ThrombosisPhase 14PARNCT02270918
Reversibility of Apixaban Anticoagulation With the Four Factor Prothrombin Complex Concentrate Kcentra
A Phase 1 study testing Kcentra and Apixaban in people with Thrombosis, run by Thomas Jefferson University at 1 site in United States.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 18 to 55 yearsHealthy volunteers can take part
- Conditions the study is for
- Thrombosis
- What is being tested?
- Kcentra and Apixaban
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 12 participants
- Where
- 1 siteUnited States
- Study dates
- Nov 2014to Dec 2014
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 55 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- In order to be eligible for participation in this trial, the subject must:
- Be a healthy male or female between ages 18-55 (inclusive) at the screening visit
- Have a body mass index (BMI) >19 and <33 (inclusive)
- If a female, subject
- 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.
- 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
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- Must be off hormonal oral or transdermal contraceptives for at least 4 weeks prior to initial dose of trial drug
- Be a nonsmoker for at least approximately 6 months
- Have serum creatinine level < 1.5 mg/dL
- Have a prothrombin time (PT) and activated partial thromboplastin time (PTT) level below the upper limit of normal
- Have platelet count within normal limits
- 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
- Be willing to provide written informed consent for the trial
- Be willing to comply with trial restrictions
Who cannot join
- 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
- Has history of cancer (excluding treated cutaneous squamous or basal cell carcinoma of >3 years previous)
- Has history of venous or arterial thromboembolic disease
- Has a history of clinically significant bleeding risks including prior serious head trauma
- Has had major surgery within 6 months prior to screening visit
- 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
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- 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
- Has a history of illicit drug abuse within six months prior to screening visit
- 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
- 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
- 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.
- Has moderate or severe hepatic disease or other clinically relevant bleeding risk
- Has positive history for hepatitis B surface antigen, hepatitis C or HIV
- Has first degree relatives with history of bleeding disorder or hypercoagulable disease
- Use of any drugs or products which at the discretion of the investigator would increase bleeding risk
- Is considered inappropriate for participation by the investigator for any reason
Trial locations and contacts
1 site in 1 country.
United States1 site
Thomas Jefferson University Hosptial
Philadelphia, Pennsylvania, 19107
About this study
Official title: 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.
Read the 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.
- Conditions
- Thrombosis
- Being tested
- Kcentra, Apixaban, Placebo
- Keywords
- Xa inhibitor, Prothrombin complex concentrate, anticoagulation
- Medical subject headings
- Thrombosis, Hemophilia B
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
KcentraDrug
Also called 4 factor prothrombin complex concentrate
IV infusion
ApixabanDrug
PlaceboDrug
| Study group | Role | What they receive |
|---|---|---|
| Apixaban with Kcentra | Active comparator | 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 Receives: Drug: Kcentra; Drug: Apixaban |
| Apixaban with placebo | Placebo comparator | Oral apixaban will be administered to steady state in healthy volunteers followed by a single infusion of saline Receives: Drug: Apixaban; Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
thrombin generation assay (TGA)
Measured: 30 minutes
Secondary outcomes (1)
Anti-factor Xa activity
Measured: 30 minutes
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 Oct 2014 (estimated)
- Study startNov 2014
- Primary completionDec 2014
- Study completionDec 2014
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for ThrombosisStudies of the same condition, open and under way.
- More trials run by Thomas Jefferson UniversityThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Single blind
- Who is masked
- Outcomes assessor
- Enrolment
- 12 participants (actual)
Sponsor and investigators
- Lead sponsor
- Thomas Jefferson University
- Sponsor type
- University, hospital or other
- Collaborators
- Bristol-Myers Squibb, CSL Behring
- Responsible party
- Sponsor
- Investigators
- Walter K Kraft, MD, Principal investigator, Thomas Jefferson University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02270918
- Sponsor's protocol ID
- 14P.366
- Acronym
- 4PAR
- Status last verified
- Jun 2016
- First submitted
- 17 Oct 2014
- Last updated
- 7 Jun 2016
- Results posted
- No
- Data monitoring committee
- No
- Individual data sharing
- Yes
Publications
Nagalla S, Thomson L, Oppong Y, Bachman B, Chervoneva I, Kraft WK. Reversibility of Apixaban Anticoagulation with a Four-Factor Prothrombin Complex Concentrate in Healthy Volunteers. Clin Transl Sci. 2016 Jun;9(3):176-80. doi: 10.1111/cts.12398. Epub 2016 May 12.
PubMed 27170068
Study at a glance
From the registry record, last updated by the sponsor on 7 Jun 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- 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
- ClinicalTrials.gov ID
- NCT02270918
- Acronym / sponsor ID
- 4PAR / 14P.366
- Conditions
- Thrombosis
- Keywords
- Xa inhibitor, Prothrombin complex concentrate, anticoagulation
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 12 participants (actual)
- Lead sponsor
- Thomas Jefferson UniversityUniversity, hospital or other
- Collaborators
- Bristol-Myers Squibb, CSL Behring
- Study start
- Nov 2014
- Primary completion
- Dec 2014 (actual)
- Study completion
- Dec 2014 (actual)
- First posted
- 21 Oct 2014 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Single blind (outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Apixaban with Kcentra | Active comparator | Drug: Kcentra, Drug: ApixabanOral apixaban will be administered to steady state in healthy volunteers followed by a single infusion of prothrombin complex concentrate Kcentra at 25 units/Kg |
| Apixaban with placebo | Placebo comparator | Drug: Apixaban, Drug: PlaceboOral apixaban will be administered to steady state in healthy volunteers followed by a single infusion of saline |
Who may qualify
- Ages
- 18 to 55 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (14 listed)
- In order to be eligible for participation in this trial, the subject must:
Key exclusion criteria (16 listed)
- 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
- Has history of cancer (excluding treated cutaneous squamous or basal cell carcinoma of >3 years previous)
- Has history of venous or arterial thromboembolic disease
- Has a history of clinically significant bleeding risks including prior serious head trauma
- Has had major surgery within 6 months prior to screening visit
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| KcentraAlso: 4 factor prothrombin complex concentrateIV infusion | Drug | Apixaban with Kcentra |
| Apixaban | Drug | Apixaban with Kcentra, Apixaban with placebo |
| Placebo | Drug | Apixaban with placebo |
Primary outcome
thrombin generation assay (TGA)
Time frame: 30 minutes
1 secondary outcome
Anti-factor Xa activity
Time frame: 30 minutes
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 7 Jun 2016.
- Results publication: PubMed 27170068Nagalla S, Thomson L, Oppong Y, Bachman B, Chervoneva I, Kraft WK. Reversibility of Apixaban Anticoagulation with a Four-Factor Prothrombin Complex Concentrate in Healthy Volunteers. Clin Transl Sci. 2016 Jun;9(3):176-80. doi: 10.1111/cts.12398. Epub 2016 May 12.
- Individual participant dataSharing planned: Yes
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Walter K Kraft, MD principal investigator
Thomas Jefferson University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Kcentra and Apixaban in people with Thrombosis, run by Thomas Jefferson University at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 14 inclusion and 16 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 7 Jun 2016. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
thrombin generation assay (TGA) (time frame: 30 minutes). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02270918, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 7 Jun 2016.