal have a risk of major bleeding of 4% in the two weeks after they develop their prolonged INR. When asked why they did not give oral vitamin K to a non-bleeding patient who has an excessively prolonged INR, physicians generally give one of three reasons: (1)They are not convinced that oral vitamin K reduces bleeding. (2) They are concerned that oral vitamin K may cause thrombosis. (3) In contrast with simply withholding warfarin, giving oral vitamin K requires a patient to visit the physician, and the physician must have a supply of vitamin K. The investigators hypothesize that the routine practice of not administering oral vitamin K to patients with excessively prolonged INR values is causing patients to have major, life-threatening and fatal bleeds. To convince physicians that oral vitamin K should be administered to all non-bleeding patients with INR values of more than 4.5, the investigators propose a study which the investigators anticipate will demonstrate that oral vitamin K reduces bleeding, does not cause thrombosis, and can be administered at home without direct physician supervision. To accomplish these goals, the investigators propose a multinational, double-blind, placebo-controlled trial. The investigators will randomize patients with INR values between 4.5 and 10.0 to receive 1.25 mg of oral vitamin K or placebo and follow them for bleeding and thrombosis. Patients with INR values of more than 10.0 will receive a single 1.25 mg dose of oral vitamin K. Successful completion of this study will establish a treatment standard supported by clinical data which will, in turn, change the way that patients taking warfarin who present with an excessively prolonged INR are treated.
This pilot study examines the use of thromboelastography (TEG), a specialized blood test, to evaluate clotting abnormalities in burn patients. The study aims to understand how burn injuries impact the body's ability to form and break down blood clots over time. Specifically, the investigators will research whether the percentage of total body surface area burned (%TBSA) is associated with changes in blood clotting, track the evolution of clotting patterns during the first four weeks following a burn injury, and explore whether these changes can predict recovery or complications. By providing new insights into clotting dynamics in burn patients, the study seeks to improve diagnostic methods, enhance monitoring strategies, and guide treatments to optimize patient care and outcomes.
This study will examine the coagulation and fibrinolysis profiles of those with autoimmune skin diseases. Blood samples will be collected from participants with active/poorly controlled immune-mediated skin diseases and mild/latent/well-controlled immune-mediated skin diseases. A one-time sample from 15 general dermatology outpatients who do not have a known or suspected diagnosis of bullous diseases, immune-mediated dermatologic condition, or cutaneous malignancy will also be collected to serve as control. Blood samples from both participant populations will be analyzed for coagulation and inflammatory markers and compared. The results of this study may help inform future studies on the utility of analyzing coagulation and fibrinolysis profiles of patients with autoimmune skin diseases.
This prospective, randomized, open-label, multi-center interventional study is designed to compare the safety and efficacy of two LMWH dosing protocols in patients admitted to the University of Iowa Hospitals with COVID-19 who meet the modified ISTH Overt DIC criteria score ≥3. Patients will be randomized to standard prophylactic dose LMWH (standard of care arm) or intermediate-dose LMWH (intervention arm).
This will be the first prospective randomized controlled clinical trial directly comparing Prothrombin Complex Concentrate (PCC) Compared to Fresh Frozen Plasma (FFP) for post cardiopulmonary bypass microvascular bleeding and factor-mediated coagulopathy. Is there a difference in bleeding and transfusion requirements in patients received PCC versus FFP?
This prospective study will aim to globally assess the coagulopathy induced during cardiac surgery with cardiopulmonary bypass (CPB) in a large pediatric population. The investigators primary objective will be the understanding of CPB-induced coagulopathy based on demographic and surgical characteristics, and coagulation assays. Secondary objective will aim at determining the relationship between coagulation assays, postoperative blood loss, and transfusion requirements. The ultimate goal will be to design an algorithm using point-of-care monitoring that could be used to guide hemostatic therapies in neonates and children undergoing cardiac surgery.To do this, investigators will examine the coagulation in the laboratory based setting.
The purpose of the study is to identify the inflammatory and coagulation pathways and mechanisms that are activated immediately following burn injury, and how they affect outcomes in terms of organ failure and death. This study also addresses the limitation of current tests (PT, PTT, and platelet counts) employed to identify coagulation disturbances in severely injured patients both in a comprehensive and rapid manner.
The investigators will obtain thromboelastography (TEG) on pediatric patients admitted to the Rady Children's Hospital ICU after traumatic brain injury on admission to our ICU and after 24 hours of care. The investigators hypothesize that TEG will identify abnormalities of coagulation that are not identified by traditional coagulation studies, i.e. prothrombin time (PT), activated partial thromboplastin time (aPTT), and international normalized ratio (INR).
Traumatic injury is a major public health problem with an immense societal cost. Despite improvements in trauma management, patients continue to suffer significant morbidity and mortality. Evidence suggests that males and females tolerate severe injury differently with a greater protection afforded to females. Determining the mechanisms responsible for these sex-based outcome differences after injury, focusing specifically on the early sex-hormone environment post-injury, may allow those at highest risk for poor outcome to be predicted and promote interventions that can improve outcomes for all injured patients. The goal of this study is to determine if the early sex hormone environment soon after injury has effects on the intensity of the immune response, resuscitation and blood transfusion requirements, and important clinical outcomes including mortality, organ failure and infection, following significant injury.
ACTG A5275 was a prospective, double-blind, randomized, placebo-controlled cross-over design pilot study evaluating the effect of atorvastatin on biomarkers of inflammation, coagulopathy, angiogenesis, and T-lymphocyte activation in HIV-1 infected individuals with suppressed HIV-1 RNA on stable protease inhibitor based antiretroviral therapy with fasting LDL cholesterol \< 130 mg/dL. Atorvastatin is a drug approved by the Food and Drug Administration (FDA) for treating high cholesterol. Atorvastatin has also been able to lower the level of inflammation blood tests in certain other diseases but has not been studied for this purpose in people who have HIV. The main goal of this experimental study is to see how taking atorvastatin affects inflammation blood tests in people infected with HIV who do not need to take medicine for high cholesterol. In addition to observing the effects of atorvastatin on the level of inflammation measured in the blood, this study evaluated if atorvastatin is safe for people with HIV who are also taking medication for HIV.
Trauma continues to be the major killer of young Americans, mainly due to hemorrhage or brain injury. In trauma centers, up to a quarter of these severely injured patients arrive with a coagulopathy and thereby experience an increased risk of death, despite the current standard of medical and surgical management. The PI for this grant proposal is a fellowship-trained trauma surgeon who works full-time at Grady Memorial Hospital (GMH), the only Level I Trauma Center in Atlanta. It is only one of four Level 1 trauma centers for the entire state of Georgia. This research is a direct extension of the retrospective research the PI has previously published. Her retrospective research discovered a previously undescribed form of coagulopathy, early trauma induced coagulopathy (ETIC), which cannot be explained by present paradigms. Two civilian trauma articles as well as military data from the Iraq war have substantiated the occurrence of ETIC, but no prospective literature has defined it or its kinetics. More importantly, the results from these studies represent a new paradigm shift, in which ETIC appears to be a primary dysfunction which is independently associated with death. Therefore, its early identification and correction is crucial for our mechanistic understanding, and ultimately, our choice of interventions and improved survival. GMH is a high-volume trauma center that sees patients with a variety of injury mechanisms, and, therefore, is the perfect setting to confirm ETIC. First, the project will confirm the prevalence of ETIC with an observational prospective cohort of injured patients. Data on the coagulation system and risk factors, both known and suspected, of all patients will be collected upon patient arrival as well as patient outcome with all identifying information protected. This is the first prospective research project that will allow simultaneous control of confounders associated with outcome and thereby scientifically validate the occurrence of ETIC. One unique component of our data collection is a focus on the timing of events as they relate to the development and consequences of coagulopathy, to account for the dynamic process. At the completion of data collection, a matched cohort of ETIC and non-ETIC blood samples will be tested for coagulation factors to provide insight into ETIC's pathophysiology. In the short term, our conclusions will assist us in our approach to resuscitation of the bleeding trauma patient as some trauma centers have already started to change protocols based on our present incomplete understanding of trauma-induced coagulopathy. In addition, the coagulation system data collected in this study will lead to pathophysiological answers and to more refined hypotheses for future research at a coagulation system level. Ultimately an understanding of ETIC will lead to a more effective, tailored treatment. Our main study hypothesis is that post-trauma coagulopathy is a primary dysfunction that occurs early after a traumatic event in up to 25% of all trauma patients triaged to Trauma Center care.
PURPOSE The purpose of this study is to learn more about multifocal lymphangioendotheliomatosis with thrombocytopenia (MLT). MLT is a rare vascular disorder characterized by multiple congenital skin and visceral lesions, profound thrombocytopenia, and gastrointestinal bleeding. The skin lesions may appear red, brown or blue, often misdiagnosed as hemangiomas. The gastrointestinal tract, liver, and lungs are the most common internal organs involved. The severe thrombocytopenia (low platelets) is believed to be the result of platelet trapping within the skin and visceral vascular lesions. Severe and chronic gastrointestinal bleeding is common during infancy and early childhood. Although a relatively newly described entity, MLT was likely previously reported as hemangiomas, blue rubber bleb nevus syndrome, diffuse hemangiomatosis, Kasabach-Merritt phenomenon, and hereditary hemorrhagic telangiectasia. The term cutaneovisceral angiomatosis with thrombocytopenia is also a term used for this same disease. This study is a longitudinal cohort study of MLT to collect detailed clinical data on the distribution of disease, disease severity, and complications. This data will be used to create diagnostic criteria and an evaluation protocol for infants with this disease
The goal of this observational study is to learn about the performance of the TEG6s in normal pediatric patients. The main questions it aims to answer are: What are the normal TEG 6S lab results in normal pediatric patients and how do they compare to existing published reference ranges. Participants and their guardians will be asked to submit a small amount of blood at the beginning of an elective operation for analysis in the TEG 6s machine.
This study in healthy volunteers is designed to assess the safety of infusing increasing doses of spray dried plasma (FrontlineODP).
Congenital heart surgery on cardio-pulmonary bypass (CPB) is associated with impacted coagulation quality and increased bleeding after separation of CPB. The current testing device used at our institution is the "TEG 5000" (Haemonetics Corporation). The novel coagulation testing device "Quantra System" (Hemosonics) has favorable properties (result within 20 minutes) allowing for a quicker identification of the coagulation problem and hence faster administration of the correct coagulation products, potentially leading to better coagulation quality and possibly reducing the need of additional blood products. The aim of this prospective observational (non-interventional, investigational only) quality improvement study is to investigate if the Quantra is reliable and valid in predicting the coagulation status when compared with our standard-of-care device TEG 5000.
The study aligns with the strategic plan of New York-Presbyterian Hospital (NYPH) to reduce allogeneic blood product use and decrease unnecessary laboratory costs. One of the NYPH Quality and Patient Safety Goals for 2013 was to improve the appropriate use of transfusion guidelines and reduce unnecessary red blood cell (RBC) transfusions. Further, this study will help to answer whether RiaSTAP is a more effective product to treat bleeding than cryoprecipitate. In addition, this trial will provide investigators with preliminary data to apply for future federal funding opportunities, such as the National Heart Lung and Blood Institute sponsored R21 grant (PAR-13-025) that encourages research grant applications from investigators who propose to study research topics in blood banking and transfusion medicine aimed at improving the safety and availability of the blood supply and the practice of transfusion medicine. The investigators anticipate future follow-on studies further investigating fibrinogen concentrate and other similar therapeutics in other perioperative populations, such as in postpartum hemorrhage or surgical ICU settings. Finally, this study involves the use of a safer therapeutic, fibrinogen concentrate, to improve patient care and patient safety. This product does not require the time-intensive process of thawing; therefore, delays in patient care can be avoided by having the product readily available in the OR.
Post-Marketing Requirement study to evaluate the safety of octaplas™ versus plasma in patients undergoing orthotopic liver transplantation (OLT). The primary objective is to assess the incidence of hyperfibrinolysis in patients undergoing (OLT) receiving octaplas™ versus regular plasma (e.g., fresh frozen plasma and other FDA and AABB approved plasma products).
Surgery for malignant pleural mesothelioma is complex and prolonged, and may involve significant blood loss with considerable blood and product transfusion. Thromboelastography (TEG) is a global assay of coagulation that uses whole blood to produce a tracing that records kinetic changes in clot formation. This study aims provide a better understanding of the coagulation profile of these patients, and will form the basis of a TEG-based transfusion algorithm for future surgeries for mesothelioma.
The purpose of this study is to compare rapid thrombelastography (r-TEG) with conventional coagulation testing for diagnosing and treating coagulation abnormalities in severely injured patients who are likely to require transfusion therapy.
In this study, investigators plan to evaluate the cardiometabolic effects of initiating gender-affirming hormone therapy among transgender women with and without HIV. As part of this study, participants will undergo cardiovascular and metabolic phenotyping within 3 months of starting and after 12 months of gender-affirming hormone therapy. Cardiovascular phenotyping will include cardiac MRI/MRS imaging to evaluate cardiac function and structure. Metabolic phenotyping will include oral glucose tolerance testing, abdominal MR imaging to evaluate visceral adiposity, and whole body, lumbar, and hip DEXA imaging to evaluate fat and lean body mass as well as bone mineral density, respectively. Traditional markers of CVD risk as well as immune, hormonal, and coagulation parameters will also be assessed longitudinally.
This study aims to standardize the treatment of pleural space (parapneumonic) infections by comparing the difference in outcomes between 2 methods of treatment: early VATS (Video Assisted Thorascopic Surgery) decortication versus fibrinolytic therapy. During treatment, the patient's coagulopathy status will also be evaluated.
Massive hemorrhage is a major cause of potentially preventable death following trauma. A common consequence of hemorrhagic shock is uncontrollable bleeding from coagulopathy, leading to death from exsanguination. Even when bleeding is controlled, patients are at increased risk of complications and mortality. Reconstituted whole blood, or component therapy with packed red blood cells (PRBCs), plasma, and platelets was introduced by the military in recent conflicts in Iraq and Afghanistan with remarkable results and has been adopted by most civilian trauma centers. Despite improving coagulopathy, it is apparent that transfusion of blood components is not equivalent to whole blood transfusion. Transfusion of high plasma volumes may be associated with increased risk of allergic reaction, transfusion associated acute lung injury (TRALI), hypervolemic cardiac failure, and acute respiratory distress syndrome (ARDS). Military services have recently reintroduced fresh whole blood (WB) for standard resuscitation of massive hemorrhage, have found that WB offers a survival advantage over component therapy, and that risks of transfusion reactions are similar for WB and PRBCs. On the civilian side, whole blood is an FDA-licensed product that has been in use in pediatric open heart surgery and autologous blood donation but is no longer commonly available for other indications. However, the military results are renewing interest in whole blood for trauma resuscitation. The use of low-antibody titer whole blood leukoreduced with a platelet-sparing filter was recently approved by the University of California Los Angeles Blood and Blood Derivatives Committee and two other trauma centers for male trauma patients. This study will test the feasibility of providing stored WB for resuscitation of patients in hemorrhagic shock and determine the effects of WB on clinical outcomes as well as the effects on coagulation, fibrinolysis, and inflammation, compared to standard blood component therapy.
Caribbean Hispanics are a population with a disproportionately high prevalence of cardio-metabolic disorders but with a limited expectation of benefits from current pharmacogenetic algorithms derived mainly in subjects of relatively pure ancestry. The investigators focus on warfarin responses to develop urgently-needed DNA-driven prescription guidelines for this population, who have arisen from European, West African and Amerindian genomic origins to produce a highly heterogeneous population. Our project combines admixture analysis and DNA-sequencing with development of more accurate rules for better predictability of warfarin dosing to immediately serve this medically underserved population.