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RecruitingNCT06100718INVISIBLE-1Updated Dec 13, 2024

Discovery of New Cancer in the 1-year Follow-up After Ischemic Stroke in Patients at Risk: The INVISIBLE-1 Study

An observational study in Cancer-related Stroke, Paraneoplastic Coagulopathy and Occult Cancer, sponsored by Insel Gruppe AG, University Hospital Bern. Recruiting at 3 sites in Switzerland. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2024-12-13.

Sponsored by Insel Gruppe AG, University Hospital Bern · Observational

Study type
Observational
Model
Cohort
Time perspective
Prospective
Enrollment
370
Ages
18 Years and older
Sex
All
01

Study summary

INVISIBLE-1 aims to prospectively follow patients up to one year after ischemic stroke to:

  1. Determine the cumulative incidence of occult cancer in patients with embolic stroke of undetermined source (ESUS) and elevated D-dimer
  2. Describe occult cancer characteristics and spontaneous course of occult cancer

Methodology

The investigators will include 370 stroke patients with elevated D-dimer (≥ 820 μg/L) at the time of stroke, suspicion of ESUS after initial workup and without known cancer. The investigators will perform a follow-up telephone interview at one year to assess the occurrence of a new cancer and characterize the course of the disease.

Significance

Determining the real incidence of occult cancer in high-risk patients will help support the implementation of screening trials in the future. Faster detection and treatment of occult cancers would significantly impact patient' outcomes by offering faster cancer treatment and optimal secondary stroke prevention.

Read the detailed description

INVISIBLE-1 is the first prospective study conducting a 1-year post-stroke follow-up telephone interview in preselected stroke patients at high-risk for occult cancer.

INVISIBLE-1 aims to:

  1. Prospectively determine the cumulative incidence of occult cancer in patients with elevated D-dimer and ESUS within 1 year after the ischemic stroke
  2. Describe occult cancer characteristics and spontaneous course of occult cancer

Hypothesis

Elevated D-dimer and suspicion of ESUS at admission may predict an underlying unknown cancer at the time of index stroke. The investigators hypothesize that the cumulative incidence of newly diagnosed cancer within 1 year after stroke reaches 15% in patients presenting these characteristics. This percentage is higher than the 10% currently known according to available retrospective studies.

Project design

To ensure the recruitment of the majority of potential occult cancer patients, the investigators set the D-dimer cut-off for inclusion of ≥ 820 μg/L at admission, based on our intern retrospective analyses of 1001 patients (OCCULT-5 score). In patients with ESUS, this cut-off was associated with a sensitivity of 91% and a specificity of 56% for the presence of an occult cancer diagnosed within 1 year after the index-stroke.

As suggested by the current evidence, the investigators decided to set the limit for diagnosis of new cancer at 1 year after the index stroke. Beyond this period, the causality is questionable in our opinion.

02

Conditions studied

  • Cancer-related Stroke
  • Paraneoplastic Coagulopathy
  • Occult Cancer
  • Ischemic Stroke
  • Embolic Stroke of Undetermined Source
  • D-dimer

Keywords

  • Cancer-related stroke
  • D-dimer
  • ESUS
  • Occult cancer
  • Ischemic stroke
03

Who can participate

Ages eligible
18 Years and older
Sexes eligible
All
Sampling method
Non-probability sample

Study population

This study aims to include 370 stroke-patients with elevated D-dimer (≥ 820 μg/L) at baseline and suspicion of ESUS after initial workup in emergency room.

Inclusion criteria

  • Informed consent as documented by signature from patient or next of kin
  • Age ≥ 18 years old
  • Acute ischemic stroke with symptom onset within 48 h before admission
  • Acute ischemic stroke with:

    • persistent signs and symptoms of stroke lasting for ≥ 24 hours OR
    • acute brain infarction documented by computer tomography (CT) or MRI
  • D-dimer ≥ 820 μg/L measured after symptom-onset and within 24h after admission
  • Embolic stroke of unknown source (ESUS)* after initial work-up (acute cerebral imaging, 12-lead electrocardiogram, cardiac monitoring for at least 24h and echocardiography)

Exclusion criteria

Exclusion Criteria:

  • Active cancer** known at time of index-stroke
  • Intravenous Thrombolysis administrated prior to D-dimer measurement: Use of external laboratory value possible if available
  • New diagnosis of central nervous system cancer
  • Patient or next of kin (in case of lacking capacity) unlikely to be compliant or available for study follow-up interview

ESUS*: According to the definition from the NAVIGATE ESUS randomized trial: Non-lacunar ischemic stroke occurring in a patient in whom investigations did not show another specifically treatable underlying stroke etiology, primarily >50% stenosis in a proximal extracranial or intracranial artery, atrial fibrillation, other major-risk cardioembolic sources, or other determined etiology.

Active Cancer**: According to the definition from the International Society on Thrombosis and Haemostasis: Cancer diagnosed within the previous six months, recurrent, regionally advanced or metastatic cancer, cancer for which treatment had been administered within six months, or hematological malignancy that is not in complete remission for more than 5 years.

► Patients with history of cancer not meeting these criteria anymore can be included in the study.

04

Study design

Observational model
Cohort
Time perspective
Prospective
Enrollment
370 participants (estimated)
Patient registry
No

Groups and cohorts

  • Study group

    Acute ischemic stroke patients at high-risk for underlying occult cancer (elevated D-dimer and suspicion of ESUS at admission)

05

What researchers measure

Primary outcomes

  1. Number of participants with newly diagnosed cancer (occult cancer)

    Time frame: Within 1 year after ischemic stroke

Secondary outcomes

  1. Determination of occult cancer characteristics

    The description of the specific characteristics of occult cancers is defined by the location of the cancer, the histological type of cancer, the date of suspicion of cancer (e.g. via imaging), the type of investigation leading to the suspicion of cancer, the date of final diagnosis via histology, the presence of metastases at diagnosis, the type of treatment provided and the date of start of treatment.

    Time frame: Within 1 year after ischemic stroke

  2. Long-term functional outcome using the modified Rankin Scale (mRS) in stroke patients with occult cancer

    The mRS (ranging from 0-6) measures the degree of disability or dependence in the daily activities of people who have suffered a stroke or other causes of neurological disability. The higher the mRS score, the more disabled or dependent the patient (mRS 6 represents death).

    Time frame: At 1 year after ischemic stroke

  3. All-cause mortality rate and cause-specific mortality rate

    Time frame: At 1 year after ischemic stroke

  4. Rate of recurrent ischemic stroke, or systemic embolism in occult cancer-related stroke

    Time frame: Within 1 year after ischemic stroke

  5. Stroke severity assessed with the National Institutes of Health Stroke Scale (NIHSS) score in patients with occult cancer

    NIHSS score is used to quantify stroke severity. It ranges from 0 to a maximum of 42 points. The higher the score, the more extensive the stroke.

    Time frame: Baseline

06

Study locations

3 of 3 sites recruiting
  • Dept. of Neurology, Centre Hospital Universitaire Vaudois
    Lausanne, Vaud 1011, Switzerland
    Recruiting
  • Dept. of Neurology, Universitätsspital Basel
    Basel, 4031, Switzerland
    Recruiting
  • Dept, of Neurology, Inselspital, University of Bern
    Bern, 3010, Switzerland
    Recruiting
07

References and documents

Individual participant data

Plan to share: No

No publications or documents are linked to this record.

08

Registry details

Key details

Study ID
NCT06100718
Lead sponsor
Insel Gruppe AG, University Hospital Bern
Responsible party
Sponsor
First posted
Oct 25, 2023
Start date
Jan 1, 2022
Primary completion
Dec 31, 2025 (estimated)
Completion
Dec 31, 2025 (estimated)
Last update
Dec 13, 2024

Study contacts

Simon Jung, MD
Contact
simon.jung@insel.ch
+41 31 63 2 43 27
Morin Beyeler, MD
Contact
morin.beyeler@insel.ch
+41 31 66 4 12 26
Simon Jung, MD
principal investigator · Inselspital, University of Bern

Oversight

Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

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