In Vitro Diagnostic Test for DOAC in Urine (PADOASU)

Doasense

Status: Completed

Conditions: Anticoagulant Therapy

Treatments: Diagnostic Test: DOAC Dipstick

Study type: Observational

Funder types: Industry; Other

Identifiers

NCT03182829

DOA-CS-002

Details and patient eligibility

About

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]"

Full 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]"

Enrollment: 880 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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]"

Trial design

880 participants in 2 patient groups

Factor Xa inhibitor

Description:

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. \[Epub ahead of print\]"

Treatment:

Diagnostic Test: DOAC Dipstick

Thrombin inhibitor

Description:

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. \[Epub ahead of print\]"

Treatment:

Diagnostic Test: DOAC Dipstick