Clinical trial NCT01070732: Paracetamol as Antipyretic and Analgesic Medication
Official title: An Open-label Non-randomized Phase IV Trial of the Clinical Efficacy of Intravenously Administered 1000mg Paracetamol as Antipyretic and Analgesic Medication
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Fever
Analgesia
Keywords: Fever
Infectious diseases
Neoplasia
Pain
cholecystectomy
Colectomy
Lead sponsor: University of Athens
Sponsor class: OTHER
First posted: 2010-02-18
Enrollment: 100
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: SUPPORTIVE_CARE

Brief summary: The present study is aiming to unravel the clinical efficacy of intravenously administered paracetamol as antipyretic and analgesic medication in various medical conditions.

Detailed description: Although modern therapeutics is targeting at prolongation of survival, despite the underlying illness, it also aims at the improvement of the quality of life. Two major symptoms affect considerably quality of life, fever and pain. Both symptoms are common denominators of a vast number of clinical situations some of which have good prognosis and some of which do not have. Among them situations like infectious diseases, hematologic malignancies, solid tumor malignancies, connective tissue disorders and factors connected to surgical operations predominate. Post-operative pain extents too long and imposes severely on the post-operative course of the patient.

A variety of compounds have been developed for the management of fever and pain, the most successful being non-steroidal anti-inflammatory drugs. They exist in a variety of forms for various types of administration. Those administered parenterally are considered more efficacious than those administered orally in terms of the rate of the achieved clinical effect. Furthermore, several conditions necessitate parenteral administration.

Paracetamol is a well-known antipyretic and analgesic compound available for many years for oral administration since intravenous infusion was hampered by water insolubility. Its pro-drug, namely, pro-paracetamol, was applied for intravenous infusion where an amount of 2g was equally potent to 1 g of paracetamol. Pro-paracetamol has been given with success as analgesic medication in women undergoing laparoscopic operation, as antipyretic in patients with hematologic malignancies, as antipyretic in children bearing infectious diseases and as antipyretic in critically ill patients.

Ready-made paracetamol for intravenous infusion has been in the market in some European countries. It has been tested in four clinical trials. In the first trial it was given as post-operative analgesia at a dose of 1g x 4 in 80 patients undergoing laparoscopic cholecystectomy. Clinical efficacy was comparable to parecoxib and valdecoxib. In three other studies, it was given as post-operative analgesia after spinal body ectomy and after resection of the third mole providing conflicting results. However, in all the three latter studies, the number of patients given paracetamol was limited.

In Greece, paracetamol for intravenous infusion at vials of 1g/6.7ml is manufactured by the company Uni-Pharma (ΑPOTEL®). Based on: a) the limited number of patients enrolled in the studies mentioned earlier, and b) the application of that form only after laparoscopic cholecystectomy and spinal body ectomy, the present study is aiming to unravel the clinical efficacy of the above formula of 1g intravenous paracetamol as antipyretic and analgesic medication in various medical conditions.

Eligibility criteria: Inclusion Criteria:

* Age greater than or equal to 18 years
* Written informed consent by the patients
* Medical condition necessitating the administration of antipyretic or analgesic medications

Exclusion Criteria:

* Αge lower than 18 years
* Lack of informed consent
* History of liver cirrhosis
* Blood creatinine greater than 3mg/dl
* Blood AST greater than 3 times the upper normal level according to the lab of the participating hospital
* History of hypersensitivity to non-steroidal ant-inflammatory drugs
* History of abuse of analgesics
* Pregnancy or lactation
* Fulminant hemorrhage of the upper or lower digestive tract
* Thrombocytopenia defined as less than 50000 platelets/μl

Primary outcomes:
measure: To evaluate the safety and efficacy of intravenously administered 1000mg ΑPOTEL® as antipyretic and analgesic medication.
timeFrame: One year
Secondary outcomes:
measure: Pharmacokinetics of paracetamol after intravenous infusion.
timeFrame: One year
measure: Effect of paracetamol after intravenous infusion in serum inflammatory mediators
timeFrame: One year
Other outcomes:
Locations:
city: Athens
country: Greece
facility: 4th Department of Internal Medicine, ATTIKON University Hospital
city: Athens
country: Greece
facility: 2nd Department of Medicine, Sismanogleion General Hospital
city: Thessaloniki
country: Greece
facility: 2nd Department of Surgery, G. Gennimatas General Hospital
Study officials:
affiliation: University of Athens, Medical School
name: Evangelos J Giamarellos-Bourboulis, MD, PhD
role: STUDY_CHAIR
affiliation: ATTIKON University Hospital of Athens
name: Helen Giamarellou, MD, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Sismanogelion General Hospital, Athens
name: George Koratzanis, MD, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: G.Gennimatas General Hospital of Thessaloniki
name: Konstantinos Atmatzidis, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Tiippana E, Bachmann M, Kalso E, Pere P. Effect of paracetamol and coxib with or without dexamethasone after laparoscopic cholecystectomy. Acta Anaesthesiol Scand. 2008 May;52(5):673-80. doi: 10.1111/j.1399-6576.2008.01650.x.
citation: Cakan T, Inan N, Culhaoglu S, Bakkal K, Basar H. Intravenous paracetamol improves the quality of postoperative analgesia but does not decrease narcotic requirements. J Neurosurg Anesthesiol. 2008 Jul;20(3):169-73. doi: 10.1097/ANA.0b013e3181705cfb.
citation: Grundmann U, Wornle C, Biedler A, Kreuer S, Wrobel M, Wilhelm W. The efficacy of the non-opioid analgesics parecoxib, paracetamol and metamizol for postoperative pain relief after lumbar microdiscectomy. Anesth Analg. 2006 Jul;103(1):217-22, table of contents. doi: 10.1213/01.ane.0000221438.08990.06.