What side effects are associated with this type of intervention?

Common treatments for reversing the anticoagulant effects of Factor Xa inhibitors, such as four-factor prothrombin complex concentrate (4F-PCC), can have several side effects. These may include thromboembolic events (e.g., deep vein thrombosis, pulmonary embolism), disseminated intravascular coagulation, and allergic reactions. Other potential side effects include headache, hypotension, and infusion-related reactions. It is important for patients to discuss these risks with their healthcare provider to ensure appropriate management.

What prior FDA approvals exist?

The FDA has approved several treatments for blood clotting disorders, particularly for reversing the effects of Factor Xa inhibitors. One notable approval is for Andexanet alfa (Andexxa), which is specifically designed to reverse the anticoagulant effects of Factor Xa inhibitors such as rivaroxaban and apixaban. Another treatment is the four-factor prothrombin complex concentrate (4F-PCC), which is used as part of standard care for urgent reversal of anticoagulation. These treatments are crucial for patients who require rapid reversal of anticoagulation due to urgent surgery or invasive procedures.

What other types of research exist?

Promising alternatives to TAK-330 for reversing the anticoagulant effects of Factor Xa inhibitors include Andexanet alfa (Andexxa), which is an FDA-approved agent specifically designed to reverse the effects of Factor Xa inhibitors. Additionally, Ciraparantag (Aripazine) is an investigational agent that has shown potential in clinical trials for reversing the effects of various anticoagulants, including Factor Xa inhibitors.

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TAK-330 for Blood Clotting Disorders

Phase 3

Recruiting

Research Sponsored by Takeda

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

In the opinion of the surgeon, the participant requires an urgent surgery/procedure that is associated with high-risk of intraoperative bleeding within 15 hours from the last dose of Factor Xa inhibitor and requires a reversal agent for suspected direct oral Factor Xa inhibitor-related coagulopathy. For participants who are beyond the 15-hour window, eligibility requires proof of elevated plasma anti Factor Xa (FXa) levels using either specific direct oral anti-coagulant (DOAC)-calibrated (apixaban, rivaroxaban or edoxaban) anti-FXa levels of greater than (>) 75 nanograms per milliliter (ng/mL), or heparin calibrated anti-FXa assay levels of >0.5 international unit per milliliter (IU/mL) at screening

Participants at least 18 years of age at enrollment

Must not have

The use of PROTHROMPLEX TOTAL as SOC 4F-PCC

Known prothrombotic disorder including primary antiphospholipid syndrome, antithrombin-3 deficiency, homozygous protein C deficiency, homozygous protein S deficiency, and homozygous factor V Leiden

Timeline

Screening 3 weeks

Treatment Varies

Follow Up at the end of the surgery/procedure

Awards & highlights

No Placebo-Only Group

Pivotal Trial

Summary

This trial compares two treatments for reversing blood thinners in patients needing urgent surgery. Both treatments help the blood clot normally again. One treatment is commonly used and has been studied extensively.

Who is the study for?

Adults on oral Factor Xa inhibitors needing urgent surgery with high bleeding risk can join. They must have a negative pregnancy test if applicable, and either took their last dose of the inhibitor within 15 hours or show elevated anti-FXa levels. Excluded are those with certain clotting/bleeding disorders, severe organ failure, recent use of heparin or other trials, breastfeeding women, imminent death prognosis, recent major cardiovascular events or active major bleeding.

What is being tested?

The trial is testing TAK-330 against standard treatment (4F-PCC) for reversing anticoagulation from Factor Xa inhibitors in patients requiring urgent surgery. Participants will be randomly assigned to one of these treatments before their procedure and followed up via telehealth after 30 days.

What are the potential side effects?

Potential side effects may include allergic reactions to medication components, increased risk of blood clots due to reversal agents like PCC constituents in TAK-330 or SOC 4F-PCC, and complications related to underlying conditions that necessitate urgent surgeries.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below

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I need urgent surgery and have a high bleeding risk due to recent Factor Xa inhibitor use.

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I am 18 years old or older.

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I am currently taking a blood thinner medication like rivaroxaban.

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:

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I am being treated with PROTHROMPLEX TOTAL as standard care.

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I have a blood clotting disorder.

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I have a known bleeding disorder.

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I haven't received blood products or specific clotting drugs in the last 7 days.

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I have septic shock with low blood pressure and high lactate levels despite treatment.

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I am on dialysis for kidney failure.

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I do not have severe liver failure.

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I have received heparin within the required time before joining the study.

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I have multiple injuries where stopping blood thinners alone won't stop the bleeding.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ within 24 hours after the end of investigational product infusion

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~within 24 hours after the end of investigational product infusion

This trial's timeline: 3 weeks for screening, Varies for treatment, and within 24 hours after the end of investigational product infusion for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Primary study objectives

Percentage of Participants With Intraoperative Effective Hemostasis

Secondary study objectives

Number of Participants With Deaths Within 30 Days Post-Surgery/Invasive Procedure

Number of Participants With Thrombotic Events

Number of Participants With Treatment-emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs) and Adverse Events of Special Interests (AESIs)

+4 more

Awards & Highlights

No Placebo-Only Group

All patients enrolled in this study will receive some form of active treatment.

Pivotal Trial

The final step before approval, pivotal trials feature drugs that have already shown basic safety & efficacy.

Trial Design

2Treatment groups

Experimental Treatment

Active Control

Group I: TAK-330 25 IU/kgExperimental Treatment1 Intervention

Participants will receive TAK-330, 25 international unit per kilogram (IU/kg) single intravenous infusion on Day 1 (prior to surgery) as an initial dose and an additional dose of 25 IU/kg TAK-330 can be administered during the surgery if deemed necessary by the surgeon. The total dose of TAK-330 administered to the participant should not exceed 50 IU/kg or 5,000 IU, whichever is smaller.

Group II: SOC 4F-PCCActive Control1 Intervention

Participants will receive 4F-PCC (excluding Prothromplex Total and activated 4F-PCC) as standard of care (SOC) on Day 1 (prior to surgery). The dose and infusion speed of the SOC 4F-PCC will be based on local institutional protocols. An additional dose of SOC 4F-PCC not exceeding total dose of 50 IU/kg or 5,000 IU, whichever is smaller can be given during the surgery if required.

0 / 12Eligibility criteria met

Research Highlights

Information in this section is not a recommendation. We encourage patients to speak with their healthcare team when evaluating any treatment decision.

Mechanism Of Action

Side Effect Profile

Prior Approvals

Other Research

Common treatments for blood clotting disorders, particularly those involving the reversal of anticoagulant effects of Factor Xa inhibitors, include agents like TAK-330 and four-factor prothrombin complex concentrate (4F-PCC). Factor Xa inhibitors prevent blood clot formation by blocking Factor Xa, a key enzyme in the coagulation cascade. Reversal agents are essential for patients requiring urgent surgery or experiencing severe bleeding, as they restore normal clotting function. TAK-330 likely neutralizes the anticoagulant effect by binding to the inhibitors, while 4F-PCC supplies the necessary clotting factors to re-establish normal coagulation, thereby reducing the risk of excessive bleeding and its complications.