Clinical Trial Details
— Status: Terminated
Administrative data
| NCT number |
NCT04653584 |
| Other study ID # |
DUMP-obs |
| Secondary ID |
|
| Status |
Terminated |
| Phase |
|
| First received |
|
| Last updated |
|
| Start date |
January 1, 2021 |
| Est. completion date |
October 25, 2021 |
Study information
| Verified date |
November 2020 |
| Source |
Assistance Publique - Hôpitaux de Paris |
| Contact |
n/a |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Observational
|
Clinical Trial Summary
Parkinson disease is the second most frequent neurodegenerative disease after Alzheimer
disease and affect 1% of the population over 60 years. The treatment of PD is based on
dopamine replacement therapies (DRT). Nausea is the most frequent adverse event whatever the
drug, occurring in 30-40% of patients at the initiation of DRT.
Domperidone, a dopamine D2 receptor antagonist with antiemetic properties, does not readily
cross the blood-brain barrier, allowing its used in PD. Domperidone may prolong the duration
of the QT interval in predisposed patients, and has been associated with proarrhythmia and
arrhythmic deaths. Arrhythmias, sudden death and cardiac arrest were reported with high
intravenous doses which has led to withdraw of the parenteral form of the drug in 1984. Two
case control studies found an increased risk of sudden death associated with domperidone use.
In these reports, the increased risk was depending on age, dose, and the use of domperidone
in combination with CYP3A4 inhibitors. Following the discussion created by this alert, the
PRAC of the EMA has issued recommendations restricting domperidone use to patients younger
than 60 years at doses below 30 mg/day and for a short period (7 days).
Because there is no alternative antiemetic drug to be used in PD, domperidone is commonly
prescribed as a preventive therapy in most PD patients initiating DRT. In this population,
usually older than 60 years, doses of 60 or 80 mg/day are commonly prescribed, for at least 2
months of the DRT escalating dose period or longer. A particular "niche" of domperidone
misuse might be patients treated with continuous subcutaneous administration of apomorphine,
a second line therapy in PD, inducing severe and prolonged nausea in almost all patients.
Little is known about the use of domperidone in PD in France, but misuse of domperidone in PD
patients is probably very high. Data collected from two French PD cohorts, COPARK and DIGPD,
showed that 8-14% of PD patients were treated with domperidone.
The aim of this proposal is to conduct a cross sectional observational study performed in
consecutive patients followed by the 24 PD expert centers of the NS Park network, general
hospitals and private practice neurologists, to describe the actual use of domperidone in PD
patients.
Description:
Domperidone is a dopamine D2 receptor antagonist with antiemetic properties. Domperidone does
not readily cross the blood-brain barrier, allowing its used in PD. Domperidone may prolong
the duration of the QT interval in predisposed patients, and has been associated with
proarrhythmia and arrhythmic deaths. Arrhythmias, sudden death and cardiac arrest were
reported with high intravenous doses which has led to withdraw of the parenteral form of the
drug in 1984. More recently, two case control studies found an increased risk of sudden death
associated with domperidone use. In these reports, the increased risk was depending on age,
dose, and the use of domperidone in combination with CYP3A4 inhibitors. Following the
discussion created by this alert, the Pharmacovigilance Risk Assessment Committee (PRAC) of
the European Medicines Agency (EMA) has issued recommendations restricting domperidone use to
patients younger than 60 years at doses below 30 mg/day and for a short period (7 days).
Because there is no alternative antiemetic drug to be used in PD, domperidone is commonly
prescribed as a preventive therapy in most PD patients initiating DRT since more than 30
years. In this population, usually older than 60 years, doses of 60 or 80 mg/day are commonly
prescribed, for at least 2 months of the DRT escalating dose period or longer. A particular
"niche" of domperidone misuse might be patients treated with continuous subcutaneous
administration of apomorphine, a second line therapy in PD, inducing severe and prolonged
nausea in almost all patients. Little is known about the use of domperidone in PD in France
in clinical practice, but misuse of domperidone in PD patients is probably very high. Data
collected from two French PD cohorts, COPARK and DIGPD, showed that 8-14% of PD patients were
treated with domperidone, extrapolating 10,000 to 20,000 potentially exposed patients at
particularly high risk of sudden death.
The aim of this proposal is to conduct a cross sectional observational study of domperidone
prescription in PD patients consecutively recruited by neurologists both in University
hospitals (24 PD expert centers, thanks to NS-Park/FCRIN network), general hospitals and
private neurologists. This will provide insights about the current prescription of
domperidone, their doses and duration, the PD patients' profiles, and the different
indications for which it is prescribed.
This project will allow describing the use and misuse of domperidone in the PD population in
France. This prospective study will take advantage of the recently released national database
for PD, supported by the French Plan for Neurodegenerative Disease and by the French Network
for Parkinson's disease and Movement Disorders (NS-Park/FCRIN network). This study will help
to set up a tool and standardized operating procedures that can be used for subsequent
similar studies on clinical practice in neurodegenerative diseases through a large network of
academic and private specialists. This information will help Regulatory Authorities to
communicate about the safety profile of the drug. Finally, our results obtained in the French
population will be compared to those from the European Union countries using domperidone and
from which data has been published.
