A New Formulation of Intravenous Paracetamol for Fever Management

Phase 4

Completed

• Conditions: Fever
• Interventions: Drug: APOTEL max; Drug: Placebo

• Registration Number: NCT02283203
• Lead Sponsor: Uni-Pharma Kleon Tsetis Pharmaceutical Laboratories S.A.

Brief Summary

The efficacy of intravenous paracetamol has never been compared with other drugs for the management of fever due to infections. Available data come from clinical studies conducted in healthy volunteers subject to experimental endotoxemia. The present study compares the efficacy of the new ΑPOTEL Μax® formulation versus placebo for the management of fever of infectious origin.

Detailed Description

A new formulation of paracetamol for intravenous administration has been manufactured in Greece by the industry Uni-Pharma (ΑPOTEL Μax®). According to this new formulation, 1g of paracetamol is provided as a flask diluted into 100ml volume with the possibility of immediate connection with the infusion device of the patient. This formulation provides the advantage of a dilution ready-to-use which equals considerable financial benefit; nursing staff is not pre-occupied with the preparation of dilutions and the amount of consumables required for the preparation of this dilution is significantly decreased. Taking into consideration that the antipyretic effect of intravenous paracetamol has never been studied compared with other agents in patients and available data come from studies in volunteers with experimental endotoxemia, the present study compares the efficacy of the new ΑPOTEL Μax® formulation versus placebo for the management of fever of infectious origin (fever due to infection of the upper respiratory tract, of the lower respiratory tract, acute pyelonephritis or of the skin and soft tissues).

Study Timeline

• Study First Submitted: 2014-10-19
• Study First Submitted QC: 2014-10-31
• Study First Posted: 2014-11-05
• Study Start: 2015-02
• Status Verified: 2016-03
• Primary Completion: 2016-03
• Study Completion: 2016-03
• Last Update Submitted: 2016-03-21
• Last Update Posted: 2016-03-22

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 80

Inclusion Criteria

1. Written informed consent by the patient
2. Patient of either gender
3. Age equal to or greater than 18 years old
4. Fever onset less than 24 hours
5. Body temperature greater than or equal to 38.50C.
6. Infection of the upper respiratory tract or of the lower respiratory tract or acute pyelonephritis or infection of the skin and soft tissues that can explain fever onset.

Exclusion Criteria

1. Age below 18 years old
2. Denial for written consent
3. Intake of paracetamol for any reason either orally or intravenously or intramuscularly the last 12 hours
4. Intake of any non-steroidal anti-inflammatory drug the last 8 hours
5. Intake of any steroidal anti-inflammatory drug the last 12 hours
6. History of liver cirrhosis
7. Serum creatinine greater than 3 mg/dl
8. Aspartate aminotransferase more than 3 times greater than the upper normal limit for the hospital lab
9. Known allergy to non-steroidal anti-inflammatory drugs or to paracetamol
10. Pregnancy or lactation
11. Active bleeding of the upper or the lower gastrointestinal tract
12. Thrombocytopenia defined as any absolute platelet count below 50000/mm3.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
APOTEL max	APOTEL max	Active drug; water for injection at a volume of 100ml with added 1g of paracetamol and inactive ingredients (ΑPOTEL max®), infused within 15 minutes. Available in 100ml bags.
Placebo	Placebo	Placebo; water for injection at a volume of 100ml with added inactive ingredients, infused within 15 minutes. Available in 100ml bags.

Primary Outcome Measures

Name	Time	Method
Body temperature as a measure of to compare the efficacy of intravenously administered ΑPOTEL Μax® over placebo for the achievement of defervescence.	3 hours	The comparative efficacy of intravenously administered ΑPOTEL Μax® over placebo for the achievement of defervescence; defervescence is defined as any body temperature equal to or lower than 37.1 degC.

Secondary Outcome Measures

Name	Time	Method
Need for the administration of rescue drug.	30 hours	The comparison between the two study groups on the frequency and time to administration of rescue drug.
Correlation between serum concentrations of free active paracetamol and metabolites with the clinical efficacy of paracetamol	30 hours	The correlation between the achievement of defervescence and the concentrations of free active paracetamol and its metabolites in the serum of the patients.
Comparison of defervescence with the rescue drug in the paracetamol arm with the placebo arm	30 hours	The correlation between defervescence with the rescue drug with the efficacy of the initially administered type of study drug (placebo over active drug).
The administration of other antipyretics by the attending physicians after rescue drug in each study group	30 hours	The correlation between achievement of defervescence with the rescue drug and the need of further administration of other drugs as antipyretics at the discretion of the attending physicians.

Trial Locations

Locations (6)

Attikon Hospital; 🇬🇷 Haidari/Athens, Greece

University Hospital of Crete; 🇬🇷 Herakleion, Greece

General Hospital of Chalkida; 🇬🇷 Chalkida, Greece

Thriasion Elefsis General Hospital; 🇬🇷 Magoula Attikis, Greece

University Hospital of Patras; 🇬🇷 Rion/Patras, Greece

General Hospital Of Thessaloniki Ippokratio; 🇬🇷 Thessaloniki, Greece