Phase 3 Study on the Efficacy and Safety of Human Plasma Derived Antithrombin (Atenativ) in Heparin-Resistant Patients Scheduled to Undergo Cardiac Surgery Necessitating Cardiopulmonary Bypass

NCT06096116 | Recruiting Phase 3 FDA Drug

• 1 other identifier: ATN-108
• Study Type: interventional
• Target: 120
• Locations: 9 countries
• Sites: 24

Brief Summary

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)

Conditions

Acquired Antithrombin Deficiency

Keywords

heparin resistance; antithrombin deficiency; cardiopulmonary bypass; cardiac surgery

Outcome Measures

Primary Outcomes (1)

• Restoring heparin responsiveness

  The percentage of patients in each group in whom no further therapy containing antithrombin (i.e. frozen plasma or other antithrombin concentrates) is needed for restoring pre-CPB heparin responsiveness after administration of Atenativ or placebo, and for maintaining it during CPB

  During surgery (from the time of the first surgical incision to the time at which the final suture or staple is placed)

Secondary Outcomes (20)

• Amounts of further therapy for restoring heparin responsiveness

  During surgery (from the time of the first surgical incision to the time at which the final suture or staple is placed)

• Change in activated clotting time (ACT) values

  Within 5 minutes following intravenous administration of 500 U/kg unfractionated heparin (UFH) and between 2-10 minutes after IMP infusion

• Change in antithrombin plasma levels

  Within 10 minutes before IMP infusion and between 2 and 10 minutes after IMP infusion, within 10 minutes after the end of CPB, at the end of surgery, and at 24 hours after the start of IMP infusion

• Change in heparin usage

  From end of IMP infusion to the end of surgery

• FP unit use

  From the start of IMP infusion until 24 hours following IMP infusion, and until discharge or 7 days after surgery, whichever comes first

Study Arms (3)

Low-dose Atenativ

EXPERIMENTAL

Patients will receive a single bolus of 30 international units (IU)/kg body weight (BW) Atenativ.

Drug: Human plasma derived antithrombin

High-dose Atenativ

EXPERIMENTAL

Patients will receive a single bolus of 60 international units (IU)/kg body weight (BW) Atenativ.

Drug: Human plasma derived antithrombin

Placebo

PLACEBO COMPARATOR

Patients will receive a saline bolus dose

Drug: Placebo

Interventions

Placebo DRUG

Half of the patients in the placebo group will be randomised to receive a volume of placebo corresponding to the low dose of Atenativ and the other half to receive a volume of placebo corresponding to a high dose of Atenativ

Placebo

Human plasma derived antithrombin DRUG

A solvent/detergent and heat-treated antithrombin concentrate derived from human plasma

High-dose Atenativ; Low-dose Atenativ

Eligibility Criteria

• Age: 18 Years - 85 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Planned cardiac surgery with CPB
• Heparin-resistant patients (pre-CPB Hemochron ACT less than 480 s in the measurement taken between 2-5 minutes following intravenous administration of 500 U/kg UFH)
• Patients between 18 and 85 years of age, inclusive
• Freely given written or electronic informed consent
• In female patients of childbearing potential, a pre-existing negative pregnancy test within 14 days prior to surgery

You may not qualify if:

• Receiving, or have received within the timeframes specified, one or more of the following medications prior to the start of surgery:
• vitamin K antagonists (within 3 days)
• direct oral anticoagulants (within 2 days)
• thienopyridines (ticlopidine within 14 days, prasugrel within 7 days, or clopidogrel within 5 days), unless platelet function is satisfactory according to local standard of care assessment
• ticagrelor (within 5 days), unless platelet function is satisfactory according to local standard of care assessment
• glycoprotein IIb/IIIa antagonist (within 24 hours)
• Pre-existing coagulopathy, a history of bleeding problems, or a laboratory-diagnosed bleeding disorder (e.g., von Willebrand disease, platelet disorder)
• Renal insufficiency, defined as serum creatinine level \>2.0 mg/dL
• Thrombocytosis, defined as platelet count \>400,000 per μL
• Known hypersensitivity or allergic reaction to antithrombin or any of the excipients in Atenativ, i.e., human albumin, sodium chloride, acetyl tryptophan, caprylic acid
• History of anaphylactic reaction(s) to blood or blood components
• Refusal to receive transfusion of blood or blood-derived products
• Current participation in another interventional clinical trial or previous participation in the current trial
• Treatment with any IMP within 30 days prior to screening visit

Sponsors & Collaborators

• Octapharma: lead

Study Sites (24)

Stanford University School of Medicine

Stanford, California, 94305-5101, United States

RECRUITING

University of Miami

Miami, Florida, 33136, United States

RECRUITING

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

NOT YET RECRUITING

Duke University Medical Center

Durham, North Carolina, 27710-1000, United States

RECRUITING

Atrium Health Wake Forest Baptist

Winston-Salem, North Carolina, 27157, United States

RECRUITING

The Ohio State University

Columbus, Ohio, 43214, United States

RECRUITING

OU Health University of Oklahoma Medical Center

Oklahoma City, Oklahoma, 73104, United States

RECRUITING

University of Texas Southwestern Medical Center

Dallas, Texas, 75390, United States

RECRUITING

University Hospital Innsbruck

Innsbruck, Austria

RECRUITING

Vienna General Hospital AKH, Medical University of Vienna

Vienna, Austria

RECRUITING

Royal Columbian Hospital

New Westminster, British Columbia, V3L0A4, Canada

RECRUITING

Kingston Health Sciences Centre

Kingston, Ontario, K7L2V7, Canada

NOT YET RECRUITING

Toronto General Hospital

Toronto, Ontario, M5G2C4, Canada

NOT YET RECRUITING

Montreal Heart Institute

Montreal, Quebec, H1T1C8, Canada

NOT YET RECRUITING

Center of Cardiovascular and Transplant Surgery

Brno, Czechia

RECRUITING

Institute for Clinical and Experimental Medicine

Prague, Czechia

RECRUITING

CHU de Reims, Hôpital Robert Debré

Reims, France

TERMINATED

CHU de Rennes

Rennes, France

WITHDRAWN

Hospital of Lithuanian university of Health sciences Kauno Klinikos

Kaunas, Lithuania

RECRUITING

Institute for Cardiovascular Diseases C.C. Iliescu

Bucharest, Romania

RECRUITING

University Medical Centre Ljubljana

Ljubljana, Slovenia

RECRUITING

Royal Papworth Hospital

Cambridge, United Kingdom

RECRUITING

University Hospital Coventry and Warwickshire

Coventry, United Kingdom

RECRUITING

The James Cook University Hospital

Middlesbrough, United Kingdom

RECRUITING

MeSH Terms

Conditions

Antithrombin III Deficiency

Condition Hierarchy (Ancestors)

Blood Coagulation Disorders, Inherited; Blood Coagulation Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Blood Protein Disorders; Thrombophilia; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Central Study Contacts

Cristina Solomon, MD

CONTACT

+41 79 585 90 42; Cristina.Solomon@octapharma.com

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, OUTCOMES ASSESSOR
• Masking Details: Triple (Participant, Care Provider, Outcomes Assessor) The patients, care provider administering IMP, and outcomes assessors will be blinded from treatment allocations. Delegated study personnel preparing the IMP will be unblinded.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 17, 2023
• First Posted: October 23, 2023
• Study Start: August 21, 2024
• Primary Completion (Estimated): March 1, 2028
• Study Completion (Estimated): March 1, 2028
• Last Updated: February 2, 2026

Record last verified: 2026-01

Data Sharing

• IPD Sharing: Will not share

Locations

AU (2); FR (2); US (8); GB (3); CZ (2); LI (1); SL (1); CA (4); RO (1)