Thrombolysis in Factor Xa-inhibitors Trial

NCT06878066 | Recruiting Phase 3 DMC

• 1 other identifier: 2023-509907-34-01
• Study Type: interventional
• Target: 300
• Locations: 1 country
• Sites: 13

Brief Summary

This study looks at whether stroke patients who take FXa inhibitors (a type of blood thinner) can safely receive clot-busting treatment (IVT). IVT is a common emergency treatment for stroke, but current guidelines say it should not be given to people who have taken FXa inhibitors in the last 48 hours. This is because doctors worry that IVT might cause dangerous bleeding in the brain. However, new research suggests that IVT might be safe for these patients. Some studies even show that stroke patients on FXa inhibitors who receive IVT do not have a higher risk of brain bleeding than other stroke patients. But because these studies were not designed as full medical trials, doctors still avoid IVT for this group. The SIFT trial will compare two groups of stroke patients who take FXa inhibitors: One group will receive IVT to see if it helps them recover better. One group will not receive IVT, which is the current standard. Doctors will check if IVT helps with recovery and if it causes any serious bleeding. If IVT is found to be safe and effective, this study could change stroke treatment guidelines and help more patients get life-saving care. Right now, some guidelines say that stroke patients on FXa inhibitors should have a blood test before getting IVT, to measure how much of the drug is in their system. But these tests are not available in most hospitals, and waiting for results could delay important treatment. The SIFT trial will not require this test before giving IVT. More and more people use FXa inhibitors to prevent strokes, but right now, they are being denied IVT based on old rules. If this study proves that IVT is safe for them, it could help doctors give better care to thousands of stroke patients.

Conditions

Stroke; Stroke (in Patients With Atrial Fibrillation); Ischemic Stroke; Acute Ischemic Stroke; Anticoagulant Therapy; Factor Xa Inhibitor; Intracranial Hemorrhages; Hemorrhagic Transformation Due to Acute Stroke; Bleeding in the Brain

Keywords

Thrombolysis; Acute Ischemic Stroke; Ischemic Stroke; Factor Xa Inhibitors; Atrial Fibrillation-Related Stroke; Intravenous Thrombolysis; Tissue Plasminogen Activator; Tenecteplase; Alteplase; Symptomatic Intracranial Hemorrhage; SIFT Trial; Stroke; Acute stroke; Direct Oral Anticoagulants; DOACs

Outcome Measures

Primary Outcomes (1)

• Early neurological improvement (ENI)

  Early neurological improvement, defined as a reduction of ≥8 points on the National Institutes of Health Stroke Scale (NIHSS), or NIHSS of 0-1 at 24 hours (22-36 h).

  24 hours (22-36 h).

Secondary Outcomes (6)

• NIHSS change

  24 hours (22-36 hours)

• Infarct volume

  24 hours ± 12 hours.

• mRS (modified Rankin Scale) score

  90 days (+/- 2 weeks)

• Symptomatic Intracranial Hemorrhage (sICH)

  36 hours

• Any Intracranial Hemorrhage (ICH)

  36 hours

Study Arms (2)

IVT

ACTIVE COMPARATOR

Intravenous Thrombolysis (IVT) with Alteplase or Tenecteplase

Drug: thrombolysis therapy

NO IVT

NO INTERVENTION

Standard Care Without Thrombolysis

Interventions

thrombolysis therapy DRUG

All treatment and monitoring routines are according to the hospitals' standard operating procedures (SOP), and both drugs (Alteplase (ALP) and Tenecteplase (TNK)) are approved drugs for the indication AIS with similar efficacy and safety profile. SIFT is designed to test the hypothesis that intravenous thrombolysis (IVT) (tenecteplase 0.25 mg/kg or alteplase 0.9 mg/kg intravenously) is efficient and safe in acute ischemic stroke patients (AIS) with recent ingestion (last 48 hours) of an Factor Xa (FXa) inhibitor who otherwise are eligible for IVT.

Also known as: Alteplase, Tenecteplase

IVT

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Participant must be 18 years of age or older.
• Ingestion of FXa inhibitors within the last 48 hours of symptom onset (or ongoing prescription of FXa inhibitor if unknown)
• Clinical diagnosis of AIS with disabling neurological deficit
• Presenting within 4.5 h of symptom onset or after awakening with symptoms of AIS with FLAIR-DWI mismatch on MRI as judged by the (neuro-) radiologist.
• Informed consent

You may not qualify if:

• Endovascular treatment eligible patients with isolated large vessel occlusion of the intracranial internal carotid artery (ICA), the M1 segment of the middle cerebral artery (MCA), or both confirmed by CT or MR angiography and expected time from randomization to groin puncture of \<30 minutes.
• Systolic BP \>185 mmHg or diastolic BP \>110 mmHg despite antihypertensive treatment.
• Known bleeding diathesis; manifest or recent severe bleeding; significant bleeding disorder last 6 months.
• Arterial puncture at a non-compressible site; biopsy or lumbar puncture \<7 days; major surgery, traumatic external heart massage, obstetrical delivery or serious trauma \<14 days; history of intracranial haemorrhage; stroke \<2 months, CNS neurosurgery \<2 months; serious head trauma \<2 months; pericarditis; sepsis; bacterial endocarditis; pericarditis; acute pancreatitis; neoplasm with increased bleeding risk; any serious medical illness likely to interact with treatment (i.e. aortic dissection); confounding pre-existent neurological or psychiatric disease.
• Any condition that, in the opinion of the treating physician, puts a patient at risk if treated with thrombolysis (i.e. signs of cerebral hemorrhage, known cerebral amyloid angiopathy, CT with signs of early ischemia greater than one-third of the middle cerebral artery territory).
• Prior/Concomitant Therapy
• Use of a) direct thrombin (II) inhibitor (Dabigatran) or b) warfarin with an INR ≥1.8; c) heparin \<48 h; d) treatment dose of LMWH \<24 h.
• Prior/Concurrent Clinical Study Experience
• Hypersensitivity to Alteplase or Tenecteplase

Sponsors & Collaborators

• Guri Hagberg: lead
• Klinbeforsk: collaborator
• Clinical Trial Unit (CTU), Oslo University Hospital: collaborator

Study Sites (13)

Dept. of Medicine, Baerum Hospital

Bærum, Gjettum, 1346, Norway

RECRUITING

Dept of Medicine, Helse More and Romsdal Health Trust, Aalesund Hospital

Ålesund, 6017, Norway

RECRUITING

Dept of Medicine, Haraldsplass deaconal Hospital

Bergen, 5009, Norway

RECRUITING

Dept. Of Neurology, Haukeland University Hopsital

Bergen, 5009, Norway

RECRUITING

Dept of Neurology, Drammen Hospital Trust

Drammen, 3004, Norway

RECRUITING

Dept of Neurology, Ostfold Hospital Trust, Kalnes

Grålum, 1714, Norway

RECRUITING

Dept of Neurology, Hospital of Southern Norway, SSHF

Kristiansand, 4615, Norway

RECRUITING

Dept of Neurology, Innlandet Hospital Trust, Lillehammer

Lillehammer, 2609, Norway

RECRUITING

Dept. of Neurology, Oslo University Hospital

Oslo, 0450, Norway

RECRUITING

Dept of Neurology, Stavanger University Hospital

Stavanger, 4011, Norway

RECRUITING

Dept. of Neurology, Tromso University Hospital

Tromsø, 9019, Norway

RECRUITING

Dept. Of Medicine, St.Olav Hospital, Trondheim

Trondheim, 7030, Norway

RECRUITING

Dept of Neurology, Vesfold Hospital Trust, Tonsberg

Tønsberg, 3103, Norway

RECRUITING

Related Links

• CTIS Portal where the primary trial protocol and references are accessible

MeSH Terms

Conditions

Stroke; Ischemic Stroke; Intracranial Hemorrhages

Interventions

Thrombolytic Therapy; Tissue Plasminogen Activator; Tenecteplase

Condition Hierarchy (Ancestors)

Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Vascular Diseases; Cardiovascular Diseases; Hemorrhage; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Drug Therapy; Therapeutics; Serine Endopeptidases; Endopeptidases; Peptide Hydrolases; Hydrolases; Enzymes; Enzymes and Coenzymes; Serine Proteases; Plasminogen Activators; Blood Coagulation Factors; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Biological Factors

Study Officials

• Håkon Ihle-Hansen, MD, PhD

  Dept. of Medicine, Baerum Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Guri Hagberg, MD, PhD

CONTACT

+47 92821843; guhagb@ous-hf.no

Kim L Schultz, MD

CONTACT

+47 40859583; kimsch@ous-hf.no

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: MD, PhD

Model Details: A pragmatic phase III, multicenter, prospective, randomized, open label, blinded endpoint (PROBE), registry-linked, trial.

Study Record Dates

• First Submitted: March 10, 2025
• First Posted: March 14, 2025
• Study Start: March 14, 2025
• Primary Completion (Estimated): December 31, 2028
• Study Completion (Estimated): December 31, 2037
• Last Updated: September 2, 2025

Record last verified: 2025-08

Locations

NO (13)