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Acute Major BleedingPhase 3NCT02281201

Study of a Prothrombin Complex Concentrate for Rapid Reversal of Coagulopathy Induced by Vitamin K Antagonists in Japanese Subjects

A Phase 3 study testing BE1116 (Prothrombin Complex Concentrate) in people with Acute Major Bleeding and Reversal of Coagulopathy, run by CSL Behring at 11 sites in Japan.

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 and safety of a Prothrombin Complex Concentrate (PCC), BE1116. BE1116 will be used for the rapid reversal of coagulopathy induced by vitamin K antagonists in Japanese subjects who require immediate correction of international normalized ratio (INR) due to a major bleed… Read more about this study

Who is it for?
Ages 20 years and older
What is being tested?
BE1116 (Prothrombin Complex Concentrate)
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
11 participants
Where
11 sitesJapan
Study dates
Oct 2014to Mar 2016
Phase
Phase 3
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 20 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Male and female Japanese subjects greater than or equal to 20 years
  • Subjects currently on vitamin K antagonist (VKA) therapy
  • INR greater than or equal to 2 within 3 hours before start of BE1116 infusion
  • Urgent reversal of VKA therapy for a surgical or invasive medical procedure is required within 24 hours of the start of BE1116 infusion, or presentation with an acute major bleed

Who cannot join

  • Subjects for whom administration of I.V. vitamin K and VKA withdrawal, alone, can adequately correct the subject's coagulopathy before the infusion of BE1116
  • Subjects in whom lowering the INR to within the normal range is not a treatment goal
  • Use of anticoagulants other than VKAs (or expected use within 1 day)
  • Medical history for which PCCs are contraindicated
  • History of thromboembolic event within 3 months of screening
  • Congenital or acquired abnormality of hemostasis other than receipt of VKAs
Show all 16Show fewer
  • Administration of whole blood, plasma, plasma fractions, or platelets within 2 weeks prior to the start of BE1116 infusion
  • For subjects with intracranial hemorrhage (ICH):
  • Glasgow Coma Score (GCS) < 7
  • Intracerebral hematoma volume > 30 cm3 as assessed by computed tomography (CT) scan
  • For subdural hematomas: maximum thickness ≥ 10 mm, midline shift ≥ 5 mm, or acute subdural hematomas (based on neurosurgeon review)
  • For subarachnoid hemorrhage: any evidence of hydrocephalus, or Hunt and Hess Scale > 2, or concomitant subdural hematoma
  • Infratentorial ICH location
  • Epidural hematomas
  • Intraventricular rupture of hemorrhage
  • Requires surgical intervention

Trial locations and contacts

11 sites in 1 country.

11 sites in 1 country

Japan11 sites

  • Tohoku University Hospital

    Aoba-ku, Sendai, 980-8574

  • St. Luke's International Hospital

    Chūō, Tokyo, 104-8560

  • Osaka National Hospital

    Chuo-ku, Osaka, 540-0006

  • Kyushu Medical Center

    Chūōku, Fukuoka, 810-8563

  • Kinki University

    Higashiosaka, Osaka, 577-0818

  • Nippon Medical School Chiba Hokusoh Hospital

    Kamagari, Inzai, 270-1694

  • Kurashiki Central Hospital

    Miwa, Kurashiki, 710-0052

  • Nippon Medical School Hospital

    Sendagi, Bunkyo, 113-8603

  • National Cerebral and Cardiovascular Center

    Suita, Osaka, 565-0873

  • National Center for Global Health and Medicine

    Toyama, Shinjuku, 162-0052

  • Osaka University Hospital

    Yamadaoka, Suita, 565-0871

Other trials in Japan

About this study

Official title: An Open-label, Uncontrolled, Single-arm, Multicenter Phase IIIb Study to Assess the Efficacy and Safety of BE1116 in Japanese Subjects Receiving Vitamin K Antagonist Therapy With an Elevated INR and Either Acute Major Bleeding or a Requirement for Urgent Reversal of Vitamin K Antagonist Therapy for a Surgical or Invasive Medical Procedure

The purpose of this study is to evaluate efficacy and safety of a Prothrombin Complex Concentrate (PCC), BE1116. BE1116 will be used for the rapid reversal of coagulopathy induced by vitamin K antagonists in Japanese subjects who require immediate correction of international normalized ratio (INR) due to a major bleed or emergency surgery.

Being tested
BE1116 (Prothrombin Complex Concentrate)

What participants receive

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

  • BE1116 (Prothrombin Complex Concentrate)Biological

    Also called Beriplex® P/N, KcentraTM, Confidex®

Study groups in NCT02281201
Study groupRoleWhat they receive
BE1116ExperimentalSingle intravenous (I.V.) infusion, dosage depending on baseline INR and body weight
Receives: Biological: BE1116 (Prothrombin Complex Concentrate)

What is being measured

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

  1. Percentage of Subjects With a Rapid Reversal of VKA Effect

    A rapid reversal of (Vitamin K antagonist) VKA effect is a reduction of the INR to ≤ 1.3 at 30 minutes after the end of infusion.

    Measured: At baseline and at 30 minutes after the end of infusion

Secondary outcomes (15)

  1. Percentage of Subjects Achieving Hemostatic Efficacy During Surgery

    Hemostatic efficacy is the binary endpoint of effective or non-effective hemostasis, where 'effective' is a hemostatic efficacy rating of "very good" or "satisfactory", and 'non-effective' is a hemostatic efficacy rating of "questionable" or "none".

    Measured: From the start of surgery/procedure until the end of surgery/procedure

  2. Percentage of Subjects Achieving Hemostatic Efficacy of Stopping an Ongoing Major Bleed

    Hemostatic efficacy is the binary endpoint of effective or non-effective hemostasis, where 'effective' is a hemostatic efficacy rating of "excellent" or "good," and 'non-effective' is a hemostatic efficacy rating of "poor/none".

    Measured: Baseline CT scan, baseline haematology or the end of infusion, until 24 hours after the end of infusion

  3. Increase in Plasma Levels of Factor (F)II, FVII, FIX, and FX, and Protein C and Protein S

    The increase in plasma levels is assessed through response and in vivo recovery (IVR) of FII, FVII, FIX, FX, and protein C and protein S. The incremental IVR [(IU/dL)/(IU/kg)] is 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

  4. Percentage of Subjects With INR Correction

    The time taken from the start of infusion to INR correction (defined as an INR ≤ 1.3) is recorded. The percentage of participants with INR correction is calculated.

    Measured: From the start of infusion until INR correction, up to 24 hours after the end of infusion

  5. Percentage of Subjects With INR Correction at Various Times After the End of Infusion

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

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

  6. Percentage of Subjects Who Receive Red Blood Cells

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

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

  7. Percentage of Subjects Who Receive 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. TEAEs are defined as adverse events that developed or worsened following exposure to investigational medicinal product. Serious TEAEs are treatment-emergent serious adverse events (SAEs).

    Measured: From the start of infusion up to the allowed time window of the Day 14 visit for non-serious AEs and from the start of infusion up to the allowed time window of the Day 45 visit for SAEs

  10. Mean modified Rankin Scale for all subjects with intracranial haemorrhage

    Measured: Before infusion and at Day 45

  11. Mean Predicted and Actual Blood Loss (mls) for all Surgical/Invasive Procedures

    Measured: From the start of surgery/procedure until the end of surgery/procedure

  12. Mean Volume (mls) of Wound Drainage for all Surgical/Invasive Procedures

    Measured: From the start of wound drainage until the end of wound drainage, up to the final safety follow-up visit (Day 45)

  13. Mean Time (mins) Between Last Suture and Cessation of Wound Drainage for all Surgical/Invasive Procedure

    Measured: From the time of last suture until the end of wound drainage, up to the final safety follow-up visit (Day 45)

  14. Vital signs

    Percentage of participants with a clinically significant change in vital signs (including blood pressure, respiratory rate, temperature and pulse rate)

    Measured: At baseline and until 24 hours after the end of infusion

  15. Viral serology

    Percentage of participants with negative viral serology (for Human immunodeficiency virus, Hepatitis B, Hepatitis A, Hepatitis C and Parvovirus B19) before infusion who become positive after infusion.

    Measured: At baseline and until Day 45

Timeline

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

  1. First posted3 Nov 2014 (estimated)
  2. Study startOct 2014
  3. Primary completionJan 2016
  4. Study completionMar 2016

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
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
11 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02281201
Sponsor's protocol ID
BE1116_3004
Status last verified
Apr 2016
First submitted
27 Oct 2014
Last updated
4 May 2016
Results posted
No

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing BE1116 (Prothrombin Complex Concentrate) in people with Acute Major Bleeding and Reversal of Coagulopathy, run by CSL Behring at 11 sites in Japan.

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 4 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 4 May 2016. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 11 sites in Japan. 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?

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?

Percentage of Subjects With a Rapid Reversal of VKA Effect (time frame: At baseline and at 30 minutes after the end of infusion). 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 NCT02281201.

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 4 May 2016.

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