Study Results
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View full resultsBasic Information
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COMPLETED
880 participants
OBSERVATIONAL
2018-08-22
2019-06-05
Brief Summary
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This trial is conducted to assess the performance and handling of the IVD for oral direct factor Xa and thrombin inhibitors from urine samples of patients on treatment with DOACs in an actual point-of-care setting in comparison to results obtained by liquid chromatography tandem mass spectrometry (LC-MS/MS) from urine samples.
"publication Thromb Haemost. 2019 Nov 8. doi: 10.1055/s-0039-1700545. \[Epub ahead of print\]"
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Detailed Description
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The trial investigates the sensitivity and specificity of a POCT for DOAC, i.e., the rate of correct positive, false positive, correct negative and false negative results in the point-of-care setting. The IVD is a test to determine absence or presence of DOAC in urine - Test A tests for oral direct factor Xa inhibitors (rivaroxaban, apixaban, and edoxaban), Test B for oral thrombin inhibitors (dabigatran).
Two groups of patients will be included:
* Test group A: Patients under therapy with oral direct factor Xa inhibitor (rivaroxaban, apixaban, and edoxaban) (n=440)
* Test group B: Patients under therapy with oral thrombin inhibitors (dabigatran) (n=440) No control group of patients not treated with a DOAC is required, as patients take either oral direct factor Xa inhibitors (Test group A) or oral thrombin inhibitors (Test group B), never both. Thus, patients in Test group A are negative for oral thrombin inhibitors and can serve as negative control for Test group B, and vice versa.
The point-of-care test (POCT) is a color-indicator diagnostic medical urine dipstick test for assessing the presence of oral direct factor Xa inhibitor (rivaroxaban, apixaban, and edoxaban) and thrombin inhibitors (dabigatran). The principle of the diagnostic test is based on the development of different colors on the indicator part of the dipstick in the presence or absence of oral direct factor Xa (rivaroxaban, apixaban, and edoxaban) and thrombin inhibitors (dabigatran). The colors for the test were chosen so that they could easily be read by the naked eye, with little possibility of incorrect identification of colors. The results for presence or absence will be compared with the concentration of DOAC analyzed by LC-MS/MS.
Two groups of medications (thrombin inhibitors, factor Xa inhibitors) will be tested with the IVD and test results compared to bioanalytical results in urine.
The objective of the investigation is to show that the proportion of false negative and false positive tests with the IVD is below 5%.
The required sample size to show that the assumed rate of 2.5% false-negative/false-positive tests is statistically significant lower than 5% would require 384 patients per each test group, with α=0.05 and β=0.20 (80% power). Accounting for a potential drop-out rate of 12%, a sample size of n=440 patients per test group was considered adequate to demonstrate adequate performance of the IVD. This sample size has been assessed with the SAS procedure PROC POWER (SAS Institute Inc., Cary, NC, USA, release 9.3) using the ONESAMPLEFREQ statement under the assumption that the test will be conducted as a 1-sided test with a null proportion of 0.05.
For each diagnostic test the proportions of false negative and false positive results will be assessed together with confidence intervals. The urine concentration serves as a gold standard. Furthermore, McNemar tests will be conducted in order to compare the sensitivity, the specificity, accuracy, negative predictive value, positive predictive value and likelihood probability of the two different medications. Kappa coefficients will be calculated in order to quantify the strength of agreement between two diagnostic test methods.
As the study design is not randomized the two groups will be compared according to biographic data (i.e. age, gender, concentration in urine) by common statistical tests (Chi2 test, t-test) in order to investigate their equality. In the case of differences between groups statistical adjustment will be done (i.e. propensity score) in order to avoid the influence of a bias.
The Performance Assessment will be conducted at the patient's family doctor or medical practice/outpatient care unit (referred to as "investigational site" in the following).
The Performance Assessment will consist of a single visit, which is performed during a routine visit at the investigational site.
The Performance Assessment starts with first patient signing informed consent (FPFV) and ends with the last patient providing the last sample (last patient last visit, LPLV).
"publication Thromb Haemost. 2019 Nov 8. doi: 10.1055/s-0039-1700545. \[Epub ahead of print\]"
Conditions
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Study Design
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OTHER
PROSPECTIVE
Study Groups
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Factor Xa inhibitor
Patients on treatment with Apixaban, Edoxaban or Rivaroxaban are included into the evaluation study at the outpatient care unit. Patients receive treatment for a specific clinical indication such as non-valvular atrial fibrillation or venous thromboembolism since one week or longer. During the study visit DOAC Dipstick test and liquid-chromatography mass-specrotmery are performed to identify absence or presence of Factor Xa inhibitor in urine.
"publication Thromb Haemost. 2019 Nov 8. doi: 10.1055/s-0039-1700545. \[Epub ahead of print\]"
DOAC Dipstick
Patients collect a sample of urine for analysis.
"publication Thromb Haemost. 2019 Nov 8. doi: 10.1055/s-0039-1700545. \[Epub ahead of print\]"
Thrombin inhibitor
Patients on treatment with Dabigatran are included included into the evaluation study at the outpatient care unit. Patients receive treatment for a specific clinical indication such as non-valvular atrial fibrillation or venous thromboembolism since one week or longer. During the study visit DOAC Dipstick test and liquid-chromatography mass-specrotmery are performed to identify absence or presence of Thrombin inhibitor in urine.
"publication Thromb Haemost. 2019 Nov 8. doi: 10.1055/s-0039-1700545. \[Epub ahead of print\]"
DOAC Dipstick
Patients collect a sample of urine for analysis.
"publication Thromb Haemost. 2019 Nov 8. doi: 10.1055/s-0039-1700545. \[Epub ahead of print\]"
Interventions
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DOAC Dipstick
Patients collect a sample of urine for analysis.
"publication Thromb Haemost. 2019 Nov 8. doi: 10.1055/s-0039-1700545. \[Epub ahead of print\]"
Other Intervention Names
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Eligibility Criteria
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Inclusion Criteria
* Age \>18 years
* Patient is either under therapy with rivaroxaban, apixaban, and edoxaban or dabigatran for at least 1 week
Exclusion Criteria
* Patients not able to understand the informed consent or severe mentally disabled.
* Patients in the end-stage of a severe disease.
"publication Thromb Haemost. 2019 Nov 8. doi: 10.1055/s-0039-1700545. \[Epub ahead of print\]"
18 Years
ALL
No
Sponsors
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CRS Clinical Research Services Mannheim GmbH
INDUSTRY
Heidelberg University
OTHER
Medical Care Center Dr. Limbach and Colleagues, Heidelberg, Germany
OTHER
Doasense GmbH
INDUSTRY
Responsible Party
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Principal Investigators
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Job Harenberg, Professor
Role: PRINCIPAL_INVESTIGATOR
Pneumonologische Schwerpunktpraxis Heidelberg, Privatpraxis Harenberg
Locations
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Universitätsherzzentrum Bad Krozingen, Klinik für Kardiologie und Angiologie II
Bad Krozingen, , Germany
Herz- und Diabeteszentrum NRW, Klinik für Kardiologie
Bad Oeynhausen, , Germany
Vivantes Klinikum im Friedrichshain
Berlin, , Germany
Gerinnungszentrum Sucker
Berlin, , Germany
Vivantes Klinikum Neukölln
Berlin, , Germany
Klinikum Coburg GmbH, II. Medizinische Klinik
Coburg, , Germany
Krankenhaus der Augustinerinnen gGmbH, Klinik für Kardiologie und internistische Intensivmedizin
Cologne, , Germany
Klinikum Darmstadt - Gefäßzentrum
Darmstadt, , Germany
Praxis Innere Medizin, Kardiologie und Angiologie
Dessau, , Germany
Städtisches Klinikum Dresden, II. Medizinische Klinik
Dresden, , Germany
Medizinische Fakultät Carl Gustav Carus, Medizinische Klinik und Poliklinik I
Dresden, , Germany
Cardioangiologisches Centrum Bethanien
Frankfurt, , Germany
Klinik für Kardiologie und Angiologie I
Freiburg im Breisgau, , Germany
Universitätsklinikum Hamburg-Eppendorf, II. Medizinische Klinik und Poliklinik
Hamburg, , Germany
Kliniken Landkreis Heidenheim
Heidenheim, , Germany
Zentrum für Blutgerinnungsstörungen, MVZ Labor Dr. Reising-Ackermann und Kollegen
Leipzig, , Germany
Zentrum für Praevention und Rehabilitation
Siegen, , Germany
Die Parkkardiologie
Stahnsdorf, , Germany
Countries
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References
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Harenberg J, Du S, Wehling M, Zolfaghari S, Weiss C, Kramer R, Walenga J. Measurement of dabigatran, rivaroxaban and apixaban in samples of plasma, serum and urine, under real life conditions. An international study. Clin Chem Lab Med. 2016 Feb;54(2):275-83. doi: 10.1515/cclm-2015-0389.
Du S, Weiss C, Christina G, Kramer S, Wehling M, Kramer R, Harenberg J. Determination of dabigatran in plasma, serum, and urine samples: comparison of six methods. Clin Chem Lab Med. 2015 Jul;53(8):1237-47. doi: 10.1515/cclm-2014-0991.
Harenberg J, Du S, Kramer S, Weiss C, Kramer R, Wehling M. Patients' serum and urine as easily accessible samples for the measurement of non-vitamin K antagonist oral anticoagulants. Semin Thromb Hemost. 2015 Mar;41(2):228-36. doi: 10.1055/s-0035-1544158. Epub 2015 Feb 15.
Harenberg J, Schreiner R, Hetjens S, Weiss C. Detecting Anti-IIa and Anti-Xa Direct Oral Anticoagulant (DOAC) Agents in Urine using a DOAC Dipstick. Semin Thromb Hemost. 2019 Apr;45(3):275-284. doi: 10.1055/s-0038-1668098. Epub 2018 Aug 22.
Harenberg J, Beyer-Westendorf J, Crowther M, Douxfils J, Elalamy I, Verhamme P, Bauersachs R, Hetjens S, Weiss C; Working Group Members. Accuracy of a Rapid Diagnostic Test for the Presence of Direct Oral Factor Xa or Thrombin Inhibitors in Urine-A Multicenter Trial. Thromb Haemost. 2020 Jan;120(1):132-140. doi: 10.1055/s-0039-1700545. Epub 2019 Nov 8.
Provided Documents
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Document Type: Study Protocol
Document Type: Statistical Analysis Plan
Related Links
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Homepage DOASENSE GmbH
Other Identifiers
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DOA-CS-002
Identifier Type: -
Identifier Source: org_study_id
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