Activated CHARcoal in Poisoned Patient - Pilot Trial

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 also 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 effect and potential risks associated with the use of AC. This study is particularly focused on whether early administration of activated charcoal can reduce the severity of poisoning outcomes, shorten hospital stays, and mitigate healthcare costs.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 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 and who did not received AC. The targeted primary outcomes includes: 1) recruitment success (100 patients total at the poison centre associated with hospitals and greater than one patient enrolled/hospital/month), 2) protocol adherence (at least 85% of the patient randomized in the intervention 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) Less than 5% loss to follow-up. As for the large-scale clinical trial if pilot trial shows feasability, the primary outcome will be progression of toxicity as measured using the Poison Severity Score, a patient-oriented metric frequently used in toxicology; mortality, length of stay in both the intensive care unit and hospital, quality of life as measured by the EQ-5D-5L, and changes in the SOFA score for adults and the PELODS score for children.

METHODS: This randomized concealed multicenter trial will take place in one poison centre and five academic hospitals within the provincial network of the centre antipoison du Québec. Patients presenting to the Emergency rooms with a proven or suspected ingestion of a substance absorbed by activated charcoal and the ones who can receive the intervention within 6 hours of proven or suspected intoxication 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. 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.

• Progression of toxicity (descriptive measure of delta Poison Severity Score - PSS max - PSS at randomization calculated at the end of each case) [Срок оценки: 3 months]
• Mortality [Срок оценки: 3 months]
• Length of stay in the intensive care unit and hospital [Срок оценки: 3 months]
• Duration of mechanical ventilation [Срок оценки: 3 months]
• functional outcomes (descriptive measure: "back to baseline" or "not back to baseline" calculated at the moment of medical discharge, death or decision of withdrawal of life support) [Срок оценки: 6 months]
• adverse events [Срок оценки: 3 months]