In Vitro Diagnostic Test for DOAC in Urine

Anticoagulant Therapy Clinical Trial

— PADOASU  

Official title:

Post Marketing Study of an in Vitro Diagnostic Test for Direct Oral Anticoagulants (Apixaban, Edoxaban, Rivaroxaban, Dabigatran) in Urine

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03182829
• Other study ID #: DOA-CS-002
• Status: Completed
• Start date: August 22, 2018
• Est. completion date: June 5, 2019

Study information

• Verified date: March 2022
• Source: Doasense GmbH
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

This trial is conducted to assess the performance and handling of the in vitro diagnostic (IVD) device for oral direct factor Xa and thrombin inhibitors from urine samples of patients on treatment with direct oral anticoagulants Apixaban, Edoxaban, Rivaroxaban, and Dabigatran (DOAC) in an actual point-of-care (POCT) setting in comparison to results obtained by liquid chromatography tandem mass spectrometry (LC-MS/MS) from urine samples.

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]"

Description:

This prospective, open-label, controlled, not randomized Performance Assessment will be conducted as a multicenter Performance Assessment in Germany.

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]"

Recruitment information / eligibility

• Status: Completed
• Enrollment: 880
• Est. completion date: June 5, 2019
• Est. primary completion date: April 9, 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Fully signed and dated written informed consent

• 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 provide urine samples.

• 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]"

Related Conditions & MeSH terms

• Anticoagulant Therapy

Intervention

Diagnostic Test:
• 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]"

Locations

Country	Name	City	State
Germany	Universitätsherzzentrum Bad Krozingen, Klinik für Kardiologie und Angiologie II	Bad Krozingen
Germany	Herz- und Diabeteszentrum NRW, Klinik für Kardiologie	Bad Oeynhausen
Germany	Gerinnungszentrum Sucker	Berlin
Germany	Vivantes Klinikum im Friedrichshain	Berlin
Germany	Vivantes Klinikum Neukölln	Berlin
Germany	Klinikum Coburg GmbH, II. Medizinische Klinik	Coburg
Germany	Klinikum Darmstadt - Gefäßzentrum	Darmstadt
Germany	Praxis Innere Medizin, Kardiologie und Angiologie	Dessau
Germany	Medizinische Fakultät Carl Gustav Carus, Medizinische Klinik und Poliklinik I	Dresden
Germany	Städtisches Klinikum Dresden, II. Medizinische Klinik	Dresden
Germany	Cardioangiologisches Centrum Bethanien	Frankfurt
Germany	Klinik für Kardiologie und Angiologie I	Freiburg
Germany	Universitätsklinikum Hamburg-Eppendorf, II. Medizinische Klinik und Poliklinik	Hamburg
Germany	Kliniken Landkreis Heidenheim	Heidenheim
Germany	Krankenhaus der Augustinerinnen gGmbH, Klinik für Kardiologie und internistische Intensivmedizin	Köln
Germany	Zentrum für Blutgerinnungsstörungen, MVZ Labor Dr. Reising-Ackermann und Kollegen	Leipzig
Germany	Zentrum für Praevention und Rehabilitation	Siegen
Germany	Die Parkkardiologie	Stahnsdorf

Sponsors (4)

Lead Sponsor	Collaborator
Doasense GmbH	Clinical Research Services, Mannheim, Germany, Institute Medical Statistics, Medical Faculty Mannheim, Medical Care Center Dr. Limbach and Colleagues, Heidelberg, Germany

Country where clinical trial is conducted

Germany, 

References & Publications (5)

Du S, Weiss C, Christina G, Krämer S, Wehling M, Krämer 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. — View Citation

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 Multic — View Citation

Harenberg J, Du S, Krämer S, Weiss C, Krämer 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. Review. — View Citation

Harenberg J, Du S, Wehling M, Zolfaghari S, Weiss C, Krämer 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. — View Citation

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Accuracy of Factor Xa and Thrombin Inhibitors Pads of DOAC Dipstick From Urine Samples	Liquid chromatography mass spectrometry versus DOAC Dipstick, qualitative analysis of results	during urine collection and bioanalytical quantification, any time between August 2018 and April 2019

External Links

•   Homepage DOASENSE GmbH