Clinical trial NCT02283203: A New Formulation of Intravenous Paracetamol for Fever Management
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Fever
Keywords: Paracetamol
Management of fever
Infections
Lead sponsor: Uni-Pharma Kleon Tsetis Pharmaceutical Laboratories S.A.
Sponsor class: INDUSTRY
Collaborators: name: Attikon Hospital
name: University Hospital of Patras
name: University Hospital of Crete
name: Thriasio General Hospital of Elefsina
name: General Hospital Of Thessaloniki Ippokratio
name: General Hospital of Chalkida
First posted: 2014-11-05
Enrollment: 80
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL

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).

Eligibility criteria: 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.

Primary outcomes:
measure: Body temperature as a measure of to compare the efficacy of intravenously administered ΑPOTEL Μax® over placebo for the achievement of defervescence.
timeFrame: 3 hours
Secondary outcomes:
measure: Need for the administration of rescue drug.
timeFrame: 30 hours
measure: Comparison of defervescence with the rescue drug in the paracetamol arm with the placebo arm
timeFrame: 30 hours
measure: Correlation between serum concentrations of free active paracetamol and metabolites with the clinical efficacy of paracetamol
timeFrame: 30 hours
measure: The administration of other antipyretics by the attending physicians after rescue drug in each study group
timeFrame: 30 hours
Other outcomes:
Locations:
city: Chalkida
country: Greece
facility: General Hospital of Chalkida
city: Haidari/Athens
country: Greece
facility: Attikon Hospital
city: Herakleion
country: Greece
facility: University Hospital of Crete
city: Magoula Attikis
country: Greece
facility: Thriasion Elefsis General Hospital
city: Rion/Patras
country: Greece
facility: University Hospital of Patras
city: Thessaloniki
country: Greece
facility: General Hospital Of Thessaloniki Ippokratio
Study officials:
affiliation: Attikon Hospital
name: Dimitrios Boumpas, MD, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: University Hospital of Patras
name: Charalambos Gogos, MD, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: University Hospital of Crete
name: George Samonis, MD, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Thriasio General Hospital of Elefsina
name: Styliani Sympardi, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: University Hospital of Thessaloniki Hippokrateion
name: Asterios Karagiannis, MD, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: General Hospital of Halkida
name: Nikolaos Tsokos, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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. doi: 10.1254/jphs.13133fp. Epub 2014 Jan 30.