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| ID | Type | Description | Link |
|---|---|---|---|
| 2024-518739-12-00 | EU Trial (CTIS) Number |
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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.
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:
Secondary endpoints:
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Combined gastrointestinal decontamination | Experimental | Patients receive activated charcoal and polyethylene glycol |
|
| Control - standard treatment group | Active Comparator | Patients receive activated charcoal according to French guidelines |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Combination of activated charcoal with polyethylene glycol for digestive decontamination | Drug | 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 ingested. |
| Measure | Description | Time Frame |
|---|---|---|
| Percentage change in the plasma concentration of the toxic substance | The primary endpoint is the percentage change in the plasma concentration of the toxic substance at 24 hours compared with the value at randomization. The percentage variation is calculated as 100 x (Concentration at 24 hours post-randomization-Concentration at randomization)/ Concentration at randomization | 24 hours post-randomization |
| Measure | Description | Time Frame |
|---|---|---|
| Percentage change in plasma concentration of toxicant | The percentage variation is calculated as: At 48 hours : 100 x (Concentration at 48 hours post-randomization-Concentration at randomization)/ Concentration at randomization At 72 hours : 100 x (Concentration at 48 hours post-randomization-Concentration at randomization)/ Concentration at randomization At 96 hours : 100 x (Concentration at 48 hours post-randomization-Concentration at randomization)/ Concentration at randomization |
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Inclusion Criteria:
Patient aged ≥18, intoxicated and hospitalised in intensive care AND
Exclusion Criteria:
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Voicu Sebastian, MD | Contact | 0149958442 | +33 | sebastian.voicu@aphp.fr |
| Megarbane Bruno, Professor | Contact | 0149958442 | +33 | bruno.megarbane@aphp.fr |
| Name | Affiliation | Role |
|---|---|---|
| Voicu Sebastian, MD | APHP(ASSISTANCE PUBLIQUE DES HOPITAUX DE PARIS) | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Sebastian Voicu | Recruiting | Paris | 75010 | France |
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Prospective randomized controlled single-center clinical trial using open-label administration of the study drugs The intervention group will receive activated charcoal at the dose of 25-100g and serial activated charcoal 50g 6 times/day if sustained-release forms or drugs with enterohepatic circulation were ingested. Polyethylene glycol will be administered after activated charcoal at the maximum dose of 1L of polyethylene glycol/15kg of ideal body weight. Treatment with polyethylene glycol will be stopped if clear rectal effluent is observed before 24 hours and/or the maximum dose is reached.
The standard treatment group will be treated according to the French guidelines with activated charcoal 25-100g and serial activated charcoal 50g 6 times/day if sustained-release forms or drugs with enterohepatic circulation were ingested.
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| Standard Treatment (Guideline-Based) | Drug | 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. |
|
| 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 | All concentrations up to the 96th hour post-randomization will be used to generate the area under the curve, and this will be reported as percentage of the concentration at randomization | 96 hours post-randomization |
| Number of days alive without mechanical ventilation for 28 days post-randomization | Patients who leave the hospital after extubation and before the 28th day of randomization will be considered as being free of mechanical ventilation from extubation to the 28th day post randomization | 28 days post randomization |
| Number of days alive out of critical care for 28 days post-randomization | This will be defined as the interval from the moment the patient is ready to leave the intensive care until the 28th day of randomization. This will avoid lengthening the theoretical duration of ICU stay due to lack of ward beds | 28 days post randomization |
| The number of vomiting episodes | The polyethylene glycol and activated charcoal may induce vomiting, therefore the number of vomiting episodes will be recorded and compared between groups | through the study complétion, an average of 7 days |
| Number of ventilator-associated pneumonias | Number of pneumonias occurring through the study completion, an average of 7 days | through the study complétion, an average of 7 days |
| Number of episodes of upper abdominal pain | Polyethyleneglycol may cause upper abdominal pain, therefore the number of upper abdominal pain episodes will be recorded and compared between groups | through the study complétion, an average of 7 days |
| Number of episodes of diarrhoea | Diarrhea is a therapeutic effect of the polyethylene glycol, therefore the number of diarrhea episodes will be recorded and compared between groups | through the study complétion, an average of 7 days |
| Presence of hypersensitivity reactions | Polyethylene glycol may cause allergic reactions such as anaphylactic shock, angioedema, urticaria, rash and pruritus, therefore the presence of allergic reactions will be recorded and compared between groups | through the study complétion, an average of 7 days |
| ID | Term |
|---|---|
| D011041 | Poisoning |
| D000881 | Anthrax |
| ID | Term |
|---|---|
| D064419 | Chemically-Induced Disorders |
| D016863 | Bacillaceae Infections |
| D016908 | Gram-Positive Bacterial Infections |
| D001424 | Bacterial Infections |
| D001423 | Bacterial Infections and Mycoses |
| D007239 | Infections |
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| ID | Term |
|---|---|
| D011092 | Polyethylene Glycols |
| ID | Term |
|---|---|
| D005026 | Ethylene Glycols |
| D006018 | Glycols |
| D000438 | Alcohols |
| D009930 | Organic Chemicals |
| D011108 | Polymers |
| D046911 | Macromolecular Substances |
| D001697 | Biomedical and Dental Materials |
| D008420 | Manufactured Materials |
| D013676 | Technology, Industry, and Agriculture |
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