Trial document




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  DRKS00013909

Trial Description

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Title

Influence of Metabolic Profiles on Drug Safety in Routine Care

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Trial Acronym

EMPAR

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URL of the Trial

http://www.bfarm.de/empar

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Brief Summary in Lay Language

The EMPAR research project is financially supported by the Innovation Fund of the Federal Joint Committee (Gemeinsamer Bundesausschuss). The objective of this study is to identify opportunities in pharmacogenetics to increase the safety of drug therapy in future patients’ healthcare. We aim to include about 10,000 participants, insured by the health insurance provider TK.
Variants of genes that influence degradation and transport of drugs and therefore are involved in their availability and effect in the body will be analysed. These genes determine the metabolic profile and the type of drug metabolism, respectively. In the course of this study, these gene variants will be investigated by analysis of the study participants’ buccal swab. The incidence of adverse drug reactions within past four years will be examined in groups with different metabolic profiles. By means of routine data of the health insurance provider TK, different metabolic profiles and their impact on the incidence of adverse drug reactions upon normal dosing and planned therapy will be compared. In this study, special characteristics of metabolic profiles will be investigated in regard to the safety of drug therapy. Additionally, it will be examined whether including these special characteristics into individual therapy design is applicable in future. The long-term goal is the implementation of early pharmacogenetic tests in daily practice for an individual therapy and treatment.

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Brief Summary in Scientific Language

The EMPAR study is a retrospective, non-interventional cohort study funded by the Innovation Fund of the Federal Joint Committee (Gemeinsamer Bundesausschuss). The objective of the study is to analyse pharmacogenetic risk factors that are important for drug therapy by means of endpoints relevant for healthcare based on statutory health insurance data. Specifically, the study addresses the question of whether genetic differences have an impact on the use of statutory health insurance services e.g. hospitalisation, nursing care level or drug prescription and change of medication. The long-term goal is to implement the use of pharmacogenetic testing of metabolic profiles in routine care. The collection of patient relevant metabolic risk profiles concerning side effects or resistance to therapy will improve treatment in terms of quality of patient care and economic efficiency.
We aim to include a study sample of about 10,000 patients insured by the health insurance provider TK (18 years and older) who take at least one drug whose metabolization is known to depend on genetic variants. This means, there is clinical evidence that genetic differences have an impact on the pharmacokinetics and/or pharmacodynamics of the drug in question. A panel of pharmacogenetically most important markers will be genotyped from buccal swab of each patient. This pharmacogenetic data on drug metabolism and elimination will be collected as individual-level data and combined and analysed with the TK cross-sector routine care data. Pharmacogenetic, -epidemiologic and -economic analysis using health care utilization scores (Charlson, Elixhauser, ICD diagnoses, Rx-Risk, chronic disease scores, etc.) will be applied. Machine learning techniques will be used to estimate the benefit of testing metabolic profiles in routine care in terms of prevention of adverse drug reactions and decrease of costs in health insurance services.

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Organizational Data

  •   DRKS00013909
  •   2018/07/06
  •   [---]*
  •   yes
  •   Approved
  •   339/17, Ethik-Kommission der Medizinischen Fakultät der Rheinischen Friedrich-Wilhelms-Universität Bonn
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Secondary IDs

  • [---]*
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Health Condition or Problem studied

  •   D50.0 -  Iron deficiency anaemia secondary to blood loss (chronic)
  •   Y57.9 -  Drug or medicament, unspecified
  •   D62 -  Acute posthaemorrhagic anaemia
  •   D65.1 -  [generalization D65: Disseminated intravascular coagulation [defibrination syndrome]]
  •   D68.33 -  [generalization D68.3: Haemorrhagic disorder due to circulating anticoagulants]
  •   D68.35 -  [generalization D68.3: Haemorrhagic disorder due to circulating anticoagulants]
  •   D69.80 -  [generalization D69.8: Other specified haemorrhagic conditions]
  •   D69.9 -  Haemorrhagic condition, unspecified
  •   G45 -  Transient cerebral ischaemic attacks and related syndromes
  •   G95.1 -  Vascular myelopathies
  •   H11.3 -  Conjunctival haemorrhage
  •   H21.0 -  Hyphaema
  •   H31.3 -  Choroidal haemorrhage and rupture
  •   H34.0 -  Transient retinal artery occlusion
  •   H34.1 -  Central retinal artery occlusion
  •   H34.2 -  Other retinal artery occlusions
  •   H34.8 -  Other retinal vascular occlusions
  •   H34.9 -  Retinal vascular occlusion, unspecified
  •   H35.6 -  Retinal haemorrhage
  •   H43.1 -  Vitreous haemorrhage
  •   H45.0 -  Vitreous haemorrhage in diseases classified elsewhere
  •   H92.2 -  Otorrhagia
  •   I21 -  Acute myocardial infarction
  •   I22 -  Subsequent myocardial infarction
  •   I23 -  Certain current complications following acute myocardial infarction
  •   I24 -  Other acute ischaemic heart diseases
  •   I25 -  Chronic ischaemic heart disease
  •   I26 -  Pulmonary embolism
  •   I60 -  Subarachnoid haemorrhage
  •   I61 -  Intracerebral haemorrhage
  •   I62 -  Other nontraumatic intracranial haemorrhage
  •   I63 -  Cerebral infarction
  •   I64 -  Stroke, not specified as haemorrhage or infarction
  •   I65 -  Occlusion and stenosis of precerebral arteries, not resulting in cerebral infarction
  •   I66 -  Occlusion and stenosis of cerebral arteries, not resulting in cerebral infarction
  •   I71 -  Aortic aneurysm and dissection
  •   I72 -  Other aneurysm and dissection
  •   I74 -  Arterial embolism and thrombosis
  •   I79.0 -  Aneurysm of aorta in diseases classified elsewhere
  •   I80 -  Phlebitis and thrombophlebitis
  •   I81 -  Portal vein thrombosis
  •   I82 -  Other venous embolism and thrombosis
  •   I85.0 -  Oesophageal varices with bleeding
  •   I87.0 -  Postthrombotic syndrome
  •   J94.2 -  Haemothorax
  •   K26.0 -  Duodenal ulcer; Acute with haemorrhage
  •   K26.1 -  Duodenal ulcer; Acute with perforation
  •   K26.2 -  Duodenal ulcer; Acute with both haemorrhage and perforation
  •   K26.4 -  Duodenal ulcer; Chronic or unspecified with haemorrhage
  •   K26.5 -  Duodenal ulcer; Chronic or unspecified with perforation
  •   K26.6 -  Duodenal ulcer; Chronic or unspecified with both haemorrhage and perforation
  •   K25.0 -  Gastric ulcer; Acute with haemorrhage
  •   K25.1 -  Gastric ulcer; Acute with perforation
  •   K25.2 -  Gastric ulcer; Acute with both haemorrhage and perforation
  •   K25.4 -  Gastric ulcer; Chronic or unspecified with haemorrhage
  •   K25.5 -  Gastric ulcer; Chronic or unspecified with perforation
  •   K25.6 -  Gastric ulcer; Chronic or unspecified with both haemorrhage and perforation
  •   K27.0 -  Peptic ulcer, site unspecified; Acute with haemorrhage
  •   K27.1 -  Peptic ulcer, site unspecified; Acute with perforation
  •   K27.2 -  Peptic ulcer, site unspecified; Acute with both haemorrhage and perforation
  •   K27.4 -  Peptic ulcer, site unspecified; Chronic or unspecified with haemorrhage
  •   K27.5 -  Peptic ulcer, site unspecified; Chronic or unspecified with perforation
  •   K27.6 -  Peptic ulcer, site unspecified; Chronic or unspecified with both haemorrhage and perforation
  •   K28.0 -  Gastrojejunal ulcer; Acute with haemorrhage
  •   K28.1 -  Gastrojejunal ulcer; Acute with perforation
  •   K28.2 -  Gastrojejunal ulcer; Acute with both haemorrhage and perforation
  •   K28.4 -  Gastrojejunal ulcer; Chronic or unspecified with haemorrhage
  •   K28.5 -  Gastrojejunal ulcer; Chronic or unspecified with perforation
  •   K28.6 -  Gastrojejunal ulcer; Chronic or unspecified with both haemorrhage and perforation
  •   K29.0 -  Acute haemorrhagic gastritis
  •   K31.82 -  [generalization K31.8: Other specified diseases of stomach and duodenum]
  •   K55.0 -  Acute vascular disorders of intestine
  •   K55.1 -  Chronic vascular disorders of intestine
  •   K55.22 -  [generalization K55.2: Angiodysplasia of colon]
  •   K57.01 -  [generalization K57.0: Diverticular disease of small intestine with perforation and abscess]
  •   K57.03 -  [generalization K57.0: Diverticular disease of small intestine with perforation and abscess]
  •   K57.11 -  [generalization K57.1: Diverticular disease of small intestine without perforation or abscess]
  •   K57.13 -  [generalization K57.1: Diverticular disease of small intestine without perforation or abscess]
  •   K57.21 -  [generalization K57.2: Diverticular disease of large intestine with perforation and abscess]
  •   K57.23 -  [generalization K57.2: Diverticular disease of large intestine with perforation and abscess]
  •   K57.31 -  [generalization K57.3: Diverticular disease of large intestine without perforation or abscess]
  •   K57.33 -  [generalization K57.3: Diverticular disease of large intestine without perforation or abscess]
  •   K57.41 -  [generalization K57.4: Diverticular disease of both small and large intestine with perforation and abscess]
  •   K57.43 -  [generalization K57.4: Diverticular disease of both small and large intestine with perforation and abscess]
  •   K57.51 -  [generalization K57.5: Diverticular disease of both small and large intestine without perforation or abscess]
  •   K57.53 -  [generalization K57.5: Diverticular disease of both small and large intestine without perforation or abscess]
  •   K57.81 -  [generalization K57.8: Diverticular disease of intestine, part unspecified, with perforation and abscess]
  •   K57.83 -  [generalization K57.8: Diverticular disease of intestine, part unspecified, with perforation and abscess]
  •   K57.91 -  [generalization K57.9: Diverticular disease of intestine, part unspecified, without perforation or abscess]
  •   K57.93 -  [generalization K57.9: Diverticular disease of intestine, part unspecified, without perforation or abscess]
  •   K62.5 -  Haemorrhage of anus and rectum
  •   K66.1 -  Haemoperitoneum
  •   K76.3 -  Infarction of liver
  •   K92.0 -  Haematemesis
  •   K92.1 -  Melaena
  •   K92.2 -  Gastrointestinal haemorrhage, unspecified
  •   M25.0 -  Haemarthrosis
  •   M31.1 -  Thrombotic microangiopathy
  •   M62.2 -  Ischaemic infarction of muscle
  •   N02 -  Recurrent and persistent haematuria
  •   R04 -  Haemorrhage from respiratory passages
  •   R23.3 -  Spontaneous ecchymoses
  •   R31 -  Unspecified haematuria
  •   R57.1 -  Hypovolaemic shock
  •   R58 -  Haemorrhage, not elsewhere classified
  •   S06.33 -  [generalization S06.3: Focal brain injury]
  •   S06.34 -  [generalization S06.3: Focal brain injury]
  •   S06.4 -  Epidural haemorrhage
  •   S06.5 -  Traumatic subdural haemorrhage
  •   S06.6 -  Traumatic subarachnoid haemorrhage
  •   S06.8 -  Other intracranial injuries
  •   S26.0 -  Injury of heart with haemopericardium
  •   S27.1 -  Traumatic haemothorax
  •   S27.31 -  [generalization S27.3: Other injuries of lung]
  •   S36.01 -  [generalization S36.0: Injury of spleen]
  •   S36.11 -  [generalization S36.1: Injury of liver or gallbladder]
  •   S36.81 -  [generalization S36.8: Injury of other intra-abdominal organs]
  •   T00.9 -  Multiple superficial injuries, unspecified
  •   T45.5 -  Poisoning: Anticoagulants
  •   T79.2 -  Traumatic secondary and recurrent haemorrhage
  •   T79.4 -  Traumatic shock
  •   Y57 -  Other and unspecified drugs and medicaments
  •   M60.1 -  Interstitial myositis
  •   M60.8 -  Other myositis
  •   M60.9 -  Myositis, unspecified
  •   G72.0 -  Drug-induced myopathy
  •   M62.8 -  Other specified disorders of muscle
  •   M62.9 -  Disorder of muscle, unspecified
  •   M79.1 -  Myalgia
  •   M79.7 -  Fibromyalgia
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Interventions/Observational Groups

  •   In the course of this study, the pharmacogenetic profiles of participants will be investigated by analysis of their buccal swab. The genetic variant information provided by these profiles will be matched with health insurance data. The data will be used to assess the benefit of determining metabolic profiles in routine care in terms of prevention of adverse drug reactions and decrease of costs in health insurance services. Therefore, participant groups with initial prescription of anticoagulants or cholesterol lowering remedy in 2014-2015 and at least one of the investigated diagnoses after initial prescription will be compared to adequate participant groups without incidence of the investigated diagnoses after initial prescription. Additionally, a screening for special metabolic profiles of insured persons with at least one Y57.9! diagnosis (ICD 10) will be performed during the observation period.
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Characteristics

  •   Non-interventional
  •   Other
  •   Other
  •   Open (masking not used)
  •   [---]*
  •   Other
  •   Pharmacogenetics
  •   Other
  •   N/A
  •   N/A
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Primary Outcome

On the basis of the primary outcomes, the study will examine whether genetic differences have an impact on the incidence of adverse drug reactions and therefore, the utilization of statutory health insurance services. In 2013-2016 the subsequent primary outcomes provided via routine care data of the health insurance provider Techniker Krankenkasse will be assessed:

Utilisation of health care insurance services /

Hospitalization due to adverse drug reactions /

Referral to a specialist due to medication problems /

Change of medication during the observation period /

Incidence of incapacity for work

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Secondary Outcome

On the basis of the secondary outcomes, the study will examine whether there is a possible benefit of cost reductions for health insurance services by determining the metabolic profile to predict and prevent adverse drug reactions in routine care. Thus, the effect of pharmacogenetic profiles on the incidence of adverse drug reactions and therefore, on the costs due to health insurance services will be examined. In 2013-2016 the subsequent secondary outcomes provided via routine care data of the health insurance provider Techniker Krankenkasse will be assessed:

Costs for drugs and treatment /
Sickness benefit

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Countries of Recruitment

  •   Germany
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Locations of Recruitment

  • other 
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Recruitment

  •   Actual
  •   2018/07/24
  •   10000
  •   Monocenter trial
  •   National
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Inclusion Criteria

  •   Both, male and female
  •   18   Years
  •   no maximum age
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Additional Inclusion Criteria

Age of ≥18 years /

Initial prescription of at least one anticoagulant or cholesterol lowering agent in a time frame of 01.01.2014-31.12.2015 or intake of at least one drug with verified pharmacogenetic effect, especially due to CYP2C9-, CYP2C19- und CYP2D6-variants that caused at least one Y57.9! diagnosis (ICD-10 code) in the observation period /

Written informed consent

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Exclusion Criteria

Inapplicable metabolic profile results /

Oncologic phenotype (ICD 10: all C-diagnoses and D0x, D4x, D37, D38, D39) /

Severe F-diagnoses ( ICD 10: F0x.x, F2x.x, F7x.x, F8x.x, F31.x, F33.x, F38.x, F39.x, F42.x, F43.x, F44.x, F60.x, F61.x, F62.x, F63.x, F69.x, F91.x, F92.x, F93.x, F94.x, F95.x, F98.x, F1x.2, F1x.3, F1x.4, F1x.5, F1x.6, F1x.7, F1x.8, F1x.9, F30.1, F30.2, F30.8, F30.9, F32.2, F32.3, F32.8, F32.9, F34.8 ,F34.9, F45.2, F45.4, F45.8, F45.9, F48.1, F48.8, F48.9, F50.4, F50.5, F53.1, F53.8, F53.9, F65.2, F65.3, F65.4, F65.6, F65.8, F65.9, F68.1, F68.8, F90.1) /

Known genetic hematopoietic diseases upon initial prescription of anticoagulant (ICD 10 Code: D55, D56 D57, D58, D61.0, D64.0, D64.4, D66, D67, D68.0, D68.1, D68.2, D71, D72.0, D74.0, D80.0, D82) /

Y69! diagnosis (Unspecified misadventure during surgical and medical care) in parallel with Y57.9! diagnosis /

Myopathy, myositis or muscle pain before initial prescription of cholesterol lowering agents (ICD 10 Code: M60.1, M60.8, M60.9, G72.0, M62.8, M62.9, M79.1, M79.7) /

Criteria due to TK customer management

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Addresses

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    • Bundesinstitut für Arzneimittel und Medizinprodukte
    • Ms.  Prof. Dr.  Julia C.  Stingl 
    • Kurt-Georg-Kiesinger-Allee 3
    • 53175  Bonn
    • Germany
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  • start of 1:1-Block address scientific-contact
    • Bundesinstitut für Arzneimittel und Medizinprodukte
    • Ms.  Prof. Dr.  Julia   Stingl 
    • Kurt-Georg-Kiesinger-Allee 3
    • 53175  Bonn
    • Germany
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    start of 1:1-Block address contact scientific-contact
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  • start of 1:1-Block address public-contact
    • EMPAR Hotline, TKgesundheit GmbH
    • -  -  - 
    • Mexikoring 33
    • 22297  Hamburg
    • Germany
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Sources of Monetary or Material Support

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    • Innovationsausschuss beim Gemeinsamen Bundesausschuss
    • Wegelystr. 8
    • 10623  Berlin
    • Germany
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Status

  •   Recruiting ongoing
  •   [---]*
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Trial Publications, Results and other Documents

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* This entry means the parameter is not applicable or has not been set.