Combined Gastrointestinal Decontamination in Acute Severe Poisoning

Официальное название

Reduction of Digestive Absorption of Toxic Substances by Combined Digestive Decontamination in Intensive Care - Randomized Single-center Study

Обзор

Gastrointestinal absorption of high dose medication (toxicant) ingested under solid form for suicidal purposes, is prolonged in patients who need intensive care admission and mechanical ventilation. This is due to the large ingested amounts, slowed blood circulation in the digestive system due to low blood pressure, and the formation of conglomerates of pills (pharmacobezoars). We make the hypothesis that combined decontamination of the digestive system with activated charcoal plus polyethylene glycol may reduce absorption of the ingested toxicant compared with standard care. Two hundred patients requiring admission to intensive care and mechanical ventilation due to the effect of the ingested toxicant, will be included in a 1:1 randomized fashion over 24 months in the intervention group receiving combined decontamination and standard care group receiving activated charcoal according to guidelines. The main objective is to show a decrease in the concentration of the toxicant after 24h of randomization.

Подробное описание

Rationale - digestive absorption of toxic substances ingested in solid form is prolonged in severely intoxicated patients admitted to intensive care and requiring intubation and mechanical ventilation. This prolonged absorption is favoured by the large quantity of tablets/pills ingested, the formation of pharmacobezoars, delayed formulations, co-ingestion of transit slowing agents (such as substances with an anticholinergic effect) and mesenteric hypoperfusion in the event of hypotension slowing absorption.

Digestive decontamination with activated charcoal combined with intestinal purging with polyethylene glycol (PEG) appears to be effective in pharmacokinetic studies, but its benefits have never been studied in intoxicated patients, particularly after admission to intensive care. Digestive decontamination using activated charcoal and polyethylene glycol could reduce toxic concentrations at 24 hours compared with the standard treatment group.

Main objective: To show the greatest reduction in the plasma concentration of the toxicant(s) (ingested parent molecules) at H24 of randomisation in the intervention group receiving activated charcoal + intestinal purge compared with the control group.

primary endpoint: Percentage change in the plasma concentration of the toxic substance(s) (ingested parent molecules) at 24 hours compared with its/their value(s) at randomisation.

Secondary objectives:

* To show the greater reduction in the plasma concentration of the toxic substance(s) (ingested parent molecules) at H48, H72 and H96 of randomisation in the intervention group compared with the control group; * To demonstrate a reduction in the number of days of mechanical ventilation and the length of time spent in intensive care in the intervention group compared with the control group; * To demonstrate the good tolerance of treatment by digestive decontamination in the intervention group.

Secondary endpoints:

* Percentage change in plasma concentration of toxicant(s) (ingested parent molecules) at H48, H72 and H96 compared with the value at randomisation * Area under the concentration curve up to the 96th hour expressed as a percentage of the concentration at randomisation * Number of days alive without mechanical ventilation for 28 days post-randomisation * Number of days alive without resuscitation for 28 days post-randomisation * Number of episodes of vomiting * Number of ventilator-associated pneumonias * Number of episodes of upper abdominal pain and diarrhoea; * Presence of hypersensitivity reactions such as anaphylactic shock, angioedema, urticaria, rash and pruritus.

Вмешательства

• Препарат Combination of activated charcoal with polyethylene glycol for digestive decontamination
  A dose of 25-100g of activated charcoal via the nasogastric tube will be administered, followed by polyethylene glycol1L/15-20 kg ideal body weight at a flow rate of 1L/hour. polyethylene glycol will be continued until clear stools are obtained, a maximum of 24h of treatment of until the maximum dose of 1L per 15 kg of ideal body weight are administered. Serial activated charcoal 50g 6 times/day will be administered if prolonged-release forms or drugs with enterohepatic circulation were ingest
• Препарат Standard Treatment (Guideline-Based)
  Patients receive activated charcoal according to French guidelines - activated charcoal 25-100g and serial activated charcoal 50g 6 times/day if sustained-release forms or drugs with enterohepatic circulation as routine treatment.

Первичные конечные точки

• Percentage change in the plasma concentration of the toxic substance [Срок оценки: 24 hours post-randomization]

Вторичные конечные точки (9)

• Percentage change in plasma concentration of toxicant [Срок оценки: 48, 72 and 96 hours post-randomization]
• Area under the concentration curve up to the 96 th hour expressed as a percentage of the concentration at randomization [Срок оценки: 96 hours post-randomization]
• Number of days alive without mechanical ventilation for 28 days post-randomization [Срок оценки: 28 days post randomization]
• Number of days alive out of critical care for 28 days post-randomization [Срок оценки: 28 days post randomization]
• The number of vomiting episodes [Срок оценки: through the study complétion, an average of 7 days]
• Number of ventilator-associated pneumonias [Срок оценки: through the study complétion, an average of 7 days]
• Number of episodes of upper abdominal pain [Срок оценки: through the study complétion, an average of 7 days]
• Number of episodes of diarrhoea [Срок оценки: through the study complétion, an average of 7 days]
• Presence of hypersensitivity reactions [Срок оценки: through the study complétion, an average of 7 days]

Критерии участия

Критерии включения

Patient aged ≥18, intoxicated and hospitalised in intensive care AND

• Main drug toxicant of functional type (any psychotropic or cardiotropic), adsorbable by activated charcoal And
• Main toxicant identified by the history taken by a healthcare professional on the ward or during care prior to the ward And
• Main toxicant identified within 3 hours of admission if the patient is already intubated on admission, or within 3 hours of intubation if the patient is intubated on the ward AND
• Patient intubated for effects attributed to the toxic agent (neuro-respiratory or haemodynamic failure) AND
• Patient with nasogastric tube or planned nasogastric tube and no contraindications AND
• Main toxicant whose assay can be performed by the toxicology laboratory at Lariboisière Hospital AND Inclusion according to the emergency clause
• Written informed consent from a parent/relative/trusted person. In the absence of a parent/relative/trusted person, the patient may be included under the emergency procedure and consent will be obtained as soon as possible.

Критерии исключения

• No social security affiliation
• Non-intubated patient
• Contraindication to the administration of one of the study products (e.g. suspected digestive perforation, intestinal obstruction, inflammatory bowel disease, etc.)
• Inability to insert a nasogastric tube
• Repeated vomiting prior to inclusion, making digestive decontamination impossible
• Digestive haemorrhage in progress or during the previous month
• Ingestion of metals (e.g. iron, caesium, thallium, lead, copper, cadmium)
• Isolated or predominant alcohol poisoning (e.g. ethyl alcohol, ethylene glycol, methanol)
• Intoxication by gas (e.g. carbon monoxide or fire fumes)
• Intoxication by a caustic product (acids or bases)
• Main toxicant ingested under liquid form
• Intoxication by a toxic lesion
• Intoxication by a non-medicated product (e.g. party drugs)
• Intubation for causes not attributed to the ingested toxic substance (e.g. massive inhalation pneumonia)
• In-body carrier of drug pellets
• Pregnant or breast-feeding patients
• Patients being treated for dementia
• Patient under guardianship or curatorship
• Patients under legal protection
• Patients deprived of their liberty

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

Франция · 1 центр

• Sebastian Voicu — Paris

Идентификаторы

NCT: NCT07201311 · APHP231308 · 2024-518739-12-00

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

Открыть это исследование на ClinicalTrials.gov ↗