Slctr

A randomised controlled trial of the efficacy of activated charcoal in paracetamol overdose

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SLCTR Registration Number

SLCTR/2019/011

Date of Registration

15 Mar 2019

The date of last modification

Jul 29, 2020

Application Summary

Scientific Title of Trial

A randomised controlled trial of the efficacy of activated charcoal in paracetamol overdose

Public Title of Trial

A randomised controlled trial on the efficacy of activated charcoal in lowering blood paracetamol concentrations in paracetamol overdose patients.

Disease or Health Condition(s) Studied

Paracetamol overdose

Scientific Acronym

None

Public Acronym

None

Brief title

Activated charcoal for paracetamol overdose

Universal Trial Number

U1111-1219-1473

Any other number(s) assigned to the trial and issuing authority

ERC/2018/24(Ethics Review Committee, Faculty of Medicine and Allied Sciences, Rajarata University of Sri Lanka)

Trial Details

What is the research question being addressed?

Does activated charcoal have any beneficial effects on either absorption or clearance of paracetamol, which will be reflected in a relative reduction in the dose-adjusted Area Under the Curve (AUC) or AUC/dose

Type of study

Interventional

Study design

Allocation

Randomized controlled trial

Masking

Masking not used

Control

Standard therapy/practice

Assignment

Parallel

Purpose

Treatment

Study Phase

Phase 4

Intervention(s) planned

Study Setting: Emergency Treatment Unit and the Medical Wards of Teaching Hospital, Anuradhapura.
Method of Randomisation: Simple randomization.
Activated Charcoal 50g dissolved in 100ml water orally administered (by the patient him/her self) under the supervision of a clinical research assistant (MBBS or BSc nursing graduate) on presentation(only if less than 8h from ingestion).Activated charcoal is not given for paracetamol poisoning in the study setting as a standard practice. Only the intervention group will receive activated charcoal. Controls will receive the standard treatment in the ward setting.
All the patients in both arms will receive standard N-Acetylcystine (NAC) regimen practiced in the Teaching Hospital, Anuradhapura.
This is an open-labelled study.

Inclusion criteria

All patients (>16y) with paracetamol overdoses (>5g) presenting within 8h of ingestion.

Exclusion criteria

Staggered paracetamol overdoses and late presentations (>8h).

Primary outcome(s)

The primary outcome will be a clinically significant reduction in the Area Under Curve (AUC) of in patients receiving charcoal compared to those not receiving charcoal. Area Under the Curve (AUC) = [Dose] * [Fraction Absorbed (F)] / [Clearance (CL)]. The AUC will be estimated by first modelling the data using population analysis techniques to determine the best fit to all of the data for patients taking paracetamol in the trial. Once a final model is established this will be used to estimate the individual predicted AUC for each patient which will then be compared between those receiving and not receiving charcoal. A 20% reduction in the AUC/dose will be regarded as clinically significant based on previous pharmacokinetic-pharmacodynamic studies

[
The blood samples will be collected in all patients (both groups) on following time points after the ingestion of paracetamol. 1. Time of admission 2. 4hours 3. 8hours 4. 12hours 5. 24hours 6. 48hours 7. 72hours 8. 96hours 9. 120hours AUC will be calculated based on the paracetamol concentration data of all the blood samples, after the trial has finished.
]

Secondary outcome(s)

(1) Reduction of the apparent half-life of elimination (t1/2?) in patients receiving charcoal compared to those not receiving charcoal.The decline of the Paracetamol plasma concentration is not due to elimination alone. Other factors such as absorption rate or distribution rate influence the declining of plasma concentration. In such conditions, the observed half-life is not a true elimination half-life hence called apparent half-life of elimination (time taken for paracetamol concentration to become 50% of the initial concentration.

(2) Proportion of patients with a ALT >150IU/L after 24 hours of ingestion.

(3) Proportion of patients who have their on-admission ALT values doubled by 24 hours.

(4) Proportion of patients with an ALT >1000IU/L (hepatotoxicity)

(5) Proportion of patients with adverse effects of charcoal such as vomiting and aspiration pneumonitis.

(6) Reduction in other biomarkers of hepatotoxicity at 24 hours (miRNA-122 and INR at 24h.)

[
(1) 4,8,12,24,48,72,96,120 hours post ingestion

(2) 24 hours post ingestion

(3) 24 hours post ingestion

(4) 48 hours post ingestion

(5) 24 hours post ingestion

(6) 24 hours post ingestion
]

Target number/sample size

160 in each arm (total of 320 participants)

Countries of recruitment

Sri Lanka

Anticipated start date

2019-04-01

Anticipated end date

2021-01-31

Date of first enrollment

2019-11-01

Date of study completion

Recruitment status

Recruiting

Funding source

South Asian Clinical Toxicology Collaboration

Regulatory approvals

State of Ethics Review Approval

Status

Approved

Date of Approval

2018-12-12

Approval number

Ref. No: ERC/2018/24)

Details of Ethics Review Committee

Name:	Ethics Review Committee, Faculty of Medicine & Allied Health Science, Rajarata University of Sri Lanka
Institutional Address:	Secretary, Ethics Review Committee, Faculty of Medicine and Allied Sciences, Rajarata University of Sri Lanka, Saliyapura 50008
Telephone:	0252053633
Email:	ethicsreviewcommittee@gmail.com

Contact & Sponsor Information

Contact person for Scientific Queries/Principal Investigator

N. K. Anjana Silva
Senior Lecturer
Department of Parasitology Faculty of Medicine and Allied Sciences Rajarata University of Sri Lanka Saliyapura 50008 Sri Lanka
0252226388
0714400313

nkanjanasilva@gmail.com
http://www.rjt.ac.lk/med/index.php/component/content/article/212

Contact Person for Public Queries

Primary study sponsor/organization

South Asian Clinical Toxicology Collaboration

Faculty of Medicine, University of Peradeniya, Peradeniya, Sri Lanka
+94814479822
+94814479822
enquiry@sactrc.org
https://www.sactrc.org/

Secondary study sponsor (If any)

Trial Completion details

Do the investigators plan to share identified individual clinical trial participant-level data (IPD)?

Yes

IPD sharing plan description

The de-identified IPD that will be shared : sex, dose of ingestion, time of ingestion, time of admission, case or control, time of charcoal administration, NAC, serial data of blood paracetamol levels, serial liver enzyme levels, complications and the outcome (death/full recovery) When: at the time of publishing the trial results as a journal article. By what mechanism: We will link the raw data tables as supplementary data to the journal article. The data tables will be either deposited at the journal site if the publishing journal facilitates such. If the journal does not support such, we will deposit the data files at the digital repositopry of the Rajarata University and the link to the data atables will be generated and published in the journal article.. The above specified data will be accessible for anyone without any barrier for any secondary analysis.

Study protocol available

Protocol version and date

Not Available

Protocol URL

Not Available

Results summary available

Date of posting results

Date of study completion

Final sample size

Date of first publication

Link to results

Brief summary of results