Clinical trial NCT06096116: 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
Official title: Phase 3, Double-blind, Placebo-controlled, Multicentre Study on the Efficacy and Safety of Human Plasma Derived Antithrombin (Atenativ) in Heparin-Resistant Patients Scheduled to Undergo Cardiac Surgery Necessitating Cardiopulmonary Bypass
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE3
Conditions: Acquired Antithrombin Deficiency
Keywords: heparin resistance
antithrombin deficiency
cardiopulmonary bypass
cardiac surgery
Lead sponsor: Octapharma
Sponsor class: INDUSTRY
First posted: 2023-10-23
Enrollment: 120
Sex: ALL
Minimum age (years): 18
Maximum age (years): 85
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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)


Eligibility criteria: 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, 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. Known hypersensitivity or allergic reaction to antithrombin or any of the excipients in Atenativ i.e., human albumin, sodium chloride, acetyl tryptophan, caprylic acid
5. History of anaphylactic reaction(s) to blood or blood components
6. Refusal to receive transfusion of blood or blood-derived products
7. Current participation in another interventional clinical trial or previous participation in the current trial
8. Treatment with any IMP within 30 days prior to screening visit

Primary outcomes:
measure: Restoring heparin responsiveness
timeFrame: During surgery (from the time of the first surgical incision to the time at which the final suture or staple is placed)
Secondary outcomes:
measure: Amounts of further therapy for restoring heparin responsiveness
timeFrame: During surgery (from the time of the first surgical incision to the time at which the final suture or staple is placed)
measure: Change in activated clotting time (ACT) values
timeFrame: Within 5 minutes following intravenous administration of 500 U/kg unfractionated heparin (UFH) and between 2-10 minutes after IMP infusion
measure: Change in antithrombin plasma levels
timeFrame: 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
measure: Change in heparin usage
timeFrame: From end of IMP infusion to the end of surgery
measure: FP unit use
timeFrame: From the start of IMP infusion until 24 hours following IMP infusion, and until discharge or 7 days after surgery, whichever comes first
measure: Amounts of further antithrombin concentrate for maintaining heparin responsiveness
timeFrame: From placement of the final suture or staple until 24 hours following IMP infusion, to discharge or 7 days after surgery, whichever comes first
measure: Transfusion of allogenic blood products
timeFrame: 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
measure: Administration of coagulation factor concentrates
timeFrame: 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
measure: Administration of other haemostatic-relevant therapies
timeFrame: 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
measure: Postoperative chest tube drainage
timeFrame: From the start of IMP infusion to 24 hours after infusion and until discharge or 7 days after surgery, whichever comes first
measure: Need for reoperation due to bleeding
timeFrame: 24 hours after the start of IMP infusion
measure: Cell saver volume
timeFrame: During surgery (from the time of the first surgical incision to the time at which the final suture or staple is placed)
measure: Adverse events
timeFrame: From the start of IMP infusion until hospital discharge or 7 days after IMP administration, whichever comes first
measure: Serious adverse events
timeFrame: From the start of IMP infusion until 28 days after IMP administration
measure: Survival status
timeFrame: At hospital discharge or 7 days after IMP administration (whichever comes first) and at 28 days (+ 4 days) after IMP administration
measure: Red Blood Cell count
timeFrame: Within 10 minutes before IMP infusion, between 2-10 minutes after IMP infusion, within 10 minutes after the end of CPB, at the end of surgery, and at 24 hours after infusion
measure: White Blood Cell count
timeFrame: Within 10 minutes before IMP infusion, between 2-10 minutes after IMP infusion, within 10 minutes after the end of CPB, at the end of surgery, and at 24 hours after infusion
measure: Haemoglobin levels
timeFrame: Within 10 minutes before IMP infusion, between 2-10 minutes after IMP infusion, within 10 minutes after the end of CPB, at the end of surgery, and at 24 hours after infusion
measure: Haematocrit
timeFrame: Within 10 minutes before IMP infusion, between 2-10 minutes after IMP infusion, within 10 minutes after weaning from CPB, at the end of surgery, and at 24 hours after infusion
measure: Platelet count
timeFrame: Within 10 minutes before IMP infusion, between 2-10 minutes after IMP infusion, within 10 minutes after weaning from CPB, at the end of surgery, and at 24 hours after infusion
Other outcomes:
Locations:
city: Stanford
country: United States
facility: Stanford University School of Medicine
state: California
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
city: Durham
country: United States
facility: Duke University Medical Center
state: North Carolina
city: Winston-Salem
country: United States
facility: Atrium Health Wake Forest Baptist
state: North Carolina
city: Columbus
country: United States
facility: The Ohio State University
state: Ohio
city: Oklahoma City
country: United States
facility: OU Health University of Oklahoma Medical Center
state: Oklahoma
city: Dallas
country: United States
facility: University of Texas Southwestern Medical Center
state: Texas
city: Innsbruck
country: Austria
facility: University Hospital Innsbruck
city: Vienna
country: Austria
facility: Vienna General Hospital AKH, Medical University of Vienna
city: Brno
country: Czechia
facility: Center of Cardiovascular and Transplant Surgery
city: Prague
country: Czechia
facility: Institute for Clinical and Experimental Medicine
city: Reims
country: France
facility: CHU de Reims, Hôpital Robert Debré
city: Rennes
country: France
facility: CHU de Rennes
city: Kaunas
country: Lithuania
facility: Hospital of Lithuanian university of Health sciences Kauno Klinikos
city: Vilnius
country: Lithuania
facility: Vilnius University Hospital Santaros Klinikos
city: Bucharest
country: Romania
facility: Institute for Cardiovascular Diseases C.C. Iliescu
city: Ljubljana
country: Slovenia
facility: University Medical Centre Ljubljana
city: Cambridge
country: United Kingdom
facility: Royal Papworth Hospital
Study officials:
References: