Subcutaneous Route and Pharmacology of Metoclopramide (SOPHA-Méto)

University Hospital of Bordeaux

Status and phase

Completed

Phase 3

Conditions

Vomiting

Nausea

Treatments

Drug: metoclopramide intravenous

Study type

Interventional

Funder types

Other

Identifiers

NCT02466984

CHUBX2014/10

Details and patient eligibility

About

Subcutaneous (SC) route has become a standard of care of many drugs administration in palliative medicine. A preliminary study showed that, although it was widely adopted among palliative care practitioners for routinely prescribed medications, standards of proof are still lacking for many molecules. Among them, metoclopramide is a largely employed drug for nausea and vomiting treatment, particularly in palliative care and oncology. Therefore, the investigator aim to study absorption and efficacy of subcutaneous administration of metoclopramide.

Full description

In this cross-over study, each patient receives subcutaneous and intravenous metoclopramide, with a randomized order of administration. During each perfusion phases, metoclopramide is administrated with continuous flow, doses being increased every two days, first from 10 to 20 and then from 20 to 30 mg/d. In order to guarantee plasmatic balance during route change, the first dose of the second phase is extended for three days. Metoclopramide plasmatic concentration is measured at inclusion and at the end of each dose administration, with a total of 7 dosages.

Principal purpose of this research is to clarify subcutaneous bioavailability of metoclopramide. For this meaning, the mean difference between all subcutaneous and intravenous concentration ratios is compared. Secondary purposes consist of: calculating metoclopramide subcutaneous bioavailability for each study dose (10, 20 and 30 mg/d); describing dose-bioavailability relation for subcutaneous metoclopramide; comparing dose-concentration relationship of intravenous and subcutaneous metoclopramide; studying local tolerance by checking all inflammatory signs surrounding injection site; evaluating clinical efficacy by comparing between the two groups the number of vomiting episodes, use of Serotonin receptor antagonists and the nausea scores on a 11-level numerical scale.

Eighteen patients have to be analysed at least. For each patient not having completed the study, one more will be included in order to reach the eighteen necessary patients. Therefore, it is expected to include twenty-four patients. Included population characteristics will be described. A three-dimensional analysis with period, subject and dose is performed to determine metoclopramide absolute bioavailability. For secondary criteria, dose-concentration relation is analysed with a four-dimensional analysis; dose-bioavailability and dose-concentration relations are described by linear and log-linear regression. For principal purpose, only results of patients having completed the study are part of this aforementioned analyse.

Enrollment

5 patients

Sex

All

Ages

18+ years old

Volunteers

No Healthy Volunteers

Inclusion and exclusion criteria

Inclusion Criteria:

Man or woman > 18 years
Patients hospitalized at the palliative medical care unit of University Hospital Bordeaux
Patient whose life expectancy is greater to 4 weeks
Patients suffering from nausea the day of inclusion with a greater than or equal score to 3/10 on a numerical scale (FR) from 0 to 10 and / or have had at least one vomiting within three days prior to inclusion
Patients may be infused through an IV and subcutaneous (SC)
Patient can communicate verbally or in writing
Patients affiliates or beneficiaries of a social security fund
Patient has given his written consent

Exclusion criteria

Pregnant or breastfeeding women
Current Treatment for severe and progressive threatening disease
Treatment with oral or injectable metoclopramide within 3 days prior to inclusion
Treatment with levodopa or dopamine agonists in progress
Neuroleptic Processing
Patient with lesion occlusive syndrome
Patients at risk of gastrointestinal perforation
Patient with clinical signs of gastrointestinal bleeding
Parkinson's disease
Patients with epilepsy not controlled by anti-seizure treatment
Patients suffering from liver failure
Patients with a heart rate less than 60 beats / min at baseline
Patients with systolic blood pressure less than or equal to 90 mmHg at baseline
History of allergy to metoclopramide
History of allergy to ondansetron
Previous history of tardive dyskinesia to neuroleptics or metoclopramide
Previous history of pheochromocytoma
Previous history of methemoglobinemia with metoclopramide
History of deficit NADH-cytochrome b5 reductase
Patient deprived of liberty by judicial or administrative decision
Major protected by law
Exclusion period Patient relative over another protocol.

Exclusion criteria

Pregnant woman (blood β-HCG dosage ≥ 5 IU / L)
Patients with a creatinine clearance less than or equal to 60 mL / min at baseline
Patient with cardiac conduction disorders on ECG
Patients with electrolyte imbalance in electrolytes