Atenativ for Antithrombin Deficiency

Recruiting at 17 trial locations

Overseen By Sigurd Knaub, PhD

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 3

Recruiting

Sponsor: Octapharma

Must not be taking: Warfarin, Anticoagulants, Antiplatelets

Disqualifiers: Coagulopathy, Renal insufficiency, others

Pivotal Trial (Near Approval)

Prior Safety Data

Trial Summary

What is the purpose of this trial?

The primary objective of this study is to evaluate the efficacy of two different doses of Atenativ, versus placebo, in restoring and maintaining heparin responsiveness in adult patients undergoing cardiac surgery necessitating cardiopulmonary bypass (CPB)

Will I have to stop taking my current medications?

You may need to stop taking certain medications before participating in the trial. Specifically, you should not have taken warfarin within 3 days, direct oral anticoagulants within 2 days, ticlopidine within 14 days, prasugrel within 7 days, clopidogrel within 5 days, ticagrelor within 5 days, or glycoprotein IIb/IIIa antagonists within 1 day before the start of surgery.

Is Atenativ (Human Plasma Derived Antithrombin) safe for humans?

Atenativ, used to treat antithrombin deficiency, is generally considered safe for humans, especially in high-risk situations like surgery or pregnancy. However, there is limited data on its use, and more research is needed to clarify when it should be used. ^{1 2 3 4 5}

How is the drug Atenativ unique in treating antithrombin deficiency?

Atenativ is unique because it is a human plasma-derived antithrombin concentrate specifically used to increase antithrombin levels in patients with hereditary antithrombin deficiency, especially during high-risk situations like surgery or pregnancy. Unlike long-term anticoagulant therapies, Atenativ is used for short-term thromboprophylaxis to prevent blood clots without the increased risk of bleeding. ^{4 6 7 8 9}

Eligibility Criteria

This trial is for adults aged 18-85 who need heart surgery with cardiopulmonary bypass and are resistant to heparin, a common blood thinner (their blood doesn't thin enough after taking it). They must be able to consent and women of childbearing age need a recent negative pregnancy test.

Inclusion Criteria

I am scheduled for heart surgery with a heart-lung machine.

Freely given written or electronic informed consent

I am between 18 and 85 years old.

Exclusion Criteria

I have taken blood thinners or clot-preventing drugs within the specified timeframes.

I haven't taken any experimental drugs in the last 30 days.

I have a bleeding disorder or a history of bleeding problems.

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive Atenativ or placebo to evaluate efficacy in restoring heparin responsiveness during cardiac surgery

During surgery

1 visit (in-person)

Postoperative Monitoring

Participants are monitored for changes in heparin usage, transfusion needs, and adverse events

24 hours post-surgery

Follow-up

Participants are monitored for safety and effectiveness after treatment

28 days

Treatment Details

Interventions

• Human Plasma Derived Antithrombin (Atenativ) (Anticoagulant)

Trial Overview The study tests two doses of Atenativ, a drug derived from human plasma, against a placebo. The goal is to see if Atenativ can make heparin work better in patients during heart surgery that requires them to be connected to a heart-lung machine.

Participant Groups

Group I: Low-dose Atenativ Experimental Treatment 1 Intervention

Group II: High-dose Atenativ Experimental Treatment 1 Intervention

Group III: Placebo Placebo Group 1 Intervention

Patients will receive a saline bolus dose

Who Is Running the Clinical Trial?

Octapharma

Lead Sponsor

Trials

86

Recruited

11,300+

Wolfgang Marguerre

Octapharma

Chief Executive Officer since 1983

MBA from INSEAD

Wolfgang Frenzel

Octapharma

Chief Medical Officer since 2010

MD from University of Vienna

Findings from Research

This study involved 43 children with congenital antithrombin deficiency, revealing that 44% had experienced venous thromboembolism (VTE), with a median age of diagnosis at 12.8 years.

The research found that children with missense mutations in the SERPINC1 gene had a significantly higher 5-year VTE-free survival rate (92%) compared to those with null mutations (66.7%), highlighting the critical role of genetic testing in assessing risk.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Impact of SERPINC1 mutation on thrombotic phenotype in children with congenital antithrombin deficiency-first analysis of the International Society on Thrombosis and Haemostasis pediatric antithrombin deficiency database and biorepository. Kumar, R., Bakeer, N., Dawson, J., et al.[2023]

The study identified two families with type I inherited antithrombin deficiency, revealing specific gene mutations: a heterozygotic deletion (3239-3240delCT) in one proband and a nonsense mutation (3206A-->T) in another, both affecting the antithrombin gene.

Plasma levels of antithrombin antigen and activity were measured, showing reduced levels (126 mg/L and 49% for proband 1; 117 mg/L and 48% for proband 2), confirming the clinical phenotype associated with these genetic mutations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Two new mutations of AT gene in type I inherited antithrombin deficiency.]. Chen, Q., Lu, YL., Xu, GQ., et al.[2018]

Antithrombin (AT) deficiency, which affects 1 in 500 to 1 in 5000 people, increases the risk of venous thromboembolism (VTE) and pregnancy loss, with type IIa being the most thrombophilic variant.

Diagnosis of AT deficiency requires careful testing to rule out acquired causes, and while specialized tests can help classify the type of deficiency, they are not routinely used in clinical practice despite their potential to inform treatment strategies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Inherited antithrombin deficiency: a review. Patnaik, MM., Moll, S.[2022]

Antithrombin (AT) is a crucial natural anticoagulant that not only helps prevent blood clots but also has anti-inflammatory effects, making it important for managing conditions like hereditary AT deficiency, which carries a high risk of venous thromboembolism.

Optimizing AT levels is vital during high-risk situations such as surgery and pregnancy, and there is ongoing research to identify specific patient groups that would benefit most from targeted AT therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Antithrombin Therapy: Current State and Future Outlook. Rodgers, GM., Mahajerin, A.[2023]

A novel heterozygous G13328A missense mutation in the antithrombin (AT) gene was identified, leading to type I hereditary antithrombin deficiency in a family, which is linked to increased risk of thrombosis.

The mutation resulted in significantly reduced levels of antithrombin antigen and activity, with the mutant protein showing only 40% and 68% of the normal levels in cell experiments, highlighting the mutation's impact on AT function.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[A heterozygous point mutation G13328A in antithrombin gene causes thrombosis]. Zhou, RF., Shi, GC., Fu, QH., et al.[2006]

Hereditary antithrombin (AT) deficiency is a rare genetic condition that significantly increases the risk of venous thromboembolism (VTE) by three to seven times compared to other thrombophilias, with individuals having a lifetime risk of over 50%.

While long-term anticoagulant therapy is not recommended for asymptomatic patients due to bleeding risks, short-term thromboprophylaxis is advised during high-risk situations like surgery or pregnancy, with treatment options including plasma-derived AT and human recombinant AT to maintain adequate AT levels.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Role of antithrombin concentrate in treatment of hereditary antithrombin deficiency. An update. Rodgers, GM.[2022]

Congenital antithrombin deficiency is a serious inherited condition that significantly increases the risk of thrombosis, requiring careful long-term management and anticoagulation, especially during high-risk situations like surgery and pregnancy.

Antithrombin concentrates are effective for both treating and preventing acute venous thrombosis in individuals with this deficiency, although current evidence mainly comes from retrospective studies, highlighting the need for more comprehensive research to guide treatment decisions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Management of antithrombin deficiency: an update for clinicians. Bravo-Pérez, C., Vicente, V., Corral, J.[2020]

In a Phase I clinical study, antithrombin III (ATIII) concentrate was shown to be effective in maintaining plasma ATIII levels and preventing thromboembolism in patients with congenital ATIII deficiency, with no thromboembolic events reported in 10 subjects treated prophylactically.

The treatment was well tolerated, with no evidence of infectious transmissible agents, indicating a safe option for managing both congenital and acquired ATIII deficiencies, although survival rates varied significantly based on the underlying conditions in acquired cases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical experience with antithrombin III concentrate in treatment of congenital and acquired deficiency of antithrombin. The Antithrombin III Study Group. Schwartz, RS., Bauer, KA., Rosenberg, RD., et al.[2019]

Antithrombin (AT) is crucial for regulating blood clotting, and deficiencies in AT, whether hereditary or acquired, significantly increase the risk of thromboembolism and complications during pregnancy, including fetal loss and severe preeclampsia.

Treatment for AT deficiency often involves antithrombotic therapy, and in cases of very low AT levels, patients may need higher doses of heparin or AT concentrates, which can improve blood flow to the placenta and potentially mitigate risks associated with preeclampsia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Antithrombin abnormalities and perinatal management. Kobayashi, T.[2019]

References

1. England pubmed.ncbi.nlm.nih.gov

Impact of SERPINC1 mutation on thrombotic phenotype in children with congenital antithrombin deficiency-first analysis of the International Society on Thrombosis and Haemostasis pediatric antithrombin deficiency database and biorepository. [2023]

2. China pubmed.ncbi.nlm.nih.gov

[Two new mutations of AT gene in type I inherited antithrombin deficiency.]. [2018]

3. England pubmed.ncbi.nlm.nih.gov

Inherited antithrombin deficiency: a review. [2022]

4. United States pubmed.ncbi.nlm.nih.gov

Antithrombin Therapy: Current State and Future Outlook. [2023]

5. China pubmed.ncbi.nlm.nih.gov

[A heterozygous point mutation G13328A in antithrombin gene causes thrombosis]. [2006]

6. Germany pubmed.ncbi.nlm.nih.gov

Role of antithrombin concentrate in treatment of hereditary antithrombin deficiency. An update. [2022]

7. England pubmed.ncbi.nlm.nih.gov

Management of antithrombin deficiency: an update for clinicians. [2020]

8. United States pubmed.ncbi.nlm.nih.gov

Clinical experience with antithrombin III concentrate in treatment of congenital and acquired deficiency of antithrombin. The Antithrombin III Study Group. [2019]

9. United Arab Emirates pubmed.ncbi.nlm.nih.gov

Antithrombin abnormalities and perinatal management. [2019]