Reversibility of Apixaban Anticoagulation With the Four Factor Prothrombin Complex Concentrate Kcentra (4PAR)

June 6, 2016 updated by: Thomas Jefferson University

A Phase I Placebo-Controlled, Open-Label, Crossover Study to Assess the Reversibility of Apixaban Anticoagulation With the Four Factor Prothrombin Complex Concentrate Kcentra in Healthy Volunteers

Apixaban is an anticoagulant (also known as blood thinner) approved by the Food and Drug Administration (FDA) for reducing the risk of stroke and systemic embolism in patients with non-valvular atrial fibrillation. It has no reliable method of reversal. Kcentra is an FDA approved drug derived from blood that is used as an antidote to treat people with bleeding associated with taking the well-known anticoagulant warfarin. This is a Phase I, placebo-controlled, single site, open-label, crossover trial to evaluate the reversibility apixaban anticoagulation with Kcentra.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

Oral anticoagulants are effective in the treatment and prevention of venous and arterial thrombotic events. For more than 50 years the only class of anticoagulant available had been the vitamin K antagonist (VKA), warfarin, which requires frequent blood work for monitoring. Apixaban is a new approved anticoagulant that is used to treat patients who have blood clots or are at risk for developing blood clots. Unlike warfarin, the use of apixaban does not require frequent blood work for monitoring and is associated with lower bleeding risk. All anticoagulation therapies are associated with spontaneous or provoked bleeding risk and reversal of their blood thinning effects might be needed. Reversal of anticoagulation may also be needed in cases where emergent or urgent surgery is indicated. There is currently no available reversal agent for apixaban. Prothrombin complex concentrate (PCC) contain clotting factors and can replace factors inhibited by anticoagulants. In a recent study in the Netherlands a four factor prothrombin complex concentrate, Cofact (not available in the USA) was shown to be able to reverse the anticoagulation effects of another factor Xa inhibitor, rivaroxaban. Kcentra is a four factor prothrombin complex concentrate that was FDA approved in 2013 and is used as an antidote to treat people with bleeding associated with taking warfarin. It contains clotting factors II, VII, IX and X derived from donated blood and could be effective in reversing the anticoagulation effects of the factor Xa inhibitor, apixaban. No effective reversal agent for apixaban exists. Physicians struggle with bleeding in patients who are on apixaban. Indeed, this is not an uncommon problem for patients who suffer brain bleeds or trauma. This study could potentially identify Kcentra as reversal agent for patients taking apixaban. This study will test the hypothesis that Kcentra has the potential to significantly reduce the anticoagulation effect of apixaban as measured by thrombin generation assay at 30 minutes post infusion of Kcentra as compared to placebo infusion in subjects dosed to steady state with apixaban.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
12

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Pennsylvania
      • Philadelphia, Pennsylvania, United States, 19107
        • Thomas Jefferson University Hosptial

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

14 years to 51 years (Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • In order to be eligible for participation in this trial, the subject must:

    1. Be a healthy male or female between ages 18-55 (inclusive) at the screening visit
    2. Have a body mass index (BMI) >19 and <33 (inclusive)

    3. If a female, subject

      1. Can be of childbearing potential and must demonstrate a urine β-hCG level consistent with the nongravid state at the pretrial (screening) visit and agree to use (and/or have their partner use) an acceptable method of birth control beginning at the pretrial visit throughout the trial (including washout intervals between treatment periods) and until 2 weeks after the last dose of trial drug in the last treatment period.
      2. Can be of non-childbearing potential which is defined as: a female who is postmenopausal without menses for at least 1 year and an Follicle stimulating hormone value in the postmenopausal range upon pretrial (screening) evaluation and/or a female who is status post hysterectomy, oophorectomy or tubal ligation
      3. Must be off hormonal oral or transdermal contraceptives for at least 4 weeks prior to initial dose of trial drug
    4. Be a nonsmoker for at least approximately 6 months
    5. Have serum creatinine level < 1.5 mg/dL
    6. Have a prothrombin time (PT) and activated partial thromboplastin time (PTT) level below the upper limit of normal
    7. Have platelet count within normal limits
    8. Be willing to refrain from the use of anticoagulants and antiplatelet medications including aspirin and non-steroidal anti-inflammatory drugs (NSAIDs) during the entire period of study participation
    9. Be willing to provide written informed consent for the trial
    10. Be willing to comply with trial restrictions

Exclusion Criteria:

  1. Has a history of clinically significant endocrine, gastrointestinal, cardiovascular, hematological, hepatic, immunological, renal, respiratory, genitourinary or major neurological (including stroke and chronic seizures) abnormalities or diseases
  2. Has history of cancer (excluding treated cutaneous squamous or basal cell carcinoma of >3 years previous)
  3. Has history of venous or arterial thromboembolic disease
  4. Has a history of clinically significant bleeding risks including prior serious head trauma
  5. Has had major surgery within 6 months prior to screening visit
  6. Is unable to refrain from or anticipates the use of any medication, including prescription and non-prescription drugs or herbal remedies for 2 weeks prior to trial start date until the post-trial visit
  7. Is unable to refrain from using any drugs or substance known to be inhibitors or inducers of cytochrome P450 (CYP) enzymes including grapefruit products for 2 weeks prior to dosing and throughout the study, until the post-trial visit
  8. Has a history of illicit drug abuse within six months prior to screening visit
  9. Consumes greater than 3 glasses of alcoholic beverages (1 glass is approximately equivalent to: beer [354 mL/12 ounces], wine [118 mL/4 ounces], or distilled spirits [29.5 mL/1 ounce]) per day and cannot refrain from alcohol for the duration of the trial
  10. Has a history of significant multiple and/or severe allergies (e.g. food, drug), or has had an anaphylactic reaction or significant intolerability to prescription or non-prescription drugs or food
  11. Has known anaphylactic or severe systemic reactions to any components of study drugs (including heparin induced thrombocytopenia) or contraindication to the administration of PCC or any other related blood products.
  12. Has moderate or severe hepatic disease or other clinically relevant bleeding risk
  13. Has positive history for hepatitis B surface antigen, hepatitis C or HIV
  14. Has first degree relatives with history of bleeding disorder or hypercoagulable disease
  15. Use of any drugs or products which at the discretion of the investigator would increase bleeding risk
  16. Is considered inappropriate for participation by the investigator for any reason

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Crossover Assignment
  • Masking: Single

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Active Comparator: Apixaban with Kcentra
Oral apixaban will be administered to steady state in healthy volunteers followed by a single infusion of prothrombin complex concentrate Kcentra at 25 units/Kg
Drug: Apixaban
Drug: Kcentra
IV infusion
Other Names:
  • 4 factor prothrombin complex concentrate
Placebo Comparator: Apixaban with placebo
Oral apixaban will be administered to steady state in healthy volunteers followed by a single infusion of saline
Drug: Placebo
Drug: Apixaban

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Time Frame
thrombin generation assay (TGA)
Time Frame: 30 minutes
30 minutes

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Time Frame
Anti-factor Xa activity
Time Frame: 30 minutes
30 minutes

Other Outcome Measures

Other Outcome Measures

For clinical trials, a planned measurement described in the protocol that is used to determine the effect of an intervention/treatment on participants. For observational studies, a measurement or observation that is used to describe patterns of diseases or traits, or associations with exposures, risk factors, or treatment. Types of outcome measures include primary outcome measure and secondary outcome measure.
Outcome Measure
Time Frame
prothrombin time (PT)
Time Frame: 30 minutes
30 minutes
activated partial thromboplastin time (PTT)
Time Frame: 30 minutes
30 minutes

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Thomas Jefferson University

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
Bristol-Myers Squibb
CSL Behring

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Walter K Kraft, MD, Thomas Jefferson University

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
November 1, 2014

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
December 1, 2014

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
December 1, 2014

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
October 17, 2014

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
October 20, 2014

First Posted (Estimate)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
October 21, 2014

Study Record Updates

Last Update Posted (Estimate)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
June 7, 2016

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
June 6, 2016

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
June 1, 2016

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • 14P.366

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

Yes

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Cookie Settings

We use cookies to ensure that we give you the best experience on our website. For more details carefully read our Privacy and Cookies Policy. ...>>>You can change your preferences or withdraw your consent at any time by deleting the cookies from your website or computer as described in the policy. Please accept it and choose your preferences by ticking the corresponding boxes in the "Manage Settings" section below. Please carefully read our Terms of Service before you proceed with using any part of this website.
«Manage Settings