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Home » Trials » SLCTR/2017/036

A randomized controlled trial of oral vs intravenous antidotes for acute paracetamol poisoning

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SLCTR Registration Number

SLCTR/2017/036

Date of Registration

09 Oct 2017

The date of last modification

Jul 01, 2020


Application Summary

Scientific Title of Trial

A randomized controlled trial of oral vs intravenous antidotes for acute paracetamol poisoning

Public Title of Trial

Paracetamol pilot study - Oral Vs Intravenous antidotes

Disease or Health Condition(s) Studied

Liver cell injury in paracetamol overdose

Scientific Acronym

None

Public Acronym

None

Brief title

Comparison of oral vs intravenous antidotes in acute paracetamol poisoning

Universal Trial Number

U1111-1199-2734

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

2015/EC/67 (ERC: Peradeniya)


Trial Details

What is the research question being addressed?

Is oral N-acetylcysteine (NAC) or oral methionine better compared to intravenous NAC therapy in preventing liver cell injury (hepatotoxicity) following acute paracetamol overdose?

Type of study

Interventional

Study design

Allocation

Randomized controlled trial

Masking

Masking not used

Control

Active

Assignment

Parallel

Purpose

Treatment

Study Phase

Phase 1

Intervention(s) planned

Patients will be randomized 1:1:1 to the three treatments using the randomisation option in the REDCap software.

Randomisation will be done at the place where patient will be treated (in the emergency department or ward) by the research assistant in the presence of the treating doctor.

Arm 1: Intravenous acetylcysteine: 300 mg/kg given over a period of 21 hours. The above dose will be given at three different rates of infusion i.e. 150 mg/kg in 200 mL of normal saline over 60 min, followed by 50 mg/kg in 500 mL of normal saline over 4 hours and finally 100 mg/kg in 1000 mL of normal saline over 16 hours.
Arm 2: Oral acetylcysteine: 140 mg/kg loading dose and a dose of 70 mg/kg every 4 hours.
Arm 3: Oral Methionine: 2.5 g every 4 hours for 24 hours.
The intervention will be administered by the treating team and the outcomes will be assessed by study team who will be not blind to the interventional status.

Inclusion criteria

Patients >16 years of age with acute paracetamol poisoning. i.e who present within 10 hours of ingestion and whose plasma paracetamol levels falls above Prescott normogram line.

Exclusion criteria

  1. Patients presenting more than 10 hours after poisoning.
  2. Patients who have already received an antidote (possible in other hospitals prior to transfer).
  3. Patients who have received charcoal (which would interfere with oral antidotes).
  4. Patients under the age of 16.
  5. Patients who are unable to give the amount of paracetamol ingested and the time of ingestion
  6. Patients who are institutionalized for any mental health condition.
  7. Patients with known cognitive impairment (e.g. dementia).
  8. Patients with an unrelated life threatening illness (e.g. terminal cancer).
  9. Patients who are known to be pregnant or breast feeding. (This is simply a practical decision. There are no known risks these patients will be subjected to by being treated with these antidotes)
  10. Patients who have had a paracetamol overdose in the previous 4 weeks or have taken a significant dose of any other toxic substance in addition to paracetamol.
  11. Patients who are on warfarin.
  12. Patients who have taken a staggered dose of paracetamol (over more than a 2-hour period).

Primary outcome(s)

1.

Rise of ALT to more than 50% of the baseline value within 24 hours.

 [

On admission and at 8, 16, 24, and 36 hours post ingestion, and thereafter daily until discharge.

]

Secondary outcome(s)

1.

ALT above 1000 IU/L at any time point

[

On admission and at 8, 16, 24, and 36 hours post ingestion, and thereafter daily until discharge.

]
2.

INR > 2 at any time point

[

On admission and at 8, 16, 24, and 36 hours post ingestion, and thereafter daily until discharge.

]
3.

miR122 levels.

 [

Patients with ALT>150U/L at any time during their admission. The time points at which miR-122 levels are measured will be decided post-hoc. Paracetamol sulphate, paracetamol glucuronide and paracetamol mercaptopuric acid levels will be measured in the urine collected during the first 24 hours.

]
4.

APAP-adduct concentrations: PPA – Paracetamol Protein Adduct Paracetamol cysteine (APAP – CYS)

 [

On admission and at 8, 16, 24, and 36 hours post ingestion, and thereafter daily until discharge.

]
5.

Length of hospital stay and number of days spent in the Intensive Care Unit.

 [

At discharge

]
6.

Adverse antidote effects including nausea, vomiting, rash, hypotension, bronchospasm.

[

On admission and at 8, 16, 24, and 36 hours post ingestion, and thereafter daily until discharge.

]
7.

Proportion with full adherence to standard regimen in each arm for 24 hours

[

At 24 hours of initiating treatment

]
8.

Acute kidney injury: Serum creatinine (AKIN criteria)

 [

On admission and at 8, 16, 24, and 36 hours post ingestion, and thereafter daily until discharge.

]
9.

Severe acute liver injury: ALT level of above 150U/L or ALT level of above 50U/L when clinical symptoms and signs of hepatotoxicity are present. The clinical symptoms and signs of hepatotoxicity which would be used in this regard are:-
(i) Liver tenderness
(ii) Late onset (>24 hours) vomiting
(iii) Signs of liver failure (Jaundice etc.)

 [

On admission and at 8, 16, 24, and 36 hours post ingestion, and thereafter daily until discharge.

]
10.

Death

 [

Any time point.

]

Target number/sample size

300 (100 in each arm)

Countries of recruitment

Sri Lanka

Anticipated start date

2017-10-11

Anticipated end date

2020-10-11

Date of first enrollment

2018-03-01

Date of study completion

Recruitment status

Recruiting

Funding source

South Asian Clinical Toxicology Research Collaboration (SACTRC)

Regulatory approvals

Not applicable


State of Ethics Review Approval

Status

Approved

Date of Approval

2015-10-13

Approval number

2015/EC/67; title “A randomized clinical trial of Oral vs. Intravenous antidotes for paracetamol poisoning (Amended/extended 28.06.2017)

Details of Ethics Review Committee

Name: Ethics Review Committee, Faculty of Medicine, University of Peradeniya
Institutional Address:Galaha Road, Kandy, Sri Lanka
Telephone:+94-812396361
Email: chairpersonierc@gmail.com

Contact & Sponsor Information

Contact person for Scientific Queries/Principal Investigator

Prof.Indika Bandara Gawarammana
Professor in Medicine
Faculty of Medicine, University of Peradeniya, Peradeniya, Sri Lanka
+94812384556
+94714225081
+94814479822
indikagaw@gmail.com

Contact Person for Public Queries

Seyed Shahmy
Manager Operations
SACTRC, Faculty of Medicine University of Peradeniya, Peradeniya, Sri Lanka
+94812387992
+94773938949
+94814479822
shahmy@sactrc.org

Primary study sponsor/organization

South Asian Clinical Toxicology Research Collaboration (SACTRC)

Faculty of Medicine University of Peradeniya Peradeniya
+94812384556 +94814479822
+94814479822
enquiry@sactrc.org
www.sactrc.org

Secondary study sponsor (If any)

None





Trial Completion details

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

IPD sharing plan description

Not Available

Study protocol available

Protocol version and date

Not Available

Protocol URL

Not Available

Results summary available

No

Date of posting results

Date of study completion

Final sample size

Date of first publication

Link to results

Brief summary of results


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