Post Marketing Study of an in Vitro Diagnostic Test for Direct Oral Anticoagulants (Apixaban, Edoxaban, Rivaroxaban, Dabigatran) in Urine
Conditions: Anticoagulant Therapy
Sponsor: Doasense GmbH

 
CRS Study No.:  
177/16-09.DE 
Sponsor Study No.: 
DOA-CS-002 
ClinicalTrials.gov ID: NCT03182829 
 
Post Marketing Study Plan, Version 7.0, 04 May 2018 
 Page 1 of 31 
Post Marketing Study Plan 
Post Marketing Study of an in vitro diagnostic test for direct oral 
anticoagulants (Apixaban, Edoxaban, Rivaroxaban, Dabigatran) in urine 
Version: 
Version 7.0, 04 May 2018  
Previous Version: 
N/A  
 
Identifier: 
CRS Study No.:  
177/16-09.DE 
Sponsor Study No.: 
DOA-CS-002 
ClinicalTrials.gov ID: NCT03182829 
Lead Investigator: 
Prof. Dr. med. Job Harenberg 
Privatpraxis 
Handschuhsheimer Landstrasse 62 
69121 Heidelberg, Germany 
Phone: 
+49 (0) 6221-484110 
 
+49 (0) 6221-825 9785 
Fax: 
+49 (0) 6221-472655 
E-Mail: 
 j.harenberg@doasense.de 
Sponsor: 
DOASENSE GmbH 
Waldhofer Strasse 102 
69123 Heidelberg, Germany 
Phone: 
+49 (0) 6221-825 9785 
Fax: 
+49 (0) 6221-825 9786 
The Post Marketing Study will be carried out and essential documents will be kept and 
archived in accordance with Good Clinical Practice Guideline. 
This document is a confidential communication of the sponsor.  
No unpublished information contained herein will be published or disclosed without prior approval by the 
sponsor. However, this document can be disclosed to authorized representatives of national or international 
regulatory authorities under the condition that they respect its confidential nature. 
 

I .ICRS-MANNHEIM 
.,rclinical Research Services
CRS Study .No.: 
111/16-09.DE 
Sponsor Study No.: 
DOA-CS-002 
ClinicalTrials.gov ID: NCT03182829 
1 
Approval of the Post Marketing Study 
By signing below, the signatories agree to conduct the Post Marketing Study 
according to this Study Plan. 
1.1 
Sponsor 
Prof. Dr. fob Harenber 
Managing Director 
DOASENSE GmbH 
1.2 
Lead Investigator 
Post Marketing Study Plan , Version 7.0, 04May 2018 
Date 
Page 2 of 31 

 
CRS Study No.:  
177/16-09.DE 
Sponsor Study No.: 
DOA-CS-002 
ClinicalTrials.gov ID: NCT03182829 
 
Post Marketing Study Plan, Version 7.0, 04 May 2018 
 Page 4 of 31 
2 
Synopsis 
Title of the clinical 
investigation: 
Post Marketing Study of an in vitro diagnostic test for direct oral 
anticoagulants (Apixaban, Edoxaban, Rivaroxaban, Dabigatran) in 
urine 
Objectives: 
Assess the accuracy and specificity of the in vitro diagnostic (IVD) 
test for oral direct Factor Xa and Thrombin inhibitors from urine 
samples of patients 
Diagnosis and main 
criteria for inclusion: 
Adult patients (>18 years) either under therapy with Rivaroxaban, 
Apixaban, and Edoxaban, or with Dabigatran for at least 1 week 
Design: 
Prospective, open-label, controlled, not-randomized, multicenter 
Methodology: 
Comparison of the test strip results after visual reading and 
reflectance photometric reading to the results of bioanalytical 
quantification of Rivaroxaban, Apixaban, and Edoxaban or 
Dabigatran 
Blinding: 
Not applicable. 
Control: 
Patients taking oral direct Factor Xa inhibitors (Test group A) are 
negative for an oral Thrombin inhibitor and can serve as negative 
control for Test group B (test for oral Thrombin inhibitor), and vice 
versa 
Number of patients: 
880 (n=440 under therapy with oral direct Factor Xa inhibitor, n=440 
under therapy with oral Thrombin inhibitor) 
Test products: 
Direct oral anticoagulant (DOAC) urine dipstick test 
Primary endpoints: 
True positive and true negative rate of the point of care test (POCT) 
by comparison with the results obtained by bioanalytical 
quantification 
Secondary endpoints: 
Investigator readings of POCT test results as compared to LC-
MS/MS 
Results obtained by the reflectance photometric reading 
(DOASENSE Reader) as compared to naked eye reading 
Results of the questionnaire 
Plan for statistical 
analyses: 
For each diagnostic test the proportions of false negative and false 
positive results will be assessed together with confidence intervals.  
 

 
CRS Study No.:  
177/16-09.DE 
Sponsor Study No.: 
DOA-CS-002 
ClinicalTrials.gov ID: NCT03182829 
 
Post Marketing Study Plan, Version 7.0, 04 May 2018 
 Page 5 of 31 
Table 2-1: Assessments at the visit  
Assessment 
Day 1 
Informed consent 
X 
Demographic data 
X 
Medication history (DOACs, other) 
X 
Collection of urine sample 
X 
Visual reading presence/absence of DOACs (IVD) 
X 
Reflectance photometric reading (DOASENSE Reader) of the 
dipstick 
X 
Urine aliquot for bioanalysis 
X 
Completion of questionnaire 
X 
DOACs: direct oral anticoagulants, IVD: in vitro diagnostic test 

CRS Study No.:  
177/16-09.DE 
Sponsor Study No.: 
DOA-CS-002 
ClinicalTrials.gov ID: NCT03182829 
Post Marketing Study Plan, Version 7.0, 04 May 2018 
 Page 6 of 31 
3 
Table of contents 
1 
APPROVAL OF THE POST MARKETING STUDY 
2 
1.1 
Sponsor 
2 
1.2 
Lead Investigator 
2 
1.3 
Investigator at participating site 
3 
2 
SYNOPSIS 
4 
3 
TABLE OF CONTENTS 
6 
4 
ABBREVIATIONS 
9 
5 
ETHICS AND LEGAL ASPECTS 
10 
5.1 
Ethics Committee and Competent Authority 
10 
5.2 
Ethical conduct of the Post Marketing Study 
10 
5.3 
Patient Information and procedure for obtaining consent 
10 
5.4 
Data protection and data access 
11 
5.5 
Compliance statement 
11 
6 
KEY PERSONNEL INVOLVED IN THE POST MARKETING STUDY 
12 
7 
INTRODUCTION 
13 
7.1 
Background and test principle 
13 
7.2 
Description of the in vitro diagnostic test 
14 
7.3 
Rationale of the Post Marketing Study 
14 
7.4 
Risks and benefits of the investigational device and Post Marketing Study 
procedures 
14 
8 
CLINICAL INVESTIGATION OBJECTIVES AND ENDPOINTS 
15 
8.1 
Primary objective 
15 
8.2 
Secondary objectives 
15 
9 
DESIGN OF THE POST MARKETING STUDY 
16 

CRS Study No.:  
177/16-09.DE 
Sponsor Study No.: 
DOA-CS-002 
ClinicalTrials.gov ID: NCT03182829 
Post Marketing Study Plan, Version 7.0, 04 May 2018 
 Page 7 of 31 
9.1 
Overall design and plan-description of the Post Marketing Study 
16 
9.2 
Discussion of Post Marketing Study design, including the choice of control 
groups 
17 
9.3 
Selection of population 
17 
9.3.1 
Inclusion criteria 
17 
9.3.2 
Exclusion criteria 
18 
9.3.3 
Discontinuation of patients from treatment or assessment 
18 
9.3.4 
Patient replacement 
18 
9.3.5 
Premature discontinuation of the Post Marketing Study 
18 
9.3.6 
Patient identification 
18 
9.4 
Identification and description of the In vitro Diagnostic Test 
19 
9.4.1 
Identification, traceability and labelling of the In vitro Diagnostic Test 
19 
9.4.2 
Emergency procedures 
19 
9.4.3 
Method of assigning patients to test arms 
19 
9.4.4 
Blinding 
20 
9.4.5 
Restrictions and precautions 
20 
9.5 
Procedures and assessments related to the Post Marketing Study 
20 
9.5.1 
Visit description 
20 
9.5.2 
Population characteristics 
21 
9.5.3 
Performance endpoints 
21 
9.5.4 
Safety endpoints 
24 
9.5.5 
Anticipated adverse device effects 
25 

CRS Study No.:  
177/16-09.DE 
Sponsor Study No.: 
DOA-CS-002 
ClinicalTrials.gov ID: NCT03182829 
Post Marketing Study Plan, Version 7.0, 04 May 2018 
 Page 8 of 31 
9.6 
Statistical methods and determination of sample size 
25 
9.6.1 
Statistical and analytical plans 
25 
9.6.2 
Sample size determination 
25 
10 DATA COLLECTION 
26 
10.1 
Case Report Form and Questionnaire 
26 
10.2 
Document and data control 
26 
10.3 
Source data 
26 
10.4 
Data management 
26 
10.5 
Document retention 
27 
11 QUALITY ASSURANCE AND QUALITY CONTROL, AUDITS, AND 
INSPECTIONS 
27 
11.1 
Quality control and quality assurance 
27 
11.2 
Monitoring 
27 
11.3 
Audit 
27 
11.4 
Inspection 
28 
12 CONFIDENTIALITY OF PATIENT DATA 
28 
13 POST MARKETING STUDY REPORT 
29 
14 PUBLICATION POLICY 
29 
15 INSURANCE 
29 
16 RESPONSIBILITIES AND FINANCES 
29 
17 REFERENCES 
30 
18 AMENDMENTS 
30 
19 APPENDIX 
31 

 
CRS Study No.:  
177/16-09.DE 
Sponsor Study No.: 
DOA-CS-002 
ClinicalTrials.gov ID: NCT03182829 
 
Post Marketing Study Plan, Version 7.0, 04 May 2018 
 Page 9 of 31 
4 
Abbreviations 
 
BfArM 
Federal Institute for Drugs and Medical Devices (Bundesinstitut für 
Arzneimittel und Medizinprodukte) competent authority 
BMI 
Body mass index, calculated as body weight [kg] divided by the 
square of the body height [m] 
CA 
Competent Authority 
CE 
Certification (Conformité Européene [European Conformity]) 
CRF 
Case Report Form 
DIN EN 
German Industrial Standard European Standard (Deutsche 
Industrienorm Euronorm) 
DOAC 
Direct oral anticoagulant 
EC 
Ethics Committee 
FPFV 
First Patient First Visit  
IVD 
In vitro diagnostic 
LC-MS/MS 
Liquid chromatography-tandem mass spectrometry 
LPLV 
Last Patient Last Visit 
MPG 
German Act on Medical Devices (Medizinproduktegesetz) 
PID 
Patient identification number 
POCT 
Point-of-care test 
SOP 
Standard operating procedure 
 

 
CRS Study No.:  
177/16-09.DE 
Sponsor Study No.: 
DOA-CS-002 
ClinicalTrials.gov ID: NCT03182829 
 
Post Marketing Study Plan, Version 7.0, 04 May 2018 
 Page 10 of 31 
5 
Ethics and legal aspects 
5.1 
Ethics Committee and Competent Authority 
This Post Marketing Study will be submitted to 
 the competent authority (CA, Bundesinstitut für Arzneimittel und 
•
Medizinprodukte, BfArM [Federal Institute for Drugs and Medical Devices]) 
for notification, and 
 to the responsible Ethics Committee (EC) for medical professional consultation  
•
according to the applicable regulatory and legal requirements.  
No approval is required as per §23 b, German Act on Medical Devices 
(Medizinproduktegesetz, MPG), as no invasive sampling or treatment is planned. 
Both bodies will be notified if there are substantial changes in the planned 
assessment. 
5.2 
Ethical conduct of the Post Marketing Study  
The Post Marketing Study will be performed in accordance with the ethical 
principles that have their origin in the Declaration of Helsinki.  
5.3 
Patient Information and procedure for obtaining consent 
The investigator or sub-investigator of the investigational site (i.e., the patient’s 
family doctor or medical practice/outpatient care unit) will inform patients about 
all aspects of the Post Marketing Study, in particular about the characteristics and 
objectives, duration and extent of participation, about test methods used.  
The information will be non-technical language, and patients will be able to ask 
questions. 
Informed consent has to be given voluntarily and in writing. 
Patients will also be informed about the anticipated risks and benefits, data 
protection and access to their personal data in the context of the Post Marketing 
Study.  
Patients and investigators (or sub-investigator) have to sign the informed consent 
twice, one original will be given to the patient, and one will remain with the 
investigator. 

 
CRS Study No.:  
177/16-09.DE 
Sponsor Study No.: 
DOA-CS-002 
ClinicalTrials.gov ID: NCT03182829 
 
Post Marketing Study Plan, Version 7.0, 04 May 2018 
 Page 11 of 31 
5.4 
Data protection and data access 
The investigator and the patient will agree in writing to the direct access to patient 
data to examine, analyze, verify, and reproduce any records that are important to 
the assessment of the Post Marketing Study.  
All parties granted access to the data agree to take any precaution necessary to 
ensure the confidentiality of the patient’s data and the sponsor’s proprietary 
information.  
All clinical investigation related records and data of the patients will be 
pseudonymized.  
Each patient will receive a unique patient identification number (PID) identifying 
the patient in the investigation site’s patient database and identified in the clinical 
investigation with a specific identifier (e.g., random number or participant 
number). 
The investigator ensures that any documents or data disclosed to the sponsor do 
not contain any information disclosing the identity of the patient.  
5.5 
Compliance statement 
This Post Marketing Study will be conducted and reported in accordance to the 
current versions of 
 Ethical principles that have their origin in the Declaration of Helsinki, 1964,  
•
 In vitro diagnostic medical device directive 98/79/European Community 
•
 German Act on Medical Devices, and the German medical device ordinance 
•
(Medizinprodukteverordnung) 
 DIN EN 13612 Performance Assessment of in vitro diagnostic medical devices  
•
as applicable. 

 
CRS Study No.:  
177/16-09.DE 
Sponsor Study No.: 
DOA-CS-002 
ClinicalTrials.gov ID: NCT03182829 
 
Post Marketing Study Plan, Version 7.0, 04 May 2018 
 Page 12 of 31 
6 
Key personnel involved in the Post Marketing Study   
Sponsor 
DOASENSE GmbH 
Waldhofer Strasse 102 
69123 Heidelberg, Germany 
 
Sponsor’s representative 
Prof. Dr. med. Job Harenberg 
DOASENSE GmbH 
Waldhofer Strasse 102 
69123 Heidelberg, Germany 
Phone: 
+49 (0) 6221-825 9785 
Fax: 
+49 (0) 6221-825 9786 
Mobile: +49 (0) 172 62 36 014 
Email: 
j.harenberg@doasense.de 
 
Statistics 
Prof. Dr. Christel Weiß, Dipl Math 
Medical Statistics, Biomathematics, and Information Processing 
Medical Faculty Mannheim of the University of Heidelberg 
Ludolf-Krehl-Straße 13-17 
68167 Mannheim, Germany 
Phone: 
+49 (0) 621 383 – 9901/9904 
Fax: 
+49 (0) 621 383 – 9909 
 
Lead investigator 
Prof. Dr. med. Job Harenberg 
Privatpraxis 
Handschuhsheimer Landstrasse 62 
69121 Heidelberg, Germany 
Phone: 
+49 (0) 6221-484110 
 
+49 (0) 6221-825 9785 
Fax: 
+49 (0) 6221-472655 
Mobile: +49 (0) 172 62 36 014 
Email: 
j.harenberg@doasense.de 

 
CRS Study No.:  
177/16-09.DE 
Sponsor Study No.: 
DOA-CS-002 
ClinicalTrials.gov ID: NCT03182829 
 
Post Marketing Study Plan, Version 7.0, 04 May 2018 
 Page 13 of 31 
Medical Science Liason 
Dr. med. Uwe Spannagel 
Mariannhillstraße 2c 
97074 Würzburg, Germany 
Phone: 
+49 (0) 931 320 77 75 
Fax: 
+49 (0) 931 320 77 76 
e-mail: 
u.spannagel@doasense.de 
The sponsor and the lead investigator will approve and sign the Post Marketing 
Study including its amendments. 
Each investigator will sign the Post Marketing Study Plan including its 
amendments. 
The investigator at the study site may delegate tasks to adequately trained 
personnel. A list of personnel and tasks will be maintained at the respective site. 
7 
Introduction 
7.1 
Background and test principle 
The in vitro diagnostic (IVD) test assessed in this study is a dipstick to test for 
absence or presence of direct oral anticoagulants (DOACs) in urine.  
The test can be of value in clinical situations, where establishing the absence or 
presence of DOACs in the patient prior to procedures is important for clinical 
decision making, such as emergency procedures, stroke (before starting 
thrombolytic therapy), trauma, general surgery or other invasive procedures. 
Trained personnel can perform the test and results are rapidly available. 
The point-of-care test (POCT) is a color-indicator diagnostic medical urine 
dipstick test for assessing the presence of oral direct Factor Xa inhibitors 
(Rivaroxaban, Apixaban, and Edoxaban) and Thrombin inhibitor (Dabigatran). 
These DOACs show a high renal clearance by immediate glomerular filtration – 
which allows testing for these substances in urine when they are present in blood. 
Chromogenic assays in urine showed a high sensitivity and specificity, and a low 
inter-observer variability [1][2]. 

 
CRS Study No.:  
177/16-09.DE 
Sponsor Study No.: 
DOA-CS-002 
ClinicalTrials.gov ID: NCT03182829 
 
Post Marketing Study Plan, Version 7.0, 04 May 2018 
 Page 14 of 31 
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 [1]. 
7.2 
Description of the in vitro diagnostic test 
The dipstick test consists of a plastic strip with 4 indicator test pads (Figure 7-1): 
 
 
Figure 7-1: Schematic representation of DOAC Dipstick 
The container contains a reference color scale for the visual comparison of the test 
results.  
7.3 
Rationale of the Post Marketing Study  
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.  
7.4 
Risks and benefits of the investigational device and Post Marketing Study 
procedures 
No interventions or invasive procedures in the patients are planned. 
The patients will not have additional risks due to participation in the investigation, 
and will not benefit directly by participating. Only patients who already take oral 
direct Factor Xa or Thrombin inhibitors will be included into the trial. They will 
provide a spontaneous urine sample for testing and will not come into contact 
with the test itself.  

 
CRS Study No.:  
177/16-09.DE 
Sponsor Study No.: 
DOA-CS-002 
ClinicalTrials.gov ID: NCT03182829 
 
Post Marketing Study Plan, Version 7.0, 04 May 2018 
 Page 15 of 31 
8 
Clinical investigation objectives and endpoints 
8.1 
Primary objective 
Primary objective of the investigation is to  
 Assess the accuracy and specificity of the IVD for oral direct Factor Xa and 
•
Thrombin inhibitors from urine samples of patients 
Primary endpoint:  
 True positive and true negative rate of the POCT by comparison with the 
•
results obtained by bioanalytical quantification 
8.2 
Secondary objectives 
Secondary objectives of the investigation are:  
 Comparison of the investigator-assessed POCT results with the results obtained 
•
by reflectance photometric reading (DOASENSE Reader) 
 Determination of the sensitivity and specificity of the results of the reflectance 
•
photometric reading (DOASENSE Reader) by means of concentrations of 
Rivaroxaban, Apixaban, Edoxaban and Dabigatran determined by LC-MS/MS 
 Investigate the handling and usability of the IVD for oral direct Factor Xa and 
•
Thrombin inhibitors in clinical setting using a questionnaire for the  
investigator / sub-investigator 
Secondary endpoints:  
 Investigator readings of POCT test results 
•
 Results obtained by the reflectance photometric reading (DOASENSE Reader) 
•
 Concentrations of Rivaroxaban, Apixaban, Edoxaban and Dabigatran 
•
determined by LC-MS/MS 
 Results of the questionnaire 
•

 
CRS Study No.:  
177/16-09.DE 
Sponsor Study No.: 
DOA-CS-002 
ClinicalTrials.gov ID: NCT03182829 
 
Post Marketing Study Plan, Version 7.0, 04 May 2018 
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9 
Design of the Post Marketing Study  
9.1 
Overall design and plan-description of the Post Marketing Study  
This prospective, open-label, controlled, not randomized Post Marketing Study 
will be conducted as a multicenter Post Marketing Study in Germany.  
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 an oral Thrombin inhibitor 
•
(Dabigatran) (n=440) 
The Post Marketing Study will be conducted at the patient’s family doctor or 
medical practice/outpatient care unit (referred to as “investigational site” in the 
following).  
The Post Marketing Study will consist of a single visit, which is performed during 
a routine visit at the investigational site.  
The Post Marketing Study starts with first patient signing informed consent 
(FPFV) and ends with the last patient providing the last sample (last patient last 
visit, LPLV). 
Patients fulfilling the criteria described in Sections 9.3.1 and 9.3.2 will be 
included in the Post Marketing Study after having given informed consent. 
Each patient will participate for approximately 1 h in the Post Marketing Study. 
Medical personnel at the site will record the patient’s demographic data (see 
Section 9.5.2).  
Patients will provide a sample of spontaneous urine.  
The urine samples will be tested in the outpatient care unit with the IVD and the 
DOASENSE Reader. In addition, aliquots of urine will be analyzed by LC-
MS/MS. 
The personnel performing the test will complete a questionnaire on handling of 
the IVD. 
Primary endpoints are described in Section 8.1. 

 
CRS Study No.:  
177/16-09.DE 
Sponsor Study No.: 
DOA-CS-002 
ClinicalTrials.gov ID: NCT03182829 
 
Post Marketing Study Plan, Version 7.0, 04 May 2018 
 Page 17 of 31 
9.2 
Discussion of Post Marketing Study design, including the choice of control 
groups  
This clinical Post Marketing Study investigates the sensitivity and specificity of a 
POCT for DOACs, 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 DOACs in urine – Test A 
(pad 3) tests for oral direct Factor Xa inhibitors (Rivaroxaban, Apixaban, and 
Edoxaban), Test B (pad 4) for an oral Thrombin inhibitor (Dabigatran).  
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 an oral Thrombin 
inhibitor (Test group B), never both. Thus, patients in Test group A are negative 
for an oral Thrombin inhibitor and can serve as negative control for Test group B, 
and vice versa. 
The presence or absence of oral direct Factor Xa inhibitors or an oral Thrombin 
inhibitor will be determined with 3 methods: 
 Naked-eye reading by the investigator or delete by comparing the colors after 
•
end of the reactions to the reference color scale 
 Reflectance photometric reading using the DOASENSE Reader 
•
 Analysis of the concentrations of Rivaroxaban, Apixaban, Edoxaban and 
•
Dabigatran LC-MS/MS in urine. The sensitivity and specificity of this method 
is at least 98% [1][2].  
9.3 
Selection of population  
The patients participating in this Post Marketing Study will be recruited directly at 
the point of care, i.e., the respective outpatient care unit. Only patients fulfilling 
all of the inclusion criteria and none of the exclusion criteria will be included. 
9.3.1 
Inclusion criteria 
 Patient is able to understand and follow instructions of the study 
•
 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 

 
CRS Study No.:  
177/16-09.DE 
Sponsor Study No.: 
DOA-CS-002 
ClinicalTrials.gov ID: NCT03182829 
 
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 Page 18 of 31 
9.3.2 
Exclusion criteria 
Only patients fulfilling none of the criteria below will be included: 
 Patient not able to provide urine samples. 
•
 Patient not able to understand the informed consent or severe mentally 
•
disabled. 
 Patients in the end-stage of a severe disease. 
•
9.3.3 
Discontinuation of patients from treatment or assessment 
Patients are free to withdraw their participation any time following written 
informed consent. The data of these patients will be discarded and eliminated 
from the assessment (drop-out patients). 
9.3.4 
Patient replacement 
Not applicable.  
9.3.5 
Premature discontinuation of the Post Marketing Study  
The sponsor has the right to terminate the entire Post Marketing Study or parts 
thereof at any time.  
The investigator has the right to terminate participation in the Post Marketing 
Study at any time. 
A premature termination must be discussed between the involved parties before 
becoming effective. 
There are no statistical criteria for clinical investigation termination. 
9.3.6 
Patient identification 
Patients will be identified by their medical records of the investigational site. 
With signing of informed consent, the patients will be assigned a specific 
identification number for the Post Marketing Study.  
The investigator will maintain a patient identification log, which lists all patients 
enrolled in the Post Marketing Study, with an identification code linked to their 
names, alternative identification or contact information. This list will not be 
provided to the sponsor. 

 
CRS Study No.:  
177/16-09.DE 
Sponsor Study No.: 
DOA-CS-002 
ClinicalTrials.gov ID: NCT03182829 
 
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9.4 
Identification and description of the In vitro Diagnostic Test 
9.4.1 
Identification, traceability and labelling of the In vitro Diagnostic Test 
Table 9-1: DOAC urine test strip 
Name: 
DOAC Dipstick 
Manufacturer: 
DOASENSE GmbH, Heidelberg 
Model/Type: 
DOASENSE REF Number: 0001 
Lot number: 
DS 18021901 
Expiration date: 
2018 08 
Intended use: 
Urine dipstick to test for presence or absence of DOACs 
Contraindications: 
known intolerance to DOACs 
CE certification: 
CE marked DIMDI registration number: DE/CA 
38/00141004 
Packaging: 
Container (12 test strips) including reference color chart 
CE: Certification (Conformité Européene [European Conformity])  
DOAC: Direct oral anticoagulant 
The packaging and the instructions for use will indicate that the device is only 
intended for the Post Marketing Study according to this Study Plan. 
The sponsor will supply the investigators and clinical investigation sites with the 
test, including all relevant documentation.  
Used test strips will be discarded into the standard containers of the site for 
collection of tubes containing blood or urine samples. Unused test strips will be 
returned to the sponsor.  
9.4.2 
Emergency procedures 
Not required. 
9.4.3 
Method of assigning patients to test arms 
Two groups of patients will participate in the test, based on their DOAC therapy. 
The same test will be performed in each patient’s urine sample. 

 
CRS Study No.:  
177/16-09.DE 
Sponsor Study No.: 
DOA-CS-002 
ClinicalTrials.gov ID: NCT03182829 
 
Post Marketing Study Plan, Version 7.0, 04 May 2018 
 Page 20 of 31 
9.4.4 
Blinding 
Not applicable. 
9.4.5 
Restrictions and precautions 
The IVD has to be handled according to handling instructions. No special 
requirements or precautions (e.g., gloves) have to be taken. 
Urine sample handling by the site personnel has to be performed according to 
standard procedures of the site. 
9.5 
Procedures and assessments related to the Post Marketing Study  
All measurements are carried out according to standard medical methods of the 
investigational site. The personnel involved is adequately trained in required 
measurements.  
All sites will receive the same model/type of reflectance photometric dipstick 
color reader (DOASENSE Reader). 
9.5.1 
Visit description 
During a routine visit in the outpatient care unit of the site, patients who match the 
entry criteria (based on their medical records at the site) will be informed about 
the Post Marketing Study, and informed consent will be obtained. 
The investigator will document the patient’s demographic characteristics 
(Section 9.5.2) and record the time of last intake of DOAC. 
Then, the patients will provide a sample of urine and give it to the respective site 
personnel. No further action is required by the patient. 
The site personnel will put two aliquots of urine (5 mL) into provided test tubes 
for bioanalysis (Section 9.5.3.2) and prepare the sample for shipment according to 
the shipment instructions.  
Then, they will perform the visual and reflectance photometric reading of the 
dipstick (Section 9.5.3.1).  
Thereafter, they will complete the questionnaire.  

 
CRS Study No.:  
177/16-09.DE 
Sponsor Study No.: 
DOA-CS-002 
ClinicalTrials.gov ID: NCT03182829 
 
Post Marketing Study Plan, Version 7.0, 04 May 2018 
 Page 21 of 31 
Case report forms (CRFs) and completed questionnaires will be sent to: 
Prof. Dr. Christel Weiß, Dipl Math 
Medical Statistics, Biomathematics, and Information Processing 
Medical Faculty Mannheim of the University of Heidelberg 
Ludolf-Krehl-Straße 13-17 
68167 Mannheim, Germany  
9.5.2 
Population characteristics 
The following data will be recorded for each patient in a CRF: 
 Age (years) 
•
 Sex 
•
 Body weight (kg) 
•
 Body height (cm)1 
•
 Medical and surgical history relevant to DOAC treatment 
•
 Medication history – DOAC (type, start of treatment, last intake before 
•
providing urine sample) 
 Other medication history relevant to DOAC therapy 
•
Data will be taken from the patient’s medical records. 
9.5.3 
Performance endpoints 
Patients will collect a sample of urine into the container usually used at the site 
and hand it over to the site personnel. 
The site personnel will put two aliquots of 5 mL into the test tubes provided for 
bioanalytical measurements (see Section 9.5.3.2), and perform direct urine tests as 
described in Section 9.5.3.1. After completion of the test, the remaining urine is 
discarded. 
At start of study, and after every 12th examination (one per test tube) of patient 
urine samples, the visual reading and reflectance photometric reading procedures 
described below will be performed on one negative control (0 ng/mL) and one 
positive control (800 ng/mL) for each group of inhibitors: Dabigatran (Thrombin 
inhibitor) and Rivaroxaban (Factor Xa inhibitor). 
                                                 
1 Body mass index deleted, as not required. 

 
CRS Study No.:  
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Sponsor Study No.: 
DOA-CS-002 
ClinicalTrials.gov ID: NCT03182829 
 
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9.5.3.1 
Urine dipstick test – visual and reflectance photometric color reading 
Please note: Site personnel with known red-green blindness/ weakness cannot 
perform the test. 
The site personnel will perform the urine test as follows: 
The test strip is dipped into urine or into control samples for 2 to 3 seconds, so all 
test pads are wet with urine. Then, the test strip is placed on a flat surface (room 
temperature, at light) with the pads facing upwards (so color changes can be 
seen). After 10 Minutes the site personnel will compare the results visually with 
the reference scale on the dipstick container. Then, the dipstick will be placed into 
the reflectance photometric reader according to the handling instructions. 
The results will be documented in the CRF by the study personnel and the printout 
of the reflectance photometric color reader (DOASENSE Reader) will be copied 
and fixed with an adhesive into the CRF. 
 
After 10 minutes, the reactions on the pads are completed:  
 
Test Pad 1: (Creatinine)  
• 
The color of pad 1 corresponds to colors “norm.” on the tube label  
creatinine in urine is normal. Pad 3 and pad 4 can be evaluated. 
• 
The color of pad 1 is darker than the colors “norm.” on the tube label  
high creatinine does not affect DOAC excretion into urine.  
Pad 3 and pad 4 can be evaluated. 
• 
The color of pad 1 is “low” or lighter than the respective color of the tube 
label  creatinine in urine is low, indicating renal insufficiency.  
Colors of pad 3 and pad 4 may be false negative.  
 
 
Test Pad 2: (Urine color) 
• The color of the pad is white as the respective color marked “norm” on the 
tube label  the results of pad 1, 3 and 4 are valid. 
• The color of the pad is darker than the color printed on the tube label  
colors of pad 1, pad 3 and pad 4 may be distorted. The test is invalid.  
 
 

 
CRS Study No.:  
177/16-09.DE 
Sponsor Study No.: 
DOA-CS-002 
ClinicalTrials.gov ID: NCT03182829 
 
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Test Pad 3 (Medication Apixaban, Edoxaban, Rivaroxaban): 
• The color of pad 3 clearly is yellow as the respective color marked “neg.” on 
the tube label  direct oral Factor Xa inhibitor is absent in the urine sample.  
• The color of pad 3 is less yellow than the color marked “neg.” on the tube 
label, thus the results is “pos.”  direct oral Factor Xa inhibitor is present in 
urine.  
• The color of pad 3 is white as the respective color marked “pos.” on the tube 
label  direct oral Factor Xa inhibitor is present in urine.  
 
Test Pad 4 (Medication Dabigatran): 
• The color of pad 4 is ochre as the respective color marked “neg.” on the tube 
label  direct oral Thrombin inhibitor is absent in the urine sample.  
• The color of pad 4 is between the ochre color marked “neg.” and the rose 
color marked “pos.” on the tube label   direct oral Thrombin inhibitor is 
present in urine.  
• The color of pad 4 is rose as the respective rose color marked “pos.” on the 
tube label  direct oral Thrombin inhibitor is present in urine.  
 
If pad 3 and pad 4 are both “pos.”, the test is invalid,  
because it is unlikely that a person is treated with both types of DOACs. 
 
The study personnel will document the results in the CRF and the printout of the 
reflectance photometric color reader (DOASENSE Reader) will be copied and 
fixed with an adhesive into the CRF. 
After all readings are completed and documented, the used test strip will be 
discarded. 

 
CRS Study No.:  
177/16-09.DE 
Sponsor Study No.: 
DOA-CS-002 
ClinicalTrials.gov ID: NCT03182829 
 
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 Page 24 of 31 
9.5.3.2 
Bioanalysis of the urine samples 
The urine aliquots will be stored in a deep freezer at about -20°C2 at the study 
center. The analytical laboratory will collect one aliquot, and one sample will be 
sent to CRS for storage. 
 
 
Figure 9-1: Color chart label of pads 1, 2, 3, and 4 of the DOAC Dipstick 
 
9.5.4 
Safety endpoints 
There will be no intervention; therefore, no safety endpoints will be measured. 
                                                 
2 Storage of urine aliquots was changed to deep freezer at -20 C. 

 
CRS Study No.:  
177/16-09.DE 
Sponsor Study No.: 
DOA-CS-002 
ClinicalTrials.gov ID: NCT03182829 
 
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9.5.5 
Anticipated adverse device effects 
The patients who participate in this investigation will come into contact only with 
their own urine. They will not come in contact with any of the study materials.  
No additional study-related investigation will be performed for the study. 
Therefore, no study-related adverse events will occur. 
9.6 
Statistical methods and determination of sample size 
9.6.1 
Statistical and analytical plans 
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. 
9.6.2 
Sample size determination 
Two groups of medications (Thrombin inhibitor, 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. 

 
CRS Study No.:  
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Sponsor Study No.: 
DOA-CS-002 
ClinicalTrials.gov ID: NCT03182829 
 
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10 
Data collection 
10.1 
Case Report Form and Questionnaire 
The sponsor will provide individual CRFs to the investigator, together with 
instructions for completion. 
The investigator is responsible to complete the CRF.  
The investigator will maintain a list of personnel authorized to make entries into 
the CRF. These have to be adequately trained in the procedures of the 
investigation. 
10.2 
Document and data control 
All documents related to the Post Marketing Study will be identifiable, traceable, 
and appropriately stored. 
The investigator ensures that all data entries on the CRFs and other documentation 
are accurate, legible, complete, and entries are made in a timely manner. Copies 
of source documents or printouts of electronic source documents will be signed 
and date by a member of the investigation team. 
Any corrections in the CRF have to be clearly signed and dated by authorized site 
personnel. In case of non-obvious corrections, the reason for correction has to be 
explained. The original entry has to remain legible and may not be obscured by 
the correction. 
10.3 
Source data 
CRFs, informed consent forms and patient’s medical records are source data.  
 CRF 
•
 Signed informed consent 
•
 DOASENSE Reader printouts (signed and dated copies, as the originals are 
•
thermographic paper) 
 Questionnaire on IVD handling 
•
10.4 
Data management 
Data management procedures will be described in a separate document. 

 
CRS Study No.:  
177/16-09.DE 
Sponsor Study No.: 
DOA-CS-002 
ClinicalTrials.gov ID: NCT03182829 
 
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 Page 27 of 31 
10.5 
Document retention 
The sponsor will archive the sponsor’s file, and all relevant documentation for at 
least 10 years after end of the study, or longer if regulatory or legally required. 
The investigator will archive informed consent form and original CRFs for at least 
10 years after end of the study. 
 
11 
Quality assurance and quality control, audits, and inspections 
11.1 
Quality control and quality assurance 
The sponsor is responsible for implementing and maintaining quality assurance 
and quality control systems with written standard operating procedures (SOPs) to 
ensure that the Post Marketing Study is conducted, data are generated, 
documented (recorded), and reported in compliance with this Study Plan and the 
applicable regulatory and legal requirements. 
The sponsor is responsible for securing agreement from all involved parties to 
ensure direct access to all Post Marketing Study-related sites, source 
data/documents, and reports for the purpose of monitoring and auditing by the 
sponsor, and inspection by domestic and foreign regulatory authorities. 
Quality control should be applied to each stage of data handling to ensure that all 
data are reliable and have been processed correctly. 
Agreements, made by the sponsor with the investigator/institution and any other 
parties involved with the Post Marketing Study, should be in writing, as part of 
the protocol or in a separate agreement. 
11.2 
Monitoring 
The sponsor will appoint a monitor, who will verify that the conduct of the Post 
Marketing Study complies with this Study Plan and the applicable regulatory and 
legal requirements. 
The planned monitoring activities will be outlined in a monitoring plan, and 
reported in monitoring reports. 
11.3 
Audit 
The investigator) shall allow representatives from Quality Assurance of 
DOASENSE to have access to its study relevant documentation and raw data.  

 
CRS Study No.:  
177/16-09.DE 
Sponsor Study No.: 
DOA-CS-002 
ClinicalTrials.gov ID: NCT03182829 
 
Post Marketing Study Plan, Version 7.0, 04 May 2018 
 Page 28 of 31 
An audit is defined as an inspection and assessment on the general organization of 
the Study Monitor system, as well as study related information. 
Activities related to the Post Marketing Study and documents may be audited to 
determine if performance and assessment of the Post Marketing Study were 
compliant with the Post Marketing Study Plan and applicable regulatory and legal 
requirements. Auditors who are independent from the Post Marketing Study and 
its conduct will perform audits. 
The investigator will permit the auditors access to the facilities and documents at 
agreed times. 
11.4 
Inspection 
Regulatory authorities may conduct an official review of all Post Marketing Study 
documents, facilities, records and other material related to the clinical 
investigation / Post Marketing Study.  
The investigator must cooperate with any inspection. 
The patients will agree with signing the informed consent to the access of their 
data by authorities. 
12 
Confidentiality of patient data 
All information collected during the course of this investigation is kept strictly 
confidential.  
The patients participating in the study are identified by their PID. The monitor has 
limited access to the patient’s medical records for source data verification.  
Any information, which could identify a patient, remains with the investigator 
where it is archived with investigation documents.  
Patients will remain anonymous for the purposes of data analysis. 
Should the investigation require future review, relevant regulatory authorities and 
ECs will be allowed access to all relevant information for audit and inspection 
purposes. 

 
CRS Study No.:  
177/16-09.DE 
Sponsor Study No.: 
DOA-CS-002 
ClinicalTrials.gov ID: NCT03182829 
 
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 Page 29 of 31 
13 
Post Marketing Study Report 
Upon completion of the Post Marketing Study, the sponsor will write a clinical 
report, which includes a critical assessment of all data obtained in the 
investigation.  
The Post Marketing Study report will be approved and signed by the sponsor and 
the lead investigator.  
14 
Publication policy 
In case the sponsor intends a publication of the study results, the investigator and 
the sponsor’s representative(s) prior to publication thereon shall discuss 
manuscripts. Regard shall be given to the sponsor's legitimate interests, e.g., 
containing optimal patent protection, coordination of submissions to health 
authorities or with other ongoing studies in the same therapeutic field, protection 
of confidential data, and information, etc. 
The sponsor's comments shall be given within 30 days after receipt of the 
publication draft. If there is no consensus, the senior author of the manuscript and 
the sponsor's representative(s) shall further discuss and mutually agree on the final 
wording or disposition of the publication. 
The above-described procedure also applies to information on prematurely 
discontinued and other non-completed studies. 
Results from investigations shall not be made available to any third parties by the 
investigating team outside the publication procedure as set out above. 
The sponsor will not quote from publications by investigators in its scientific 
information and/or promotional material without full acknowledgement of the 
source (i.e., author and reference). 
15 
Insurance 
No special insurance will be taken out. The patients will provide a urine sample 
during a routine visit at the study center. 
16 
Responsibilities and finances 
Responsibilities and finances will be specified in separate contracts.  

 
CRS Study No.:  
177/16-09.DE 
Sponsor Study No.: 
DOA-CS-002 
ClinicalTrials.gov ID: NCT03182829 
 
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17 
References 
 
Harenberg J, Krämer S, Du S, Weiss C, Krämer R.: Concept of a point of 
[1]
care test to detect new oral anticoagulants in urine samples. Thrombosis 
Journal. 2013 Aug 1; 11: 15 PMC [article] PMCID: PMC3766639, PMID: 
23915217, DOI: 10.1186/1477-9560-11-15. 
 
Harenberg J, Du S, Wehling M, Zolfaghari S, Weiss C, Krämer R, et al.: 
[2]
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. PubMed [citation] PMID: 26167981. 
 
18 
Amendments 
Not applicable. 
 

 
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Sponsor Study No.: 
DOA-CS-002 
ClinicalTrials.gov ID: NCT03182829 
 
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19 
Appendix  
Handling instructions for the DOAC dipstick test/Package insert. 

0001
12
In vitro Diagnostics
DOASENSE™ GmbH, Waldhofer Str. 102, 69123 Heidelberg, Germany
Email: info@doasense.de, www.doasense.de
Expiry date
Catalogue number
Follow carefully instructions for use
Lot number
Storage temperature
CE Mark -  Device comply with the Directive 98/79/EC
Manufacturer
Content is sufficient for <n> tests
DIAGNOSTIC DOAC IN URINE DIPSTICK TEST
The results always have to be interpreted and evaluated in connection with other clinical information by a physician before diagnosing. No treatment 
decisions should be made solely on the basis of the outcomes of a DOAC Dipstick analysis. Additional laboratory analysis (e.g. determination of blood 
coagulation parameters) may be required. 
Persons with colour vision deficiency or colour blindness may not perform the DOAC Dipstick test. 
Expected Values and Reference Ranges 
Creatinine – Reference Range: 0.25 – 3.0 g/l, (2.2 – 26.5 mmol/l) (Ref.: Needleman).
Factor Xa Inhibitors – Normal values in urine are below 5ng/ml (LC-MS/MS method). Patients under DOAC treatment typically display values above 
150ng/ml (see paragraph performance characteristics). 
Thrombin Inhibitors – Normal values are below 5ng/ml (LC-MS/MS method). Patients under DOAC treatment typically display values above 150ng/ml 
(see paragraph performance characteristics) (Ref.: Schreiner). 
Performance Characteristics 
The cut off values for rivaroxaban and dabigatran by visual analysis using identification of colours as “negative” and “positive” were 100 ng/ml in normal 
human urine spiked with concentrations ranging from 0 to 1500 ng/ml. Sensitivity and specificity of detection was 0.92 and 0.93 (rivaroxaban) and 0.90 
and 0.93 (dabigatran). Using urine samples of patients treated with dabigatran, rivaroxaban and apixaban, and of control patients not treated with DOACs, 
sensitivities and specificities were all 1.0 (Ref.: Harenberg 2017). 
Concentrations of DOACs in urine are higher due to the lower volume of urine compared to the volume of distribution of DOACs in blood and were be­
low 5 ng/ml (LC-MS/MS method) in patients not treated with DOACs and above 150 ng/ml for all DOACs during steady state of treatment and 12 or 24 
hours after intake of medication (mean values 5.600 ng/ml Dabigatran, 2.700 ng/ml Rivaroxaban, 1.800 ng/ml Apixaban, n=29 each) (Ref.: Schreiner).
Interferences
No information is reported in the literature on drug-drug and drug-other compounds interactions – except the coloured compounds in urine described 
herein. The number of interactions tends to be low to very low due to the high specificity of the enzymes with the respective substrates. No interaction 
occurs between the components of pad 3 with pad 4 and vice versa. 
Heparins do not react on pads 3 and 4 (Harenberg 2017).
Coloured compounds in urine such as bilirubin, urobilinogen and blood (macrohaematuria) may modify the results of pad 1, pad 3 and pad 4. The impact 
of the colour of the urine sample can be assessed by pad 2 (see above for interpretation).
Creatinine – In urines with high buffering capacity false negative reading may be obtained. With high concentrations of ketone bodies (>50 mmol/l) false 
positive reading may occur. Blood >2000 Ery/μl may cause false positive results.
Storage Conditions 
The recommended storage temperature of the closed test strip tube container is between +2 °C to +30 °C. Each device may be used until the expirati­
on date printed on the label. After opening, the tube has to be closed tightly immediately after removing of the strips used for evaluation, and the closed 
tube has to be stored away from direct sunlight at tempe¬ratures not exceeding +30 °C. Storage above +30 °C will adversely affect the stability and test 
performance of the product.
References
Schreiner R et al. Determination of rivaroxaban, apixaban, edoxaban and dabigatran by ultra-performance liquid chromatography-tandem mass-spectro­
metry and chromogenic assays from urine samples of patients. J Thromb Haemostas 2017, Abstract, in press.
Harenberg J, et al. Reliability and validity of a point of care test from urine samples of patients on therapy with apixaban, rivaroxaban and dabigatran. J 
Thromb Haemostas 2017, Abstract, in press.
Harenberg J, et al Measurement of dabigatran, rivaroxaban and apixaban in samples of plasma, serum and urine, under real life conditions. An interna­
tional study. Clin Chem Lab Med. 2016 Feb;54(2):275-283. 
Du S, et al. Determination of dabigatran in plasma, serum, and urine samples: comparison of six methods. Clin Chem Lab Med. 2015 Jul;53(8):1237-1247. 
Harenberg J, et al. 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):228-236. 
Favaloro EJ, et al. Laboratory testing in the era of direct or non-vitamin K antagonist oral anticoagulants: a practical guide to measuring their activity and 
avoiding diagnostic errors. Semin Thromb Hemost. 2015 Mar;41(2):208-227.
Harenberg J, et al. Concept of a point of care test to detect new oral anticoagulants in urine samples. Thromb J. 2013 Aug 1;11(1):15.
Needleman SB, Porvaznik M, Ander D. Creatinine analysis in single collection urine specimens. J Forensic Sci. 1992 Jul;37(4):1125-1133.
USED SYMBOLS 
Intended Use:
The diagnostic test strip DOAC Dipstick is intended for qualitative detection of the absence or presence of direct oral anticoagulants (DOAC
in human urine by visual identification of colours. The DOAC Dipstick is an in vitro diagnostics test intended for professional use only.
Summary and Explanation 
The clinical importance of positive results of a DOAC in human urine relates to the presence of DOAC in blood. DOACs are excreted rapidly into 
urine starting 1 to 2 hours after intake of the medication. A specific and rapid detection indication by a point of care test may support diagnosis 
of anticoagulant therapy with DOACs especially in emergency medicine. Medical decision-making may be accelerated. Typical indications are pa­
tients with ischemic or haemorrhagic stroke with indication for fibrinolytic therapy or administration of a specific antidote, major trauma, emergen­
cy procedures, spontaneous thrombotic and bleeding events during oral anticoagulant therapy, and situations without available medication history. 
Material Provided with the Test
Test strip:	
 	
	
	
                 12
Test strip tube container with printed colour scale and cap:	                    1
Instructions for Use: 	
 	
	
                   1
Materials Required but Not Provided 
Clean container made of Polypropylene for sample collection.
Timer.
Principle of the DOAC Test Strip
The test consists of a change of colour upon reaction of Factor Xa or Thrombin with a Factor Xa or Thrombin chromogenic substrate in relation to the 
amount of DOAC present in the urine sample. Colours for oral direct Factor Xa and Thrombin inhibitors are different. The colour of the pads on the test 
strips changes within 10 min and can be identified by naked eye. The colours allow the detection of DOAC in a urine sample, with interpretation as “ne­
gative” in the absence of a DOAC and as “positive” in the presence of a DOAC. Respective colours for comparison are printed on the test tube contai­
ning the test strips.  
The DOAC Dipstick has four different test pads used for analysis, as follows:
Schematic of the DOAC Dipstick:
 
1 
3 
2 
4 
       
         Area with test pads	
	
	
Handling area
Pad 1 for determination of Creatinine
Pad 2 for assessing the colour of urine (without reagents)
Pad 3 for determination of oral direct Factor Xa inhibitor
Pad 4 for determination of oral direct Thrombin inhibitor
Principle of Tests 
Creatinine – The test is based on reaction of creatinine with 3.5-dinitrobenzoic acid in alkaline medium (Benedict-Behre reaction).
Factor Xa Inhibitors – The test is based on the release of a chromophore from a Factor Xa specific peptide by Factor Xa and the inhibition by an oral 
direct Factor Xa inhibitor.
Thrombin Inhibitors – The test is based on the release of a chromophore from a Thrombin specific peptide by Thrombin and the inhibition by an oral 
direct Thrombin inhibitor.
Urine Colour – This pad does not contain any reagents and is used for assessing the impact of the colour of the patient urine used.
Warning and Precautions
Do not use expired devices.
Do not reuse the test components.
Follow good laboratory practice and safety guidelines. Wear lab coats, disposable latex gloves and protective glasses where necessary.
Prepared or used test strips have to be treated as hazardous waste according to national biohazard and safety guidelines or regulations.
All reagents of this kit have been found to be uninfectious. However, a presence of used materials with human urine can­
not exclude infectious agents. For this reason used test strips should be treated as potential biohazards in use and for disposal.
If Contamination of clothing occurs: Rinse skin with water or shower.	
Avoid contact with skin and eye. If skin irritation occurs: Consult a physician in all serious cases of health damage.
In case of an accidental ingestion wash up the mouth and drink approximately 0.5 
l of water. In case of eye contact rinse the eye quickly and thoroughly using a stream of clean water. Procedure Notes Before Performing the 
Test
Do not use test strips with an expiry date that has already passed. Carefully read the instructions for use before starting the test.
The instructions must be followed exactly to obtain accurate results. 
This test is for professional in vitro diagnostic use only. 
Do not touch test pads of the strip. Handle the test strips only at the handling area opposite to the area with the test pads. 
Do not open the tube containing the test strips unless you are ready to conduct the test.
Remove only as many test strips as required and reseal the tube immediately with the cap. The cap contains a desiccant.
Collection of Urine Sample:
1. Each urine sample must be collected in a clean container made of Polypropylene. Only freshly collected urine may be used. 
2. Shake the container smoothly before dipping the test strip. 
3. Use urine immediately after collection.
Assay Procedure - Use of test strips: 
1. Immerse the test strip for 2 to 3 seconds into the urine sample so that all test pads are completely covered by the urine.
2. After removing the test strip from the urine, some liquid may be attached at the borders or edges of the test strips. Whip off the excess urine on a filter 
paper or on a cellulose or cotton wool surface to absorb runoff. The test pads should not be touched.
3. Place the test strip on a flat surface, so that you can see the test pads, and wait for 10 minutes (incubation time of tests). Use a timer to control the time.
4. After 10 minutes incubation time immediately compare the test pads by naked eye to the corresponding colour scales on the label of the tube contai­
ner. Refer to the next section regarding the visual determination of the colours. 
Visual Determination of Colours:
Colours are compared to colours of a colour scale, which is printed on the label of the container tube containing the test strips by naked eye.
Start by comparing the colour of test pad 2 (“Urine Colour”) to the respective colour area on the label.
Test Pad 2 Interpretation:
If the colour of pad 2 is different to the colour printed on the tube, the tests of pad 1, pad 3 and pad 4 are invalid, as their respective colours may be 
falsified by the impact of excess urine colour. Thereafter, identify the colour of test pad 1 and compare to the colour of pad 1 on the label of the tube or 
the package insert.
Test Pad 1 Interpretation:
If the colour of pad 1 indicates a “high” creatinine value, the test results of pad 3 and pad 4 are invalid. 
Then identify the colour of test pad 3 or of test pad 4 depending on the type of DOAC the patient is treated with. If therapy with a specific DOAC is unk­
nown, both pad 3 and pad 4 should be identified by naked eye. Compare the colour of pad 3 and or pad 4 with the colour scales printed on the tube.
All colours different from the colour ”negative” (“neg.”) as shown on the tube label are “positive” (“pos.”).
Test Pad 3 Interpretation (medication apixaban, rivaroxaban):
•	
If the colour of pad 3 clearly is as yellow as the respective colour marked “neg.” on the label colour scale, the result is negative, indicating that no 
Factor Xa Inhibitor anticoagulant is present in the urine sample. 
•	
If the colour of pad 3 is not clearly as yellow as the respective colour marked “neg.” on the label and more similar to the yellow colour marked “pos.” 
on the label colour scale, the result is positive, indicating that the Factor Xa Inhibitor anticoagulant is present in urine. 
•	
If the colour of pad 3 clearly is white or tends to be similar to the respective white colour marked “pos.” on the label colour scale, the result is po­
sitive, indicating that the Factor Xa Inhibitor anticoagulant is present in urine. 
Test Pad 4 Interpretation (medication dabigatran):
•	
If the colour of pad 4 is ochre as the respective colour marked “neg.” on the colour scale on the tube, no Thrombin Inhibitor anticoagulant is present 
in urine. 
•	
If the colour of pad 4 is not ochre as the respective colour marked “neg.” on the colour scale of the tube, the result is  “pos.” as shown on the label 
colour scale, indicating that the Thrombin Inhibitor anticoagulant is present in urine. 
•	
If the colour of pad 4 is purple similar to the respective purple colour marked “pos.” on the label colour scale, the Thrombin Inhibitor anticoagulant 
is present in urine. 
If both pad 3 and pad 4 are “pos.”, then the test is invalid.
Limitations
The test results are qualitative. No quantitative interpretation should be made based on the test results.
DOAC Dipstick
 
EN
Date of Revision: 30.6.2017
10020484

0001
12
In vitro Diagnostikum
  
DOASENSE™ GmbH, Waldhofer Str. 102, 69123 Heidelberg, Germany
Email: info@doasense.de, www.doasense.de
Verfallsdatum
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Verwendungszweck
Der diagnostische Teststreifen DOAC Dipstick ist für die qualitative Bestimmung der Abwesenheit oder Anwesenheit direkter oraler Antikoagulantien 
(DOAK bzw. englisch DOAC) in menschlichem Urin durch visuelle Identifikation von Farben vorgesehen. Der DOAC Dipstick ist ein in-vitro diagnostischer 
Test nur für Fachgebrauch durch medizinisches Personal.  
Zusammenfassung und Erläuterung
Die klinische Bedeutung eines positiven Ergebnisses eines DOAK in menschlichem Urin geht einher mit der Anwesenheit des DOAK in Blut. DOAK wer­
den schnell in den Urin ausgeschieden, beginnend 1 bis 2 Stunden nach der Einnahme der Medikation. Eine spezifische und schnelle Erfassung durch 
einen patientennahen Point-of-Care-Test (POCT) könnte die Diagnostik der gerinnungshemmenden Therapie mit DOAK unterstützen, insbesondere in der 
Akutmedizin. Die medizinische Entscheidungsfindung könnte beschleunigt werden. Typische Indikationen zum Einsatz eines solchen Tests sind Patien­
ten mit einem ischämischen oder hämorrhagischen Schlaganfall, bei einer Indikation zu einer fibrinolytischen Therapie eines thrombotischen Ereignisses 
unter DOAK, die Überprüfung der Notwendigkeit der Verabreichung eines Antidot für DOAK, bei schwerem Trauma, vor Notfalleingriffen, bei spontanen 
thrombotischen Ereignissen oder schweren Blutungen unter einer blutverdünnenden Therapie, oder in Situationen in denen eine Medikamentenanamne­
se nicht verfügbar ist.
Materialien eines Testkits
Teststreifen:	
 	
	
	
12
Behälter für die Teststäbchen, bedruckt mit der 
Farbskala und Verschluss mit Trockenmittel:	 	
 1
Gebrauchsanweisung: 	
 	
	
 1
Andere Materialien, die benötigt aber nicht enthalten sind:
Sauberer Behälter aus Polypropylen für die Sammlung von Urin.
Zeitmesser.
Prinzip des Teststreifen für DOAK
Der Test beruht auf einem Farbumschlag durch die Einwirkung von den Gerinnungsenzymen Faktor Xa und Thrombin auf die Freisetzung eines Farb­
stoffs, der an ein Substrat gebunden ist. Die Freisetzung des Substrats ist negativ proportional abhängig von der Menge an DOAK in Urin.  Die Farben 
sind unterschiedlich für Faktor Xa Hemmer und Thrombin Hemmer der DOAK. Sie entwickeln sich über 10 Minuten auf den Testfeldern und können 
mit dem bloßen Auge identifiziert werden. Sie erlauben eine Feststellung der Ab- oder Anwesenheit eines DOAK in Urin und werden als “negativ” oder 
“positiv” bewertet. Entsprechende Farben sind auf dem Behälter der Teststreifen zum Vergleich für die Zuordnung zu “negativ” und “positiv” abgebildet. 
Der Teststreifen “DOAC Dipstick” besteht aus vier verschiedenen Feldern: 
      Fläche mit Testfeldern	
                                    Fläche zur Handhabung
Feld 1: Bestimmung von Kreatinin
Feld 2: Identifikation der Urinfarbe (keine Reagenzien) 
Feld 3. Bestimmung direkter Faktor Xa Hemmer der DOAK
Feld 4: Bestimmung direkter Thrombin Hemmer der DOAK
Prinzip der Tests 
Kreatinin – Der Test beruht auf einer Reaktion von Kreatinin mit 3.5-Dinitrobenzol Säure in alkalischem Medium (Benedict-Behre-Reaktion).
Faktor Xa Hemmer – Der Test beruht auf der Freisetzung eines Farbstoffs von einem Faktor Xa spezifischen Substrat durch das Enzym und einer Hem­
mung von Faktor Xa durch einen oralen Faktor Xa Hemmer.
Thrombin Hemmer – Der Test beruht auf einer Freisetzung eines Farbstoffs von einem Thrombin spezifischen Substrat durch das Enzym und einer He­
mmung von Thrombin durch einen oralen Thrombin Hemmer.
Urinfarbe – Dieses Feld enthält keine Reagenzien und wird zur Feststellung der Farbe des Urins der Patienten benutzt. 
Warnung und Vorsichtsmaßnahmen
Nicht benutzen nach Ablauf des Verfallsdatums auf dem Behälter. 
Einen Teststreifen nicht mehrfach benutzen.
Die Richtlinien für Gute Laborpraxis beachten: Laborkittel, Einmalhandschuhe und Schutzbrillen tragen, wenn nötig. 
Gebrauchsfertige oder benutzte Teststäbchen sollen als gefährlicher Abfall behandelt werden, entsprechend den nationalen Richtlinien für gefährliche 
Biostoffe und Sicherheitsrichtlinien. 
Alle Reagenzien des Test sind nicht infektiös. In Gegenwart von Urin können infektiöse Agenzien nicht ausgeschlossen werden. Aus diesem Grund sollten 
die Teststäbchen wie gefährliche Biostoffe zur Nutzung und Entsorgung behandelt werden. 
DOAC Dipstick
DIAGNOSTISCHER TESTSTREIFEN ZUR ANALYSE VON DOACS IN URIN
DE
Schematische Darstellung des DOAC Dipstick
 
1 
3 
2 
4 
 
 
Bei einer Verunreinigung der Kleidung durch die Teststreifen bzw. Urin: Behandlung der Haut mit Wasser oder Dusche. 
Kontakt mit Haut oder Auge vermeiden. Falls eine Hautirritation durch Berührung der Testfelder erfolgt: bei gesundheitlichen Schäden Hausarzt oder 
Facharzt aufsuchen. Bei Kontakt mit dem Auge dieses umgehend und ausgiebig mit  sauberem Wasser spülen. Bei einem unbeabsichtigten Verschlucken 
den Mund ausgiebig mit Wasser spülen und etwa 0,5 l Wasser trinken. 
Zur Beachtung vor Nutzung des Test
Teststreifen nicht nach Verfallsdatum nutzen. 
Sorgfältig die Gebrauchsanweisung lesen. 
Die Gebrauchsanweisung muss genau befolgt werden, um ein zuverlässiges Ergebnis zu erhalten. 
Der Test ist nur für den Fachgebrauch durch medizinisches Personal als in-vitro Diagnostikum zu nutzen. 
Die Testfelder des Teststreifens nicht berühren. Den Testreifen nur auf der zur Handhabung vorgesehenen Seite anfassen, die sich am an dem Ende des 
Teststreifens befindet, auf welchem keine Testfelder aufgebracht sind. 
Den Behälter erst unmittelbar vor der Durchführung des Tests öffnen. 
Nur  so viele Teststreifen aus dem Behälter nehmen wie erforderlich. Den Behälter unmittelbar nach dem Entnehmen von Teststreifen wieder mit dem 
Deckel verschließen. Der Deckel enthält ein Trockenmittel. 
Gewinnung der Urinprobe:
1. Jede Urinprobe muss in einem sauberen Behälter aus Polypropylen gesammelt werden. Nur frisch gesammelter Urin darf verwendet werden. 
2. Den Behälter vor Eintauchen des Teststäbchens leicht schütteln. 
3. Den Urin unmittelbar nach dem Sammeln für den Test verwenden. 
Ablauf des Tests – Benutzung der Teststreifen:
1. Den Teststreifen 2 bis 3 Sekunden in den Urin eintauchen, so dass alle Testfelder mit Urin bedeckt sind. 
2. Nach Herausnehmen des Testreifens aus dem Urin Reste des Urin an der Unterseite und den Rändern des Teststre ifens vorsichtig über ein aufsau­
gendes Papier streifen. Die Fläche mit den Testfeldern darf nicht berührt werden. 
3. Den Teststreifen für 10 Minuten mit der Rückseite auf eine glatte Oberfläche legen. Die Zeitdauer mit einem Zeitmesser prüfen.  
4. Nach 10 Minuten umgehend die Farben der Testfelder mit dem Auge beurteilen und mit den korrespondierenden Farben auf dem Etikett des Behälters 
vergleichen. Zur Interpretation der Farben siehe den nächsten Abschnitt.
Visuelle Bestimmung der Farben:
Die Farben der Testfelder werden mit der Farbskala auf dem Etikett des Behälters verglichen. 
Beginnen Sie indem Sie die Farbe von Feld 2 des Teststreifens mit der Farbe „Urinfarbe“ auf dem Etikett des Behälters vergleichen. 
Feld 2 Interpretation:
Falls die Farbe von Feld 2 eindeutig anders ist als die Farbe des entsprechenden Felds auf dem Etikett des Behälters, so ist der Test ungültig, da die 
Farben der übrigen Testfelder durch die Urinfarbe verfälscht werden könnten. Der Test ist nicht verwertbar. 
Anschließend wird die Farbe von Feld 1 des Testreifens abgelesen und mit den Farben von Feld 1 auf dem Etikett des Behälters verglichen.
Feld 1 Interpretation:
Wenn die Farbe von Feld 1 der Farbe „high“ auf dem Etikett des Behälters entspricht, dürfen Feld 3 und Feld 4 nicht interpretiert werden. Der Test ist 
dann ungültig, weil ein erhöhter Wert von Kreatinin falsche Werte für Feld 3 und Feld 4 ergeben kann. Der Test ist nicht verwertbar.
Danach werden die Farben von Feld 3 bzw. Feld 4 in der Farbe identifiziert, welche abhängig von dem DOAK das der Patient einnimmt, reagieren. Ist die 
Einnahme des spezifischen DOAK nicht bekannt, sollen beide Testfelder ausgewertet werden. Die Farben von Feld 3 und Feld 4 werden mit den Farben 
der Farbskala auf dem Etikett des Behälters verglichen.
 
Alle Farben, die nicht eindeutig der Farbe „negativ“ („neg.“) der Farbskala auf dem Etikett des Behälters entsprechen, sind als „positiv“ 
(„pos.“) zu interpretieren. 
Feld 3 Interpretation (Behandlung mit Apixaban, Rivaroxaban):
• Wenn die Farbe auf Feld 3 eindeutig gelb ist wie die Farbe „neg.“ der entsprechenden Farbskala auf dem Etikett des Behälters, dann ist das Ergebnis 
der Untersuchung negativ und bedeutet, dass sich kein oraler Faktor Xa Hemmer im Urin befindet. 
• Wenn die Farbe auf Feld 3 nicht eindeutig so gelb ist wie die Farbe „neg.“ der entsprechenden Farbskala auf dem Etikett des Behälters, dann ist das 
Ergebnis der Untersuchung „pos.“ (siehe Etikett des Behälters), d. h. positiv. Dies bedeutet, dass sich ein oraler Faktor Xa Hemmer im Urin befindet. 
• Wenn die Farbe auf Feld 3 eindeutig weiß ist wie die Farbe „pos.“ der entsprechenden Farbskala auf dem Etikett des Behälters, dann ist das Ergebnis 
der Untersuchung positiv und bedeutet, dass sich ein oraler Faktor Xa Hemmer im Urin befindet. 
Feld 4 Interpretation (Behandlung mit Dabigatran):
• Wenn die Farbe auf Feld 4 eindeutig ocker ist wie die Farbe „neg.“ der entsprechenden Farbskala auf dem Etikett des Behälters, dann ist das Ergebnis 
der Untersuchung negativ und bedeutet, dass sich kein oraler Thrombin Hemmer im Urin befindet. 
• Wenn die Farbe auf Feld 4 nicht eindeutig so ocker ist wie die Farbe „neg.“ der entsprechenden Farbskala auf dem Etikett des Behälters, dann ist das 
Ergebnis der Untersuchung „pos.“ (siehe Etikett des Behälters), d. h. positiv. Dies bedeutet, dass sich ein oraler Thrombin Hemmer im Urin befindet. 
• Wenn die Farbe auf Feld 4 eindeutig rosa ist wie die Farbe „pos.“ der entsprechenden Farbskala auf dem Etikett des Behälters, dann ist das Ergebnis 
der Untersuchung positiv und bedeutet, dass sich ein oraler Thrombin Hemmer sich im Urin befindet. 
Wenn Feld 3 und Feld 4 beide das Ergebnis “pos.” anzeigen, ist der Test ungültig und nicht verwertbar.
Limitierungen
Es handelt sich um qualitative Testergebnisse. Eine Interpretation zu quantitativen Werten darf aus den Ergebnissen nicht abgeleitet werden. 
Die Ergebnisse dürfen nur in Zusammenhang mit den klinischen Informationen zu dem Patienten interpretiert werden. Eine Therapieentscheidung darf 
nur von einem Arzt und unter Hinzuziehung der klinischen Informationen zu dem Patienten vorgenommen werden. Eine Therapieentscheidung auss­
chließlich auf Basis des Ergebnisses des DOAC Dipstick Tests ist nicht zulässig. Zusätzliche klinische, laborchemische oder gerinnungsanalytische Un­
tersuchungen können erforderlich sein. 
Personen mit einer Farbsehschwäche oder Farbenblindheit dürfen den DOAC Dipstick Test nicht durchführen. 
Erwartete Werte und Referenzbereiche
Kreatinin – Referenzbereich: 0,25 – 3,0 g/l, (2,2 – 26,5 mmol/l) (Ref.: Needleman).
Faktor Xa Hemmer – Normale Werte in Urin sind kleiner als 5ng/ml (LC-MS/MS Methode). Patienten unter einer Behandlung mit DOAK zeigen typisch­
erweise Werte größer als 150ng/ml (siehe Paragraph Leistungsnachweis). 
Thrombin Hemmer – Normale Werte liegen unter 5ng/ml (LC-MS/MS Methode). Patienten unter einer Behandlung mit DOAK zeigen typischerweise Werte 
größer als 150ng/ml (siehe Paragraph Leistungsnachweis)  (Ref.: Schreiner). 
Leistungsnachweis
Die Cut-off Werte von „negativ“ („neg.“) und „positiv“ („pos.“) für Rivaroxaban und Dabigatran liegen bei 100 ng/ml, gemessen anhand von menschlichen 
Urinproben, die mit 0 ng/ml bis 1500 ng/ml Rivaroxaban und Dabigatran versetzt worden sind. Die Sensitivität und Spezifität an dieser Umschlagsgrenze 
der Konzentration beträgt 0,92 und 0,93 für Rivaroxaban sowie 0,90 und 0,93 für Dabigatran. Bei Urinproben von Patienten unter Behandlung mit Apixa­
ban, Rivaroxaban oder Dabigatran liegen die Sensitivität und Spezifität des Nachweises für alle DOAK bei 1,0 im Vergleich zu Urin von Personen ohne 
Behandlung mit DOAK (Ref.: Harenberg 2017). 
Die Konzentrationen von DOAK in Urin sind höher als in Blut oder Plasma wegen des geringeren Verteilungsvolumens in Urin. Die Konzentrationen von 
DOAK in Urin und Blut sind bei nicht mit DOAK behandelten Personen gleich niedrig (kleiner 5 ng/ml (LC-MS/MS Methode). Unter DOAK Therapie be­
tragen die Konzentrationen in Urin 12 bis 24 Stunden nach Einnahme mindestens 150 ng/ml und im Mittel etwa 5.600 ng/ml für Dabigatran, 2.700 ng/ml 
für Rivaroxaban, 1.800 ng/ml für Apixaban (n=29 oder 30 je Gruppe) (Ref.: Schreiner).
Wechselwirkungen
In der Literatur gibt es keine Informationen zu medikamentösen oder anderen Wechselwirkungen für den Nachweis in Urin – außer den genannten 
Wechselwirkungen der Farbsubstanzen. Eine Wechselwirkung von oralen Faktor Xa Hemmern mit Feld 4 und von oralen Thrombin Hemmern mit Feld 
3 besteht nicht (Harenberg 2017). 
Heparine reagieren nicht mit Feld 3 und Feld 4 (Harenberg 2017).
Farbige Substanzen im Urin wie Bilirubin, Urobilinogen und Blut (Makrohaematurie) können die Farben von Feld 1, Feld 3 und Feld 4 beeinflussen. Eine 
nicht-normale Urinfarbe kann durch Feld 2 beurteilt werden (siehe Interpretation der Ergebnisse).
Kreatinin – Urin mit einer hohen Kapazität an puffernder Lösung wie Ketone (>50 mmol/l)  können hohe Konzentrationen vortäuschen. Blut >2000 Ery/
μl kann die Farbe des Testfeldes beeinflussen. 
Lagerung
Die empfohlene Temperatur für die Lagerung der Teststreifen in den Behältern beträgt +2 °C bis +30 °C. Die Teststreifen müssen innerhalb des Halt­
barkeitsdatums genutzt werden, welches auf dem Behälter angegeben ist. Nach dem Öffnen des Behälters muss er mit der Verschlusskappe gleich nach 
Entnahme der Teststreifen wieder verschlossen werden. Die Aufbewahrung des Behälters erfolgt unter Vermeidung von direkter Sonneneinstrahlung bei 
Temperaturen 30° Celsius nicht überschreiten. Temperaturen über 30° Celsius können die Stabilität und Funktionsfähigkeit des Teststreifens beeinträchti­
gen. 
Literatur
Schreiner R et al. Determination of rivaroxaban, apixaban, edoxaban and dabigatran by ultra-performance liquid chromatography-tandem mass-spec­
trometry and chromogenic assays from urine samples of patients. J Thromb Haemostas 2017, Abstract, in press.
Harenberg J, et al. Reliability and validity of a point of care test from urine samples of patients on therapy with apixaban, rivaroxaban and dabigatran. J 
Thromb Haemostas 2017, Abstract, in press.
Harenberg J, et al Measurement of dabigatran, rivaroxaban and apixaban in samples of plasma, serum and urine, under real life conditions. An interna­
tional study. Clin Chem Lab Med. 2016 Feb;54(2):275-283. 
Du S, et al. Determination of dabigatran in plasma, serum, and urine samples: comparison of six methods. Clin Chem Lab Med. 2015 Jul;53(8):1237-
1247. 
Harenberg J, et al. 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):228-236. 
Favaloro EJ, et al. Laboratory testing in the era of direct or non-vitamin K antagonist oral anticoagulants: a practical guide to measuring their activity 
and avoiding diagnostic errors. Semin Thromb Hemost. 2015 Mar;41(2):208-227.
Harenberg J, et al. Concept of a point of care test to detect new oral anticoagulants in urine samples. Thromb J. 2013 Aug 1;11(1):15.
Needleman SB, Porvaznik M, Ander D. Creatinine analysis in single collection urine specimens. J Forensic Sci. 1992 Jul;37(4):1125-1133.
SYMBOLE 
Datum der letzten Bearbeitung: 30.6.2017
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