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Intravenous versus subcutaneous route pharmacokinetics of paracetamol (acetaminophen) in palliative care patients: study protocol for a randomized trial (ParaSCIVPallia).

ABSTRACT: BACKGROUND:Among palliative care (PC) patients who are administered paracetamol, the subcutaneous (SC) route is often an alternative to the intravenous (IV) route. Yet pharmacological and clinical data on whether these are equivalent pharmacokinetically are lacking. Many French palliative teams are now empirically using paracetamol by the SC route, but there are no data to support this practice. This trial aims to compare the pharmacokinetic (PK) parameters of paracetomol between the IV and SC routes in PC patients. METHODS/DESIGN:This is a randomized, open, crossover study in two PC centers. The primary endpoints are AUC0-t, AUC0-?, Cmax, Vd, and t1/2. All adverse events will be reported for a safety analysis. Twenty adult PC patients with an IV device having spontaneous pain not related to care, with a numeric pain rate scale >?3/10, or having a systematic prescription of paracetamol as the usual treatment will be included. All patients also have to meet all eligibility criteria. CONCLUSION:This is the first study comparing PK parameters for IV paracetamol versus SC paracetamol in PC patients. TRIAL REGISTRATION:ClinicalTrials.gov, NCT03944044. Registered on 4 June 2019. Committee for the protection of persons (CPP) 18.09.05.58206 approval 4 October 2018. National Drug Safety Agency (ANSM; Agence Nationale de Sécurité Médicament) MEDAECNAT-2018-09-00009 approval 29 November 2018.

SUBMITTER: Vernant M

PROVIDER: S-EPMC6998185 | biostudies-literature | 2020 Feb

REPOSITORIES: biostudies-literature

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Intravenous versus subcutaneous route pharmacokinetics of paracetamol (acetaminophen) in palliative care patients: study protocol for a randomized trial (ParaSCIVPallia).

Vernant Marine M Lepoupet Marie M Creveuil Christian C Alix Antoine A Gourio Charlotte C Peyro-Saint-Paul Laure L Lelong-Boulouard Veronique V Guillaumé Cyril C

Trials 20200204 1

<h4>Background</h4>Among palliative care (PC) patients who are administered paracetamol, the subcutaneous (SC) route is often an alternative to the intravenous (IV) route. Yet pharmacological and clinical data on whether these are equivalent pharmacokinetically are lacking. Many French palliative teams are now empirically using paracetamol by the SC route, but there are no data to support this practice. This trial aims to compare the pharmacokinetic (PK) parameters of paracetomol between the IV ...[more]

PMID: 32019598

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Project description:IntroductionSubcutaneous infusion (SC) or hypodermoclysis is an old perfusion technique that is often used off-label although it has been shown to be effective. Acetaminophen (paracetamol) subcutaneous injection is performed in some centers despite the lack of conclusive evidence on its effectiveness. This study aims to evaluate the efficacy of subcutaneous infusion of Acetaminophen in the treatment of pain and fever in geriatrics and in palliative care and to determine its safety profile and possible side effects.Material and methodsThis experimental study was conducted between 2018 and 2019 on adult patients in palliative care or in geriatrics in several hospitals and nursing homes in Lebanon. Primary outcomes were change in temperature; change in pain score on the numerical rating scale (NS) or on the Algoplus scale after 60 min from the start of the infusion; and the appearance of local side effects at the infusion site. Changes in the various parameters at 30 min and 180 min were also evaluated as secondary outcomes.ResultsThirty-one patients were included in the study, with a total of 120 doses of acetaminophen. At 60 min, the mean decrease in pain on the NS was 5.35 points, while the mean decrease in temperature was 0.79 degrees Celsius. At 60 min, 75%, CI = [47.62-92.73] of the patients who received acetaminophen for pain and 66.67%, CI = [38.38-88.17] of those who received it for fever had clinically significant improvement. The overall effect of subcutaneous acetaminophen, defined as any clinically significant effect on pain or fever, was 70.97%, CI = [51.96-85.78]. The overall effect at 30 min and at 180 min was 23.33%, CI = [9.93-42.28] and 87.10%, CI = [70.17-96.37], respectively. The side effects reported 30 min after the injection and observed after at least one of the doses were: local edema in 16 patients (51.61%), induration in one patient (3.23%), local pain in one patient (3.23%) and local heat in one patient (3.23%). At 180 min, only 2 patients (6.45%) still had edema at the infusion site.ConclusionSubcutaneous administration of acetaminophen is effective and well tolerated in geriatric and palliative care patients. It is appropriate when no other route is available, especially for home-based care. Comparative studies are needed to allow the expansion of this practice.

Project description:The CD20-specific monoclonal antibody rituximab (MabThera(®), Rituxan(®)) is widely used as the backbone of treatment for patients with hematologic disorders. Intravenous administration of rituximab is associated with infusion times of 4-6 hours, and can be associated with infusion-related reactions. Subcutaneous administration of rituximab may reduce this and facilitate administration without infusion-related reactions. We sought to determine the feasibility of achieving equivalent efficacy (measured by endogenous B-cell depletion) and long-term durability of CD20 target coverage for subcutaneously administered rituximab compared with intravenous dosing. In these preclinical studies, male cynomolgus monkeys were treated with either intravenous rituximab or novel subcutaneous formulation of rituximab containing human recombinant DNA-derived hyaluronidase enzyme. Peripheral blood samples were analyzed for serum rituximab concentrations, peripheral B-cell depletion, and CD20 target coverage, including subset analysis according to CD21+ status. Distal lymph node B-cell depletion and CD20 target coverage were also measured. Initial peak serum concentrations of rituximab were significantly higher following intravenous administration than subcutaneous. However, the mean serum rituximab trough concentrations were comparable at 2 and 7 days post-first dose and 9 and 14 days post-second dose. Efficacy of B-cell depletion in both peripheral blood and distal lymph nodes was comparable for both methods. In lymph nodes, 9 days after the second dose with subcutaneous and intravenous rituximab, B-cell levels were decreased by 57% and 42% respectively. Similarly, levels of peripheral blood B cells were depleted by >94% for both subcutaneous and intravenous dosing at all time points. Long-term recovery of free unbound surface CD20 levels was similar, and the duration of B-cell depletion was equally sustained over 2 months for both methods. These results demonstrate that, despite initial peak serum drug level differences, subcutaneous rituximab has similar durability, pharmacodynamics, and efficacy compared with intravenous rituximab.

Dataset Information

Intravenous versus subcutaneous route pharmacokinetics of paracetamol (acetaminophen) in palliative care patients: study protocol for a randomized trial (ParaSCIVPallia).

Publications

Intravenous versus subcutaneous route pharmacokinetics of paracetamol (acetaminophen) in palliative care patients: study protocol for a randomized trial (ParaSCIVPallia).

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