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

Phase 3RecruitingNCT06096116

Octapharma120 enrolled

Overview

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)

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

TRIPLE

Enrollment

120

Conditions

Acquired Antithrombin Deficiency

Interventions

Human plasma derived antithrombinDRUG

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

PlaceboDRUG

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

Eligibility

Sex: ALLMin age: 18 YearsMax age: 85 Years

Medical Language ↔ Plain English

Inclusion Criteria: 1. Planned cardiac surgery with CPB 2. 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) 3. Patients between 18 and 85 years of age, inclusive 4. Freely given written or electronic informed consent 5. In female patients of childbearing potential, a pre-existing negative pregnancy test within 14 days prior to surgery Exclusion Criteria: 1. Receiving, or have received within the timeframes specified, one or more of the following medications prior to the start of surgery: 1. vitamin K antagonists (within 3 days) 2. direct oral anticoagulants (within 2 days) 3. 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 4. ticagrelor (within 5 days), unless platelet function is satisfactory according to local standard of care assessment 5. glycoprotein IIb/IIIa antagonist (within 24 hours) 2. Pre-existing coagulopathy, a history of bleeding problems, or a laboratory-diagnosed bleeding disorder (e.g., von Willebrand disease, platelet disorder) 3. Renal insufficiency, defined as serum creatinine level \>2.0 mg/dL 4. Thrombocytosis, defined as platelet count \>400,000 per μL 5. Known hypersensitivity or allergic reaction to antithrombin or any of the excipients in Atenativ, i.e., human albumin, sodium chloride, acetyl tryptophan, caprylic acid 6. History of anaphylactic reaction(s) to blood or blood components 7. Refusal to receive transfusion of blood or blood-derived products 8. Current participation in another interventional clinical trial or previous participation in the current trial 9. Treatment with any IMP within 30 days prior to screening visit

Locations (24)

Outcomes

Primary Outcomes

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

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

Secondary Outcomes

Amounts of further therapy for restoring heparin responsiveness

The comparison between the amounts of further therapy containing antithrombin (i.e., FP or antithrombin concentrates) needed for restoring pre-CPB heparin responsiveness, after administration of Atenativ or placebo, and for maintaining it during CPB

Time frame: 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

The comparison between the change in ACT values following infusion of each of the Atenativ doses and placebo

Time frame: 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

The comparison between the change in antithrombin plasma levels following infusion of each of the Atenativ doses and placebo

Time frame: 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

The comparison between heparin usage following the infusion of each of the Atenativ doses and infusion of placebo

Time frame: From end of IMP infusion to the end of surgery

Central Contacts

Cristina Solomon, MD

CONTACT

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

Data from ClinicalTrials.gov

This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.

Stanford University School of Medicine

Stanford, California, United States

University of Miami

Miami, Florida, United States

RECRUITING

Massachusetts General Hospital

Boston, Massachusetts, United States

NOT_YET_RECRUITING

Duke University Medical Center

Durham, North Carolina, United States

RECRUITING

Atrium Health Wake Forest Baptist

Winston-Salem, North Carolina, United States

RECRUITING

The Ohio State University

Columbus, Ohio, United States

RECRUITING

OU Health University of Oklahoma Medical Center

Oklahoma City, Oklahoma, United States

RECRUITING

University of Texas Southwestern Medical Center

Dallas, Texas, United States

RECRUITING

University Hospital Innsbruck

Innsbruck, Austria

RECRUITING

Vienna General Hospital AKH, Medical University of Vienna

Vienna, Austria

RECRUITING

...and 14 more locations

FP unit use

The comparison between the number of units of FP transfused for reasons other than restoring or maintaining heparin responsiveness, both intraoperatively (from the start of Atenativ or placebo infusion until the start of CPB, during CPB, and from the end of CPB until the end of surgery) and postoperatively (from the end of surgery until 24 hours after the start of Atenativ or placebo infusion and until discharge or 7 days after surgery, whichever comes first), as well as cumulatively

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

Amounts of further antithrombin concentrate for maintaining heparin responsiveness

The comparison between postoperative use of antithrombin concentrates for reasons other than restoring heparin responsiveness (from the end of surgery until 24 hours after the start of Atenativ or placebo infusion and until discharge or 7 days after surgery, whichever comes first)

Time frame: From placement of the final suture or staple until 24 hours following IMP infusion, to discharge or 7 days after surgery, whichever comes first

Transfusion of allogenic blood products

The comparison between transfusion of other allogeneic blood products (e.g., red blood cells \[RBCs\], platelets, cryoprecipitate, whole blood, albumin, other transfusion), both intraoperatively (from the start of Atenativ or placebo infusion until the start of CPB, during CPB, and from the end of CPB until the end of surgery) and postoperatively (from the end of surgery until 24 hours after the start of Atenativ or placebo infusion and until discharge or 7 days after surgery, whichever comes first), as well as cumulatively

Time frame: From the start of IMP infusion until 24 hours after the start of Atenativ or placebo infusion and until discharge or 7 days after surgery, whichever comes first

Administration of coagulation factor concentrates

The comparison between administration of coagulation factor concentrates (fibrinogen concentrate, factor XIII concentrate, recombinant activated factor VII, other therapy)", both intraoperatively (from the start of Atenativ or placebo infusion until the start of CPB, during CPB, and from the end of CPB until the end of surgery) and postoperatively (from the end of surgery until 24 hours after the start of Atenativ or placebo infusion and until discharge or 7 days after surgery, whichever comes first), as well as cumulatively

Time frame: From the start of IMP infusion until 24 hours after the start of Atenativ or placebo infusion and until discharge or 7 days after surgery, whichever comes first

Administration of other haemostatic-relevant therapies

The comparison between administration of other haemostatic-relevant therapies (i.e., tranexamic acid, aminocaproic acid, protamine, other therapies), both intraoperatively (from the start of Atenativ or placebo infusion until the start of CPB, during CPB, and from the end of CPB until the end of surgery) and postoperatively (from the end of surgery until 24 hours after the start of Atenativ or placebo infusion and until discharge or 7 days after surgery, whichever comes first), as well as cumulatively

Time frame: From the start of IMP infusion until 24 hours after the start of Atenativ or placebo infusion and until discharge or 7 days after surgery, whichever comes first

Postoperative chest tube drainage

The comparison between postoperative chest tube drainage volume at 24 hours after the start of Atenativ or placebo infusion, and the comparison between total chest tube drainage volume until discharge or 7 days after surgery, whichever comes first

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

Need for reoperation due to bleeding

Comparison of the need for reoperation for bleeding, including description of the cause of bleeding (surgical vs. non-surgical)

Time frame: 24 hours after the start of IMP infusion

Cell saver volume

The comparison between cell saver volume until the end of surgery

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

Adverse events

Incidence of adverse events, including all related and non-related, non-serious adverse events

Time frame: From the start of IMP infusion until hospital discharge or 7 days after IMP administration, whichever comes first

Serious adverse events

Incidence of serious adverse events

Time frame: From the start of IMP infusion until 28 days after IMP administration

Survival status

Number of patients surviving in all three cohorts

Time frame: At hospital discharge or 7 days after IMP administration (whichever comes first) and at 28 days (+ 4 days) after IMP administration

Red Blood Cell count