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NCT ID: NCT06304714 Not yet recruiting - Hemorrhage Clinical Trials

Effects of Bothrops Spp. Snake Envenomation on Willebrand Factor Activity in Martinique and French Guiana

WBOTHROPS
Start date: April 1, 2024
Phase:
Study type: Observational

In 2017, the World Health Organization placed snakebites at the top of its list of neglected tropical diseases in an effort to facilitate funding for prevention programs, improve access to anti-venom, and stimulate new research in this area. Between 5 and 25 cases per 100 000 inhabitants are reported per year in French Guiana and Martinique. Before the era of anti-venom immunotherapy, envenomations by Bothrops snake bites in French Guiana and Martinique could quickly become life-threatening with a mortality rate close to 30%. Today, the administration of fragments of Fab or (Fab')2 immunoglobulins gives anti-venoms an excellent capacity to neutralise venom toxins, which has reduced mortality to less than 1% in the case of early hospital treatment In French Guiana, envenomation by Bothrops bites is characterized by local signs such as intense pain, rapidly expanding oedema, haemorrhagic phlyctenes and sometimes muscle necrosis. The local inflammatory and haemorrhagic damage is related to the enzymatic activities of the toxins contained in the venom (metallo-proteinases, disintegrins, and phospholipases A2, in particular). At the systemic level, venom serine proteases and metalloproteinases activate the coagulation cascade by multiple mechanisms (activation of coagulation factors X and V and of protrombin, thrombin-like and fibrinogenolytic enzymatic properties) and are responsible for the collapse of coagulation factors making the blood incoagulable. The metalloproteinases "hemorrhagins" destroy the vessel wall and are the cause of locoregional and systemic hemorrhage. Envenomations by bites of Bothrops lanceolatus in Martinique have particular characteristics. Despite the genetic similarity with their congeners in French Guiana, envenomation by bites of Bothrops lanceolatus is characterized by the development of very intense local inflammatory signs (little haemorrhage) and the occurrence of thrombotic complications such as cerebral, pulmonary or myocardial infarction. The mechanisms behind this thrombotic presentation are not known. The large amount of metalloproteinases in the composition of Bothrops lanceolatus venom is believed to be responsible for destruction of vascular endothelium and pro-thrombotic state. Bothrops lanceolatus bite envenomations have been reported to be frequently complicated by generalized infections, disseminated intravascular coagulation and the occurrence of multi-visceral failure syndrome. This observation suggests abnormalities in endothelial function in which changes in Willebrand factor expression have been implicated. The investigators hypothesize that plasma Willebrand factor (VW) activity and the intensity of endothelial activation are different depending on the Bothrops snake species involved in the bites in Guyana and Martinique. Due to the specific properties of the venoms of each Bothrops species, the activity of the Willebrand factor (VW) and the consequences in terms of endothelial activation would be different and responsible for the clinico-biological characteristics according to the geographical origin of the snakes. The investigators will demonstrate that the accumulation of Willebrand factor (VW) and the increase in its activity are responsible for the endothelial activation and micro-thrombosis observed during envenomations by Bothrops lanceolatus bites, whereas the decrease in its activity induced by the venoms of endemic Bothrops from Guyana is responsible for haemorrhagic phenomena. This study will highlight the importance of changes in Willebrand factor activity on endothelial activation and the initiation of micro-thrombosis in the case of Bothrops lanceolatus envenomations and on primary haemostasis and bleeding disorders in the case of endemic Bothrops in Guyana. This new knowledge is important insofar as individualised therapeutic management can be proposed. Indeed, several studies have shown that adjuvant treatment of thrombotic microangiopathies, such as thrombotic thrombocytopenic purpura, with blood products (fresh frozen plasma) or plasma exchange, improves endothelial dysfunction and the prognosis of patients.

NCT ID: NCT06151301 Not yet recruiting - Clinical trials for Acute Hydrocarbon Toxicity

Evaluation of the Role of Poisoning Severity Score, Serum Procalcitonin and C-reactive Protein in Acute Hydrocarbon Intoxicated Cases Admitted to the Poison Control Center Ain Shams University Hospitals

Start date: December 1, 2023
Phase:
Study type: Observational

Hydrocarbons are a primary energy source in modern society. They are present in many common household and occupational products, including motor fuels, paint thinners, cleaning agents, lotions, and industrial solvents. Unfortunately, these products are also used as agents of abuse and typically inhaled . They are derived mainly from petroleum (kerosene, gas, naphtha) or wood (turpentine, pine oil). They can be found in liquid, gas, or solid form depending on their properties. All hydrocarbons can be toxic, but aromatic (ring-shaped) and halogenated hydrocarbons typically have more severe toxicity . Toxicity occurs in various ways including through inhalation, ingestion, aspiration, and dermal exposure. Frequently, these exposures occur during attempted recreational use of the substances and sometimes for self-injurious behavior

NCT ID: NCT06108557 Not yet recruiting - Clinical trials for Organophosphate Poisoning

Paraoxonase-1 Pseudo Cholinesterase Organophosphate Toxicity Enzyme in Prediction the Severity and Outcome of Acute Organophosphate Poisoning and Its Correlation With Pseudo Cholinesterase Enzyme Level.

Start date: January 2024
Phase: N/A
Study type: Interventional

The aim of the present study is to: Evaluate the serum Paraoxonase-1 level in cases with organophosphate compounds poisoning and to correlate it᾿s level with the severity, outcome of acutely organophosphate poisoned cases . Evaluate the serum pseudocholinestrase level in cases with organophosphate compounds poisoning and to correlate it with the Paraoxonase-1 level in those cases.

NCT ID: NCT06045793 Not yet recruiting - Cocaine Abuse Clinical Trials

Comparing Efficacy & Safety Of TNX-1300 To Placebo With UC For Treatment Of Acute Cocaine Intoxication In ED Subjects (CATALYST)

CATALYST
Start date: December 11, 2023
Phase: Phase 2
Study type: Interventional

This is a Phase 2 single-blind, randomized, multicenter study to compare the efficacy and safety of a single dose of TNX-1300 to placebo with usual care in patients with acute cocaine intoxication within the emergency department setting.

NCT ID: NCT05649891 Not yet recruiting - Pneumonia Clinical Trials

Checklists Resuscitation Emergency Department

Start date: September 2023
Phase: N/A
Study type: Interventional

The study will systematically evaluate how an emergency manual-a collection of checklists and fact sheets-affects the performance of resuscitation teams during the management of priority one patients in an emergency department.

NCT ID: NCT05647707 Not yet recruiting - Clinical trials for Carbon Monoxide Poisoning

The Efficacy of L-Carnitine in the Management of Acute Carbon Monoxide Poisoning

Start date: December 15, 2022
Phase: Phase 2
Study type: Interventional

Carbon monoxide (CO) poisoning results in high morbidity and mortality worldwide. CO is described as a "silent killer" because CO is colorless, odorless, and tasteless but highly toxic. The diagnosis of acute CO poisoning depends on the history of exposure to a source of fire in a closed space along with the clinical and laboratory findings. The pathophysiology of CO poisoning is not fully understood; however, it is proved that CO induces hypoxia by forming carboxyhemoglobin (COHb) and shifting the oxygen dissociation curve to the left. The molecular mechanisms of CO poisoning include oxidative injury through the generation of free radicals. In addition, oxygen therapy might enhance the reactive oxygen species (ROS) production and result in reperfusion injury. Free radicals could induce a serious impact on vital organs, including the heart, and brain. L-Carnitine is an endogenous mitochondrial constituent that contributes to normal mitochondrial activities. L-Carnitine is an antioxidant with potent ROS scavenging ability. ROS-mediated pathology of CO suggests that antioxidants are potentially useful agents in the alleviation of CO toxicity. Thus, the current study will investigate the therapeutic efficacy of L-Carnitine in improving the prognosis of acute CO poisoning. The current clinical trial will include patients with moderate and severe acute carbon monoxide poisoning according to Poisoning Severity Score.

NCT ID: NCT05632094 Not yet recruiting - Clozapine Poisoning Clinical Trials

The Efficacy of L-Carnitine in the Management of Acute Clozapine Intoxication

Start date: June 2023
Phase: Phase 2
Study type: Interventional

Clozapine is a dibenzodiazepine that is used atypical antipsychotic drug. Clozapine-induced cytotoxicity could be attributed to increases in reactive oxygen species (ROS) that oxidize mitochondrial proteins and disrupt cellular respiration. L-Carnitine (4-N-trimethylammonium-3-hydroxybutyric acid) is an endogenous mitochondrial membrane compound that is essential for the normal functions of mitochondria. L-Carnitine is an effective ROS scavenger that prevents lipid peroxidation. In an animal study, it was observed that clozapine decrease L-Carnitine level in plasma which results in metabolic disorders. Subsequently, the use of supplementation L-Carnitine was recommended to attenuate clozapine-induced side effects. An in-vitro study investigated the cytotoxic effects of clozapine on human lymphocytes and the possible protective role of L-Carnitine, the results revealed that clozapine-induced cytotoxicity attributed to oxidative stress and mitochondrial dysfunction which significantly improved upon L-Carnitine administration. In clinical toxicology, acute clozapine toxicity results in significant morbidities and mortalities in absence of a specific antidote. Therefore, it is essential to adopt pharmaceutical intervention based on the proposed mechanism of clozapine-induced cytotoxicity. The objective of the current research is to assess the potential beneficial effects of L-Carnitine on the acute clozapine poisoning outcome. The study will include patients with moderate and severe acute clozapine poisoning. The patient's condition will be assessed on admission using a Poisoning Severity Score. Patients with acute clozapine poisoning will be assigned randomly into two groups; the Conventional group and the L-Carnitine group. Then, all patients will be closely followed up for vital signs, Glasgow Coma Scale, and Electrocardiogram. Clinical and laboratory reassessments will be performed. Lastly, the outcomes will be assessed and statistical analysis of the results will be performed. Ethical approval was obtained from the Research Ethics Committee of the Faculty of Medicine, Alexandria University. This Ethics Committee is constituted and operates according to ICH GCP Guidelines and applicable local and institutional regulations and guidelines that govern the Ethics Committees operation. Written informed consent will be obtained from clozapine-intoxicated patients or their guardians (minors or those with disturbed mental status). Full details regarding the study's aim and procedures will be provided to all participants. A code number will be assigned to ensure confidentiality and anonymous analysis of data.

NCT ID: NCT05471479 Not yet recruiting - Clinical trials for Charcoal, Decontamination, Poisoning

Activated CHARcoal in Poisoned Patient

CHARPP-RCT
Start date: June 1, 2023
Phase: Phase 4
Study type: Interventional

BACKGROUND: Activated charcoal (AC) is one of the interventions more frequently recommended by poison centers. For instance, in 2020, 32,646 poisoned patients were treated with AC in the United States. This decontamination method has the potential to prevent toxicity and to decrease its severity, but its use is associated with adverse effects and has a poor palatability. Therefore, we developed a research program named CHARPP (activated CHARcoal in Poisoned Patients) aiming to describe the risks and benefits associated with the use of AC. The Clinical Toxicology Recommendations Collaborative (CTRC) already published a systematic review and is currently working on recommendations of use. The first phase of our research program included: a retrospective study and a validation of the Poison Severity Score. The last phase includes a randomized controlled trial (RCT) preceded by a feasibility study in adults and children to compare outcomes in patients who received AC as per the CTRC recommendations vs those who did not. OBJECTIVES: This concerns the CHARPP RCT feasibility study which aims to evaluate the possibility of conducting a large multicenter RCT comparing outcomes between poisoned patients who received AC as per the CTRC recommendations and who received AC as per current practice. The targeted primary outcomes includes: 1) recruitment success (100 patients total at the two poison centers associated with academic hospitals and greater than one patient enrolled/hospital/month), 2) protocol adherence (at least 95% of the patient randomized in the CTRC recommendations group received AC in less than two hours after group allocation if AC was recommended or did not received it if it was not recommended) and, 3) lost to follow-up (less than 5%). As secondary outcomes, progression of toxicity measured by the Poison Severity Score (and the SOFA score for adults or PELODS score for children), mortality, length of stay in the intensive care unit and hospital, duration of mechanical ventilation, functional outcomes and adverse events will also be described for both groups. METHODS: This randomized concealed multicenter trial will take place in at least two poison centres and at least four Canadian academic hospitals including at least one pediatric center. Patients who presented to the hospital less than 8h after the ingestion of a potentially toxic dose of a carbo-adsorbable substance will be included. Patients requiring or who will likely require another gastro-intestinal decontamination method, who have a contraindication to receive AC, or who ingested a substance with an entero-hepatic circulation requiring multi-dose AC will be excluded. Once the poison centre has identified an eligible patient, we will use a web-based system to perform a randomization in random blocks of two or four. The specialist in poison information will then refer either to the CTRC recommendations or to their current protocols for the use of AC. Co-interventions will be standardized as per the poison centre protocols. Follow up will be done every 8h by the poison centres who will also collect data regarding progression of toxicity and relevant outcomes. The research assistant who will extract data will be blinded to study allocation. Only a descriptive analysis will be done for the pilot trial. Data from paediatric patients will be analysed separately. A data and safety monitoring board independent from the study group will follow the results and approve or not the continuation of the study. RELEVANCE: This will be an excellent opportunity to develop collaborations between poison centers and key actors who will be involved in a larger trial. The results of the research program CHARPP have the potential to influence policies, poison centers recommendations, clinicians' practices and to improve poisoned patients' outcomes.

NCT ID: NCT05334667 Not yet recruiting - Clinical trials for Aluminium Phosphide Poisoning

CRRT Versus Plasmapheresis in Aluminum Phosphide Poisoning

AlP
Start date: June 2022
Phase: N/A
Study type: Interventional

Aluminum phosphide (AlP) is a solid fumigant pesticide sold as tablets in use since the 1940s. It is considered to be an ideal pesticide because of its cheapness, efficiency, and easy availability in the market and is widely used as a grain preservative worldwide.The mortality in cases of aluminum phosphide poisoning varies between 60% and 90%, even in experienced and well-equipped hospitals. Patients mostly die due to cardiovascular collapse, refractory shock, severe acidemia, fulminant hepatic failure, and or adult respiratory distress syndrome. Continuous renal replacement therapy (CRRT) is a slow and smooth continuous extracorporeal blood purification, which is designed to replicate depurative function of the kidney. It is usually implemented over 24 h to several days with an aim of gentle correction of fluid overload and removal of excess uremic toxins. Furthermore, many observational studies considered CRRT as the predominant form of RRT in the intensive care unit (ICU) for critically ill patients with AKI and/or multiorgan failure, along with acute brain injury or other causes of increased intracranial pressure or generalized brain edema. The effectiveness of CRRT is mainly due to its accurate volume control, steady acid-base and electrolyte correction, and achievement of hemodynamic stability in adults and pediatrics. Plasmapheresis (PPH) can rapidly and effectively remove toxic substances and their potentially toxic metabolites from the blood compartment, especially those with high protein-binding. As the potential benefit of therapeutic plasma exchange is increasingly recognized, its use is becoming more widespread, and case reports have confirmed its value in the treatment of drug overdose. The application of plasmapheresis dramatically reversed the severe biochemical and clinical manifestations and was able to prevent serious co-occurrence.

NCT ID: NCT05310188 Not yet recruiting - Pesticide Poisoning Clinical Trials

Cholinesterase, Amylase, Lipase and Neutrophil-to-lymphocyte Ratio in Acute Pesticide Poisoning Cases

Start date: April 2022
Phase:
Study type: Observational

To estimate diagnostic levels of amylase, lipase, pseudocholinestrase and neutrophili lymphocytic ratio to different pesticide poisoning. In addition to detect prognostic values of theses enzymes & NLR and its relation to the outcome of all pesticide poisoning. To assess descriptive sociodemographic criteria of these poisoned cases, mode of toxicity, type of pesticide poisoning at emergency room, any other associated toxicity as well as the clinical outcome.