rFVIIa for Hemorrhagic Stroke

(FASTEST Trial)

Recruiting at 94 trial locations

Overseen By James Grotta, MD

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Joseph Broderick, MD

Must not be taking: Anticoagulants, Pro-coagulants, Heparin, others

Disqualifiers: Coma, Disability, Thrombosis, others

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 6

Duration: Immediate (within 2 hours of stroke onset)

860 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a treatment called Recombinant Activated Factor VII (rFVIIa) for individuals who have experienced a sudden brain bleed (hemorrhagic stroke). The goal is to determine if administering rFVIIa within two hours of the stroke can reduce bleeding and improve recovery over six months. Participants will receive either rFVIIa or a placebo (a harmless substance resembling the treatment) to compare results. Ideal candidates for this trial are those who have recently experienced a spontaneous brain bleed and can begin treatment within 120 minutes of the stroke. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants a chance to contribute to potentially groundbreaking treatment advancements.

Do I need to stop my current medications to join the trial?

The trial requires that you have not used oral anticoagulants, pro-coagulant drugs, or low-molecular weight heparin within certain time frames before enrollment. If you are taking these medications, you may need to stop them to participate.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research shows that Recombinant Activated Factor VII (rFVIIa) usually reduces bleeding. In some studies, it stopped or lessened bleeding in most patients. However, possible side effects are important to consider. Some research has found a higher risk of serious blood clots, such as heart attacks or strokes, when using rFVIIa. These clots, known as thromboembolic events, can form in blood vessels.

In another study, while rFVIIa helped slow brain bleeding, it did not always lead to better survival or recovery. This indicates that even though it might help with bleeding, it doesn't always improve overall health outcomes. Ongoing studies focus on safety, especially monitoring for serious side effects like these blood clots. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for stroke?

Recombinant Activated Factor VII (rFVIIa) is unique because it targets blood clotting directly to stop bleeding in the brain following a hemorrhagic stroke. Unlike standard treatments that focus on controlling blood pressure or managing symptoms, rFVIIa acts by quickly promoting clot formation, potentially limiting the damage from the stroke. Researchers are excited about rFVIIa because it can be administered rapidly via an IV injection within two hours of stroke onset, offering a promising and fast-acting intervention to minimize brain injury.

What evidence suggests that rFVIIa might be an effective treatment for hemorrhagic stroke?

Research has shown that Recombinant Activated Factor VII (rFVIIa), which participants in this trial may receive, can help slow brain bleeding after a hemorrhagic stroke. Studies have found that administering rFVIIa within a few hours of a stroke can reduce the size of the bleed, offering promise for better recovery. However, while rFVIIa effectively controls bleeding, it has not consistently improved survival or long-term recovery. The treatment aids blood clotting, which can stop the bleeding. For years, it has managed bleeding in other conditions, such as hemophilia, demonstrating its ability to help the body form clots. ^{1 2 6 7 8}

Who Is on the Research Team?

Joseph Broderick, MD

Principal Investigator

University of Cincinnati

Are You a Good Fit for This Trial?

This trial is for adults aged 18-80 who've had a spontaneous hemorrhagic stroke and can start treatment within 2 hours of onset. It's not for those with certain pre-existing conditions, drug dependencies, recent participation in other trials, or women who are pregnant/lactating. Patients must be able to follow the trial protocol.

Inclusion Criteria

Efforts to obtain informed consent per EFIC guidelines (U.S.) or adherence to country-specific emergency research informed consent regulations (Canada, Germany, Spain, U.K., Japan)

I have had a stroke caused by bleeding in my brain.

I can take the study medication within 2 hours of my stroke or when I was last well.

Exclusion Criteria

I am not allergic or sensitive to the study medication.

My bleeding is in the brainstem or cerebellum.

Recent (within 30 days) participation in any investigational drug or device trial or earlier participation in any investigational drug or device trial for which the duration of effect is expected to persist until to the time of FASTEST enrollment

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive rFVIIa or placebo as an IV injection within 120 minutes of stroke onset

Immediate (within 2 hours of stroke onset)

1 visit (in-person)

Initial Follow-up

Participants are monitored for growth of ICH with CT scans at baseline and 24 hours

24 hours

2 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness with remote assessments at 30 and 90 days

90 days

2 visits (remote)

Long-term Follow-up

Participants' outcomes are assessed at 180 days using the Modified Rankin Scale

180 days

1 visit (remote)

What Are the Treatments Tested in This Trial?

Interventions

• Placebo
• Recombinant Activated Factor VII (rFVIIa)

Trial Overview The FASTEST Trial is testing if Recombinant Activated Factor VII (rFVIIa), given quickly after a hemorrhagic stroke starts, can improve recovery at six months compared to standard care. Half will get rFVIIa and half a placebo to see which works better.

How Is the Trial Designed?

Group I: Recombinant Activated Factor VII (rFVIIa) Active Control 1 Intervention

rFVIIa given as IV injection over 2 minutes within 120 minutes of stroke onset

Group II: Placebo Placebo Group 1 Intervention

Matching placebo given as IV injection over 2 minutes within 120 minutes of stroke onset

Recombinant Activated Factor VII (rFVIIa) is already approved in European Union, United States for the following indications:

Approved in European Union as NovoSeven for:

• Hemophilia A and B with inhibitors
• Acquired hemophilia
• Congenital factor VII deficiency
• Glanzmann thrombasthenia

Approved in United States as NovoSeven RT for:

• Hemophilia A and B with inhibitors
• Acquired hemophilia
• Congenital factor VII deficiency
• Glanzmann thrombasthenia

Approved in United States as Sevenfact for:

• Hemophilia A and B with inhibitors
• Acquired hemophilia
• Congenital factor VII deficiency

Approved in European Union as Cevenfacta for:

• Hemophilia A and B with inhibitors
• Acquired hemophilia
• Congenital factor VII deficiency

Who Is Running the Clinical Trial?

Joseph Broderick, MD

Lead Sponsor

Trials

1

Recruited

860+

National Institute of Neurological Disorders and Stroke (NINDS)

Collaborator

Trials

1,403

Recruited

655,000+

Novo Nordisk A/S

Industry Sponsor

Trials

1,578

Recruited

3,813,000+

Lars Fruergaard Jørgensen

Novo Nordisk A/S

Chief Executive Officer since 2017

MSc in Finance and Business Administration, Aarhus School of Business, Aarhus University, Denmark

Martin Holst Lange

Novo Nordisk A/S

Chief Medical Officer since 2021

MD from University of Copenhagen

Published Research Related to This Trial

In a retrospective analysis of 5 very low birth weight preterm infants with disseminated intravascular coagulation (DIC) and severe gastrointestinal bleeding, recombinant activated Factor VII (rFVIIa) was effective in stopping intestinal hemorrhage in 3 out of the 5 cases.

While rFVIIa showed promise as a rescue therapy for hemorrhagic shock, it was ineffective in patients with severe acidosis, hypothermia, and thrombopenia, highlighting the need for careful patient selection.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Recombinant activated Factor VII as a hemostatic agent in very low birth weight preterms with gastrointestinal hemorrhage and disseminated intravascular coagulation. Fischer, D., Schloesser, R., Buxmann, H., et al.[2011]

Recombinant activated factor VII (rFVIIa) was successfully used in a Jehovah's Witness patient who was anticoagulated with warfarin and had an acute subdural hematoma, demonstrating its potential efficacy in managing bleeding in patients with coagulation abnormalities.

The use of rFVIIa allowed for the surgical evacuation of the hematoma without excessive blood loss, leading to a good recovery for the patient, highlighting its safety and effectiveness in critical situations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Recombinant activated factor VII for a warfarinised Jehovah's Witness with an acute subdural haematoma. Goldberg, R., Drummond, KJ.[2013]

Recombinant activated coagulation factor VII (rFVIIa) is highly effective in treating bleeding episodes in pediatric patients with congenital hemophilia with inhibitors, achieving effectiveness in 95.4% of cases across various age groups.

The treatment is considered safe, with adverse reactions similar to those seen in adults, and only one confirmed thrombotic event related to rFVIIa, indicating a favorable safety profile for pediatric use.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and efficacy of recombinant factor VIIa by pediatric age cohort: reassessment of compassionate use and trial data supporting US label. Croteau, SE., Nakar, C., Neufeld, EJ., et al.[2018]

Recombinant activated factor VII (rFVIIa) is used to treat hemophilic patients with inhibitors against coagulation factors, but the evidence supporting its efficacy is weak due to limited sample sizes and study variability across eight randomized controlled trials involving 256 patients.

The authors recommend that rFVIIa treatment should be tailored to the individual's thrombin generation ability rather than solely relying on weight, suggesting that tests like thromboelastography could enhance treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Evidence supporting the use of recombinant activated factor VII in congenital bleeding disorders. Johansson, PI., Ostrowski, SR.[2021]

In a study of 32 patients undergoing vascular surgery, the use of recombinant activated factor VII (rFVIIa) effectively controlled severe bleeding in 29 patients, demonstrating its potential as a haemostatic agent when conventional methods fail.

Despite its effectiveness, the use of rFVIIa is recommended cautiously due to the lack of randomized controlled trials confirming its safety and efficacy in vascular patients, along with its high cost of approximately $4080 for a 4.8 mg dose.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Recombinant activated factor VII in the treatment of intractable non-surgical bleeding following major vascular procedures]. Koncar, IB., Savić, N., Davidović, LB., et al.[2019]

Recombinant activated factor VII (rFVIIa) is effective in treating bleeding episodes in patients with antibodies against coagulation factors VIII and IX, demonstrating its established role in managing specific bleeding disorders.

Recent applications of rFVIIa have expanded to include the management of uncontrolled bleeding in various congenital and acquired haemostatic abnormalities, indicating its potential versatility in clinical settings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Recombinant factor VIIa. An update on its clinical use. Franchini, M., Zaffanello, M., Veneri, D.[2005]

In a large phase III study involving 560 actively hemorrhaging trauma patients, recombinant activated factor VII (rFVIIa) did not increase the overall risk of adverse events or mortality compared to placebo, indicating its safety in this critical setting.

While there was a slight imbalance in reported myocardial infarctions in the rFVIIa group, the use of rFVIIa was associated with a significantly lower rate of acute respiratory distress syndrome compared to the placebo group (3.0% vs. 7.2%), suggesting potential benefits in respiratory outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Recombinant activated factor VII safety in trauma patients: results from the CONTROL trial. Dutton, RP., Parr, M., Tortella, BJ., et al.[2020]

In a study of 59 patients receiving off-label recombinant activated factor VII (rFVIIa) in major teaching hospitals in Paris, 82% of prescriptions were found to be adequate or acceptable according to established guidelines.

The use of rFVIIa was particularly appropriate in multiple trauma cases, with 100% of prescriptions meeting the necessary criteria, and 83% in obstetrical cases, indicating a high level of adherence to recommended practices.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Off-label use of recombinant factor VII (rFVIIa) in teaching hospitals in Paris in 2010]. Bardon, J., Fink, J., de Montblanc, J., et al.[2016]

Recombinant activated factor VII (rFVIIa) is an effective hemostatic agent primarily used to treat bleeding in hemophilic patients with inhibitors, demonstrating its efficacy in managing severe bleeding episodes.

In addition to its established use in hemophilia, rFVIIa is increasingly being applied to treat uncontrolled bleeding in various congenital and acquired hemostatic disorders, indicating its expanding role in clinical practice.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Recombinant factor VIIa: a review on its clinical use. Franchini, M.[2018]

Recombinant activated Factor VII (rFVIIa) is effective in managing severe bleeding in hemophilia patients with inhibitors and shows promise as an adjuvant therapy for critical bleeding from trauma, demonstrating rapid and significant hemostasis.

The use of rFVIIa can reduce the need for blood transfusions and improve clinical outcomes in patients experiencing massive blood loss, highlighting its potential as a powerful treatment option in emergency situations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The emerging role of recombinant activated Factor VII (rFVIIa) in the treatment of blunt traumatic haemorrhage. Rizoli, SB., Chughtai, T.[2019]

In a study of 46 patients with intracerebral hemorrhage treated with recombinant-activated factor VII (rFVIIa), no significant difference in treatment outcomes was observed based on the timing of treatment (within 3 hours vs. 3 to 4 hours after symptom onset).

The study found that rFVIIa treatment did not significantly reduce ICH growth or improve outcomes compared to a control group, and thrombotic adverse events occurred in 11.1% of treated patients, suggesting the need for further criteria to identify which patients may benefit from this treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The effect of activated factor VII for intracerebral hemorrhage beyond 3 hours versus within 3 hours. Hallevi, H., Gonzales, NR., Barreto, AD., et al.[2019]

Recombinant-activated factor VII (rFVIIa) is effective in managing bleeding in hemophiliacs with inhibitors and shows promise as a hemostatic agent in nonhemophilic patients, acting quickly and with minimal complications.

Ongoing clinical trials aim to evaluate the safety and efficacy of rFVIIa for reversing coagulopathy in various conditions, including trauma and CNS hemorrhage, which could expand its use beyond hemophilia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The emerging role of recombinant-activated factor VII in neurocritical care. Fewel, ME., Park, P.[2018]

Citations

1. nejm.org nejm.org/doi/full/10.1056/NEJMoa042991

Recombinant Activated Factor VII for Acute Intracerebral ... Treatment with rFVIIa within four hours after the onset of intracerebral hemorrhage limits the growth of the hematoma, reduces mortality, and improves ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9933458/

Recombinant Factor VIIa for Hemorrhagic Stroke Treatment at ... rFVIIa activates coagulation and platelet activity(12) and reduced HE in phase II and phase III trials,(7, 13, 14) A trial of tranexamic acid ...

3. sciencedirect.com sciencedirect.com/science/article/pii/S2475037924003650

Recombinant factor VIIa: new insights into the mechanism ... rFVIIa has been used to manage bleeding in persons with hemophilia and inhibitors for over 30 years, its mechanisms of action is still being studied.

4. annalsthoracicsurgery.org annalsthoracicsurgery.org/article/S0003-4975(08)01013-8/fulltext

Efficacy and Safety of Recombinant Activated Factor VII to ... ... rFVIIa reduced growth of the hematoma but did not improve survival or functional outcome after intracerebral hemorrhage [22. 22. Mayer, S.A. ∙ Brun, N.C. ...

5. nejm.org nejm.org/doi/full/10.1056/NEJMoa0707534

Efficacy and Safety of Recombinant Activated Factor VII for ... Hemostatic therapy with rFVIIa reduced growth of the hematoma but did not improve survival or functional outcome after intracerebral hemorrhage.

6. nejm.org nejm.org/doi/full/10.1056/NEJMoa1006221

Safety of Recombinant Activated Factor VII in Randomized ... We found an increased risk of arterial thromboembolic events among patients who received off-label rFVIIa as compared with patients who received ...

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC4317095/

ten years of data on off-licence use of recombinant activated ... Reduction or cessation of bleeding was reported in 74% and 28-day survival was 71% but outcomes varied depending on clinical context. pH strongly correlated ...

8. nacblood.ca nacblood.ca/sites/default/files/2024-07/2024-07-17%20NAC%20Statement%20on%20Recombinant%20Factor%20VIIa_0.pdf

NAC STATEMENT ON RECOMBINANT FACTOR VIIA Very low-dose recombinant Factor VIIa administration for cardiac surgical bleeding reduces red blood cell transfusions and renal risk: a matched ...