Study of four-factor prothrombin complex concentrate, OCTAPLEX, in patients with acute major bleeding on direct oral anticoagulant (DOAC) therapy with factor Xa inhibitor

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Octapharma AG

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Hemic and Lymphatic Diseases [C15]

Trial duration

7 Jul 2022 → 26 Feb 2026

Decision date (initial)

2024-10-14

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

External identifiers

EU CT number

2024-515485-14-00

EudraCT number

2021-000740-21

ClinicalTrials.gov

NCT04867837

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Safety

To demonstrate superior haemostatic effectiveness of OCTAPLEX dosed at 50 IU/Kg body weight vs. 15 IU/Kg body weight for emergency reversal of the anticoagulant effect of DOACs in patients with major bleeding associated with factor Xa inhibition.

Secondary objectives 2

1. To evaluate the effect of OCTAPLEX on thrombin generation in patients with acute major bleeding on DOAC therapy with factor Xa inhibitor.
2. To evaluate the safety of OCTAPLEX in patients with acute major bleeding on DOAC therapy with factor Xa inhibitor.

Conditions and MedDRA coding

Acute major bleeding in patients receiving DOAC therapy with factor Xa inhibitor

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 4

1. Patients on oral factor Xa inhibitor therapy and with known or suspected baseline anti-factor Xa activity of at least 100 ng/mL: Patients who received or who are believed by the investigator to have received a dose of oral factor Xa inhibitor and who have a baseline antifactor Xa activity of at least 100 ng/mL according to the locally available test (e.g., chromogenic assay) performed outside of the study as part of standard of care OR -Patients who received or who are believed by the investigator to have received their latest dose of oral factor Xa inhibitor (e.g., rivaroxaban ≥ 10 mg, apixaban ≥2.5 mg, edoxaban ≥30 mg) ≤8 hours prior to enrolment OR -Patients who received or who are believed by the investigator to have received their latest dose of oral factor Xa inhibitor (e.g., rivaroxaban ≥ 10 mg, apixaban ≥2.5 mg, edoxaban ≥30 mg) >8 hours prior to enrolment or at an unknown time, but for whom the investigator suspects a baseline anti-factor Xa activity of at least 100 ng/mL and assesses that the administration of OCTAPLEX is clinically indicated
2. Aged ≥18 years
3. Patients who have given written informed consent or for whom written informed consent has been obtained from the patient's legally authorised representative on their behalf - Wherever possible, prospective written informed consent will be obtained before enrolment from the patient or, if they are incapable of providing it, from their legally authorised representative;- If prospective written informed consent is not possible, deferred consent procedures will be permitted outside the US if approved by the local ethics committee or otherwise permitted under local regulations;- When deferred consent procedures are used outside the US, written informed consent should be obtained from the patient as soon as they recover the capacity to provide it, or otherwise from their legally authorised representative
4. Patients who have acute major bleeding defined as follows: - Bleeding that is life-threatening or uncontrolled, e.g., with signs or symptoms of haemodynamic compromise, such as severe hypotension, poor skin perfusion, or low cardiac output that cannot be otherwise explained OR - Symptomatic bleeding in critical organs (intracranial, intraspinal, intraocular, gastrointestinal ,retroperitoneal, intra-articular, pericardial, or intramuscular with compartment syndrome) OR - - Acute overt bleeding associated with a fall in haemoglobin (Hgb) level of ≥2 g/dL, OR a Hgb level ≤8 g/dL if no baseline Hgb level is available, OR in the opinion of the investigator that the patient's Hgb level will fall to ≤8 g/dL with resuscitation

Exclusion criteria 17

1. Patients with ‘Do not resuscitate’ (DNR) orders
2. Patients with acute trauma for which reversal of DOAC therapy with factor Xa inhibitor alone would not be expected to control the bleeding event
3. Hgb decrease without accompanying evidence of source of bleeding
4. Acute coronary syndrome, ischaemic stroke or venous thromboembolism (VTE) within the preceding 3 months
5. Patients with a history, within the last 3 months, of disseminated intravascular coagulation (DIC) or hyperfibrinolysis
6. Patients with a known congenital bleeding disorder
7. Known inhibitors to coagulation factors II, VII, IX, or X; heparininduced, type II thrombocytopenia; or immunoglobulin A (IgA) deficiency with known antibodies against IgA
8. Known hypersensitivity to plasma-derived products or heparin
9. Patients who received haemostatic agents, including plasma, platelets, PCC, activated PCC (aPCC), recombinant factor VIIa, or recombinant factor Xa inactivated-zhzo (andexanet alfa), for the current bleeding event prior to enrolment (antifibrinolytic drugs and local haemostatic agents are allowed)
10. Patients who received ticlopidine within 14 days, prasugrel within 7 days, clopidogrel within 5 days, ticagrelor within 5 days , dipyridamole within 1 day or cangrelor within 1 hour preceding the bleeding event
11. Patients on enoxaparin therapy for thromboembolic prophylaxis
12. A score of less than 7 on the Glasgow Coma Scale in non-intubated patients or an estimated intracerebral haematoma volume of more than 60 mL (Patients intubated or sedated at the time of screening may be enrolled if intubation or sedation were done for non-neurologic reasons)
13. Patients with expected survival of less than 24 hours, in the opinion of the investigator (in collaboration with other medical experts as appropriate per usual local practice)
14. Patients scheduled to undergo surgery in less than 12 hours, with the exception of minor/surgeries and invasive procedures which are allowed for diagnostic or therapeutic reasons or if intended to address a second (non-index) bleeding event
15. Patients who are pregnant or breastfeeding at the time of enrolment
16. Patients previously enrolled in this study
17. Patients participating in another interventional clinical treatment study currently or during the past 1 month prior to study inclusion

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. The proportion of patients in whom OCTAPLEX demonstrates haemostatic effectiveness, i.e., binary outcome of effective (rating of excellent or good) or non-effective (rating of poor/none) in management of major bleeding events.

Secondary endpoints 4

1. Change in endogenous thrombin potential (ETP) as measured by thrombin generation assay (TGA) from baseline to 1 hour after OCTAPLEX administration
2. 30-day event rate of thromboembolic events (TEEs) and all-cause mortality
3. Occurrence of adverse events (AEs) during a 48-hours follow up period after OCTAPLEX administration
4. Vital signs and laboratory parameters during a 48-hours follow up period after OCTAPLEX administration

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 2

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Octapharma AG

Sponsor organisation

Octapharma AG

Address

Seidenstrasse 2

City

Lachen SZ

Postcode

8853

Country

Switzerland

Scientific contact point

Organisation

Octapharma AG

Contact name

Assoc. Prof., MD, MBA, VP, Clinical R&D Haematology

Public contact point

Organisation

Octapharma AG

Contact name

Assoc. Prof., MD, MBA, VP, Clinical R&D Haematology

Third parties 7

Locations

6 EU/EEA countries · 24 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Oversight and notifications

Regulatory notifications under CTR Articles 38, 52, 53, 54 and 77

Temporary halts 4 · Art. 38 CTR

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 32 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

8 submissions — initial application plus substantial / non-substantial modifications