Paracetamol Route in Palliative Care Patients (PARASCIVPALLIA)

Study Overview
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Brief Summary
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Background: Among palliative-care patients, subcutaneous route is often an alternative to intravenous route yet pharmacological and clinical data are lacking. Many French palliative crew are now using empirically paracetamol by subcutaneous route also there is no data to support this practice. The aim of the present study is to compare pharmacokinetics parameters between intravenous and subcutaneous route for palliative-care patients. Methods/design: A randomized, open, crossover, bicenter study in two palliative care centers. The aim is to demonstrate the pharmacokinetic equivalence between the two routes of administration. Data analysis will be performed by Wilcoxn's signed Rank Test with an alpha risk of 5 percent. All adverse events will be reported for a safety analysis. Discussion: This trial may permit, if a pharmacokinetic equivalence is established, to build randomized controlled trials to then assess the efficacy and tolerability of subcutaneous paracetamol administration.

Official Title
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Paracetamol Route in Palliative Care Patients : Intravenous Versus Subcutaneous Route Pharmacokinetics, Study Protocol for a Randomized Equivalence Pilot Trial

Conditions
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Palliative Care

Intervention / Treatment
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* Other: Paracetamol route in palliative-care patients: intravenous versus subcutaneous route Pharmacokinetics study protocol


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients ≥ 18 years old, hospitalized Patients in a palliative care situation Patients having an intravenous device with the presence of a venous reflux (be implantable venous site, picc-line, central track) Patients having a spontaneous pain, not related to care, with a numeric pain rate scale (NPRS) > 3/10 or have a systematic prescription of paracetamol in the usual treatment Patients able to do an auto-evaluation of their pain by NPRS No contraindications of paracetamol No contraindications of alternative antalgic (low opioids, strong opioids, Non-steroidal anti-inflammatory) Possibility to not take paracetamol in the previous 24 hours before inclusion Patients with a blood test dating back less than 7 days, with no severe renal or hepatic failure Patients related with a French social security regime Patients accept to participate in the study, with written consent. Exclusion Criteria: Patients under legal protection Patients who participate in another study less than 30 days before Patients weighing less than 50 kg Patients having a contraindication to subcutaneous route Pregnant or breastfeeding woman Patients who having a paracetamol administration less than 24 hours before the beginning of the inclusion Patients who having a low opioid less than 2 hours before or a strong opioid less than one hour before the beginning of administration of paracetamol Patients having a fever No possibility of communication

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Interventional Model Description: This is a comparative, randomized, open, crossover, bicenter clinical trial with SC and IV paracetamol injections successively given to each patient.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: Subcutaneous route first<br>The first route of administration is designated by randomization. In the subcutaneous group, patients received intravenous route in a second time. | Other: Paracetamol route in palliative-care patients: intravenous versus subcutaneous route Pharmacokinetics study protocol<br>* Compare the pharmacokinetic (PK) of SC and intravenous (IV) routes in the same patient in a palliative care situation, to determine if there is a PK equivalence between these two modes of administration of Paracetamol.<br>|
| Other: Intravenous route first<br>The first route of administration is designated by randomization. In the intravenous group, patients received subcutaneous route in a second time. | Other: Paracetamol route in palliative-care patients: intravenous versus subcutaneous route Pharmacokinetics study protocol<br>* Compare the pharmacokinetic (PK) of SC and intravenous (IV) routes in the same patient in a palliative care situation, to determine if there is a PK equivalence between these two modes of administration of Paracetamol.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| paracetamolemia dosage after intravenous route | measurement of paracetamol blood concentration after intravenous route | At injection time | 
| paracetamolemia dosage after intravenous route | measurement of paracetamol blood concentration after intravenous route | 15 minutes after injection | 
| paracetamolemia dosage after intravenous route | measurement of paracetamol blood concentration after intravenous route | 60 minutes after injection | 
| paracetamolemia dosage after intravenous route | measurement of paracetamol blood concentration after intravenous route | 90 minutes after injection | 
| paracetamolemia dosage after intravenous route | measurement of paracetamol blood concentration after intravenous route | 120 minutes after injection | 
| paracetamolemia dosage after intravenous route | measurement of paracetamol blood concentration after intravenous route | 240 minutes after injection | 
| paracetamolemia dosage after intravenous route | measurement of paracetamol blood concentration after intravenous route | 360 minutes after injection | 
| paracetamolemia dosage after intravenous route | measurement of paracetamol blood concentration after intravenous route | 480 minutes after injection | 
| paracetamolemia dosage after subcutaneous route | measurement of paracetamol blood concentration after subcutaneous route | at injection time | 
| paracetamolemia dosage after subcutaneous route | measurement of paracetamol blood concentration after subcutaneous route | 15 minutes after injection | 
| paracetamolemia dosage after subcutaneous route | measurement of paracetamol blood concentration after subcutaneous route | 30 minutes after injection | 
| paracetamolemia dosage after subcutaneous route | measurement of paracetamol blood concentration after subcutaneous route | 45 minutes after injection | 
| paracetamolemia dosage after subcutaneous route | measurement of paracetamol blood concentration after subcutaneous route | 60 minutes after injection | 
| paracetamolemia dosage after subcutaneous route | measurement of paracetamol blood concentration after subcutaneous route | 90 minutes after injection | 
| paracetamolemia dosage after subcutaneous route | measurement of paracetamol blood concentration after subcutaneous route | 120 minutes after injection | 
| paracetamolemia dosage after subcutaneous route | measurement of paracetamol blood concentration after subcutaneous route | 240 minutes after injection | 
| paracetamolemia dosage after subcutaneous route | measurement of paracetamol blood concentration after subcutaneous route | 360 minutes after injection | 
| paracetamolemia dosage after subcutaneous route | measurement of paracetamol blood concentration after subcutaneous route | 480 minutes after injection | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| pain scale | numeric sale (0-10) | at injection time | 
| pain scale | numeric sale (0-10) | 15 minutes after injection time | 
| pain scale | numeric sale (0-10) | 60 minutes after injection time | 
| pain scale | numeric sale (0-10) | 90 minutes after injection time | 
| pain scale | numeric sale (0-10) | 120 minutes after injection time | 
| pain scale | numeric sale (0-10) | 240 minutes after injection time | 
| pain scale | numeric sale (0-10) | 360 minutes after injection time | 
| pain scale | numeric sale (0-10) | 480 minutes after injection time | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Paracetamol, Acetaminophen, Palliative care, Subcutaneous administration, intravenous administration, pharmacokinetic