Cancer-related StrokeINVISIBLE-1NCT06100718
Discovery of New Cancer in the 1-year Follow-up After Ischemic Stroke in Patients at Risk: The INVISIBLE-1 Study
An observational study of Cancer-related Stroke and Paraneoplastic Coagulopathy, run by Insel Gruppe AG, University Hospital Bern at 3 sites in Switzerland.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Cancer-related Stroke, Paraneoplastic Coagulopathy, Occult Cancer
- How many people
- 370 participants
- Where
- 3 sitesSwitzerland
- Study dates
- 1 Jan 2022to 31 Dec 2025
- Phase
- Observational
- Are there results?
- Not yet: the study is under way
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 years and older
- All sexes
- Adult, Older adult
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.
Who may be able to join
- 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)
Who cannot join
- 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.
Trial locations and contacts
3 sites in 1 country. Contact the study team or a site near you to ask about taking part.
Switzerland3 sites, 3 recruiting
- Recruiting
Dept. of Neurology, Universitätsspital Basel
Basel, 4031
Mira Katan, MD, +41 61 328 45 06, Mira.Katan@usb.ch
Johannes Frenger, +41 61 265 25 25, Johannes.Frenger@usb.ch
- Recruiting
Dept, of Neurology, Inselspital, University of Bern
Bern, 3010
Simon Jung, MD, +41 31 63 2 43 27, Simon.jung@insel.ch
Morin Beyeler, MD, +41 31 66 4 12 26, Morin.beyeler@insel.ch
- Recruiting
Dept. of Neurology, Centre Hospital Universitaire Vaudois
Lausanne, Canton of Vaud, 1011
Michel Patrik, +41 79 556 8416, patrik.michel@chuv.ch
Davide Strambo, +4121 314 17 74, Davide.Strambo@chuv.ch
About this study
INVISIBLE-1 aims to prospectively follow patients up to one year after ischemic stroke to:
- Determine the cumulative incidence of occult cancer in patients with embolic stroke of undetermined source (ESUS) and elevated D-dimer
- Describe occult cancer characteristics and spontaneous course of occult cancer
Read more
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:
- Prospectively determine the cumulative incidence of occult cancer in patients with elevated D-dimer and ESUS within 1 year after the ischemic stroke
- 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.
- Conditions
- 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
- Medical subject headings
- Ischemic Stroke
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
| Study group | Role | What they receive |
|---|---|---|
| Study group | Acute ischemic stroke patients at high-risk for underlying occult cancer (elevated D-dimer and suspicion of ESUS at admission) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of participants with newly diagnosed cancer (occult cancer)
Measured: Within 1 year after ischemic stroke
Secondary outcomes (5)
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.
Measured: Within 1 year after ischemic stroke
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).
Measured: At 1 year after ischemic stroke
All-cause mortality rate and cause-specific mortality rate
Measured: At 1 year after ischemic stroke
Rate of recurrent ischemic stroke, or systemic embolism in occult cancer-related stroke
Measured: Within 1 year after ischemic stroke
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.
Measured: Baseline
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted25 Oct 2023
- Study start1 Jan 2022
- Primary completion31 Dec 2025 (estimated)
- Study completion31 Dec 2025 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Cancer-related StrokeStudies of the same condition, open and under way.
- More trials run by Insel Gruppe AG, University Hospital BernThe 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
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 370 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Insel Gruppe AG, University Hospital Bern
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Simon Jung, MD, Principal investigator, Inselspital, University of Bern
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06100718
- Sponsor's protocol ID
- 2021-01797
- Other IDs
- 2021-01797
- Acronym
- INVISIBLE-1
- Status last verified
- Dec 2024
- First submitted
- 9 Oct 2023
- Last updated
- 13 Dec 2024
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 13 Dec 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Discovery of New Cancer in the 1-year Follow-up After Ischemic Stroke in Patients at Risk: The INVISIBLE-1 Study
- ClinicalTrials.gov ID
- NCT06100718
- Acronym / sponsor ID
- INVISIBLE-1 / 2021-01797
- Conditions
- 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
- Study type
- Observational
- Recruitment status
- Recruiting
- Enrolment
- 370 participants (estimated)
- Lead sponsor
- Insel Gruppe AG, University Hospital BernUniversity, hospital or other
- Study start
- 1 Jan 2022 (actual)
- Primary completion
- 31 Dec 2025 (estimated)
- Study completion
- 31 Dec 2025 (estimated)
- First posted
- 25 Oct 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.
INVISIBLE-1 aims to prospectively follow patients up to one year after ischemic stroke to:
- Determine the cumulative incidence of occult cancer in patients with embolic stroke of undetermined source (ESUS) and elevated D-dimer
- 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.
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:
- Prospectively determine the cumulative incidence of occult cancer in patients with elevated D-dimer and ESUS within 1 year after the ischemic stroke
- 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.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Study group | – | –Acute ischemic stroke patients at high-risk for underlying occult cancer (elevated D-dimer and suspicion of ESUS at admission) |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Age groups
- Adult, Older adult
- 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.
Key inclusion criteria (8 listed)
- 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:
- D-dimer ≥ 820 μg/L measured after symptom-onset and within 24h after admission
Key exclusion criteria (7 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
Number of participants with newly diagnosed cancer (occult cancer)
Time frame: Within 1 year after ischemic stroke
5 secondary outcomes
Determination of occult cancer characteristics
Time frame: Within 1 year after ischemic stroke
Long-term functional outcome using the modified Rankin Scale (mRS) in stroke patients with occult cancer
Time frame: At 1 year after ischemic stroke
All-cause mortality rate and cause-specific mortality rate
Time frame: At 1 year after ischemic stroke
Rate of recurrent ischemic stroke, or systemic embolism in occult cancer-related stroke
Time frame: Within 1 year after ischemic stroke
Stroke severity assessed with the National Institutes of Health Stroke Scale (NIHSS) score in patients with occult cancer
Time frame: Baseline
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 13 Dec 2024.
- Individual participant dataSharing planned: No
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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.
Simon Jung, MD principal investigator
Inselspital, University of Bern
3 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Cancer-related Stroke and Paraneoplastic Coagulopathy, run by Insel Gruppe AG, University Hospital Bern at 3 sites in Switzerland.
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 8 inclusion and 7 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: looking for participants now, as of the sponsor's last update on 13 Dec 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 sites in Switzerland. Whether a site is taking part right now should be confirmed with that site. See every site.
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.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Simon Jung, MD (+41 31 63 2 43 27, simon.jung@insel.ch), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of participants with newly diagnosed cancer (occult cancer) (time frame: Within 1 year after ischemic stroke). 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 13 Dec 2024.