Urgent SurgeryPhase 3ANNEXA-RSNCT05926349
A Study of Andexanet Alfa in Patients Requiring Urgent Surgery or Procedure
A Phase 3 study testing Andexanet alfa in people with Urgent Surgery, run by AstraZeneca.
Trial summary
The study will aim to find out if the drug andexanet alfa is safe and effective in preventing major bleeding during urgent surgery or invasive procedures. The study will compare the use of andexanet alfa to the usual care given at the study center. Read more about this study
- Who is it for?
- Ages 18 to 130 years
- Conditions the study is for
- Urgent Surgery
- What is being tested?
- Andexanet alfa
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 0 participants
- Where
- No sites listed yet
- Study dates
- 2 Aug 2024to 7 Sep 2027
- Phase
- Phase 3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 130 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- The patient requires, in the opinion of the Investigator, urgent surgery or procedure and requires reversal of direct oral FXa inhibition.
- The patient requires urgent surgery or procedure within 12 hours of informed consent.
- The patient requires urgent surgery or procedure that is expected to be associated with a high risk of bleeding or bleeding to occur into a critical organ.
- The patient has taken an oral FXa inhibitor (such as apixaban, rivaroxaban, or edoxaban) within 15 hours or more, prior to start of surgery or procedure.
- Female patients of childbearing potential must have a negative pregnancy test at Screening.
- Willingness to use highly effective methods of contraception (for male and female patients who are fertile).
Who cannot join
- The patient requires surgeries or procedures that have a very low chance of causing significant, uncontrollable bleeding, such as small skin procedures, cataract surgery, and minor dental procedures.
- The patient has acute life-threatening bleeding at the time of Screening.
- The patient will undergo a surgery or procedure which will require the use of heparin.
- Patient who is not expected to live for more than three months due to other health problems or has specifically requested not to be resuscitated if their heart stops beating.
- Prior to screening, the patient had either experienced low platelet count due to heparin use with or without blood clots or had a genetic condition that affects blood clotting.
- Patient has acute decompensated heart failure, cardiogenic shock, sepsis, or septic shock at the time of Screening.
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- Patient has history of heparin-induced thrombocytopenia (with or without thrombosis) or inherited coagulopathy (eg, anti-thrombin III deficiency, anti-phospholipid antibody syndrome, protein C/S deficiency, Factor V Leiden) at the time of Screening.
- Previously diagnosed with a bleeding disorder (eg, platelet function disorder, hemophilia, Von Willebrand disease, or coagulation factor deficiency).
- Prior known hypersensitivity to andexanet alfa.
- Use of andexanet alfa 30 days prior to Screening.
- Patient diagnosed with dementia.
- Any prohibited medication as determined in the study.
About this study
Official title: A Randomized Study of Andexanet Alfa Compared to Usual Care in Patients Receiving a Factor Xa Inhibitor Who Require Urgent Surgery or Procedure (ANNEXA-RS)
The study will aim to find out if the drug andexanet alfa is safe and effective in preventing major bleeding during urgent surgery or invasive procedures. The study will compare the use of andexanet alfa to the usual care given at the study center.
Read the detailed description
This study will be an open-label, randomised, controlled, prospective, multicenter study. The study will include patients requiring urgent surgery or procedure that needs to be performed within 15 hours of the last dose of blood-thinning drug (direct oral activated Factor X (FXa) inhibitor).
The study will comprise of the following periods:
- Screening, followed by surgery or procedure and study intervention.
- Follow-up period: there will be four follow-up visits over a duration of approximately 30 days.
- Follow-up visit for patients with positive anti-andexanet alfa antibody test: patients with a positive anti-andexanet alfa antibody response at day 30 will have a follow-up anti-andexanet alfa antibody test approximately 120 days post-surgery or procedure.
Patients will be randomised in the ratio of 1:1 to receive either andexanet alfa or usual care.
- Conditions
- Urgent Surgery
- Being tested
- Andexanet alfa, Usual Care
- Keywords
- Andexanet alfa, Blood Thinners
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Andexanet alfaDrug
Also called Andexxa®, Ondexxya®
Andexanet is a recombinant version of human FXa
Usual CareDrug
As per the label of the chosen usual care product(s) and/or usual care standards.
| Study group | Role | What they receive |
|---|---|---|
| Andexanet Alfa Group | Experimental | Patients will receive andexanet alfa as IV bolus followed by an infusion. Receives: Drug: Andexanet alfa |
| Usual Care Group | Active comparator | Patients will receive treatment based on the Investigator's discretion, according to regional, local/institutional guidelines or practices. Receives: Drug: Usual Care |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of patients achieving effective intraoperative hemostasis
Intraoperative hemostasis will be assessed according to the categories as per 4-point hemostasis scale: Excellent - Normal hemostasis, Good - Mildly abnormal hemostasis (eg. slight oozing from surgical wounds), Moderate - Moderate abnormality in intraprocedural hemostasis (eg. controllable bleeding), Poor - Severe hemostatic abnormality (eg. severe refractory hemorrhage). Hemostasis will be considered to be effective if the intraoperative hemostasis category is 'excellent' or 'good', and ineffective if the intraoperative hemostasis category is 'moderate' or 'poor'.
Measured: From start to the end of surgery or procedure on Day 0
Secondary outcomes (2)
Change from Baseline in anti-FXa activity measured through blood samples
The ability of andexanet alfa to rapidly reverse the anticoagulation effect of FXa inhibitors by reduction of anti-FXa activity when compared to usual care.
Measured: Baseline to start of surgery or procedure
Change from Baseline in anti-FXa activity measured through blood samples
The ability of andexanet alfa to sustainably reverse the anticoagulation effect of FXa inhibitors by reduction of anti-FXa activity when compared to usual care at two hours post start of surgery or procedure will be assessed.
Measured: Baseline to two hours post start of surgery or procedure
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted3 Jul 2023
- Study start2 Aug 2024 (estimated)
- Primary completion5 Jan 2027 (estimated)
- Study completion7 Sep 2027 (estimated)
Why it stopped: Business decision
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Urgent SurgeryStudies of the same condition, open and under way.
- More trials run by AstraZenecaThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- AstraZeneca
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05926349
- Sponsor's protocol ID
- D9604C00001
- Acronym
- ANNEXA-RS
- Status last verified
- Oct 2024
- First submitted
- 9 Jun 2023
- Last updated
- 26 Oct 2024
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal. All requests will be evaluated as per the AZ disclosure commitment: https://astrazenecagrouptrials.pharmacm.com /ST/Submission/Disclosure. Yes, indicates that AZ are accepting requests for IPD, but this does not mean all requests will be shared.
Study at a glance
From the registry record, last updated by the sponsor on 26 Oct 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Randomized Study of Andexanet Alfa Compared to Usual Care in Patients Receiving a Factor Xa Inhibitor Who Require Urgent Surgery or Procedure (ANNEXA-RS)
- ClinicalTrials.gov ID
- NCT05926349
- Acronym / sponsor ID
- ANNEXA-RS / D9604C00001
- Conditions
- Urgent Surgery
- Keywords
- Andexanet alfa, Blood Thinners
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- WithdrawnReason stopped: Business decision
- Enrolment
- 0 participants (actual)
- Lead sponsor
- AstraZenecaIndustry (pharma, biotech, devices)
- Study start
- 2 Aug 2024 (estimated)
- Primary completion
- 5 Jan 2027 (estimated)
- Study completion
- 7 Sep 2027 (estimated)
- First posted
- 3 Jul 2023 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The study will aim to find out if the drug andexanet alfa is safe and effective in preventing major bleeding during urgent surgery or invasive procedures. The study will compare the use of andexanet alfa to the usual care given at the study center.
Detailed description
This study will be an open-label, randomised, controlled, prospective, multicenter study. The study will include patients requiring urgent surgery or procedure that needs to be performed within 15 hours of the last dose of blood-thinning drug (direct oral activated Factor X (FXa) inhibitor).
The study will comprise of the following periods:
- Screening, followed by surgery or procedure and study intervention.
- Follow-up period: there will be four follow-up visits over a duration of approximately 30 days.
- Follow-up visit for patients with positive anti-andexanet alfa antibody test: patients with a positive anti-andexanet alfa antibody response at day 30 will have a follow-up anti-andexanet alfa antibody test approximately 120 days post-surgery or procedure.
Patients will be randomised in the ratio of 1:1 to receive either andexanet alfa or usual care.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Andexanet Alfa Group | Experimental | Drug: Andexanet alfaPatients will receive andexanet alfa as IV bolus followed by an infusion. |
| Usual Care Group | Active comparator | Drug: Usual CarePatients will receive treatment based on the Investigator's discretion, according to regional, local/institutional guidelines or practices. |
Who may qualify
- Ages
- 18 to 130 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- The patient requires, in the opinion of the Investigator, urgent surgery or procedure and requires reversal of direct oral FXa inhibition.
- The patient requires urgent surgery or procedure within 12 hours of informed consent.
- The patient requires urgent surgery or procedure that is expected to be associated with a high risk of bleeding or bleeding to occur into a critical organ.
- The patient has taken an oral FXa inhibitor (such as apixaban, rivaroxaban, or edoxaban) within 15 hours or more, prior to start of surgery or procedure.
- Female patients of childbearing potential must have a negative pregnancy test at Screening.
Key exclusion criteria (12 listed)
- The patient requires surgeries or procedures that have a very low chance of causing significant, uncontrollable bleeding, such as small skin procedures, cataract surgery, and minor dental procedures.
- The patient has acute life-threatening bleeding at the time of Screening.
- The patient will undergo a surgery or procedure which will require the use of heparin.
- Patient who is not expected to live for more than three months due to other health problems or has specifically requested not to be resuscitated if their heart stops beating.
- Prior to screening, the patient had either experienced low platelet count due to heparin use with or without blood clots or had a genetic condition that affects blood clotting.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Andexanet alfaAlso: Andexxa®, Ondexxya®Andexanet is a recombinant version of human FXa | Drug | Andexanet Alfa Group |
| Usual CareAs per the label of the chosen usual care product(s) and/or usual care standards. | Drug | Usual Care Group |
Primary outcome
Number of patients achieving effective intraoperative hemostasis
Time frame: From start to the end of surgery or procedure on Day 0
Intraoperative hemostasis will be assessed according to the categories as per 4-point hemostasis scale: Excellent - Normal hemostasis, Good - Mildly abnormal hemostasis (eg. slight oozing from surgical wounds), Moderate - Moderate abnormality in intraprocedural hemostasis (eg. controllable bleeding), Poor - Severe hemostatic abnormality (eg. severe refractory hemorrhage). Hemostasis will be considered to be effective if the intraoperative hemostasis category is 'excellent' or 'good', and ineffective if the intraoperative hemostasis category is 'moderate' or 'poor'.
2 secondary outcomes
Change from Baseline in anti-FXa activity measured through blood samples
Time frame: Baseline to start of surgery or procedure
Change from Baseline in anti-FXa activity measured through blood samples
Time frame: Baseline to two hours post start of surgery or procedure
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 26 Oct 2024.
- Individual participant dataSharing planned: Yes. Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal. All requests will be evaluated as per the AZ disclosure commitment: https://astrazenecagrouptrials.pharmacm.com /ST/Submission/Disclosure. Yes, indicates that AZ are accepting requests for IPD, but this does not mean all requests will be shared.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Andexanet alfa in people with Urgent Surgery, run by AstraZeneca.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 12 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: withdrawn, as of the sponsor's last update on 26 Oct 2024. Status can change between updates, so confirm with the study contact before making plans.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was withdrawn before enrolling participants, so there are no results.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of patients achieving effective intraoperative hemostasis (time frame: From start to the end of surgery or procedure on Day 0). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 26 Oct 2024.