Activated CHARcoal in Poisoned Patient (CHARPP-RCT)

CHARPP (Activated CHARcoal in Poisoned Patient): RCT Pilot Study

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.

Study Overview

• Status: Not yet recruiting
• Conditions: Charcoal, Decontamination, Poisoning
• Intervention / Treatment: Drug: Activated Charcoal

• Study Type: Interventional
• Enrollment (Anticipated): 850
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Maude St-Onge, MD PhD FRCPC; Phone Number: 418-932-5357; Email: maude.st-onge.med@ssss.gouv.qc.ca

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 1 second to 125 years (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Patients who presented to the hospital less than 8h after the ingestion of a potentially toxic dose of a carbo-adsorbable substance

Exclusion Criteria:

• Patients requiring or who will likely require another gastro-intestinal decontamination method;
• who have a contraindication to receive AC;
• who ingested a substance with an entero-hepatic circulation requiring multi-dose AC.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Single Group Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: AC as per the Clinical Toxicology Recommendations Collaborative recommendations	Drug: Activated Charcoal; Activated charcoal administered as per Clinical Toxicology Recommendations Collaborative or as per current practices
Active Comparator: AC as per current practice	Drug: Activated Charcoal; Activated charcoal administered as per Clinical Toxicology Recommendations Collaborative or as per current practices

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
recruitment success	100 patients total at the two poison centers associated with academic hospitals and greater than one patient enrolled/hospital/month	6 months
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	6 months
lost to follow-up	less than 5%	6 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
mortality		6 months
progression of toxicity (descriptive measure of delta Poison Severity Score - PSS max - PSS at randomization calculated at the end of each case)	measured by the delta Poison Severity Score (min = 0 - better outcome; max = 4 - worse outcome) (and the SOFA - sequential organ failure assessment - score for adults or PELOD -paediatric logistic organ dysfunction - score for children) and available drug levels	6 months
length of stay in the intensive care unit and hospital		6 months
duration of mechanical ventilation		6 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)		6 months
adverse events		6 months

Collaborators and Investigators

• Sponsor: Laval University
• Investigators: Principal Investigator: Maude St-Onge, MD PhD FRCPC, CHU de Québec - Université Laval

Study record dates

Study Major Dates

• Study Start (Anticipated): June 1, 2023
• Primary Completion (Anticipated): June 1, 2024
• Study Completion (Anticipated): December 1, 2024

Study Registration Dates

• First Submitted: July 14, 2022
• First Submitted That Met QC Criteria: July 20, 2022
• First Posted (Actual): July 22, 2022

Study Record Updates

• Last Update Posted (Actual): July 22, 2022
• Last Update Submitted That Met QC Criteria: July 20, 2022
• Last Verified: July 1, 2022

More Information

Terms related to this study

• Keywords: trial; toxicity; activated charcoal; decontamination; poisoning; intoxication
• Additional Relevant MeSH Terms: Chemically-Induced Disorders; Poisoning; Physiological Effects of Drugs; Protective Agents; Antidotes; Charcoal
• Other Study ID Numbers: CHARPP - pilot study

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes