HemorrhageNCT02565836
Fixed-dose Activated Versus Variable-dose Inactivated Prothrombin Complex Concentrate for Warfarin-associated Major Bleed
An observational study of Hemorrhage, run by Rush University Medical Center.
Trial summary
This study aims to assess a fixed-dose regimen of activated prothrombin complex concentrate (FEIBA VH, Baxter) versus the variable, manufacturer recommended, dose regimen of inactivated prothrombin complex concentrate (Kcentra, CSL Behring) for reversal of warfarin-associated major hemorrhage. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Hemorrhage
- What is being tested?
- fixed-dose activated prothrombin complex concentrate and variable-dose inactivated prothrombin complex concentrate
- Type of treatment
- Injection or infusion
- How many people
- 342 participants
- Where
- No sites listed yet
- Study dates
- Oct 2015to 30 Sep 2016
- Phase
- Observational
- 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 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Study population: Patients administered a prothrombin complex concentrate as part of routine care for INR normalization due to a major bleed will be assessed for inclusion.
Who may be able to join
- Pre-treatment INR lab value greater than 1.5
- Receipt of treatment with a 4-factor PCC for INR normalization due to warfarin-associated major hemorrhage
Who cannot join
- Patients treated with a PCC for an urgent invasive procedure without active hemorrhage
- Patients treated with PCC not taking a VKA
- Unavailable pre- or post-treatment INR lab values
- Pregnant patients
About this study
Official title: Reversal of Warfarin-associated Major Hemorrhage: a Multicenter, Retrospective Cohort Study of Fixed-dose Activated (FEIBA VH) Versus Variable-dose Inactivated (Kcentra) Prothrombin Complex Concentrate
This study aims to assess a fixed-dose regimen of activated prothrombin complex concentrate (FEIBA VH, Baxter) versus the variable, manufacturer recommended, dose regimen of inactivated prothrombin complex concentrate (Kcentra, CSL Behring) for reversal of warfarin-associated major hemorrhage.
Read the detailed description
Warfarin, a vitamin K antagonist (VKA), is the most frequently prescribed oral anticoagulant. Warfarin-associated major hemorrhage occurs at a rate of 1.7% to 3.4% in routine clinical practice and warrants rapid reversal of anticoagulation by correcting supratherapeutic international normalized ratio (INR) values.
Warfarin inhibits synthesis of vitamin K dependent coagulation factors II, VII, IX, and X, and strategies for reversal of warfarin-associated coagulopathy are aimed at restoring deficient factors. Four-factor prothrombin complex concentrates (PCCs) contain the coagulation factors which warfarin inhibits and are an attractive option for rapid reversal due to ease of reconstitution and no requirement for blood-type matching.
Manufacturer dosing recommendations exist for PCCs based on patient weight, baseline INR, and target INR, but studies have suggested fixed dosing strategies in an effort to determine the most efficacious dose for VKA-reversal while sparing adverse events. These studies have also utilized different PCC formulations, with some studies utilizing 4-factor activated PCC (aPCC), which denotes product containment of factor VII in an activated state.
In the United States, product availability is limited to a single 4-factor aPCC (FEIBA VH, Baxter) indicated for hemophilia patients with inhibitors and a single 4-factor inactivated PCC (Kcentra, CSL Behring) approved for VKA-reversal. Various institutions choose to utilize off-label fixed dosing strategies of 4-factor aPCC in an effort to administer the lowest possible dose to reverse VKAs, while others utilize manufacturer recommended dosing of 4-factor inactivated PCC.
- Conditions
- Hemorrhage
- Being tested
- fixed-dose activated prothrombin complex concentrate, variable-dose inactivated prothrombin complex concentrate
- Keywords
- Vitamin K 1, prothrombin complex concentrates, warfarin
- Medical subject headings
- Hemorrhage
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
fixed-dose activated prothrombin complex concentrateDrug
Also called FEIBA, FEIBA VH
FEIBA VH 500 units IV one time for INR less than 5. FEIBA VH 1000 units IV one time for INR greater than 5.
Check INR after infusion and may repeat dose if INR still elevated
variable-dose inactivated prothrombin complex concentrateDrug
Also called Kcentra
Kcentra 25 units/kg IV one time for INR less than 4. Kcentra 35 units/kg IV one-time for INR 4 to 6. Kcentra 50 units/kg IV one-time for INR greater than 6.
Check INR after infusion and may repeat dose if INR still elevated.
| Study group | Role | What they receive |
|---|---|---|
| fixed-dose aPCC | Patients receiving fixed-dose activated prothrombin complex concentrate (FEIBA VH) for reversal of warfarin-associated major hemorrhage. Receives: Drug: fixed-dose activated prothrombin complex concentrate | |
| variable-dose PCC | Patients receiving vairable-dose inactivated prothrombin complex concentrate (Kcentra) for reversal of warfarin-associated major hemorrhage. Receives: Drug: variable-dose inactivated prothrombin complex concentrate |
What is being measured
The primary outcome is the main question the study is designed to answer.
Achievement of INR less than or equal to 1.5
The number of patients achieving a goal INR of less than or equal to 1.5 within 60 minutes following administration of 4-factor fixed-dose aPCC (FEIBA VH) versus variable-dose inactivated PCC (Kcentra) for reversal of warfarin-associated major hemorrhage.
Measured: 60 minutes
Secondary outcomes (1)
Incidence of mortality or thrombotic events
Incidence of mortality, deep vein thrombosis, pulmonary embolism, myocardial infarction, and ischemic cerebrovascular events within 30 days following administration of 4-factor fixed-dose aPCC (FEIBA VH) or variable-dose inactivated PCC (Kcentra) for reversal of warfarin-associated major hemorrhage.
Measured: 30 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted1 Oct 2015 (estimated)
- Study startOct 2015
- Primary completion30 Sep 2016
- Study completion30 Sep 2016
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (5)Papers the sponsor has linked to this study.
- Other trials for HemorrhageStudies of the same condition, open and under way.
- More trials run by Rush University Medical CenterThe 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
- Observational
- Observational model
- Cohort
- Time perspective
- Retrospective
- Enrolment
- 342 participants (actual)
Sponsor and investigators
- Lead sponsor
- Rush University Medical Center
- Sponsor type
- University, hospital or other
- Collaborators
- Wake Forest University Health Sciences
- Responsible party
- Sponsor
- Investigators
- Gary D Peksa, PharmD, Principal investigator, Rush University Medical CenterRobert Mokszycki, PharmD, Principal investigator, advocate christ medical center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02565836
- Sponsor's protocol ID
- 15092404
- Status last verified
- Oct 2017
- First submitted
- 24 Sep 2015
- Last updated
- 25 Oct 2017
- Results posted
- No
- Data monitoring committee
- No
Publications
Junagade P, Grace R, Gover P. Fixed dose prothrombin complex concentrate for the reversal of oral anticoagulation therapy. Hematology. 2007 Oct;12(5):439-40. doi: 10.1080/10245330701448529.
PubMed 17852462Wojcik C, Schymik ML, Cure EG. Activated prothrombin complex concentrate factor VIII inhibitor bypassing activity (FEIBA) for the reversal of warfarin-induced coagulopathy. Int J Emerg Med. 2009 Nov 26;2(4):217-25. doi: 10.1007/s12245-009-0125-8.
PubMed 20436891Khorsand N, Veeger NJ, van Hest RM, Ypma PF, Heidt J, Meijer K. An observational, prospective, two-cohort comparison of a fixed versus variable dosing strategy of prothrombin complex concentrate to counteract vitamin K antagonists in 240 bleeding emergencies. Haematologica. 2012 Oct;97(10):1501-6. doi: 10.3324/haematol.2012.063701. Epub 2012 Apr 4.
PubMed 22491734Stewart WS, Pettit H. Experiences with an activated 4-factor prothrombin complex concentrate (FEIBA) for reversal of warfarin-related bleeding. Am J Emerg Med. 2013 Aug;31(8):1251-4. doi: 10.1016/j.ajem.2013.05.008. Epub 2013 Jun 10.
PubMed 23763937Sarode R, Milling TJ Jr, Refaai MA, Mangione A, Schneider A, Durn BL, Goldstein JN. Efficacy and safety of a 4-factor prothrombin complex concentrate in patients on vitamin K antagonists presenting with major bleeding: a randomized, plasma-controlled, phase IIIb study. Circulation. 2013 Sep 10;128(11):1234-43. doi: 10.1161/CIRCULATIONAHA.113.002283. Epub 2013 Aug 9.
PubMed 23935011
Study at a glance
From the registry record, last updated by the sponsor on 25 Oct 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Reversal of Warfarin-associated Major Hemorrhage: a Multicenter, Retrospective Cohort Study of Fixed-dose Activated (FEIBA VH) Versus Variable-dose Inactivated (Kcentra) Prothrombin Complex Concentrate
- ClinicalTrials.gov ID
- NCT02565836
- Acronym / sponsor ID
- 15092404
- Conditions
- Hemorrhage
- Keywords
- Vitamin K 1, prothrombin complex concentrates, warfarin
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 342 participants (actual)
- Lead sponsor
- Rush University Medical CenterUniversity, hospital or other
- Collaborators
- Wake Forest University Health Sciences
- Study start
- Oct 2015
- Primary completion
- 30 Sep 2016 (actual)
- Study completion
- 30 Sep 2016 (actual)
- First posted
- 1 Oct 2015 (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.
This study aims to assess a fixed-dose regimen of activated prothrombin complex concentrate (FEIBA VH, Baxter) versus the variable, manufacturer recommended, dose regimen of inactivated prothrombin complex concentrate (Kcentra, CSL Behring) for reversal of warfarin-associated major hemorrhage.
Detailed description
Warfarin, a vitamin K antagonist (VKA), is the most frequently prescribed oral anticoagulant. Warfarin-associated major hemorrhage occurs at a rate of 1.7% to 3.4% in routine clinical practice and warrants rapid reversal of anticoagulation by correcting supratherapeutic international normalized ratio (INR) values.
Warfarin inhibits synthesis of vitamin K dependent coagulation factors II, VII, IX, and X, and strategies for reversal of warfarin-associated coagulopathy are aimed at restoring deficient factors. Four-factor prothrombin complex concentrates (PCCs) contain the coagulation factors which warfarin inhibits and are an attractive option for rapid reversal due to ease of reconstitution and no requirement for blood-type matching.
Manufacturer dosing recommendations exist for PCCs based on patient weight, baseline INR, and target INR, but studies have suggested fixed dosing strategies in an effort to determine the most efficacious dose for VKA-reversal while sparing adverse events. These studies have also utilized different PCC formulations, with some studies utilizing 4-factor activated PCC (aPCC), which denotes product containment of factor VII in an activated state.
In the United States, product availability is limited to a single 4-factor aPCC (FEIBA VH, Baxter) indicated for hemophilia patients with inhibitors and a single 4-factor inactivated PCC (Kcentra, CSL Behring) approved for VKA-reversal. Various institutions choose to utilize off-label fixed dosing strategies of 4-factor aPCC in an effort to administer the lowest possible dose to reverse VKAs, while others utilize manufacturer recommended dosing of 4-factor inactivated PCC.
Study design
- Observational model
- Cohort
- Time perspective
- Retrospective
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| fixed-dose aPCC | – | Drug: fixed-dose activated prothrombin complex concentratePatients receiving fixed-dose activated prothrombin complex concentrate (FEIBA VH) for reversal of warfarin-associated major hemorrhage. |
| variable-dose PCC | – | Drug: variable-dose inactivated prothrombin complex concentratePatients receiving vairable-dose inactivated prothrombin complex concentrate (Kcentra) for reversal of warfarin-associated major hemorrhage. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- Patients administered a prothrombin complex concentrate as part of routine care for INR normalization due to a major bleed will be assessed for inclusion.
Key inclusion criteria (2 listed)
- Pre-treatment INR lab value greater than 1.5
- Receipt of treatment with a 4-factor PCC for INR normalization due to warfarin-associated major hemorrhage
Key exclusion criteria (4 listed)
- Patients treated with a PCC for an urgent invasive procedure without active hemorrhage
- Patients treated with PCC not taking a VKA
- Unavailable pre- or post-treatment INR lab values
- Pregnant patients
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 |
|---|---|---|
| fixed-dose activated prothrombin complex concentrateAlso: FEIBA, FEIBA VHFEIBA VH 500 units IV one time for INR less than 5. FEIBA VH 1000 units IV one time for INR greater than 5. Check INR after infusion and may repeat dose if INR still elevated | Drug | fixed-dose aPCC |
| variable-dose inactivated prothrombin complex concentrateAlso: KcentraKcentra 25 units/kg IV one time for INR less than 4. Kcentra 35 units/kg IV one-time for INR 4 to 6. Kcentra 50 units/kg IV one-time for INR greater than 6. Check INR after infusion and may repeat dose if INR still elevated. | Drug | variable-dose PCC |
Primary outcome
Achievement of INR less than or equal to 1.5
Time frame: 60 minutes
The number of patients achieving a goal INR of less than or equal to 1.5 within 60 minutes following administration of 4-factor fixed-dose aPCC (FEIBA VH) versus variable-dose inactivated PCC (Kcentra) for reversal of warfarin-associated major hemorrhage.
1 secondary outcome
Incidence of mortality or thrombotic events
Time frame: 30 days
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 25 Oct 2017.
- Background: PubMed 17852462Junagade P, Grace R, Gover P. Fixed dose prothrombin complex concentrate for the reversal of oral anticoagulation therapy. Hematology. 2007 Oct;12(5):439-40. doi: 10.1080/10245330701448529.
- Background: PubMed 20436891Wojcik C, Schymik ML, Cure EG. Activated prothrombin complex concentrate factor VIII inhibitor bypassing activity (FEIBA) for the reversal of warfarin-induced coagulopathy. Int J Emerg Med. 2009 Nov 26;2(4):217-25. doi: 10.1007/s12245-009-0125-8.
- Background: PubMed 22491734Khorsand N, Veeger NJ, van Hest RM, Ypma PF, Heidt J, Meijer K. An observational, prospective, two-cohort comparison of a fixed versus variable dosing strategy of prothrombin complex concentrate to counteract vitamin K antagonists in 240 bleeding emergencies. Haematologica. 2012 Oct;97(10):1501-6. doi: 10.3324/haematol.2012.063701. Epub 2012 Apr 4.
- Background: PubMed 23763937Stewart WS, Pettit H. Experiences with an activated 4-factor prothrombin complex concentrate (FEIBA) for reversal of warfarin-related bleeding. Am J Emerg Med. 2013 Aug;31(8):1251-4. doi: 10.1016/j.ajem.2013.05.008. Epub 2013 Jun 10.
- Background: PubMed 23935011Sarode R, Milling TJ Jr, Refaai MA, Mangione A, Schneider A, Durn BL, Goldstein JN. Efficacy and safety of a 4-factor prothrombin complex concentrate in patients on vitamin K antagonists presenting with major bleeding: a randomized, plasma-controlled, phase IIIb study. Circulation. 2013 Sep 10;128(11):1234-43. doi: 10.1161/CIRCULATIONAHA.113.002283. Epub 2013 Aug 9.
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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.
Gary D Peksa, PharmD principal investigator
Rush University Medical Center
Robert Mokszycki, PharmD principal investigator
advocate christ medical center
Questions about this trial
What is this clinical trial studying?
An observational study of Hemorrhage, run by Rush University Medical Center.
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 2 inclusion and 4 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 25 Oct 2017. Status can change between updates, so confirm with the study contact before making plans.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
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?
Achievement of INR less than or equal to 1.5 (time frame: 60 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 NCT02565836, which also lists 5 linked publications.
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 25 Oct 2017.