Trial document




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  DRKS00016741

Trial Description

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Title

Exploratory study to assess frailty as a clinical marker for the plasma concentrations of the direct oral anticoagulants (Frailty-DOAK)

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Trial Acronym

Frailty-DOAK

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URL of the Trial

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Brief Summary in Lay Language

In geriatric medicine the term “frailty” is used to describe the age-related loss of physical strength and increased vulnerability to external stressors (e.g. diseases).
Many older patients take one of the so-called direct oral anticoagulants (DOACs: Pradaxa®, Xarelto®, Eliquis®, Lixiana®) for the prevention of blood clots and strokes. During the past years, this group of blood thinning drugs has become an alternative to the traditionally used vitamin K antagonists (e.g. warfarin).
Compared to patients of the same age but with better physical fitness, the body of older patients with "frailty" might process the intake of a DOAC differently. Therefore, the blood levels of the DOACs could be different in “frail” patients, e.g. higher. This could affect the efficacy and tolerability of these drugs.
Under medication with one of the DOACs the blood levels of these drugs are not routinely monitored. Therefore, it would be helpful to draw conclusions about the blood levels of the DOACs by means of a clinical assessment. The aim of this study is to investigate, whether in older patients the blood levels of the DOACs are associated with the degree of "frailty" of a patient.
Patients aged ≥70 years with regular intake of one of the four DOACs (Pradaxa®, Xarelto®, Eliquis®, Lixiana®) will be included in this study. By using four sets of assessments we will examine whether the participants are “frail”. Additionally, a single blood sample is drawn from each participant to determine the blood level of the routinely prescribed DOAC (Pradaxa®, Xarelto®, Eliquis® or Lixiana®).

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Brief Summary in Scientific Language

In geriatric medicine, the concept of frailty summarizes the age-associated loss of physical resources and the increasing vulnerability to external stressors.
Frailty has been identified as a prognostic marker for both morbidity and mortality in older patients. A gold standard for the diagnosis of frailty is yet to be defined. There are several instruments to assess frailty, with the “physical phenotype of frailty” by Fried et al. and the “frailty index” by Mitnitski and Rockwood being the most commonly used.

Frailty is associated with changes in the pharmacokinetics of drugs. In older “frail” patients with acute hip fracture prolonged elimination half-lives of the direct oral anticoagulants (DOACs) have been observed. This prolongation showed no correlation with the glomerular filtration rates of the participants. In recent years, the DOACs have emerged as an alternative to the vitamin K antagonists for the prevention of thromboembolic events in patients with non-valvular atrial fibrillation. Because the prevalence of atrial fibrillation increases with age, it is of great importance to guarantee the safe use of the DOACs in the older population and to identify patients with inadequately high plasma concentrations and consecutively increased risk for bleeding complications.
This exploratory study aims to evaluate the potential of different frailty assessments to act as a clinical marker for increased DOAC plasma concentrations in older patients. Patients aged ≥70 years with regular intake of one of the four DOACs (dabigatran, rivaroxaban, apixaban or edoxaban) will be included in this study. The participants will be characterized in relation to their frailty status by means of four different frailty assessments („Physical phenotype of frailty“ by Fried et al, Frailty Index, „Short Physical Performance Battery“, „FRAIL Scale“). A single blood sample will be collected from every participant in order to measure the plasma trough levels of the respective DOACs. The correlation between the different frailty assessments and the DOAC plasma trough concentrations will be analyzed.

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Organizational Data

  •   DRKS00016741
  •   2019/02/20
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  •   yes
  •   Approved
  •   S-866/2018, Ethik-Kommission I der Medizinischen Fakultät Heidelberg
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Secondary IDs

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Health Condition or Problem studied

  •   Frailty
  •   R54 -  Senility
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Interventions/Observational Groups

  •   Patients aged 70 years or older with regular intake of one of the direct oral anticoagulants (rivaroxaban, apixaban, edoxaban, dabigatran) will be assessed with four different frailty assessments („Physical phenotype of frailty“ by Fried et al, Frailty Index, „Short Physical Performance Battery“, „FRAIL Scale“). A single blood sample will be collected from every participant in order to measure the plasma trough levels of the respective DOACs.
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Characteristics

  •   Non-interventional
  •   Other
  •   Single arm study
  •   Open (masking not used)
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  •   Uncontrolled/Single arm
  •   Other
  •   Single (group)
  •   N/A
  •   N/A
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Primary Outcome

•Correlation of four frailty assessments with the plasma trough concentrations of four direct oral anticoagulants (dabigatran, rivaroxaban, apixaban, edoxaban)
-„Physical phenotype of frailty“ (Fried et al. 2001)
-Frailty Index (Searle et al. 2008)
-„FRAIL scale“ (Morley et al. 2012)
-„Short Physical Performance Battery“ (SPPB)
•Evaluation of the three groups „frail“, „pre-frail“ and „robust“ according to Fried et al. 2001 as to their ability to predict the plasma trough concentrations of the direct oral anticoagulants

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Secondary Outcome

•Correlation of selected functional parameters (e.g. gait speed, grip strength) with the plasma trough concentrations of four direct oral anticoagulants (dabigatran, rivaroxaban, apixaban, edoxaban)

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Countries of Recruitment

  •   Germany
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Locations of Recruitment

  • Medical Center 
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Recruitment

  •   Actual
  •   2019/02/27
  •   240
  •   Monocenter trial
  •   National
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Inclusion Criteria

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

•Age ≥70 years
•Regular intake of one of the direct oral anticoagulants dabigatran (Pradaxa®), rivaroxaban (Xarelto®), apixaban (Eliquis®) or edoxaban (Lixiana®) during the past ≥ 7 days
•Mentally and physically able to participate in the study (as judged by a member of the study group)
•Written informed consent

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Exclusion Criteria

•Insufficient knowledge of written and/or spoken German
•Inability to give informed consent

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Addresses

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    • Agaplesion Bethanien Krankenhaus Geriatrisches Zentrum der Universität Heidelberg
    • Mr.  Prof. Dr. med.  Jürgen M.  Bauer 
    • Rohrbacher Str. 149
    • 69126  Heidelberg
    • Germany
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    • Abteilung Klinische Pharmakologie und Pharmakoepidemiologie, Universitätsklinikum Heidelberg
    • Im Neuenheimer Feld 410
    • 69120  Heidelberg
    • Germany
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    • Agaplesion Bethanien Krankenhaus Geriatrisches Zentrum der Universität Heidelberg
    • Mr.  Prof. Dr. med.  Jürgen M.  Bauer 
    • Rohrbacher Str. 149
    • 69126  Heidelberg
    • Germany
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    • Agaplesion Bethanien Krankenhaus Geriatrisches Zentrum der Universität Heidelberg
    • Ms.  Dr. med.  Annette  Eidam 
    • Rohrbacher Str. 149
    • 69126  Heidelberg
    • Germany
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Sources of Monetary or Material Support

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    • Geriatrisches Zentrum der Universität Heidelberg
    • Rohrbacher Str. 149
    • 69126  Heidelberg
    • Germany
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Status

  •   Recruiting ongoing
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Trial Publications, Results and other Documents

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