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Blood Coagulation DisordersPhase 3NCT00708435

Efficacy and Safety Study of BERIPLEX® P/N (Kcentra) Compared With Plasma in Patients With Acute Major Bleeding Caused by Anticoagulant Therapy

A Phase 3 study testing Beriplex® P/N (Kcentra) and Fresh frozen plasma in people with Blood Coagulation Disorders and Acute Major Bleeding, run by CSL Behring at 69 sites in 6 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

The purpose of this study is to evaluate efficacy, safety and tolerance of BERIPLEX® P/N (Kcentra) compared with plasma in regard to rapid reversal of coagulopathy induced by coumarin derivatives in subjects who require immediate correction of INR (International Normalized Ratio)and to stop an acute major bleeding. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Beriplex® P/N (Kcentra) and Fresh frozen plasma
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
216 participants
Where
69 sitesin 6 countries
Study dates
Jun 2008to Nov 2010
Phase
Phase 3
Are there results?
Yes, posted in the registrySummary in the doctors' view

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

Who may be able to join

  • Male and female subjects ≥ 18 years
  • Subjects who have received oral vitamin K-antagonist therapy
  • Subjects who have acute major bleeding, defined as one of the following: life-threatening or potentially life-threatening, acute bleeding associated with a fall in hemoglobin (Hb) level ≥ 2g/dL, bleeding requiring blood product transfusion
  • INR ≥ 2 within 3 hours before start of study treatment
  • Informed consent has been obtained

Who cannot join

  • Expected survival of less than 3 days, or expected surgery in less than 1 day
  • Acute trauma for which reversal of vitamin K antagonists alone would not be expected to control the acute bleeding event
  • Use of unfractionated or low molecular weight heparin use from 24 hours prior to enrollment or expected need within 24 hours after start of infusion
  • For patients with ICH: Glasgow coma score (GCS) < 7; intracerebral hematoma volume > 30cc as assessed by ABC/21; for subdural hematomas: maximum thickness ≥ 10 mm, midline shift ≥ 5 mm; for subarachnoid hemorrhage: any evidence of hydrocephalus; infratentorial ICH location; epidural hematomas; intraventricular extension of hemorrhage; modified Rankin score (mRS) of >3 prior to ICH
  • History of thrombotic event, myocardial infarction, disseminated intravascular coagulation, cerebral vascular accident, transient ischemic attack, unstable angina pectoris, or severe peripheral vascular disease within 3 months of enrollment
  • Known history of antiphospholipid antibody syndrome or lupus anticoagulant antibodies
Show all 15Show fewer
  • Suspected or confirmed sepsis at time of enrollment
  • Administration of whole blood, plasma, plasma fractions or platelets within 2 weeks prior to inclusion into the study
  • Large blood vessel rupture (e.g. in advanced cancer patient)
  • Pre-existing progressive fatal disease with a life expectancy of less than 2 months
  • Known inhibitors to coagulation factors II, VII, IX, or X; or hereditary protein C or protein S deficiency; or heparin-induced, type II thrombocytopenia
  • Treatment with any other investigational medicinal product within 30 days prior to inclusion into the study
  • Presence or history of hypersensitivity to components of the study medication
  • Pregnant or breast-feeding women
  • Prior inclusion in this study or any other CSL Behring-sponsored Beriplex study

Trial locations and contacts

69 sites in 6 countries.

69 sites in 6 countries

United States41 sites

  • Study Site

    Albany, New York, 12208

  • Study Site

    Albuquerque, New Mexico, 87131

  • Study Site

    Allentown, Pennsylvania, 18103

  • Study Site

    Ann Arbor, Michigan, 48106

  • Study Site

    Austin, Texas, 78701

  • Study Site

    Baltimore, Maryland, 21201

  • Study Site

    Baltimore, Maryland, 21205

  • Study Site

    Birmingham, Alabama, 35248-3280

  • Study Site

    Boston, Massachusetts, 02114

  • Study Site

    Charlottesville, Virginia, 22908

  • Study Site

    Chicago, Illinois, 60612

  • Study Site

    Duluth, Minnesota, 55805

  • Study Site

    Durham, North Carolina, 27710

  • Study Site

    El Paso, Texas, 79905

  • Study Site

    Hazard, Kentucky, 41701

  • Study Site

    Hershey, Pennsylvania, 17033

  • Study Site 2

    Houston, Texas, 77030

  • Study Site

    Houston, Texas, 77030

  • Study Site

    Jackson, Mississippi, 39216

  • Study Site

    Johnson City, New York, 13790

  • Study Site

    Los Angeles, California, 90033

  • Study Site

    Minneapolis, Minnesota, 55114

  • Study Site

    New York, New York, 10003

  • Study Site

    New York, New York, 10029

  • Study Site

    New York, New York, 10032

  • Study Site

    Newark, Delaware, 19718

  • Study Site

    Oak Park, Illinois, 60302

  • Study Site

    Orlando, Florida, 32806

  • Study Site

    Philadelphia, Pennsylvania, 19107

  • Study Site

    Philadelphia, Pennsylvania, 19140

  • Study Site

    Richmond, Virginia, 23298

  • Study Site

    Rochester, New York, 14642

  • Study Site

    Royal Oak, Michigan, 48073

  • Study Site

    Salt Lake City, Utah, 84132

  • Study Site

    San Franciso, California, 94115

  • Study Site

    St Louis, Missouri, 63110

  • Study Site

    Staten Island, New York, 10305

  • Study Site

    Tampa, Florida, 33606

  • Study Site

    Temple, Texas, 76508

  • Study Site

    West Reading, Pennsylvania, 19611

  • Study Site

    Worchester, Massachusetts, 01655

Other trials in United States

Russia11 sites

  • Study Site

    Arkhangelsk

  • Study Site 1

    Barnaul

  • Study Site 2

    Barnaul

  • Study Site

    Kazan'

  • Study Site

    Kemerovo, 650002

  • Study Site 1

    Moscow

  • Study Site 2

    Moscow

  • Study Site 1

    Nizhny Novgorod

  • Study Site 2

    Nizhny Novgorod

  • Study Site 1

    Saint Petersburg

  • Study Site 2

    Saint Petersburg

Other trials in Russia

Bulgaria7 sites

  • Study Site

    Pleven

  • Study Site

    Plovdiv

  • Study Site

    Rousse

  • Study Site 1

    Sofia

  • Study Site 2

    Sofia

  • Study Site 3

    Sofia

  • Study Site 4

    Sofia

Other trials in Bulgaria

Romania6 sites

  • Study Site

    Brasov

  • Study Site 1

    Bucharest

  • Study Site 2

    Bucharest

  • Study Site 3

    Bucharest

  • Study Site

    Cluj-Napoca

  • Study Site

    Timișoara

Other trials in Romania

Belarus2 sites

  • Study Site 1

    Minsk

  • Study Site 2

    Minsk

Other trials in Belarus

Ukraine2 sites

  • Study Site

    Kharkiv

  • Study Site

    Vinnytsa

Other trials in Ukraine

About this study

Official title: An Open-label, Randomized, Multicenter Phase IIIb Study to Assess the Efficacy, Safety and Tolerance of BERIPLEX® P/N Compared With Plasma for Rapid Reversal of Coagulopathy Induced by Coumarin Derivatives in Subjects With Acute Major Bleeding

The purpose of this study is to evaluate efficacy, safety and tolerance of BERIPLEX® P/N (Kcentra) compared with plasma in regard to rapid reversal of coagulopathy induced by coumarin derivatives in subjects who require immediate correction of INR (International Normalized Ratio)and to stop an acute major bleeding.

Being tested
Beriplex® P/N (Kcentra), Fresh frozen plasma
Keywords
Anticoagulant reversal, Prothrombin, Complex, Concentrate, Coagulopathy, induced by, coumarin, derivatives, Kcentra
Medical subject headings
Blood Coagulation Disorders, Hemostatic Disorders

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Beriplex® P/N (Kcentra)Biological

    Also called Kcentra

    Intravenous infusion, dosage depending on baseline INR, amount of coagulation factor IX and body weight

  • Fresh frozen plasmaBiological

    Intravenous Infusion, dosage depending on baseline INR and body weight

Study groups in NCT00708435
Study groupRoleWhat they receive
Beriplex® P/NExperimentalNot described
Receives: Biological: Beriplex® P/N (Kcentra)
Fresh frozen plasmaActive comparatorNot described
Receives: Biological: Fresh frozen plasma

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Percentage of Participants Achieving Hemostatic Efficacy of Stopping an Ongoing Major Bleed

    Hemostatic efficacy was determined by a blinded independent board as excellent, good, or poor/none, based on prespecified definitions. Assessments of visible or non-visible musculoskeletal bleeding were made at 1 and 4 hours after the end of infusion. Hemostatic efficacy was the binary endpoint of effective or non-effective hemostasis, where 'effective' was a hemostatic efficacy rating of "excellent" or "good," and 'non-effective' was a hemostatic efficacy rating of "poor/none".

    Measured: At 1 and 4 hours after the end of infusion

  2. Percentage of Participants Who Had a Rapid Decrease of the International Normalized Ratio (INR)

    A rapid decrease of the international normalized ratio (INR) was defined as an INR ≤ 1.3 at 30 minutes after the end of the infusion. The INR is a standard way to describe the time it takes for blood to clot; an INR range of 0.8 to 1.2 is considered normal for a healthy person who is not using oral anticoagulant therapy.

    Measured: 30 minutes after end of infusion

Secondary outcomes (9)

  1. Percentage of Participants Who Had Hemostatic Efficacy for Visible or Non-visible Musculoskeletal Bleeding

    Hemostatic efficacy was determined by a blinded independent board as excellent, good, or poor/none, based on prespecified definitions. Assessments of visible or non-visible musculoskeletal bleeding were made at 3 and 6 hours after the start of infusion. Hemostatic efficacy was the binary endpoint of effective or non-effective hemostasis, where 'effective' was a hemostatic efficacy rating of "excellent" or "good," and 'non-effective' was a hemostatic efficacy rating of "poor/none".

    Measured: At 3 and 6 hours after the start of infusion

  2. Incremental in Vivo Recovery (IVR) (Response) of Factors II, VII, IX, and X, Protein C, and Protein S for Beriplex

    The incremental IVR [(IU/dL)/(IU/kg)] was calculated as follows: (IU/dL activity rise in plasma)/(IU/kg body weight infused) = [maximum increase in component plasma level within 3 hours compared to pre-infusion (IU/dL)]/{[exact dose of component in drug administered (IU)]/[body weight (kg)]}.

    Measured: Before infusion and up to 3 h after the start of infusion

  3. Plasma Levels of Factors II, VII, IX, and X, Protein C, and Protein S

    Plasma levels are presented as the percentage of normal at pre-infusion and 30 min and 24 h after the start of infusion. The plasma level assay results are reported as a potency relative to a standard, where 100% is considered to be normal.

    Measured: From preinfusion until 24 h after the start of infusion

  4. Percentage of Participants With INR Correction at Various Times After the Start of Infusion

    The time taken from the start of infusion to INR correction (defined as an INR ≤ 1.3) was recorded. The percentage of participants with INR correction was calculated at 0.5, 1, 3, 6, 12, and 24 h after the start of infusion.

    Measured: From the start of infusion until INR correction; calculated at 0.5, 1, 3, 6, 12, and 24 h after the start of infusion.

  5. Percentage of Participants With INR Correction at Various Times After Randomization

    The time taken from randomization to INR correction (defined as an INR ≤ 1.3) was recorded. The percentage of participants with INR correction was calculated at 2.5, 3, 5, 8, 14, and 26 h after randomization.

    Measured: From randomization until INR correction; calculated at 2.5, 3, 5, 8, 14, and 26 h after randomization.

  6. Transfusion of Red Blood Cells

    Red blood cells were packed red blood cells (PRBCs).

    Measured: From the start of infusion until 24 h after the start of infusion

  7. Use of Other Blood Products and Hemostatic Agents

    Other blood products and hemostatic agents containing coagulation factors (such as whole blood, plasma, albumin, platelets) not including PRBCs.

    Measured: From the start of infusion until 24 h after the start of infusion

  8. 45-Day All-cause Mortality

    Measured: Until Day 45

  9. Overall Treatment-emergent Adverse Events (TEAEs)

    Number of participants with TEAEs. Treatment-related AEs were defined as events whose relationship to study treatment was definitely related, probably related, or possibly related in the opinion of the investigator. AEs with missing relationship were considered related to treatment. Serious TEAEs were treatment-emergent SAEs. Deaths reported up to and including Day 45; one additional Beriplex death occurred after Day 45.

    Measured: From the start of infusion up to the allowed time window of the Day 10 visit for non-serious AEs and from the start of infusion up to the allowed time window of the Day 45 visit for SAEs.

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted2 Jul 2008 (estimated)
  2. Study startJun 2008
  3. Primary completionNov 2010
  4. Study completionNov 2010

Resources

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 3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
216 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00708435
Sponsor's protocol ID
BE1116_3002
Other IDs
1462, 2007-007861-19
Status last verified
Sep 2013
First submitted
1 Jul 2008
Last updated
3 Feb 2014

Publications

  • Sarode 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

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Beriplex® P/N (Kcentra) and Fresh frozen plasma in people with Blood Coagulation Disorders and Acute Major Bleeding, run by CSL Behring at 69 sites in 6 countries.

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 5 inclusion and 15 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 3 Feb 2014. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 69 sites in United States, Russia, Bulgaria, Romania, Belarus and 1 more country. 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. 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 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 13 Aug 2013). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

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?

Percentage of Participants Achieving Hemostatic Efficacy of Stopping an Ongoing Major Bleed (time frame: At 1 and 4 hours after the end of infusion). The study lists 2 primary outcomes in all. 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 NCT00708435, 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 3 Feb 2014.

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