Clinical Trial Details
— Status: Completed
Administrative data
| NCT number |
NCT03837067 |
| Other study ID # |
DUMP |
| Secondary ID |
|
| Status |
Completed |
| Phase |
|
| First received |
|
| Last updated |
|
| Start date |
July 17, 2018 |
| Est. completion date |
December 1, 2018 |
Study information
| Verified date |
July 2018 |
| 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 investigate the practices and beliefs of French neurologists
regarding use and misuse of domperidone in PD, by a qualitative approach.
Description:
Parkinson disease is the second most frequent neurodegenerative disease after Alzheimer
disease and affect 1% of the population over 60 years (150 to 170 000 patients in France).
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 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 investigate the practices and beliefs of French neurologists
regarding use and misuse of domperidone in PD, by a qualitative approach. Practices of
domperidone prescription by neurologists (from university and general hospitals and private
offices) will be evaluated using a semi-structured questionnaire survey. This qualitative
study will provide insights from the neurologists on their need for domperidone, therapeutic
alternatives and their perceived efficacy, and on the domperidone management and safety
procedures that are applied to PD patients before and after domperidone prescription.
The results of this survey on regular practices of neurologists on the use and misuse of
domperidone will provide information of the current opinions about the drug, the indications
for which it is prescribed, how contra-indications are evaluated, and their feedback on
tolerance and efficacy. This information will help Regulatory Authorities to communicate
about the safety profile of the drug.
