Paracetamol Toxicity in Septic Patients

Paracetamol-induced Liver Toxicity in Septic Patients

The investigators will examine the toxicity of therapeutic doses of paracetamol in patients in severe sepsis. Patients with fever and severe sepsis will be randomized to receive paracetamol or dypirone. The investigators will monitor blood glutathione and liver enzymes to look for potential toxicity.

Study Overview

• Status: Suspended
• Conditions: Sepsis; Fever
• Intervention / Treatment: Drug: paracetamol; Drug: dypirone

Detailed Description

Paracetamol is metabolized in liver using the glutathione system. This detoxification system is depressed during severe illness such as sepsis, trauma etc. The study will examine the toxicity of therapeutic doses of paracetamol in patients in severe sepsis. We believe that during sepsis, paracetamol metabolites are not fully detoxified and therefore are toxic to the patient.

Patients with fever and severe sepsis will be randomized to receive paracetamol or dypirone. The investigators will monitor blood glutathione (as a surrogate marker for liver glutathione), liver enzymes and various clinical data (such as length of hospitalization) to look for a potential toxicity.

• Study Type: Interventional
• Enrollment (Anticipated): 80
• Phase: Phase 3

Contacts and Locations

Study Locations

• Israel
  • Ashkelon, Israel, 78278
    • Barzilai Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• age>18y
• hospitalized to int. med. dept. or ICU

• body temp>38 and one or more from the following:

  1. pulse>90 bpm
  2. resp. rate>20/min or PaCO2<32 mmHg
  3. WBC>12000 or <4000

• one of the following:

  1. hypotension
  2. disturbed end-organ perfusion (confusion, oliguria, lactic acidosis etc.)

Exclusion Criteria:

• acute / chronic liver disease
• acute CNS disorder
• current isoniazid treatment
• alcoholism
• active malignancy
• pregnancy
• TPN or PPN

Study Plan

How is the study designed?

Design Details

• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: paracetamol treatment	Drug: paracetamol; 1 gr of paracetamol PO/PZ/PR; Other Names: acetaminophen, acamol
Active Comparator: control- dypirone treatment	Drug: dypirone; 1 gr PO/PZ/PR/IM; Other Names: optalgin

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
paracetamol induced liver toxicity	defined as ALT and/or AST > 1000 or reduction in glutathione below 50% of base line	every six months

Collaborators and Investigators

• Sponsor: Barzilai Medical Center
• Collaborators: Hadassah Medical Organization
• Investigators: Principal Investigator: Albert Grinshpun, Barziali medical center, Ashkelon

Study record dates

Study Major Dates

• Study Start: August 1, 2010
• Primary Completion (Anticipated): August 1, 2011
• Study Completion (Anticipated): August 1, 2011

Study Registration Dates

• First Submitted: August 16, 2010
• First Submitted That Met QC Criteria: August 16, 2010
• First Posted (Estimate): August 17, 2010

Study Record Updates

• Last Update Posted (Estimate): March 2, 2011
• Last Update Submitted That Met QC Criteria: March 1, 2011
• Last Verified: March 1, 2011

More Information

Terms related to this study

• Keywords: fever in severe sepsis
• Additional Relevant MeSH Terms: Pathologic Processes; Infections; Systemic Inflammatory Response Syndrome; Inflammation; Sepsis; Physiological Effects of Drugs; Peripheral Nervous System Agents; Analgesics; Sensory System Agents; Analgesics, Non-Narcotic; Antipyretics; Acetaminophen
• Other Study ID Numbers: 1662CTIL