<clinical_study>
  <!-- This xml conforms to an XML Schema at:
    https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
  <required_header>
    <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
    <link_text>Link to the current ClinicalTrials.gov record.</link_text>
    <url>https://clinicaltrials.gov/ct2/show/NCT03837067</url>
  </required_header>
  <id_info>
    <org_study_id>DUMP</org_study_id>
    <nct_id>NCT03837067</nct_id>
  </id_info>
  <brief_title>Use and Misuse of Domperidone in Parkinson's Disease in France - Dump Investigation</brief_title>
  <acronym>DUMP-invest</acronym>
  <official_title>Use and Misuse of Domperidone in Parkinson's Disease in France - Dump Investigation</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Assistance Publique - Hôpitaux de Paris</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Assistance Publique - Hôpitaux de Paris</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      Parkinson disease is the second most frequent neurodegenerative disease after Alzheimer&#xD;
      disease and affect 1% of the population over 60 years. The treatment of PD is based on&#xD;
      dopamine replacement therapies (DRT). Nausea is the most frequent adverse event whatever the&#xD;
      drug, occurring in 30-40% of patients at the initiation of DRT.&#xD;
&#xD;
      Domperidone, a dopamine D2 receptor antagonist with antiemetic properties, does not readily&#xD;
      cross the blood-brain barrier, allowing its used in PD. Domperidone may prolong the duration&#xD;
      of the QT interval in predisposed patients, and has been associated with proarrhythmia and&#xD;
      arrhythmic deaths. Arrhythmias, sudden death and cardiac arrest were reported with high&#xD;
      intravenous doses which has led to withdraw of the parenteral form of the drug in 1984. Two&#xD;
      case control studies found an increased risk of sudden death associated with domperidone use.&#xD;
      In these reports, the increased risk was depending on age, dose, and the use of domperidone&#xD;
      in combination with CYP3A4 inhibitors. Following the discussion created by this alert, the&#xD;
      PRAC of the EMA has issued recommendations restricting domperidone use to patients younger&#xD;
      than 60 years at doses below 30 mg/day and for a short period (7 days).&#xD;
&#xD;
      Because there is no alternative antiemetic drug to be used in PD, domperidone is commonly&#xD;
      prescribed as a preventive therapy in most PD patients initiating DRT. In this population,&#xD;
      usually older than 60 years, doses of 60 or 80 mg/day are commonly prescribed, for at least 2&#xD;
      months of the DRT escalating dose period or longer. A particular &quot;niche&quot; of domperidone&#xD;
      misuse might be patients treated with continuous subcutaneous administration of apomorphine,&#xD;
      a second line therapy in PD, inducing severe and prolonged nausea in almost all patients.&#xD;
      Little is known about the use of domperidone in PD in France, but misuse of domperidone in PD&#xD;
      patients is probably very high. Data collected from two French PD cohorts, COPARK and DIGPD,&#xD;
      showed that 8-14% of PD patients were treated with domperidone.&#xD;
&#xD;
      The aim of this proposal is to investigate the practices and beliefs of French neurologists&#xD;
      regarding use and misuse of domperidone in PD, by a qualitative approach.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Parkinson disease is the second most frequent neurodegenerative disease after Alzheimer&#xD;
      disease and affect 1% of the population over 60 years (150 to 170 000 patients in France).&#xD;
      The treatment of PD is based on dopamine replacement therapies (DRT). Nausea is the most&#xD;
      frequent adverse event whatever the drug, occurring in 30-40% of patients at the initiation&#xD;
      of DRT.&#xD;
&#xD;
      Domperidone is a dopamine D2 receptor antagonist with antiemetic properties. Domperidone does&#xD;
      not readily cross the blood-brain barrier, allowing its used in PD. Domperidone may prolong&#xD;
      the duration of the QT interval in predisposed patients, and has been associated with&#xD;
      proarrhythmia and arrhythmic deaths. Arrhythmias, sudden death and cardiac arrest were&#xD;
      reported with high intravenous doses which has led to withdraw of the parenteral form of the&#xD;
      drug in 1984. More recently, two case control studies found an increased risk of sudden death&#xD;
      associated with domperidone use. In these reports, the increased risk was depending on age,&#xD;
      dose, and the use of domperidone in combination with CYP3A4 inhibitors. Following the&#xD;
      discussion created by this alert, the Pharmacovigilance Risk Assessment Committee (PRAC) of&#xD;
      the European Medicines Agency (EMA) has issued recommendations restricting domperidone use to&#xD;
      patients younger than 60 years at doses below 30 mg/day and for a short period (7 days).&#xD;
&#xD;
      Because there is no alternative antiemetic drug to be used in PD, domperidone is commonly&#xD;
      prescribed as a preventive therapy in most PD patients initiating DRT since more than 30&#xD;
      years. In this population, usually older than 60 years, doses of 60 or 80 mg/day are commonly&#xD;
      prescribed, for at least 2 months of the DRT escalating dose period or longer. A particular&#xD;
      &quot;niche&quot; of domperidone misuse might be patients treated with continuous subcutaneous&#xD;
      administration of apomorphine, a second line therapy in PD, inducing severe and prolonged&#xD;
      nausea in almost all patients. Little is known about the use of domperidone in PD in France&#xD;
      in clinical practice, but misuse of domperidone in PD patients is probably very high. Data&#xD;
      collected from two French PD cohorts, COPARK and DIGPD, showed that 8-14% of PD patients were&#xD;
      treated with domperidone, extrapolating 10,000 to 20,000 potentially exposed patients at&#xD;
      particularly high risk of sudden death.&#xD;
&#xD;
      The aim of this proposal is to investigate the practices and beliefs of French neurologists&#xD;
      regarding use and misuse of domperidone in PD, by a qualitative approach. Practices of&#xD;
      domperidone prescription by neurologists (from university and general hospitals and private&#xD;
      offices) will be evaluated using a semi-structured questionnaire survey. This qualitative&#xD;
      study will provide insights from the neurologists on their need for domperidone, therapeutic&#xD;
      alternatives and their perceived efficacy, and on the domperidone management and safety&#xD;
      procedures that are applied to PD patients before and after domperidone prescription.&#xD;
&#xD;
      The results of this survey on regular practices of neurologists on the use and misuse of&#xD;
      domperidone will provide information of the current opinions about the drug, the indications&#xD;
      for which it is prescribed, how contra-indications are evaluated, and their feedback on&#xD;
      tolerance and efficacy. This information will help Regulatory Authorities to communicate&#xD;
      about the safety profile of the drug.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">July 17, 2018</start_date>
  <completion_date type="Actual">December 1, 2018</completion_date>
  <primary_completion_date type="Actual">November 1, 2018</primary_completion_date>
  <study_type>Observational</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <observational_model>Other</observational_model>
    <time_perspective>Retrospective</time_perspective>
  </study_design_info>
  <primary_outcome>
    <measure>Practices of domperidone prescription by neurologists</measure>
    <time_frame>day 1</time_frame>
    <description>Practices of domperidone prescription by neurologists : use and misuse of domperidone evaluated using a semi-structured questionnaire survey</description>
  </primary_outcome>
  <enrollment type="Actual">2300</enrollment>
  <condition>Parkinson's Disease</condition>
  <eligibility>
    <study_pop>
      <textblock>
        All neurologists in France&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Non-Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  All neurologists in France&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  None&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>N/A</minimum_age>
    <maximum_age>N/A</maximum_age>
  </eligibility>
  <location>
    <facility>
      <name>La Pitié Salpétrière Hospital</name>
      <address>
        <city>Paris</city>
        <zip>75013</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>France</country>
  </location_countries>
  <verification_date>July 2018</verification_date>
  <study_first_submitted>December 12, 2018</study_first_submitted>
  <study_first_submitted_qc>February 8, 2019</study_first_submitted_qc>
  <study_first_posted type="Actual">February 11, 2019</study_first_posted>
  <last_update_submitted>May 10, 2021</last_update_submitted>
  <last_update_submitted_qc>May 10, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">May 11, 2021</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Domperidone</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Parkinson Disease</mesh_term>
  </condition_browse>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT03837067
org study id: DUMP
nct id: NCT03837067
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
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.
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.
observational model: Other
time perspective: Retrospective
measure: Practices of domperidone prescription by neurologists
time frame: day 1
description: Practices of domperidone prescription by neurologists : use and misuse of domperidone evaluated using a semi-structured questionnaire survey
study pop: 
sampling method: Non-Probability Sample
criteria: 
gender: All
minimum age: N/A
maximum age: N/A
facility: 
country: France
responsible party type: Sponsor
mesh term: Parkinson Disease