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Direct Oral Anticoagulants Pharmacodynamics in Octogenarian Patients With Atrial Fibrillation

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ClinicalTrials.gov Identifier: NCT02623049
Recruitment Status : Recruiting
First Posted : December 7, 2015
Last Update Posted : January 11, 2019
Sponsor:
Collaborator:
Pfizer
Information provided by (Responsible Party):
shmuel fuchs, Rabin Medical Center

Brief Summary:

Background: The incidence of atrial fibrillation(AF) increases substantially with age and it is estimated that more than one third of AF patients are octogenarians. Direct oral anticoagulants (DOACs) were found favorable compared to warfarin with respect to efficacy and safety ( bleeding) across wide range of ages.

Nevertheless, the rates of bleeding among elderly patients were shown to increase substantially with all anticoagulants. Dose-adjustments of DOAC are not universally performed among patients older than 80 years old and currently there is paucity of data regarding the actual drugs level among these patients. Accordingly, the investigators sought to investigate the drug levels of the different DOACs among "real world" octogenarians who receiving guideline-recommended dosage.

Methods: A cross sectional, prospective study of 120 hospitalized and ambulatory patients who are treated with DOACs for AF.

DOACs blood levels with be compared between octogenarians (n=70) and younger patient group ( age≤70 year-old; n=50).The cohort will include: 1)Sixty patients on APIXABAN: 40 octogenarians and 20 younger than 70 years, 2)Forty patients on RIVAROXABAN: 20 octogenarians and 20 younger than 70 years, and 3) Twenty patients treated with DABIGATRAN: 10 octogenarians and 10 younger than 70 years.

DOACs Pharmacodynamic analysis will be performed using commercial kits for diluted thrombin time(DTT) and anti-factor Xa activity (AFXa). Drug level will be measured at steady state( through levels) and at Tmax after at least 4 days of complete adherence for DOAC consumption.

Study End-Points:The study main objectives are: 1) DOACs levels in octogenarians in comparison to patients younger than 70 years and 2)percentage of patients, in each group, who have target DTT or AFXa ( predicted) at steady state.

Potential significance of the study:

The results of the study may provide new data on DOACs levels in octogenarians and thus would either support current recommendations or set the ground for further studies aim to optimize DOACs dosage in this vulnerable population.


Condition or disease Intervention/treatment
Atrial Fibrillation and Flutter Other: New oral anticoagulant pharmacodynamic analysis (blood level assesment)

  Show Detailed Description

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Study Type : Observational
Estimated Enrollment : 150 participants
Observational Model: Cohort
Time Perspective: Cross-Sectional
Official Title: Direct Oral Anticoagulants Pharmacodynamics in Octogenarian Patients With Atrial Fibrillation
Study Start Date : November 2015
Estimated Primary Completion Date : December 2019
Estimated Study Completion Date : December 2019

Resource links provided by the National Library of Medicine


Group/Cohort Intervention/treatment
octogenarians patients - Apixaban
octogenarians patients who will be treated with Apixaban
Other: New oral anticoagulant pharmacodynamic analysis (blood level assesment)
younger than 70 years patients - Apixaba
younger than 70 years patients who will be treated with Apixaba
Other: New oral anticoagulant pharmacodynamic analysis (blood level assesment)
octogenarians patients - Rivaroxaban
octogenarians patients who will be treated with Rivaroxaban
Other: New oral anticoagulant pharmacodynamic analysis (blood level assesment)
younger than 70 years patients - Rivaroxaban
younger than 70 years patients who will be treated with Rivaroxaban
Other: New oral anticoagulant pharmacodynamic analysis (blood level assesment)
octogenarians patients - Dabigatran
octogenarians patients who will be treated with Dabigatran
Other: New oral anticoagulant pharmacodynamic analysis (blood level assesment)
younger than 70 years patients - Dabigatran
younger than 70 years patients who will be treated with Dabigatran
Other: New oral anticoagulant pharmacodynamic analysis (blood level assesment)



Primary Outcome Measures :
  1. Diluted thrombin time (DTT) for Dabigatran [ Time Frame: trough and peak levels after at least 4 days of drug intake (trough will be taken just before the morning dose and peak levels 2 hours after the intake of Dabigatran) ]
  2. anti FXa-activity for Apixaban and Rivaroxaban [ Time Frame: trough and peak levels after at least 4 days of drug intake (trough will be taken just before the morning dose and peak levels 3 hours after the intake of Apixaba/Rivaroxaban) ]

Biospecimen Retention:   Samples Without DNA
Blood sample


Information from the National Library of Medicine

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Ages Eligible for Study:   Child, Adult, Older Adult
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Sampling Method:   Non-Probability Sample
Study Population
Candidate for the study will be patients older than 80 years (octogenarians) and those ≤70 years who are 1) admitted to the Internal Medicine division in Rabin Medical Center or to Beit Rivka rehabilitation hospital who are on treatment of DOAC prior to their hospitalization \ rehabilitation , 2) hospitalized patients in whom DOAC will be initiated during hospitalization and 3) referred ambulatory patients on DOACs. Each potential patient will be screened for age and other risk factors for bleeding (specifically those that requires dose adjustment such as renal failure, weight, potentially interacting drugs) under DOAC treatment.
Criteria

Inclusion Criteria:

  • Octogenarian group : Age ≥ 80 years.
  • Younger age group: Age ≤ 70 years.
  • Previous diagnosis of non-valvular atrial fibrillation / flutter or new diagnosis, documented by electrocardiography
  • CHA2DS2-VASc score ≥1.
  • Hemodynamically stable patients (i.e., without cardiogenic shock or circulatory collapse).
  • Receiving DOACs for at least 4 days.
  • Stable renal function.

Exclusion Criteria:

  • Patients who are expected to stop DOACs within the 4-8 days (i.e. planned operation or invasive procedure)
  • Patients who require dose adjustment of DOACs based on clinical judgment and not on manufacturer recommendations (i.e. acute renal function deterioration with GFR less than 30 ml/min, need for dual antiplatelet therapy)
  • History of gastrointestinal conditions that could significantly impact drug absorption (such as Crohn's disease, gastrectomy).
  • A history of recent drug or alcohol abuse
  • Concomitant treatment with combined strong P-gp inhibitors and CYP3A4 inhibitors drugs (such as: grapefruit juice, itraconazole, lopinavir/ritonavir, clarithromycin, ritonavir, ketoconazole, indinavir/ritonavir, conivaptan).
  • Concomitant treatment with combined strong P-gp inducers and CYP3A4 inducers drugs (such as: avasimibe ,carbamazepine, phenytoin, phenobarbital, rifampin, St John's wort)
  • Estimated glomerular filtration rate < 30 ml/min
  • Patients with elevated liver enzymes ALT/AST > 3 x ULN or total bilirubin ≥ 1.5 x ULN.
  • Weight > 120 kg.
  • Pregnant woman.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02623049


Contacts
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Contact: Ran Nisan, PharmD 972-544892333 ranni@clalit.org.il
Contact: Maya Arlyuk 972-546841416 mayaor@clalit.org.il

Locations
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Israel
Internal Medicine B Department Recruiting
Petach Tikva, Israel, 49100
Contact: Maya Arlyuk    972546841416    mayaor@clalit.org.il   
Contact: Dora Shechter    972546339019    Doras2@clalit.org.il   
Rabin Medical Center, Beilinson Hospital Recruiting
Petach Tikva, Israel, 49100
Contact: Shmuel Fuchs, Professor    972-3-9376601\3    shmuelf@clalit.org.il   
Contact: Maya Arlyuk, Study Coordinator       mayaor@clalit.org.il   
Principal Investigator: Shmuel Fuchs, Professor         
Sponsors and Collaborators
Rabin Medical Center
Pfizer
Investigators
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Study Chair: Shmuel Fuches, MD Internal Medicine B Department, Rabin Medical Center, Beilinson Hospital
Principal Investigator: Ran Nissan, PharmD Internal Medicine B Department, Rabin Medical Center, Beilinson Hospital
Principal Investigator: Shai Shimoni, MD Internal Medicine B Department, Rabin Medical Center, Beilinson Hospital

Publications:

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: shmuel fuchs, Professor, Rabin Medical Center
ClinicalTrials.gov Identifier: NCT02623049     History of Changes
Other Study ID Numbers: 0590-15
First Posted: December 7, 2015    Key Record Dates
Last Update Posted: January 11, 2019
Last Verified: January 2019
Keywords provided by shmuel fuchs, Rabin Medical Center:
New oral anticoagulants
Blood levels
Octogenarians
Additional relevant MeSH terms:
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Atrial Fibrillation
Arrhythmias, Cardiac
Heart Diseases
Cardiovascular Diseases
Pathologic Processes
Rivaroxaban
Dabigatran
Anticoagulants
Factor Xa Inhibitors
Antithrombins
Serine Proteinase Inhibitors
Protease Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action