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

Sponsor

Octapharma (Industry)

Overall Status

Not yet recruiting

CT.gov ID

NCT06096116

Collaborator

(none)

120

Enrollment

Arms

Anticipated Duration (Months)

Study Details

Study Description

Brief Summary

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

Condition or Disease	Intervention/Treatment	Phase
Acquired Antithrombin Deficiency	Drug: Human plasma derived antithrombin Drug: Placebo	Phase 3

Study Design

Study Type:

Interventional

Anticipated Enrollment :

120 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Triple (Participant, Care Provider, Outcomes Assessor)

Masking Description:

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.

Primary Purpose:

Treatment

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

Anticipated Study Start Date :

Jun 1, 2024

Anticipated Primary Completion Date :

Sep 1, 2026

Anticipated Study Completion Date :

Sep 1, 2026

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Low-dose Atenativ	Drug: Human plasma derived antithrombin A solvent/detergent and heat-treated antithrombin concentrate derived from human plasma
Experimental: High-dose Atenativ	Drug: Human plasma derived antithrombin A solvent/detergent and heat-treated antithrombin concentrate derived from human plasma
Placebo Comparator: Placebo Patients will receive a saline bolus dose	Drug: Placebo 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

Arm

Intervention/Treatment

Experimental: Low-dose Atenativ

Drug: Human plasma derived antithrombin

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

Experimental: High-dose Atenativ

Drug: Human plasma derived antithrombin

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

Placebo Comparator: Placebo

Patients will receive a saline bolus dose

Drug: Placebo

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

Outcome Measures

Primary Outcome Measures

Restoring heparin responsiveness [IMP infusion and initiation of CPB]
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

Secondary Outcome Measures

Amounts of further therapy for restoring heparin responsiveness [IMP infusion and initiation of CPB]
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
Change in ACT values [Within 5 minutes following intravenous administration of 500 U/kg UFH and between 2-10 minutes after IMP infusion]
The comparison between the change in ACT values following infusion of each of the Atenativ doses and placebo
Change in antithrombin plasma levels [Within 10 minutes before IMP infusion and between 2-10 minutes after IMP infusion]
The comparison between the change in antithrombin plasma levels following infusion of each of the Atenativ doses and placebo
Change in heparin usage [From initiation of CBP to the end of surgery]
The comparison between heparin usage following the injection of each of the Atenativ doses and injection of placebo
Maintaining heparin responsiveness [From initiation of CBP to the end of surgery]
For subjects in whom heparin responsiveness is restored without the need for further pre-CPB therapy, the percentage of patients in each group who do not require further therapy containing antithrombin (i.e., FP or antithrombin concentrates) to maintain heparin responsiveness until the end of surgery
Amounts of further therapy for maintaining heparin responsiveness [From initiation of CBP to end of surgery]
The comparison between the amounts of further therapy containing antithrombin (i.e., FP or antithrombin concentrates) needed for maintaining heparin responsiveness from the initiation of CPB until the end of surgery, for subjects in whom heparin responsiveness is restored without the need for further pre-CPB therapy
Adverse events [Up to 28 days (+ 2 days) following therapy administration]
Incidence of adverse events in all three cohorts
Survival status [28 days (+ 2 days) following administration of IMP]
Number of patients surviving in all three cohorts
Red Blood Cell count [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]
Standard haematological parameter
White Blood Cell count [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]
Standard haematological parameter
Haemoglobin levels [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]
Standard haematological parameter
Haematocrit [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]
Standard haematological parameter
Platelet count [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]
Standard haematological parameter

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 85 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

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

Exclusion Criteria:

Receiving, or have received within the timeframes specified, one or more of the following medications prior to the start of surgery:
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)
glycoprotein IIb/IIIa antagonist (within 1 day)
Pre-existing coagulopathy, defined as a history of bleeding problems or a laboratory history of bleeding disorder (e.g., von Willebrand disease, platelet disorder)
Renal insufficiency, defined as serum creatinine level >1.5 mg/dL
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 investigational product within 30 days prior to screening visit