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Clinical Trial Details — Status: Completed

Administrative data

NCT number NCT02281201
Other study ID # BE1116_3004
Secondary ID
Status Completed
Phase Phase 3
First received October 27, 2014
Last updated May 2, 2016
Start date October 2014
Est. completion date March 2016

Study information

Verified date April 2016
Source CSL Behring
Contact n/a
Is FDA regulated No
Health authority Japan: Pharmaceuticals and Medical Devices Agency
Study type Interventional

Clinical 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 or emergency surgery.


Recruitment information / eligibility

Status Completed
Enrollment 11
Est. completion date March 2016
Est. primary completion date January 2016
Accepts healthy volunteers No
Gender Both
Age group 20 Years and older
Eligibility Inclusion Criteria:

- 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

Exclusion Criteria:

- 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

- 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

Study Design

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment


Intervention

Biological:
BE1116 (Prothrombin Complex Concentrate)


Locations

Country Name City State
Japan Tohoku University Hospital Aoba-ku Sendai
Japan St. Luke's International Hospital Chuo Tokyo
Japan Kyushu Medical Center Chuo-ku Fukuoka
Japan Osaka National Hospital Chuo-ku Osaka
Japan Kinki University Higashiosaka Osaka
Japan Nippon Medical School Chiba Hokusoh Hospital Kamagari Inzai
Japan Kurashiki Central Hospital Miwa Kurashiki
Japan Nippon Medical School Hospital Sendagi Bunkyo
Japan National Cerebral and Cardiovascular Center Suita Osaka
Japan National Center for Global Health and Medicine Toyama Shinjuku
Japan Osaka University Hospital Yamadaoka Suita

Sponsors (1)

Lead Sponsor Collaborator
CSL Behring

Country where clinical trial is conducted

Japan, 

Outcome

Type Measure Description Time frame Safety issue
Primary 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. At baseline and at 30 minutes after the end of infusion No
Secondary 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". From the start of surgery/procedure until the end of surgery/procedure No
Secondary 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". Baseline CT scan, baseline haematology or the end of infusion, until 24 hours after the end of infusion No
Secondary 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)]}. Before infusion and up to 3 h after the start of infusion No
Secondary 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. From the start of infusion until INR correction, up to 24 hours after the end of infusion No
Secondary 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. From the end of infusion until INR correction; calculated at 0.5, 1, 3, 6, 12, and 24 h after the end of infusion No
Secondary Percentage of Subjects Who Receive Red Blood Cells Red blood cells are packed red blood cells (PRBCs). From the start of infusion until 24 h after the start of infusion No
Secondary 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. From the start of infusion until 24 h after the start of infusion No
Secondary 45-Day All-cause Mortality Until Day 45 No
Secondary 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). 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 No
Secondary Mean modified Rankin Scale for all subjects with intracranial haemorrhage Before infusion and at Day 45 No
Secondary Mean Predicted and Actual Blood Loss (mls) for all Surgical/Invasive Procedures From the start of surgery/procedure until the end of surgery/procedure No
Secondary Mean Volume (mls) of Wound Drainage for all Surgical/Invasive Procedures From the start of wound drainage until the end of wound drainage, up to the final safety follow-up visit (Day 45) No
Secondary Mean Time (mins) Between Last Suture and Cessation of Wound Drainage for all Surgical/Invasive Procedure From the time of last suture until the end of wound drainage, up to the final safety follow-up visit (Day 45) No
Secondary Vital signs Percentage of participants with a clinically significant change in vital signs (including blood pressure, respiratory rate, temperature and pulse rate) At baseline and until 24 hours after the end of infusion No
Secondary 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. At baseline and until Day 45 No
See also
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Not yet recruiting NCT04867837 - Study of OCTAPLEX in Patients With Acute Major Bleeding on DOAC Therapy With Factor Xa Inhibitor Phase 3