A New Formulation of Intravenous Paracetamol for Fever Management

Fever Clinical Trial

Official title:

A Double-blind, Randomized, Placebo-controlled Phase IV Clinical Study of the Efficacy and Safety of a New Formulation of Paracetamol for the Management of Fever of Infectious Origin

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02283203
• Other study ID #: APOTEL-02
• Status: Completed
• Phase: Phase 4
• First received: October 19, 2014
• Last updated: March 21, 2016
• Start date: February 2015
• Est. completion date: March 2016

Study information

• Verified date: March 2016
• Source: Uni-Pharma Kleon Tsetis Pharmaceutical Laboratories S.A.
• Contact: n/a
• Is FDA regulated: No
• Health authority: Greece: National Organization of MedicinesGreece: Ethics Committee
• Study type: Interventional

Clinical Trial 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.

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).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 80
• Est. completion date: March 2016
• Est. primary completion date: March 2016
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator)

Related Conditions & MeSH terms

• Fever

Intervention

Drug:
• APOTEL max
The study drug is provided in a form of bag with 100ml final volume and it is directly connected to the infusion device that leads to a catheter already cannulated in one antecubital vein.
• Placebo
Placebo is provided in a form of bag with 100ml final volume and it is directly connected to the infusion device that leads to a catheter already cannulated in one antecubital vein. Placebo contains water for injection and inactive vehicles.

Locations

Country	Name	City	State
Greece	General Hospital of Chalkida	Chalkida
Greece	Attikon Hospital	Haidari/Athens
Greece	University Hospital of Crete	Herakleion
Greece	Thriasion Elefsis General Hospital	Magoula Attikis
Greece	University Hospital of Patras	Rion/Patras
Greece	General Hospital Of Thessaloniki Ippokratio	Thessaloniki

Sponsors (7)

Lead Sponsor	Collaborator
Uni-Pharma Kleon Tsetis Pharmaceutical Laboratories S.A.	Attikon Hospital, General Hospital of Chalkida, General Hospital Of Thessaloniki Ippokratio, Thriasion Elefsis General Hospital, University Hospital of Crete, University Hospital of Patras

Country where clinical trial is conducted

Greece, 

References & Publications (1)

Giamarellos-Bourboulis EJ, Spyridaki A, Savva A, Georgitsi M, Tsaganos T, Mouktaroudi M, Raftogiannis M, Antonopoulou A, Papaziogas V, Baziaka F, Sereti K, Christopoulos P, Marioli A, Kanni T, Maravitsa P, Pantelidou I, Leventogiannis K, Tsiaoussis P, Lymberopoulou K, Koutelidakis IM. Intravenous paracetamol as an antipyretic and analgesic medication: the significance of drug metabolism. J Pharmacol Sci. 2014;124(2):144-52. Epub 2014 Jan 30. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Body temperature as a measure of to compare the efficacy of intravenously administered ?POTEL ?ax® over placebo for the achievement of defervescence.	The comparative efficacy of intravenously administered ?POTEL ?ax® over placebo for the achievement of defervescence; defervescence is defined as any body temperature equal to or lower than 37.1 degC.	3 hours	No
Secondary	Need for the administration of rescue drug.	The comparison between the two study groups on the frequency and time to administration of rescue drug.	30 hours	No
Secondary	Comparison of defervescence with the rescue drug in the paracetamol arm with the placebo arm	The correlation between defervescence with the rescue drug with the efficacy of the initially administered type of study drug (placebo over active drug).	30 hours	No
Secondary	Correlation between serum concentrations of free active paracetamol and metabolites with the clinical efficacy of paracetamol	The correlation between the achievement of defervescence and the concentrations of free active paracetamol and its metabolites in the serum of the patients.	30 hours	No
Secondary	The administration of other antipyretics by the attending physicians after rescue drug in each study group	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.	30 hours	No