Paracetamol as Antipyretic and Analgesic Medication (APOTEL01)

An Open-label Non-randomized Phase IV Trial of the Clinical Efficacy of Intravenously Administered 1000mg Paracetamol as Antipyretic and Analgesic Medication

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

Study Overview

• Status: Completed
• Conditions: Analgesia; Fever
• Intervention / Treatment: Drug: Paracetamol

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.

• Study Type: Interventional
• Enrollment (Actual): 100
• Phase: Phase 4

Contacts and Locations

Study Locations

• Greece
  • Athens, Greece, 12462
    • 4th Department of Internal Medicine, Attikon University Hospital
  • Athens, Greece, 15526
    • 2nd Department of Medicine, Sismanogleion General Hospital
  • Thessaloniki, Greece
    • 2nd Department of Surgery, G. Gennimatas General Hospital

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 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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Supportive Care
• Allocation: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Paracetamol; All patients will receive one single dose of 1000mg paracetamol.

Drug: Paracetamol; All patients will receive one single dose of 1000mg paracetamol. If considered mandatory by the attending physician, similar doses may be administered latter for a maximum period of five days. The maximum allowed daily dose is 3000mg. If the attending physician believes that after the administration of at least of three doses the desired analgesic or antipyretic effect is not achieved, he may administer any other compound in his will.; Other Names: ΑPOTEL®

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
To evaluate the safety and efficacy of intravenously administered 1000mg ΑPOTEL® as antipyretic and analgesic medication.	One year

Secondary Outcome Measures

Outcome Measure	Time Frame
Pharmacokinetics of paracetamol after intravenous infusion.	One year
Effect of paracetamol after intravenous infusion in serum inflammatory mediators	One year

Collaborators and Investigators

• Sponsor: University of Athens
• Investigators: Study Chair: Evangelos J Giamarellos-Bourboulis, MD, PhD, University of Athens, Medical School; Principal Investigator: Helen Giamarellou, MD, PhD, Attikon University Hospital of Athens; Principal Investigator: George Koratzanis, MD, PhD, Sismanogelion General Hospital, Athens; Principal Investigator: Konstantinos Atmatzidis, MD, PhD, G.Gennimatas GENERAL HOSPITAL OF THESSALONIKI

Publications and helpful links

General Publications

• 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.
• 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.
• 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.

Study record dates

Study Major Dates

• Study Start: January 1, 2010
• Primary Completion (Actual): January 1, 2010
• Study Completion (Actual): January 1, 2010

Study Registration Dates

• First Submitted: February 17, 2010
• First Submitted That Met QC Criteria: February 17, 2010
• First Posted (Estimate): February 18, 2010

Study Record Updates

• Last Update Posted (Estimate): February 18, 2010
• Last Update Submitted That Met QC Criteria: February 17, 2010
• Last Verified: February 1, 2010

More Information

Terms related to this study

• Keywords: Pain; Fever; cholecystectomy; Colectomy; Neoplasia; Infectious diseases
• Additional Relevant MeSH Terms: Body Temperature Changes; Fever; Physiological Effects of Drugs; Peripheral Nervous System Agents; Analgesics; Sensory System Agents; Analgesics, Non-Narcotic; Antipyretics; Acetaminophen
• Other Study ID Numbers: APOTEL01

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No